biomedical engineering at ucl 2004 - université ... · pdf filebiomedical engineering...

BIOMEDICAL ENGINEERING AT UCL

20

04

Edited by D. Opfergelt (UCL ADRE)Special thanks to O. Tirions, M. Plevoets, A. Distelmans, F. Kinard and N. Burteau for their contribution

Cover : auditive implant Vibrant® Soundbridge TM (Medel Vibrant, Innsbruck, Austria) - Unité ORL, audiophonologieet logopédie - Dr. Pierre Garin - UCL Mont-Godinne

This compilation «Biomedical Engineering at UCL» has been stimulated by a

Working Group of the Committee for the Applications of Science (CAPAS), in

the frame of the Belgian Royal Academy Council of Applied Sciences. It has

been implemented by the Research Administration of UCL, under the supervi-

sion of Professor Paul ROUXHET, Unité de chimie des interfaces.

3

U N I V E R S I T É C A T H O L I Q U E D E L O U V A I N - B I O M E D I C A L E N G I N E E R I N G A T U C L

Foreword

This presentation aims at highlighting the topics of interest, recent achievements and current developments of

research teams at UCL in the field of Biomedical Engineering.

Biomedical Engineering is considered as the rational use of interactions between the biosciences and the sciences of

inanimate systems (materials, devices, instruments, information, management), for the well-being of humans

and higher animals.

By essence, this field is multidisciplinary. The teams represented belong to four faculties : Faculty of Medecine, Faculty

of Sciences, Faculty of Applied Sciences, Faculty of Bioengineering, Agronomy and Environment. The Université

catholique de Louvain is proud of its tradition of crossing frontiers in teaching and research. This is facilitated by

the short distance between laboratories and is demonstrated by joined projects, as well as by the

frequent involvement of graduate students in more than one laboratory.

The topics cover the main branches of Biomedical Engineering :

Bio-instrumentationRehabilitation engineeringMedical imaging and signal processingBiomaterials Sensors and biosensorsModeling of biological systems

Certain teams have their activity entirely focused on Biomedical Engineering. For other teams, particularly those invol-

ved in «Biomaterials and sensors», Biomedical Engineering is more peripheral or is one field of application among

other ones.

The summary presents a table of the different topics grouped according to the branches cited above. At the

end of the booklet, a key words index refers to the identification number of the activities concerned.

5


Content

A. BIO-INSTRUMENTATION

A.1 - Robotic and computer aided orthognathic

and craniomaxillofacial surgery

H. REYCHLER, R. OLSZEWSKI, B. RAUCENT, B. MACQ, K. TRAN DUY

A.2 - Drug delivery systems micropumps

(4M µµpompe)

B. RAUCENT

A.3 - Radiosterilization of drugs and destruction

of drugs and microorganisms in hospital aqueous

solutions, also waste waters

B. TILQUIN, A. ENGALYTCHEFF, C. SLEGERS, V. DERIDDER

B. REHABILITATION ENGINEERING

B.1 - Middle and inner ear implanted

hearing aids

M. GERSDORFF, N. DEGGOUJ, P. GARIN, M. DECAT

B.2 - Neural rehabilitation engineering

J. DELBEKE, A. DE VOLDER, F. DURET, C. VERAART

B.3 - Functional evaluation in rehabilitation

medicine

M. PENTA, J.L. THONNARD, N. HEGLUND

C. MEDICAL IMAGING AND SIGNAL PROCESSING

C.1 - Medical imaging of cerebral,

hepatic and renal function

B. VAN BEERS, G. COSNARD, C. GRANDIN, F. PEETERS

C.2 - Functional magnetic resonance (NMR, EPR)

spectroscopy and imaging in tumors

B. GALLEZ

C.3 - Biomedical data analysis and

signal processing

M. VERLEYSEN

C.4 - Medical imaging and multimodal

interfaces

B. MACQ, C. DE VLEESCHOUWER

D. BIOMATERIALS

D.1 - Bone, joint and nerve reconstruction

Ch. DELLOYE, O. CORNU, X. BANSE, E. MUNTING, P. POILVACHE,

O. BARBIER

D.2 - Biocompatibilization of polymer devices

J. MARCHAND-BRYNAERT

D.3 - Odontological biomaterials

G. LELOUP-CUMPS, J. DEVAUX, M. DEBATTY-MESTDAGH,

F. DELANNAY, S. DEMOUSTIER-CHAMPAGNE

31

29

27

25

23

21

19

17

15

13

11

9

7

6

D.4 - Efficacy of a thermoplastic polylactic

membrane on guided tissue regeneration and

guided bone reservation in periodontology

P. BERCY, D. BLASE

D.5 - Drug delivery systems

V. PREAT, R. VANBEVER

D.6 - Biomaterials surface and interface

P. BERTRAND, A. DELCORTE, C. POLEUNIS

D.7 - Biomaterial interfaces

M. DEBATTY-MESTDAGH, CH. DUPONT-GILLAIN, Y. DUFRENE,

P. ROUXHET

E. SENSORS AND BIOSENSORS

E.1 - Microsensors and microelectronic

circuits integrated on silicon and

silicon-on-insulator (SOI) substrates

D. FLANDRE

E.2 - Nano-biosensors for biomedical assays

V. BAYOT, S. DEMOUSTIER-CHAMPAGNE, A. JONAS, B. NYSTEN

E.3 - Spectrophotometric sensors for biomedical

diagnosis and control

M. MEURENS

E.4 - Electrophysiological exploration of the

pain system

L. PLAGHKI

E.5 - Development of a microarray allowing

the study of the genic expression in

prostatic cancers

J-L. GALA

E.6 - Development of microarray for

genotyping bacteria and mycobacteria

J-L. GALA

E.7 - Multigenotypic identification of pathogenic

bacteria and their resistance determinant

using biochip technology

J-L. GALA

E.8 - Pharmacogenetics of cytochrome p450,

thiopurine-methyl-transferase and multidrug

resistance

J-L. GALA

E.9 - Interfaces for respiratory monitoring in

emergency care

F. THYS, F. VERSCHUREN, J. ROESELER, M.S. REYNAERT

F. MODELING OF BIOLOGICAL SYSTEMS

F.1 - Biomedical physiopathology :

blood gas and inert gas modeling

D. RODENSTEIN, G. LIISTRO, T. CLERBAUX

F.2 - Modeling in neuroscience

P. LEFEVRE

F.3 - Bio-informatics : analysis of biochemical

networks

Y. DEVILLE, P. DUPONT

F.4 - Biological effects of microwaves and

their measurement

A. VANDER VORST, B. STOCKBROECKX

KEY WORDS INDEX 67

65

63

61

59

57

55

53

51

49

47

45

43

41

39

37

35

33

7


Robotic and computer aided orthognathic and craniomaxillofacial surgery

SENIOR SCIENTISTS :

� Hervé REYCHLER

� Raphaël OLSZEWSKI

� Benoît RAUCENT

� Benoît MACQ

� Khanh TRAN DUY

A 1

Research Field and Subjects

The research is organized along several main streams :1. computer aided orthognathic and craniomaxillofacial surgeryplanning and simulation,2. extra and intra operative robotic devices development forcraniomaxillofacial surgery,3. computer aided osteosynthesis plates positioning, 4. image guided navigation in craniomaxillofacial surgery.

The current research subjects are : 3D cephalometric analysis development, the base of planning

and simulation of craniomaxillofacial surgery,clinical validation of 3D cephalometric analysis,4D cephalometric analysis development (theory), dynamic

growth analysis of the human skull and face,biometric analysis of the human face and cranium,symmetry/asymmetry study of the human face and cranium,extra-operative robotic device for orthognathic surgery simu-

lation (OLA device), clinical use and validation of intra-operative robotic device for

orthognathic surgery, guided by information from ACRO 3D,ACROSIM 3D and ACROGUIDE 3D.

Recent achievements concern : Project HEROL aims at improving maxillo-facial surgery perfor-mances and widening its applications fields by designing themost adapted and powerful tools. In addition to an increase inthe displacement precision of the maxilla and mandible, the sys-tem simplifies the realization of fragmentary operations andprovides a solution to the condyle repositioning problem.Moreover, it will decrease time and employees needed for thepre- and per- operative phases.

The project includes the development of a software for 3D dia-gnosis, planning and simulation and a parallel robot for displa-cement measurement during the pre-operative phase.The last module of the project includes the development of asoftware to guide the surgeon during the operation. This helpwill be provided in real time and will provide information to thesurgeon either through a peripheral screen or through virtualreality stereovision glasses.

Products and Services

Clinical application of computer aided surgery in craniomax-illofacial surgery.

Important oral and craniomaxillofacial surgery.Large field of craniomaxillofacial diseases and operations.Medical software development and validation.Robotic devices development and validation.

Main Equipment

3D measuring machine3D CT Scanning and 3D IRM3D virtual reality stereovison glassesOperating rooms with optic navigation (OPTOTRAK)

Representative References

OLSZEWSKI R., REYCHLER H. Model surgery conception andachievement weaknesses. Société Royale Belge de Stoma-tologie et chirurgie maxillo-faciale-KBVSMFH, Brussels,16.03.2002.

TRAN DUY K., OLSZEWSKI R., RAUCENT B., REYCHLER H.Design of an experimental robot for orthognathic surgery.Poster PAI, KUL-Leuven, 30.10.2002.

OLSZEWSKI R., REYCHLER H. ACRO 3D : a new 3D cephalo-metric analysis. Société Royale Belge de Stomatologie etchirurgie maxillo-faciale-KBVSMFH & Association Française deschirurgiens maxillo-faciaux, Brussels, 14.03.2003.

OLSZEWSKI R., NICOLAS V., MACQ B., REYCHLER H. ACRO4D : universal analysis for four-dimensional diagnosis, 3D plan-ning and simulation in orthognathic surgery. Proceedings CARS2003, International Congress Series 2004 (2003), 1-6, 203-208.

OLSZEWSKI R., LANDENNE S., MACQ B., REYCHLER H.ACRO 3D, the 3D cephalometric analysis, from the theory tothe clinical use. Société Royale Belge de Stomatologie etchirurgie maxillo-faciale, KBVSMFH, Brussels, 20.03.2004.

OLSZEWSKI R., REYCHLER H. Les limites de la chirurgie desmodèles en chirurgie orthognathique : implications théoriqueset pratiques. Rev. Fr. Stomatol. CMF, in press.

8

Patents

Augmented reality vision method apparatus - Copyrights onACRO 4D software

Awards

H. Reychler : Dr. Honoris Causa 2001, University G.T. Popa, Lasi, Rumania.Honorary examiner European board of oro-maxillofacial surgery, 1996Honorary member of the dentists association of Lebanon, 2002

R.Olszewski :Leibinger prize 2002, Association française des chirurgiensmaxillo-faciaux, Paris.

Partnership

Mr. Dormal, (CRIF -Liège), Mr. Lebailly (CERISIC- Mons), Mr. G. Cosnard (UCL- RAIM).

Financed by the Région Wallonne.

STAFF

Total : 16

KEY WORDS FOR R&D

3D cephalometry 3D reconstructionanatomyapplication softwarebiomedical sciencebiometrycraniomaxillofacial surgeryembryology (human)growth and development (human)imaginginformaticsmedical instrumentation orthognathic surgerypaleo anthropology plastic and aesthetic surgery radiology robotsoftwarestereovision glassessurgerytomographyvirtual reality

SENIOR SCIENTISTS

Hervé [email protected]. 32 (0)2 764 57 10

Benoît [email protected]. 32 (0)10 47 25 08

Raphaël [email protected]. 32 (0)2 764 57 02


Khanh TRAN [email protected]. 32 (0)10 47 25 16

WEB SITES

www.md.ucl.ac.be/stomwww.tele.ucl.ac.be/herolwww.prm.ucl.ac.be/ceremwww.tele.ucl.ac.be/medimag

www.md.ucl.ac.be/stom

www.tele.ucl.ac.be/herol

www.prm.ucl.ac.be/cerem

www.tele.ucl.ac.be/medimag

9


Drug delivery systems micropumps (4M µpompe)

SENIOR SCIENTIST :

� Benoît RAUCENT

A 2


The main research objectives aim at developing innovativemethods and means for the miniaturization of machines,especially micropumps.

The research project “4M-µPOMPES” will focus on the designand realization of a medical MICRO-pump. This pump will be used to treat chronicle diseases such as diabetes with regular micro-injections of medicine. In the sameway as a pacemaker, the pump and its tank will be placedunder the skin in order to increase comfort.

Products and services

Design of mechatronics devices for medical application

Partnership

ULB (A. Delchambre),ULG (J. F. Debongnie)

Financed by the Région Wallonne


SMAL O., DERINE D., DEHEZ B., RAUCENT B. Design of amicro-rotative-actuator test bed. Proc. of 2003 IEEE Int. Symp.On assembly Task Planning (ISATP 2003), Besançon, July 10-11,2003, pp13-17.

DERIEN E., DEGEZ B., GRENIER D., RAUCENT B. A Survey ofElectromagnetic Micromoters. IPAS, Int. Precision AssemblySeminar, Bad Hofgastein, Austria, March 17-19, 2003, pp 85-94.

MERKEN P., SMAL O., DEBONGNIE J.F., RAUCENT B. Design andtest of a circular notch hinge. Proc. of the Int. Precision Assemblyseminar, IPAS 2004, Bad Hofgastein February 2004, pp 51-56.

SMAL O., MERKEN P., CROQUET V., DEREINE E., RAUCENT B.,DEBONGNIE J.F., DELCHAMBRE A. Design of an implantablemicropump. Proc. of the Int. Precision Assembly seminar,IPAS’2004, Bad Hofgastein February 2004, pp 185-190.

STAFF

Total : 3

KEY WORDS FOR R&D

drug delivery systemimplantable pumpmicro-hydraulicmicro-motorsmicropump

SENIOR SCIENTIST


WEB SITES

www.prm.ucl.ac.bewww.prm.ucl.ac.be/cerem

www.prm.ucl.ac.be

www.prm.ucl.ac.be/cerem

11


Radiosterilization of drugs and destruction of drugs andmicroorganims in hospital aqueous solutions, also waste waters

SENIOR SCIENTISTS :

� Bernard TILQUIN

� Alix ENGALYTCHEFF

� Catherine SLEGERS

� Véronique DERIDDER

A 3


Our research team is active in the field of the radiosterilizationof solid drugs as well as of thermolabile solid drugs.Radiosterilization by electron beams or gamma rays gives newradiolytic products in traces. The new sensibility of analyticalfacilities allows to detect and identify such compounds, buttheir concentration is too low to be toxic. The radiostability ofcompounds can be predicted by ESR measurements.For aqueous solutions, sterilization at final (terminal productionstep) is possible but theoretical approach is needed.Many antibiotics are effective against legionnaire's bacteria,ionizing radiations are highly effective and prevent the risk inirradiated water distribution system.

Some results :Radical mechanisms in the radiosterilization of metoprolol

tartrate solutions.Study of the radical mechanisms in the radiosterilization of meto-prolol tartrate aqueous solutions in order to determine the param-eters governing its radiostability. Pulse radiolysis with pseudo-first-order kinetics to measure the reaction rate constant of hydratedelectrons and hydroxyl radicals with metoprolol tartrate.Chemsimul® was used to solve the decay kinetics of transientsand to simulate the radiolysis of metoprolol tartrate solutions.

Determination of radical yields in solid-state drugs as one tech-nique to identify drugs that withstand radiosterilization : radiore-sistance of Beta blockers.This article describes a simple preliminary test to determinewhether a drug is sufficiently radioresistant to withstand radios-terilisation. The test is based on the electron spin resonance (ESR)detection of radicals produced after irradiation of a solid-statedrug, assuming that these radicals are the precursors of the finalproducts detected after dissolution of the drug. A calibration curve has therefore been established by measuringESR spectra of L-alanine irradiated at different doses. The responsefactor to quantify the radicals is the normalized double integration(DI) of the whole first-derivative ESR spectrum. The curve gives therelationship between the normalized DI and the number of radi-cals. Eight β-blockers have been chosen and their radical yielddetermined.

This is the first time that several different drugs of the samepharmacological group have been studied and compared. Theresults obtained are similar for seven of the eight β-blockers;the mean G value (excepted for nadolol) is 3 x 10-9 mol/J. Thismeans that β-blockers are radioresistant. The two most radiosensitive drugs (nadolol and esmololhydrochloride) were also studied by high-performance liquidchromatography (HPLC). No significant loss of the active compound was detected, which confirms this radioresistantproperty. Moreover, no change in color or smell was observed.Using ESR and HPLC, β-blockers were identified as potentialcandidates for radiosterilization.

Radiosterilization of cefotaxime : investigation of potentialdegradation compounds by liquid chromatography-electro-spray mass spectrometry.The nonvolatile radiolytic compounds produced by irradiationof cefotaxime were studied by liquid chromatography- electro-spray mass spectrometry method. Full scan LC-MS was first per-formed in order to obtain the m/z value of the protonated mol-ecules of all detected peaks. LC-MS-MS was then carried out onthe compounds of interest. A comparison between the MS-MSspectrum of cefotaxime and those of the radiolytic compoundsshowed that their fragmentation patterns were similar suggest-ing that they were structural analogues of the main drug. The examination of the two main fragmentation pathways alsopermitted the location of the modified substructures. Moreover,it was shown that some stereoisomers appeared with the irradiation process. The complete fragmentation pattern of cefotaxime was studied by MSn and used to obtain informationabout the structure of the radiolytic compounds. A completestructure was proposed for four of these.


International expert in radiosterilization

Main Equipment

Analytical facilities : GC-MS-FTIR; LC-MS-MS, diode array,electrophoretic capillary systems with electrochemical detec-tions, UV, CAMAG, etc.

12


N. BARBARIN, B. ROLLMANN and B. TILQUIN. Role of residualsolvents in the formation of volatile compounds after radiosteril-ization of cefotaxime. Int. J. Pharma., 178, 203-212, 1999.

M. GIBELLA, A.-S. CRUCQ, B. TILQUIN, P. STOKER and J. RAFFI.ESR studies of some irradiated pharmaceuticals. Rad. Phys. Chem.,58, 69-76, 2000.

P. PICCERELLE, J.-P. REYNIER, J. JOACHIM, B. TILQUIN andJ. RAFFI. Radio-stérilisation de médicaments : intérêt, législation ettravaux à entreprendre. J. Pharm. Belg., 55, 131-136, 2000.

A.-S. CRUCQ, C. SLEGERS, V. DERIDDER and B. TILQUIN.Radiosensitivity study of cefazolin sodium. Talanta, 52, 873-877,2000.

N. BARBARIN and B. TILQUIN. Study of nonvolatile degradationcompounds produced by radiosterilisation of cefotaxime. Rad.Phys. Chem., 60, 359-367, 2001.

N. BARBARIN, B. TILQUIN and E. DE HOFFMAN. Radio-sterilization of cefotaxime : investigation of potential degradationcompounds by liquid chromatography-electrospray mass spec-trometry. J. Chromatogr., 929, 51-61, 2001.

A. ENGALYTCHEFF, V. DERIDDER, R. DEBUYST, B. TILQUIN.Determination of radical yields in solid-state drugs as one tech-nique to identify drugs that will withstand radiosterilization :radioresistance of beta blockers. Radiation Research, 160(1), 103-109, 2003.

C. SLEGERS, G. BALDACCHINO, D. LE PARC, B. HICKEL, B. TILQUIN. Radical mechanisms in the radiosterilization of meto-prolol tartrates solutions. Pharmaceut. Res., 20 (12), 1977-1983,2003.

A. ENGALYTCHEFF, M. KOLBERG, M.L. BARRA, K.K.ANDERSON and B. TILQUIN. Multi-frequency EPR Techniques toIdentify the radicals produced in Irradiated ß-Blockers. Free RadicalResearch, 38, 59-66, 2004.

Partnership

CEA Saclay, France (B. Hickel, G. Baldacino)University Descartes, Paris, France (M. Gardes)University Orsay, Paris, France (Ch. Houee)CNRS Orléans, France (M. Charlier)

CNRS-CEA Marseille, France (J. Raffi)Funding Région wallonne

STAFF

Total : 10

KEY WORDS FOR R&D

analytical systemdrugselectron beamsgamma rayslegionnellaradiosterilizationwaste waters

SENIOR SCIENTISTS

Bernard [email protected]. 32 (0)2 764 72 30

Alix [email protected]. 32 (0)2 764 72 94

Catherine [email protected]. 32 (0)2 764 72 92

Véronique [email protected]. 32 (0)2 764 72 94

WEB SITE

www.md.ucl.ac.be/cham

www.md.ucl.ac.be/cham

13


Middle and inner ear implanted hearing aids

SENIOR SCIENTISTS :

� Michel GERSDORFF� Naima DEGGOUJ� Pierre GARIN� Monique DECAT

B 1


The implants of middle ear are intended to correct average andsevere deafnesses of the adult, which cannot effectively becompensated by the conventional audioprosthesis. It is a verynew field of industrial research in otorhinolaryngology, where itis necessary to study :

the indications for this type of implant, the technological development of the implant, the biocompatibility of the implant, the lifespan of the components, the results in term of auditive profit, the side effects, the counter-indications,the effect of bilateral cochlear implantation on auditory dis-

crimination and localisation,the effect of early implantation on language and hearing abil-

ities for children,the association of conventional hearing aid and cochlear

implant on the same ear,the local diffusion of neurotrophic drugs in the implanted

cochlea.


Animal model Auditive testsClinical analysesTechnological studies

Main Equipment

Animal laboratory AudiometryLaser vibrometry


GERSDORFF M., DERNE L., SNEPPE R., BARBAIX M.T., DUTIL-

LIEUX D., DE WILDE V., VANDERLINDEN F., VANDERBEMDEN S.Implant cochléaire et perception vibro-tactile. Rev. Laryngol.Otol. Rhinol. (Bord), 1987; 108(4) : 335-337.

GERSDORFF M., SNEPPE R., WITTEMANS S., BARBAIX M.T.,DERUE L., MONTMIRAIL C., VANDERBEMDEN S. Our experiencein rehabilitation of the severely deaf by means of a monocanalcochlear implant. Am. J. Otol., 1987 Nov; 8(6) : 537-544.

GERSDORFF M. Results of cochlear implants in children. ActaOtorhinolaryngol. belg., 1991; 45 (3) : 293-295.

GERSDORFF M., GUERIT J.M., DEGGOUJ N., DETOURTCHANINOFF M. In cochlear implants : new perspectives.B. Fraysse-O. Deguine Eds. Karger, Basel, 1993; 35-443.

GERSDORFF M., GUERIT J.M., DEGGOUJ N., DETOURTCHANINOFF M. The contribution of brain mapping inthe wearer of a cochlear implantation. Preliminary report. Adv.Otorhinolaryngol, 1993; 48 : 35-43.

DEGGOUJ N., GERSDORFF M., HUAUX H., DERUE L.Comparaison des résultats obtenus chez les enfants sourds pro-fonds porteurs de prothèses conventionnelles et les enfantsporteurs d’un implant cochléaire. Abstract présenté au 90èmeCongrès de la Société Française d’ORL, Paris, Sept. 1993;Librairie Arnette, Paris, page 122.

DEGGOUJ N., DE TOURTCHANINOFF M., GERSDORFF M.,GUERIT J.M. Intérêt du “Brain Mapping” des potentiels évoquésauditifs tardifs chez les sujets porteurs d’un implant cochléaire.Acta ORL Belgica., 1994; 48 : 245-250.

DEGGOUJ N., GERSDORFF M., VANDERBEMDEN S., DERUEL., HUAUX H., DUTILLIEUX D., MONTEYNE V., MEERT C., DENISM., MONTMIRAIL C. Indications et résultats avec l’implantcochléaire. Le langage et l’Homme., Décembre 1994; volumeXXIX Nr 3 : 263-272.

GERSDORFF M. Les Implants cochléaires. Bull. Mem. Acad. R.Med. Belg., 1997; 152(5) : 215-223; discussion 224-7.

MINET M., DEGGOUJ N., GERSDORFF M. Cochlear implanta-tion in patients with Cogan’s syndrome : a review of four cases.Eur. Arch. Otorhinolaryngol., 1997; 254 : 459-462.

DEGGOUJ N., GERSDORFF M. Imaging and cochlear Imaging.Acta ORL Belg. 52(2), 1998; 133-143.

DEGGOUJ N., PHILLIPS C., GERSDORFF M. Role of speechtherapy and sign language prior to cochlear implantation. ActaORL Belg. 52, 1998; 275-279.

14

FRAYSSE B., LAVIEILLE J.P., SCHMERBER S., ENEE V., TRUY E.,VINCENT C., VANEECLOO F.M. and STERKERS O. A multicenterstudy of the Vibrant® Soundbridge™ middle ear implant : earlyclinical results and experience. Otology & Neurotology, 2001;22 : 952-961.

FISCH U., CREMERS C.W.J., LENARZ T., WEBER B., BABIBGHI-AN G., UZIEL A., PROOPS D., O'CONNOR A.F., CHARACHON R.,HELMS J. and FRAYSSE A. Clinical experience with the Vibrant®Soundbridge™ implant device. Otology & Neurotology, 2001,22 : 962-972.

SNIK A., MYLANUS E., CREMERS C., DILLIER N., FISCH U.,GNADEBERG D., LENARZ T., MAZOLLI M., BABIGHIAN G., UZIELA., COOPER H., O'CONNOR A., FRAYSSE B., CHARACHON R.and SHEHATA-DIELER W. Multicenter audiometric results withthe Vibrant® Soundbridge™, a semi-implantable hearingdevice for sensorineural hearing impairment. Otolaryngol Clin.N. Am., 2001, 34 : 373-388.

LUETJE C.M., BRACKMAN D., BALKANY T.J., MAW J., BAKERR.S., KELSALL D., BACKOUS D., MIYAMOTO R., PARISIER S. andARTS A. Phase III clinical trial results with the Vibrant Soundbridgeimplantable middle ear hearing device : a prospective controlledmulticenter study. Otol. HNS, 2002; 126 : 97-107.

Awards

Founder member of the European Academy of Otology andNeurotology.

Member of the international network Politzer Society.

Partnership

Portmann Institute (Bordeaux, France)International research program “Implant cochléaire et aide

auditive combinés” (Toulouse, France) et Meniett®, maladie deMénière (Paris, France).

STAFF

Total : 7

KEY WORDS FOR R&D

artificial organauditory plasticitybiomechanicsbiomedical engineeringcochlear implantdeafnesshearing aidhearing lossimplantlanguage developmentmedical instrumentationotorhinolaryngologystereophony

SENIOR SCIENTISTS

Michel [email protected]. 32 (0)2 764 19 45

Naima [email protected]. 32(0)2 764 19 48

Pierre [email protected]. 32(0)2 764 19 49

Monique [email protected]. 32(0)2 764 19 40

WEB SITE

www.orlo.ucl.ac.be

www.orlo.ucl.ac.be

15


Neural rehabilitation engineering

SENIOR SCIENTISTS :

� Jean DELBEKE� Anne DE VOLDER� Florence DURET� Claude VERAART

B 2


The Neural Rehabilitation Engineering Laboratory (GREN) is devo-ted to basic and applied research in rehabilitation engineering andmore specifically artificial restoration of sensory and motor func-tions. Several projects are dealing with basic studies about motor andsensory systems, either normal or impaired, and with the designand assessment of neuroprostheses interfaced with intact biologi-cal structures, and aiming at restoring impaired functions.Damage to the central nervous system arising from trauma or dis-ease frequently results in serious disabilities. Particularly, dysfunc-tion of the motor system (e.g. : spinal cord injuries) involving a lossof mobility, and sensory ailments such as retinitis pigmentosa, orother causes of blindness, have a devastating impact on the indi-vidual's quality of life. Such conditions affect large numbers ofpatients.Our team is involved in several research projects funded by national and international agencies. Among these the laboratoryis currently coordinating research exploiting the advantages offered by a self-sizing spiral cuff nerve electrode, including a large number of recording contacts and on site microchips to improveselective recording from peripheral nerves. The result should provide access to the natural sensors for prosthetic control.Another example is the development of visual prosthesis. A spiralcuff nerve electrode has been chronically implanted intracraniallyaround the optic nerve of a retinitis pigmentosa blind volunteer.Very low current give rise to the perception of phosphenes withinthe still functional part of the patient's visual field. So far, this opticnerve visual prosthesis allows object recognition, discrimination,and grasping.


Assistance for the design of interfaces between neural struc-tures and artificial systems including electrode development andmodelling.

Main Equipment

Facility for self-sizing spiral cuff nerve electrode manufacture insterile condition.

Facilities and equipment for electro-physiological experimentation.

Maze for mobility rehabilitation studies dealing with visual, or sen-sory substitution prostheses.

Finite element modelling tools for the study of nerve activation byelectric currents.


CAPELLE C., TRULLEMANS C., ARNO P., VERAART C. A real timeexperimental prototype for enhancement of vision rehabilitationusing auditory substitution. IEEE Trans. Biomed. Eng., 1998, 45 :1279-1293.

VERAART C., RAFTOPOULOS C., MORTIMER J.T., DELBEKE J., PINSD., MICHAUX G., VANLIERDE A., PARRINI S., WANET-DEFALQUEM.C. Visual sensations produced by optic nerve stimulation using animplanted self-sizing spiral cuff electrode. Brain Research, 1998,813 : 181-186.

DE VOLDER A.G., CATALAN-AHUMADA M., ROBERT A., BOL A.,LABAR D., COPPENS A., MICHEL C., VERAART C. Changes in occip-ital cortex activity in early blind humans using a sensory substitutiondevice. Brain Research, 1999, 826 : 128-134.

ARNO P., CAPELLE C., WANET-DEFALQUE M.C., CATALAN-AHU-MADA M., VERAART C. Auditory coding of visual patterns for theblind. Perception, 1999, 28 : 1013-1029.

PARRINI S., DELBEKE J., ROMERO E., LEGAT V., VERAART C. A hybrid finite elements–spectral method for computation of theelectric potential generated by a nerve cuff electrode. Med. Biol. Eng.Comput., 1999, 37 : 733-736.

ROMERO E., CUISENAIRE O., DENEF J.F., DELBEKE J., MACQ B.,VERAART C. Automatic morphometry of nerve histological sections.J. Neuroscience Method., 2000, 97 : 111-122.

OOSTENDORP T.F., DELBEKE J. & STEGEMAN D.F. The conductivi-ty of the human skull : results of in vivo and in vitro measurements.IEEE Trans. Biomed. Eng., 2000; 47(11) : 1487-1492.

PARRINI S., DELBEKE J., LEGAT V., VERAART C. Modelling analysisof human optic nerve fibre excitation based on experimental data.Med. Biol. Eng. Comput., 2000, 38 : 454-464.

DELBEKE J., PINS D., MICHAUX G., WANET-DEFALQUE M.C., PARRINI S., VERAART C. Electrical Stimulation of Anterior VisualPathways in Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci., 2001,42 : 291-297.

ROMERO E., DENEF J.F., DELBEKE J., ROBERT A., VERAART C.

16

Neural morphological effects of long term implantation of the self-sizing spiral cuff nerve electrode. Med. Biol. Eng. Comput.,2001, 39 : 90-100.

SANABRIA-BOHORQUEZ S., DE VOLDER A., ARNO P., SIBOMANAM., COPPENS A., MICHEL C., VERAART C. Decreased benzodi-azepine receptor density in the cerebellum of early-blind human subjects. Brain Research, 2001, 888 : 203-211.

ARNO P., DE VOLDER A., VANLIERDE A., WANET-DEFALQUE M.C.,STREEL E., ROBERT A., SANABRIA-BOHORQUEZ S., VERAART C.Occipital activation by pattern recognition in the Early Blind usingauditory substitution of vision. Neuroimage, 2001, 13 : 632-645.

DE VOLDER A., TOYAMA A., KIMURA M., KIYOSAWA M.,NAKANO H., VANLIERDE A., WANET-DEFALQUE M.C., MISHINA M.& ODA K. Auditory triggered mental imagery of shape involves visual association areas in early blind humans. Neuroimage, 2001; 14 : 129-139.

DELBEKE J., WANET-DEFALQUE M.C., GERARD B., TROOSTERS M.,MICHAUX G., VERAART C. The microsystems based visual prosthesisfor optic nerve stimulation. Artificial Organs, 2002, 26 : 232-234.

DELBEKE J., OOZEER M., VERAART C. Position, size and lumi-nosity of phosphenes generated by direct optic nerve stimulation.Vision Research, 2003, 43 : 1091-1102.

Patents

VERAART C. Dispositif de réhabilitation visuelle utilisant le canalauditif. Belgian Patent n° 08900322, March 23, 1989.

GRILL W.M., CREASEY G.H., KSIENSKI D.A., VERAART C., MORTIMER J.T. Thin film implantable electrode and method of manufacture. US Patent # 5 324 322, June 28, 1994.

DELBEKE J., GÉRARD B., VERAART C. Vision RehabilitationMethod and Device. US Provisional Patent Application PCT/US60/288,583, May 3, 2001.

VERAART C., MORTIMER J.T. Device and method for productionof visual sensations by optic nerve stimulation. US Patent 6 442 431,B1, August 27, 2002.

Awards

President of the “Société d’électromyographie clinique de languefrançaise”.

Member of the board of the “Centre de recherche en neuro-sciences”, UCL.

Partnership

DELIMER sa, (founder, status of innovating society).BIO-LOGIC SYSTEMS Corp., Mundelein, Illinois, USA.NEUROTECH sa (co-founder).

Participation in European Union programs :ESPRIT (MIVIP), Quality of life (SENS), Information Society

Technologies (OPTIVIP), TMR (NEURALPRO). Région Wallonne (Belgium) : Wallonia-Development-University

program and project in Recherche d’initiative.Foundation for Medical Scientific Research.

STAFF

Total : 20

KEY WORDS FOR R&D

biomedical engineeringfunctional imagingneuroprosthesesneurosciencerehabilitation engineeringsensory substitutionvisual prosthesis

SENIOR SCIENTISTS

Jean [email protected]. 32 (0)2 764 54 45

Anne DE [email protected]. 32 (0)2 764 54 42

Florence [email protected]. 32 (0)2 764 54 40

Claude [email protected]. 32 (0)2 764 54 46

WEB SITE

www.md.ucl.ac.be/gren

www.md.ucl.ac.be/gren

17


Functional evaluation in rehabilitation medicine

SENIOR SCIENTISTS :

� Massimo PENTA� Jean-Louis THONNARD� Norman HEGLUND

B 3


The Laboratory of Rehabilitation and Physical Medicine (READ)and the Laboratory of Biomechanics and Physiology ofLocomotion (LOCO) are collaborating on the development of asolution to functional evaluation of patients undergoing reha-bilitation in various clinical settings including physical medicine,rheumatology, neurology, geriatry and the like. In the past fewyears we have developed a manual ability scale, ABILHAND,based on a new psychometric model (Rasch). This scale hasbeen translated into six languages and adapted for use in chil-dren as well as in adults.The increasing demand for healthcare competes with theincreasing demand for cost control in this sector. Therefore,most healthcare financing organisations are now urging health-care practitioners to account for the efficiency of their treat-ments, and are progressively switching the reimbursement froma structural basis (e.g. the number of beds) to an activity basis(e.g. the type of patients treated and the outcome of the treat-ments). Most functional evaluation tests used in rehabilitation consist ofmultiple-choice questionnaires. However, two major obstaclesprevent the widespread systematic use of outcome evaluationsin rehabilitation medicine :

1. the workload required to convert ’paper and pencil’ testsinto an electronic format,

2. the difficulty of analysing and interpreting test scores.

We have developed a commercial product that overcomesthese two obstacles and we are starting to commercialise it via a future spin-off of the Université catholique de Louvain, created by the end of 2004.


The main product of the spin-off company is called Outcome©.It consists of a data input and a data interpretation interface forfunctional evaluation in rehabilitation medicine.

Outcome has a test-independent and language-independentdata input interface. It allows any multiple-choice questionnai-

re to be entered either via a handheld or a desktop computer.The Outcome system is completely scalable. It is useful for a sin-gle evaluator entering data into his handheld computer all theway up to a centre where an unlimited number of evaluatorscollect and share data via a central secure database. A customevaluation report can be printed for each evaluation. Outcomecan also be interfaced with most existing management systemsfor electronic medical data. Moreover, the data can be exportedin various formats for further spreadsheet analysis.

The data interpretation module is mostly focused on the Raschmodel, that formulates the requirements for quantitative mea-surement. Each centre sends its data to a central database viaan anonymous and encrypted protocol. The tests are then cali-brated with the Rasch model in our office in order to determi-ne the level of achievement required for each question. Thecalibration of each test is then sent back to the centres allowingthem to quantitatively follow a patients’recovery on a linearscale. Computer adaptive algorithms are also implemented todecrease test length without compromising the measurementprecision. Furthermore, the calibration of a reference databasefor each test allows establishing minimal standards for the qua-lity of care and benchmarking functional status at the regional,national or international level.


PENTA M., THONNARD J.L., TESIO L. ABILHAND : a Rasch-builtmeasure of manual ability. Arch. Phys. Med. Rehabil., 1998; 79 : 1038-1042.

HAIGH R., TENNANT A., BIERING-SORENSEN F., GRIMBY G.,MARINCEK C., PHILLIPS S., RING H., TESIO L., THONNARD J.L.The use of outcome measures in physical medicine and rehabil-itation within Europe. J. Rehabil. Med., 2001; 33 : 273-8.

PENTA M., TESIO L., ARNOULD C., ZANCAN A., THONNARDJ.L. The ABILHAND questionnaire as a measure of manual abil-ity in chronic stroke patients : Rasch-based validation and rela-tionship to upper limb impairments. Stroke, 2001; 32 : 1627-1634.

BARBIER O., PENTA M., THONNARD J.L. Outcome evaluationof the hand and wrist according to the International classifica-

18

tion of functioning, disability and health. Hand Clinics, 2003;19 : 371-8.

TENNANT A., PENTA M., TESIO L., and al. Assessing andadjusting for cross-cultural validity of impairment and activitylimitation scales through differential item functioning withinthe framework of the Rasch model : the PRO-ESOR Project.Medical Care, 2004; 42(1) : I-I3748.

ARNOULD C., PENTA M., RENDERS A., THONNARD J.L. ABILHAND-Kids : a measure of manual ability in children withcerebral palsy. Neurology (In press).

Awards

Best poster award at the 2nd World Congress of theInternational Society of Physical Medicine and RehabilitationMedicine. Prague, Czech Republic, 18-22 May 2003.

Partnership

Instituto Auxologico, Milan, Italy, Prof. L. Tesio. The University of Leeds, UK, Prof. A. Tennant.

STAFF

Total : 4

KEY WORDS FOR R&D

functional evaluationhandheld computershealth-care financingpaperless medical recordRasch measurementrehabilitation medicine

SENIOR SCIENTISTS

Massimo [email protected](32) 10 47 44 25

Jean-Louis [email protected](32) 2 764 53 67

Norman [email protected](32) 10 47 44 32

WEB SITES

www.read.ucl.ac.bewww.md.ucl.ac.be/ieprwww.outcomemeasures.comwww.abilhand.org

www.read.ucl.ac.be

www.md.ucl.ac.be/iepr

www.outcomemeasures.com

www.abilhand.org

19


Medical imaging of cerebral, hepatic and renal function

SENIOR SCIENTISTS :

� Bernard VAN BEERS� Guy COSNARD� Cécile GRANDIN� Frank PEETERS

C 1


The research unit is active in the field of functional imaging inthe brain, liver and kidney with computed tomography andmagnetic resonance imaging (MRI).

Cerebral perfusion and diffusion models have been developedand validated in the context of the hyperacute phase of stroke.It has been shown that perfusion imaging is a useful tool in pre-dicting the region at risk (ischemic penumbra) around the initialinfarct core.

Neuroanatomic correlates of calculation and faces recognitionand functional reorganization of brain in children affected withcongenital hemiplegia are studied with functional magneticresonance imaging.

Hepatic perfusion models have been developed and validated.They are applied in the study of the perfusion and permeabilitychanges in diffuse liver diseases (cirrhosis and fibrosis) and theassessment of the effects of vasoactive drugs in portal hyper-tension. Applications of similar models to focal liver lesions(tumors) is a current topic of interest. Molecular diffusion andtissue elasticity are studied with MRI in diffuse and focal liverlesions before and after pharmacological treatment.

Cellular imaging is performed by MR tracking of transplantedhepatocytes marked with iron oxide particles.

Mathematical models to measure renal perfusion and glomeru-lar filtration rate have been developed. Methods based on massbalance and deconvolution have been validated in the rabbit.


Detection of cerebral activations with functional MRIMeasurements of cerebral, hepatic and renal functional

parametersLiver and brain volumetryMR monitoring of drugs effects

Main Equipment

Three 1.5 T magnetic resonance scanners

Four multislices computed tomography scannersVisual and auditory stimulation for detection of cerebral

activationsSoftware for functional image analysis


MATERNE R., VAN BEERS B.E., SMITH A.M., LECONTE I.,JAMART J., DEHOUX J.P., KEYEUX A., HORSMANS Y. Non-inva-sive quantification of liver perfusion with dynamic computedtomography and a dual-input one-compartmental model. Clin.Sci. (Lond), 2000; 99 : 517-525.

SMITH A.M., GRANDIN C.B., DUPREZ T., MATAIGNE F.,COSNARD G. Whole brain quantitative CBF and CBV measure-ments using MRI bolus tracking : comparison of methodologies.Magn. Reson. Med., 2000; 43 : 559-564.

VAN BEERS B.E., LECONTE I., MATERNE R., SMITH A.M.,JAMART J., HORSMANS Y. Hepatic perfusion parameters inchronic liver disease : dynamic CT measurements correlatedwith disease severity. AJR Am. J. Roentgenol., 2001; 176 :667-673.

VAN BEERS B.E., SEMPOUX C., DELOS M., SMITH A.M.Biodistribution of ultrasmall iron oxide particles in the rat liver.J. Magn. Reson. Imaging, 2001; 13 : 594-599.

GRANDIN C.B., DUPREZ T.P., SMITH A.M., MATAIGNE F.,PEETERS A., OPPENHEIM C., COSNARD G. Usefulness of mag-netic resonance-derived quantitative measurements of cerebralblood flow and volume in prediction of infarct growth in hyper-acute stroke. Stroke 2001; 32 : 1147-1153.

OPPENHEIM C., GRANDIN C., SAMSON Y., SMITH A.,DUPREZ T., MARSAULT C., COSNARD G. Is there an apparentdiffusion coefficient threshold in predicting tissue viability inhyperacute stroke. Stroke 2001; 32 : 2486-2491.

MATERNE R., SMITH A.M., PEETERS F., DEHOUX J.P., KEYEUXA., HORSMANS Y., VAN BEERS B.E. Assessment of hepatic perfusion parameters with dynamic MRI. Magn. Reson. Med.,2002; 47 : 135-142.

MATERNE R., ANNET L., DECHAMBRE S., SEMPOUX C., SMITH A.M., COROT C., HORSMANS Y., VAN BEERS B.E. Dynamiccomputed tomography with low- and high-molecular-mass contrastagents to assess microvascular permeability modifications in a

20

model of liver fibrosis. Clin. Sci. (Lond), 2002; 103 : 213-216.

GRANDIN C.B., DUPREZ T.P., SMITH A.M., OPPENHEIM C.,PEETERS A., ROBERT A.R., COSNARD G. Which MR-derivedperfusion parameters are the best predictors of infarct growthin hyperacute stroke? Comparative study between relative andquantitative measurements. Radiology 2002; 223 : 361-370.

DUQUE J., THONNARD J.L., VANDERMEEREN Y., SEBIRE G.,COSNARD G., OLIVIER E. Correlation between impaired dexter-ity and corticospinal tract dysgenesis in congenital hemiplegia.Brain 2003; 126 : 732-747.

VAN BEERS B.E., MATERNE R., ANNET L., HERMOYE L.,SEMPOUX C., PEETERS F., SMITH A.M., JAMART J., HORSMANSY. Capillarization of the sinusoids in liver fibrosis : noninvasiveassessment with contrast-enhanced MRI in the rabbit. Magn.Reson. Med., 2003; 49 : 692-699.

VANDERMEEREN Y., SEBIRE G., GRANDIN C.B., THONNARDJ.L., SCHLOGEL X., DE VOLDER A.G. Functional reorganizationof brain in children affected with congenital hemiplegia : fMRIstudy. Neuroimage, 2003; 20 : 289-301.

ANNET L., MATERNE R., DANSE E., JAMART J., HORSMANSY., VAN BEERS B.E. Hepatic flow parameters measured with MRimaging and Doppler sonography : correlations with the degreeof cirrhosis and portal hypertension. Radiology, 2003; 229 : 409-414.

PEETERS F., ANNET L., HERMOYE L., VAN BEERS B.E. Inflowcorrection of hepatic perfusion measurements using T1-weight-ed, fast gradient-echo, contrast-enhanced MRI. Magn. Reson.Med. 2004; 51 : 710-717.

HERMOYE L., ANNET L., LEMMERLING P., PEETERS F., JAMARF., GIANELLO P., VAN HUFFEL S., VAN BEERS B.E. Calculation ofthe renal perfusion and glomerular filtration rate from the renalimpulse response obtained with MRI. Magn. Reson. Med.2004; 51 : 1017-1025.

Awards

C. Grandin : 6th International Lucien Appel Prize forNeuroradiology, 2002.

B. Van Beers : executive board member of the EuropeanSociety for Magnetic Resonance in Medecine and Biology,2003.

STAFF

Total : 8

KEY WORDS FOR R&D

biomedical engineeringdiffusion imagingfunctional imaginggastro-enterologyimagingmagnetic resonance nephrologyneurologyperfusion imagingpharmacologyphysiological modelingradiologysignal processingstroketumor

SENIOR SCIENTISTS

Bernard VAN [email protected]. 32(0)2 764 29 45

Guy [email protected]. 32(0)2 764 29 33

Cécile [email protected]. 32(0)2 764 27 94

Frank [email protected]. 32(0)2 764 29 28

WEB SITE

www.md.ucl.ac.be/rdgn

www.md.ucl.ac.be/rdgn

21


Functional magnetic resonance (NMR, EPR) spectroscopy and imaging in tumors

SENIOR SCIENTIST :

� Bernard GALLEZ

C 2


The major theme of the research is to understand how the tumormicro-environment influences the response to treatments. Two mainareas of research are involved :

Development of sensors for monitoring the oxygen in tissues byEPR.Selection of paramagnetic materials possessing favourable featuresfor oximetry. Microencapsulation of oxygen sensors in biocompatiblefilms to improve their performance in vivo and their biocompatibility.

Applications of magnetic resonance (EPR and NMR) to character-ize the micro-environment in tumors and modulate the response toanti-cancer treatments.Use of combination therapies against cancer (vasoactive agents +radiotherapy / antiangiogenesis + radiotherapy / …) to improve theresponse of tumors to treatments : characterization of pO2, flow,oxygen consumption, permeability of vessels, nitric oxide,… and cor-relation with the tumor growth.

Other aspects : New applications of in vivo EPR : retrospective dosimetry, bone

cement formation, detection of free radicals in vivo.Functional MR imaging applied to muscle exercise.


EPR in vitro (free radicals, including spin trapping)EPR in vivo in small animalsNMR imaging in small animalsOxygen measurementsFlow measurements

Main Equipment

NMR spectrometer and imaging 4.7 Tesla for small animalsEPR spectrometer (9 GHz, X-Band) for in vitro experimentsEPR spectrometer (1 GHz, L-Band) for in vivo experimentsOxyLite (pO2 measurements by fluorescence quenching)OxyFlo (laser-doppler)


B. GALLEZ, R. DEBUYST. Detection of glass foreign bodies in softtissues using low frequency EPR spectroscopy. Appl. Magn. Reson.

20, 579-582, 2001.

J. HE, N. BEGHEIN, P. CEROKE, R.B. CLARKSON, H.M. SWARTZand B. GALLEZ. Development of biocompatible films holding para-magnetic carbon particles : evaluation of their performance and sta-bility in EPR oximetry. Magn. Reson. Med. 46, 610-614, 2001.

P. LEVÊQUE, D. LABAR, B. GALLEZ. Biodistribution, binding speci-ficity and metabolisation of [18F]fluoroethylflumazenil in rodents.Nucl. Med. Biol. 28, 809-814, 2001.

J. HE, N. BEGHEIN, R.B. CLARKSON, H.M. SWARTZ and B. GALLEZ.Microencapsulation of carbon particles used as oxygen sensors inEPR oximetry to stabilize their responsiveness to oxygen in vitro andin vivo. Phys. Med. Biol. 46, 3323-3329, 2001.

R. J. DEMEURE, B. F. JORDAN, Q.X. YANG, N. BEGHEIN, M.B. SMITH, V. GRÉGOIRE and B. GALLEZ. Removal of local field gradient artefacts in BOLD contrast imaging of head and necktumors. Phys. Med. Biol. 47, 1819-1825, 2002.

B.F. JORDAN, V. GRÉGOIRE, R. J. DEMEURE, P. SONVEAUX, O. FERON, J. O’HARA, V. VANHULLE, N. DELZENNE and B. GALLEZ.Insulin increases the sensitivity of tumors to irradiation : Involvementof an increase in tumor oxygenation mediated by a nitric oxidedependent decrease of the tumor cells oxygen consumption. CancerRes. 62, 3555-3561, 2002.

C. BAUDELET and B. GALLEZ. How Blood Oxygen LevelDependent (BOLD) contrast is correlated to the oxygen partial pres-sure of oxygen in tumors? Magn. Reson. Med. 48, 980-986, 2002.

M. ZDRAVKOVA, J.M. DENIS, B. GALLEZ and R. DEBUYST.Sensitivity of whole human teeth to fast neutrons and gamma-raysestimated by L-Band EPR spectroscopy. Radiat. Measurements 35,603-608, 2002.

M. ZDRAVKOVA, A. WIESER, N. EL-FARANAWY, B. GALLEZ, R. DEBUYST. An in vitro L-Band electron paramagnetic resonancestudy of highly irradiated whole teeth. Radiat. Protection Dosimetry,101, 497-502, 2002.

C. DAUBIOUL, N. ROUSSEAU, R. DEMEURE, B. GALLEZ, H. TAPER,B. DECLERCK and N. DELZENNE. Dietary fructans, but not cellulose,decrease triglyceride accumulation in the liver of obese Zucker Fa/Farats. J. Nutr. 132, 967-973, 2002.

P. SONVEAUX, C. DESSY, A. BROUET, B. JORDAN, V. GRÉGOIRE, B. GALLEZ, J.L. BALLIGAND and O. FERON. Modulation of the tumor vasculature functionality by ionizing radiation accounts for tumor radio-sensitization and promotes gene delivery. FASEB J.16, 1979-1981, 2002.

22

B. GALLEZ and N. BEGHEIN. Non invasive in vivo EPR monitor-ing of the methyl methacrylate polymerization during the bonecement formation : A feasibility study. Biomaterials 23, 4701-4704, 2002.

B.F. JORDAN, N. BEGHEIN, M. AUBRY, V. GRÉGOIRE and B.GALLEZ. Potentiation of radiation-induced regrowth delay byisosorbide dinitrate in FSa II murine tumors. Int. J. Cancer103,138-141, 2003.

B.F. JORDAN, P. SONVEAUX, O. FERON, V. GRÉGOIRE and B.GALLEZ. Nitric oxide mediated increase in tumor blood flow andoxygenation of tumors implanted in muscles stimulated by electricpulses. Int. J. Radiat. Oncol. Biol. Phys. 55, 1066-1073, 2003.

C. BAUDELET and B. GALLEZ. A cluster analysis of fMRI timesseries in tumors to study the heterogeneity of hemodynamicresponse to treatments. Magn. Reson. Med., 2003.

M. ZDRAVKOVA, N. CROKART, F. TROMPIER, B. ASSELINEAU, E.GAILLARD-LECANU, B. GALLEZ and R. DEBUYST. Retrospectivedosimetry after criticality accidents using low frequency EPR : astudy on whole human teeth irradiated in a mixed neutron andgamma field. Radiat. Res., 2003.

P. MAHY, M. DE BAST, B. GALLEZ, J. GUEULETTE, C.J. KOCH, P.SCALLIET and V. GRÉGOIRE. In vivo co-localization of 2-nitroimi-dazole EF5 fluorescence intensity and electron paramagnetic reso-nance oximetry in mouse tumors. Radiother. Oncol., 2003, in press.

Patents

GALLEZ B., BEGHEIN N. Carbon blacks as EPR sensors for local-ized measurements of tissue oxygenation. US Patent, 2003 sub-mitted.

Awards

Biennial price 1994-1995 of the Société Belge des SciencesPharmaceutiques.

Price 1998 of the Fondation Universitaire, section Alumni,Sciences médicales, pharmaceutiques et vétérinaires.

Price Paul Van de Velde 2000 - Nouveaux outils diagnostiquesou thérapeutiques.

Young Investigator Award of the International EPR Society2000.

Partnership

H.M. Swartz, EPR Research Center, Dartmouth Medical School,Hanover, NH, USA

R. Clarkson, University of Urban-Champaign, Urbana, IL, USAK. Mäder, University of Halle, Germany

STAFF

Total : 9

KEY WORDS FOR R&D

angiogenesisbiocompatibilitybiomaterialsbiomedical engineeringbiophysicsbiosensorscancerchemotherapyEPRfree radicalsfunctional imaginghemodynamicsimagingMRInitric oxideNMRoxygenpharmacologyradiotherapyradiosensitivityspectroscopyspin trappingtumor

SENIOR SCIENTIST


WEB SITE

www.rema.ucl.ac.be

www.rema.ucl.ac.be

23


Biomedical data analysis and signal processing

SENIOR SCIENTIST :

� Michel VERLEYSEN

C 3


Artificial neural networks are powerful, non-linear data analysistools that can be used in many disciplines. With regards to classical data analysis tools, they are particularlysuited to handle complex, noisy, stochastic and inaccurate data. They make few hypotheses on the data to analyze (they are closefrom non-parametric models), according to the «learning fromdata» paradigm. The recent evolution in the field of biomedical data analysisshows that such models are powerful in many contexts, rangingfrom biomedical signal analysis to the development of prosthe-ses. In this context, our group is active in the following subjects :

Development and use of artificial neural networks and otherlearning paradigms, for biomedical signal and data analysis.

Development of data analysis tools compatible with the noisystructure of biomedical data (for example, analysis ofphosphenes generated by a visual prosthesis for blind people).

Analysis of EEG signals with «independent component analy-sis» (ICA) methods, to remove artifacts and make medical inter-pretation easier.

Analysis of ECG signals from pregnant women by ICA meth-ods, to extract the complete foetus ECG from signal measuredon the mother's abdomen.

Other data analysis methods applied to biomedical signals ordata.


Development of software for biomedical data and signal analysis.

Collaboration with medical doctors to process data and signals, in order to make their medical interpretation easier.

Main Equipment

Availability of necessary computing resourcesAvailability of ECG recording equipment


C. ARCHAMBEAU, A. LENDASSE, C. TRULLEMANS, C. VERAART,J. DELBEKE, M. VERLEYSEN. Phosphene evaluation in a visualprosthesis with artificial neural networks. EUNITE 2001,European Symposium on Intelligent Technologies, HybridSystems and their implementation on Smart Adaptive Systems,Tenerife (Spain), 13-14 December 2001, pp. 509-515.

F. VRINS, J.A. LEE, M. VERLEYSEN, V. VIGNERON, C. JUTTEN.Improving independent component analysis performances by variable selection. IEEE Workshops on Neural Network forSignal Processing, September 17-19, 2003, Toulouse, France.

Partnership

DTI sa (Naninne, Belgium), Analysis of EEG signals.INP Grenoble (France) and Robert Debré Hospital (Paris,

France), Non invasive detection of foetal ECG.European Union Program “OPTIVIP”, Optimization of Visual

implantable prosthesis.

24

STAFF

Total : 4

KEY WORDS FOR R&D

artificial neural networksbiomedical engineeringdata analysiselectrocardiogramselectroencephalogramssignal processingvisual prosthesis

SENIOR SCIENTIST

Michel [email protected]. 32 (0)10 47 25 51

WEB SITE

www.dice.ucl.ac.be

www.dice.ucl.ac.be

25


Medical imaging and multimodal interfaces

SENIOR SCIENTISTS :

� Benoît MACQ � Christophe DE VLEESCHOUWER

C 4


The laboratory is dedicated to Digital Communication Systems,Microwave Remote Sensing, Image Processing and Security andMultimodal Interfaces.

The biomedical research is organized along three major streams : 1. functional brain imaging2. medical imaging 3. medical informatics.

Topics of current interest aim at :developing multi-modal signal processing, medical images

registration, finite element based deformable models for med-ical image analysis;

developing medical imaging system and computer graphicsso as to assist radiologists and surgeons, to avoid re-operations,to detect bladder tumours in CT scans, and to allow segmenta-tion of brain MRI for surgical planning;

conducting research in the atlas-based segmentation area inorder to automatically segment brains with large tumours foradvanced radiotherapy plan;

creating a unique framework, which integrates all the devel-opments in image processing realized in the laboratory;

studying, modelling, optimizing and implementing a solutionscene composer able to compose from several sources a visualscene adapted to a dedicated terminal and allowing the surgeon to utilize MRI-based anatomical reconstructions displayed in customized viewing modes;

developing an original software solution for the emergencyservices : method specifying modalities and devices so as tosupport processes of patient care and integrate the way a usertask is perceived;

helping surgeons for planification, simulation and intra-oper-ative follow-up in maxillo-facial surgery : global device allowingto plan and simulate the operation thanks to a new universalcephalometric analysis based on 3D concepts.


3-D DICOM Viewer.Toolbox for image processing based on VTK.

Visualization of complex medical information.Open Source JPEG2000 Coder to encode mega images -

www.openjpeg.org

Main Equipment

CamerasEEG capPDAsWall displaysWorkstations


O. CUISENAIRE, M. FERRANT, B. MACQ & G. COSNARD.Traitement digital des images médicales - l'identificationautomatique des structures cérébrales en IRM. Revue Louvain,UCL, Louvain-la-Neuve, n° 91, sept. 1998, pp. 30-32.

O. CUISENAIRE, M. FERRANT, J. THIRAN & B. MACQ. Model-based segmentation and recognition of anatomical brain struc-tures in 3D MR images. NMBIA'98, Noblesse Model-BasedImage Analysis Workshop, Glasgow, July 1-3, 1998, pp. 9-14.

M. FERRANT, O. CUISENAIRE & B. MACQ. Multi-object seg-mentation of brain structures using a computerized brain atlas.SPIE Medical Imaging 1999, San Diego, USA, Feb. 20-26, 1999,Vol. 3661, part 2, pp. 986-995.

M. FERRANT, S. WARFIELD, C. GUTTMANN, F. OLESZ & R. KIKINIS. 3D Image matching using a finite element basedelastic deformation model. MICCAI 99 - Medical ImageComputing and Computer Assisted Intervention, Cambridge,UK, 19-23 Sept. 1999, Lecture Notes in Computer Sciences -Vol. 1679, pp. 202-209.

M. FERRANT, B. MACQ et S. WARFIELD. Deformable model-ing for characterizing biomedical shape changes. DGCI 2000 -Discrete Geometry for Computer Imagery Conference,December 13-15, 2000, Uppsala, Sweden.

F. CHUTVSER, J. VAN CLEVNENBREUGEL, M. FERRANT, J. SCHOENAERS and P. SUETENS. Image-based 3D planning ofmaxillofacial distraction procedures including soft tissue impli-cations. MICCAI 2000 - Medical Image Computing and

26

Computer Assisted Intervention, October 11-14, 2000,Pittsburg, USA, Vol. 1935, pp. 999-1007.

S. AUME, M. FERRANT, B. MACQ, R. KIKINIS, and S. WARFIELD. Multiresolution signal processing on meshes forautomatic pathological shape characterization. MICCAI 2001,Utrecht, The Netherlands, October 14-17, 2001.

M. FERRANT, A. NABAVI, B. MACQ, R. KIKINIS, and S.K. WARFIELD. Registration of 3D interoperative MR images ofthe brain using a finite element biomechanical model. IEEETransactions on Medical Imaging, Vol. 20, n° 12, Dec. 2001, pp. 1384-1397.

M. FERRANT, B. MACQ & O. CUISENAIRE, Y. VANDER-MEEREN, E. OLIVIER. Registration and visualization of transcra-nial magnetic stimulation on magnetic resonance images. MICCAI 2001, Utrecht, The Netherlands, October 14-17, 2001.

M. FERRANT, B. MACQ, R. KIKINIS, and S. WARFIELD. Real-time simulation and visualization of volumetric brain deforma-tion for image guided neurosurgery. SPIE Medical Imaging2001, San Diego, USA, February 17-23, 2001, Vol. 4319, pp. 366-373.

M. FERRANT, J. THIRAN, S. WARFIELD, B. MACQ & O. CUISE-NAIRE. Surface based atlas matching of the brain usingdeformable surfaces and volumetric finite elements. MICCAI2001, Utrecht, The Netherlands, October 14-17, 2001.

S. JAUME, M. FERRANT, B. MACQ & S. WARFIELD. Multi-res-olution parameterization of meshes for improved surface basedregistration. SPIE Medical Imaging 2001, San Diego, USA,February 17-23, 2001.

D. TREVISAN, B. MACQ & J. VANDERDONCKT. Analyzinginteraction in augmented reality systems. ACM Multimedia2002 - International Workshop on Immersive TelepresenceITP'2002, Juan-les-Pins, France, December 6, 2002.

Q. NOIRHOMME, Y. VANDERMEEREN, E. ROMERO, B. MACQ.Registration of transcranial magnetic stimulation, a visualizationtool for brain functions. DSP 2002, 14th Intl Conference onDigital Signal Processing, Santorini, Greece, July 1-3, 2002, pp. 311-314.

P. D’HAESE, V. DUAY, A. DU BOIS D’AISCHE, B. MACQ & B. DAWANT. Automatic segmentation of brain structures for radiation therapy planning. SPIE Medical Image Processing, San Diego, USA, Feb. 15-20, 2003.

D. TRECISAN, B. MACQ, J. VANDERDONCKT & C. RAFTO-POULOS. Modeling interaction for image-guided procedures.SPIE Medical Imaging 2003, February 15-20, 2003, San Diego,California, USA.

S. JAUME, B. MACQ, M. FERRANT, R. KIKINIS, and S. WARFIELD. Tumor detection in the bladder wall with a meas-urement of abnormal thickness in CT scans. IEEE Trans. on Biomedical Engineering, Vol. 50 n° 3, March 2003, pp. 383-390.

STAFF

Total : 17

KEY WORDS FOR R&D

biomedical engineeringfunctional brain imagingimagingmedical informaticsradiologytomography

SENIOR SCIENTISTS

Benoît MACQ [email protected]. 32 (0)10 47 22 71

Christophe DE [email protected]. 32 (0)10 47 81 24

WEB SITES

www.tele.ucl.ac.bewww.tele.ucl.ac.be/MEDIMAGwww.openjpeg.org

www.tele.ucl.ac.be

www.openjpeg.org

www.tele.ucl.ac.be/medimag

27


Bone, joint and nerve reconstruction

SENIOR SCIENTISTS :

� Christian DELLOYE

� Olivier CORNU

� Xavier BANSE

� Everard MUNTING

� Pascal POILVACHE

� Olivier BARBIER

D 1


Major lab research interests concern the way to substitute large ske-letal or articular defects. Bone allografts are commonly used becau-se they provide immediate structural support that can be associatedwith a prosthesis or with osteosynthesis. Among several advantages,their use allows anatomical reconstruction of the skeletal defect, bio-logical union to host bone through callus formation, soft tissue adhe-rence around the grafted bone and the possibility of tendon reinser-tion on its counterpart left on the bone graft. Among possible dis-advantages, there is the risk, albeit limited, of disease transmissionthrough the implant, and a high rate of non union and fracture.These complications are related to the non vitality of the bone graft. Research projects are conducted to reduce disadvantages ofbone allografts. Methods of graft decontamination are assessed by in vitro testing(cytotoxicity). Machine tools for bone processing are conceived and assessedby the engineers team. As a bone allograft serves primarily as anosseous spacer that allows osteoconduction of host cells into itsmass, biological answer results in a progressive incorporation of thegraft into the host bone. This process however is very limited in timeand space, leaving eventually a mass of dead bone that has beenpoorly substituted by new bone. Efforts are made to overcome thislimited substitution through improvement of the revascularisationand revitalisation of the bone. The research is organised to explore the different avenues availableto achieve a better incorporation and to avoid a mechanical failure.Research fields are also conducted in hip, knee and ankle joint replacement (tribology, finite element analysis, implant stability) or cartilage repair by autologous chondrocytes transplantation. More fundamental studies are performed on the relationship between bone architecture, collagen and mineral content to better understand the concept of bone quality. Lastly, clinical and fundamental studies are performed to assess finger innervation and nerve repair after injury.


The Tissue Bank is able to deliver massive bone allografts to surgeons for skeletal reconstruction ([email protected]). The Tissue Bank is applying the European standards (http://www.eamst.org).

Research projects may cover all fields of interests from microbio-logical studies (in vitro testing of bacterial screening and decontam-ination) to in vivo model of allografts incorporation.

Mechanical and morphological assessment of allograft recon-structions may be performed. Among the different avenues toimprove allograft incorporation and bone healing, autogenous cellaugmentation represents an indirect approach. This attractive con-cept awaits further in vivo research (rat nude model of osteoinduc-tion) and clinical confirmation.

Main Equipment

Bone morphological analysisCleanroom and Cell culture facilitiesDigitalisation tableFluoroskan AscentHip walking simulatorLeitz saw 1600; Exact sawMicroradiography (Bemtograph)MicroscopyMicrotome LeicaMultiscan RC200-240Cp-QCT, model XCT Research SA+®, Stratec (RUMA)Radiographic digitizer (Widar)Tissue BankUTS model 100-1 (ERM)Zwick model Z50/TH3A (ERM)


DELLOYE C. et al. Perforations of cortical bone allografts improvetheir incorporation. Clin. Orthop., 2002 Mar; (396) : 240-7.

BANSE X. et al. Mechanical properties of adult vertebral cancel-lous bone : correlation with collagen intermolecular cross-links.J. Bone Miner. Res., 2002 Sep; 17(9) : 1621-8.

DELLOYE C., CORNU O. Incorporation of massive bone allo-grafts : can we achieve better performance? Acta Orthop. Belg.,2003 Apr; 69(2) : 104-11.

SCHECROUN N., DELLOYE C. Bone-like nodules formed byhuman bone marrow stromal cells : comparative study and charac-terization. Bone, 2003 Mar; 32(3) : 252-60.

28

DELLOYE C. et al. Bone substitutes in 2003 : an overview. ActaOrthop. Belg., 2003; 69(1) : 1-8.

CORNU O. et al. Impaction bone grafting with freeze-dried irra-diated bone. Part I. Femoral implant stability : cadaver experimentsin a hip simulator. Acta Orthop. Scand., 2003 Oct; 74(5) : 547-52.

CORNU O. et al. Impaction bone grafting with freeze-dried irra-diated bone. Part II. Changes in stiffness and compactness ofmorselized grafts. Acta Orthop. Scand., 2003 Oct; 74(5) : 553-8.

BANSE X. et al. Irreversible perforations in vertebral trabeculae?J. Bone Miner. Res., 2003 Jul; 18(7) : 1247-53.

BARBIER O. et al. Outcome evaluation of the hand and wristaccording to the international classification of functioning, disability,and health. Hand. Clin., 2003 Aug; 19(3) : 371-8.

PARE M., BEHETS C., CORNU O. Paucity of presumptive ruffinicorpuscles in the index finger pad of humans. J. Comp. Neurol.,2003 Feb 10; 456(3) : 260-6.

Awards

T. Leemrijse, EFAS-EFORT, 1999D. Dufrane, BELACT, 2000M. Mousny, Fondation St-Luc, 2000M. Mousny, Zimmer, SOBCOT, 2000A. Bavadekar, EFORT, Rhodes, 2001D. Dufrane, ESACT, Tylösand, 2001P. Poilvache, John Insall, Knee Society (USA), 2002X. Banse, Rotary, Société Royale Belge de Rhumatologie, 2003P.L. Docquier, Zimmer, SOBCOT 2004M. Mousny, Fondation Willy & Marcy De Vooght, 2004

Partnership

Civil Engineering Department, Royal Military Academy, Brussels,Belgium.

Experimental Surgery Department, Nancy University (Prof. Schmitt),France.

Orthopaedic and Trauma Department, Hôpital de Hautepierre,Strasbourg University (Prof. Simon), France.

Biochemistry Department, University of Bristol (Prof. Bailey), UK.Bone Metabolism Unit, Toronto University (Prof. Grynpas), Canada.European project on quality system for tissue banking.

STAFF

Total : 24

KEY WORDS FOR R&D

allograftsanatomopathology autologous cell therapybacteriology biomaterialsbiomechanics biomedical engineeringbone inductionbone remodelinghistomorphologyjoint tribologyorthopaedic surgery toxicitytransplantation

SENIOR SCIENTISTS

Christian [email protected]. 32 (0)2 764 29 95

Olivier [email protected]. 32 (0)2 764 53 88

Xavier [email protected]. 32 (0)2 764 29 79

Everard [email protected]. 32 (0)10 43 72 62

Pascal [email protected]. 32 (0)2 764 29 63

Olivier [email protected]. 32 (0)2 764 29 65

WEB SITE

www.orto.ucl.ac.be

www.orto.ucl.ac.be

29


Biocompatibilization of polymer devices

SENIOR SCIENTIST :

� Jacqueline MARCHAND-BRYNAERT

D 2


The laboratory is dedicated to the design and the organic syn-thesis of biologically active molecules, and to the use of suchmolecules for the biocompatibilization of polymer materials byselective surface modifications.

The molecules of interest are :peptidomimetics of the RGD sequence as ligands of αnβ3

integrins (cell membrane receptors of endothelial cells, and oth-ers);

peptidomimetics of the LDV sequence as ligands of αnβ1integrins (cell membrane receptors of leukocytes);

high-affinity inhibitors of thrombine (enzyme involved in theblood coagulation cascade).

The polymer devices of interest are :cell cultivation supports made from PET, PEEK, PS, PMMA, etc.filtration membranes made from PBT, PVDF, etc.home-made polymer films displaying chemical hetero-

geneities at the nanometer scale.

The materials surfaces are modified by :wet-chemistry treatments;covalent grafting of the biologically active molecules via

appropriate spacer-arms.

The biocompatibility of the surface-modified polymers is eva-luated by :

adhesion assays of mammalian cells;blood coagulation assays;selective cell filtration assays.


Organic synthesis of complex moleculesStructural analysis of organic moleculesSurface analysis by radiolabelling and fluorine taggingCellular adhesion assay

Main Equipment

IR (infra-red spectroscopy)UV (UV-visible spectroscopy)NMR (nuclear magnetic resonance spectroscopy)Mass (mass spectrometry)GC (gas chromatography)HPLC (high performance liquid chromatography, analytical

and preparative systems)


JAUMOTTE-THELEN S., DOZOT-DUPONT I., MARCHAND-BRYNAERT J., SCHNEIDER Y.J. The covalent grafting offibronectin and asialofetuin at the surface of poly(ethylenetherephthalate) track-etched membranes improves the adhe-sion but not the differentiation of rat hepatocytes. J. Biomed.Mater. Res., 1996, 32, 569-582.

MOUGENOT P., MARCHAND-BRYNAERT J. Reactivity assaysof surface hydroxyl chain-ends of poly(ethylene terephthalate)(PET) film and membrane using original 3H- and fluorinelabelled derivatization reagents. Macromolecules, 1996, 29, 3552-3559.

BOXUS T., DELDIME-RUBBENS M., MOUGENOT P., SCHNEI-DER Y.J., MARCHAND-BRYNAERT J. Chemical assays of end-groups displayed on the surface of poly(ethylene terephthalate)(PET) films and membranes by radiolabelling. Polym. Adv.Technol., 1996, 7, 589-598.

NOISET O., HENNEUSE C., SCHNEIDER Y.J., MARCHAND-BRYNAERT J. Surface reduction of poly(aryl ether ether ketone)(PEEK) film : UV spectrophotometric-, 3H-radiochemical- and X-ray photoelectron spectroscopic assays of the hydroxyl func-tions. Macromolecules, 1997, 30, 540-548.

NOISET O., SCHNEIDER Y.J., MARCHAND-BRYNAERT J.Surface modification of poly(aryl ether ether ketone) (PEEK) filmby covalent coupling of aminoacids through a spacer-arm. J.Polym. Sci., Part A : Polym. Chem, 1998, 35 (17), 3779-3790.

BOXUS T., TOUILLAUX R., DIVE G., MARCHAND-BRYNAERTJ. Synthesis and evaluation of RGD peptidomimetics aimed atsurface bioderivatization of polymer substrates. Bioorg. Med.Chem., 1998, 6, 1577-1595.

30

HENNEUSE-BOXUS C., POLEUNIS C., DE RO A., ADRIAENSEN Y.,BERTRAND P., MARCHAND-BRYNAERT J., Surface functionali-zation of PEEK films studied by time-of-flight secondary ionmass spectrometry and X-ray photoelectron spectroscopy.Surface Interface Anal., 1999, 27, 142-152.

NOISET O., SCHNEIDER Y.J., MARCHAND-BRYNAERT J.Fibronectin adsorption or/and covalent grafting on chemicallymodified PEEK film surfaces. J. Biomater. Sci. Polymer. Edn.,1999, 10, 657-677.

MARCHAND-BRYNAERT J., DETRAIT E., NOISET O., BOXUST., SCHNEIDER Y.J., REMACLE C. Biological evaluation of RGDpeptidomimetics, designed for the covalent derivatization ofcell culture substrates, as potential promotors of cellular adhe-sion. Biomaterials, 1999, 20, 1773-1782.

MARCHAND-BRYNAERT J. Chemical and biochemical modifi-cations of PET membranes and PEEK film by surface wet-chem-istry with a view to improving cell adhesion in polymer surfacemodification : relevance to adhesion. K.L. MIittal, R.H. LacombeEditors, VSP, Utrecht, Boston, 2000, pp 281-303.

NOISET O., SCHNEIDER Y.J., MARCHAND-BRYNAERT J.Adhesion and growth of CaCo 2 cells on surface-modified PEEKsubstrata. J. Biomater. Sci., Polymer Edn., 2000, 11, 767-786.

BILTRESSE, S., DESCAMPS D., BOXUS T., MARCHAND-BRY-NAERT J. Attachment of bis-(trifluoromethyl)aryl labels on thechain-ends of poly(ethylene terephthalate) (PET) track-etchedmembranes and films by surface wet-chemistry. J. Polymer Sci.,Part A : Polymer Chem., 2000, 38 (19), 3510-3520.

BILTRESSE S., DESCAMPS D., HENNEUSE-BOXUS C., MARC-HAND-BRYNAERT J. Effect of the chemical nature and thelength of spacer-arms on the covalent grafting of molecularprobes at the surface of PET membranes. J. Polymer Sci., PartA : Polymer Chem., 2002, 40, 770-781.

HAMBARDZUMYAN A., BILTRESSE S., DUFRENE Y., MARC-HAND-BRYNAERT J. An unprecedented surface oxidation ofpolystyrene substrates by wet-chemistry in basic conditions. J.Colloid Interface Sci., 2002, 252, 443-449.

Partnership

Baxter, Nivelles, Belgium

STAFF

Total : 8

KEY WORDS FOR R&D

adhesion, mammalian cellsbiocompatibility biologically active compoundsbiomaterialsbiomedical, engineering, sciencesenzyme inhibitorshemocompatibilitymedicinal chemistryorganic synthesispeptidomimetics polymer chemistrysurfaces and interfaces chemistry

SENIOR SCIENTIST

Jacqueline [email protected]. 32 (0)10 47 27 40

WEB SITE

www.chom.ucl.ac.be/ORGJ

www.chom.ucl.ac.be/orgj

31


Odontological biomaterials

SENIOR SCIENTISTS :

�Gaëtane LELOUP-CUMPS�Jacques DEVAUX�Michèle DEBATTY-MESTDAGH�Francis DELANNAY�Sophie DEMOUSTIER-CHAMPAGNE

D 3


CRIBIO (Centre for Research and Engineering on DentalMaterials) gathers multidisciplinary scientific and technologicalexpertises from the Université catholique de Louvain with anemphasis on dental materials research and evaluation.

The Centre pools research teams who are using analyzing andengineering techniques applied to ever developing biomaterialswith a focus on dental resin composites and ceramics.

This multidisciplinarity between materials science and dentistry,not only opens the door to scientific and technological innova-tion, but it also aims at attracting manufacturers interested inscientific evaluation and development of new as well as existingmaterials and techniques.

The aim of the center is to promote links between internationalresearch teams, research centres and companies so as to encou-rage innovative research and new collaborative projects.


CRIBIO gathers University science-minded people and providesyoung scientists an optimal environment for scientific activities(Ph.D.'s, post-docs,…).

On the other hand, one of its objectives is to collaborate withindustrial teams with a view to develop science-based techno-logical tools and data banks for use in the field of dentistry.

Main Equipment

Microscopy (optic and electronic)Spectroscopy (FTIR and Raman)ThermogravimetryElectronic Paramagnetic Resonance RheologyMechanical tests


C. PIANELLI, J. DEVAUX, S. BEBELMAN, G. LELOUP. Themicro-Raman spectroscopy, a useful tool to determine thedegree of conversion of light-activated composite resins. J. Biomed. Mater. Res. (Appl. Biomater.), 1999, 48 : 675-681.

G. LELOUP, P.E. HOLVOET, S. BEBELMAN, J. DEVAUX. Ramanscattering determination of the depth of cure of light-activatedcomposites. Influence of different clinically relevant parameters.J. Oral Rehabilitation, 2002, 29 : 510-515.

J. SABBAGH, J. VREVEN, G. LELOUP. Dynamic and staticmoduli of elasticity of resin-based materials. Dental Materials,2002, 18 : 64-71.

D. TRUFFIER-BLANC, E. PLACE, J. DEVAUX, G. LELOUP.Interfacial layer characterization in dental composite. J. OralRehabilitation, 2003, 30 : 74-77.

D. TRUFFIER-BOUTRY, X. A. GALLEZ, S. DEMOUSTIER-CHAMPAGNE, J. DEVAUX, M. MESTDAGH, B. CHAMPAGNE,G. LELOUP. Identification of Free Radicals trapped in SolidMethacrylated resins. J. Pol. Sci., Part A, Pol. Chem., 2003, 41 :1691-1699.

Partnership

CRIBIO develops contacts with University teams on nationaland international levels : Prof. Dr. Paul Lambrechts, Dept. ofOper. Dent. and Dent. Mat., U.Z. St. Rafael, K.U.Leuven; Prof.Erik Asmussen, Department of Dental Materials, School ofDentistry, University of Copenhagen, Denmark.

CRIBIO collaborates with industrial companies for dedicatedresearch and/or scientific exchanges : UCB, Kulzer, VOCO, 3M-Espe, etc.

Despite its youthfulness, CRIBIO already applied for nationaland regional research projects and grants with RegionWallonne (FIRST, "Réseaux",…) and FNRS.

32

STAFF

Total : 7

KEY WORDS FOR R&D

biomaterialsbiomedical, engineering, sciencesmacromolecular chemistrystomatology-odontology

SENIOR SCIENTISTS

Gaëtane [email protected]. 32 (0)2 764 57 25 – 32 (0)2 764 57 40

Jacques [email protected]. 32 (0)10 47 35 56

Michèle [email protected]. 32 (0)10 47 36 61

Francis [email protected]. 32 (0)10 47 24 26

Sophie [email protected]. 32 (0)10 47 40 15

WEB SITE

www.md.ucl.ac.be/cribio

www.md.ucl.ac.be/cribio

33


Efficacy of a thermoplastic polylactic membrane on guided tissue regeneration and guided bone reservationin periodontology

SENIOR SCIENTISTS :

� Pierre BERCY � Didier BLASE

D 4


Our center has worked for 10 years on the clinical application ofa polylactic acid polymer (PLA-98, Phusiline, Phisis, France) in thecontext of periodontal surgery.

The Phusiline PLA-98 bio-absorbable membrane may promoteguided tissue regeneration (G.T.R.) in infra-bony pockets as well asguided bone regeneration (G.B.R.) concerning alveolar crest andosseous defects around implants. In human subjects, no (local orsystemic) side effect was detected on a short, mid or long term.

During the treatment of deep infra-bony pockets in humans, cli-nical attachment gains in G.T.R. with the Phusiline PLA-98 mem-brane are higher compared to flap surgery without interpositionof any membrane and even more while compared to root plan-ning. With the increase of the initial pocket’s depth, the clinicalattachment gain improves. Better results are obtained for non-smokers, mesial localizations and the maxillary. Long-term studiesshow an exceptional stability of the clinical attachment gains innon-smokers within 10 years. With time smokers lose a part of theregenerated attachment, but nevertheless we can’t consider nico-tine as a contra-indication of this technique.

The Phusiline PLA-98 membrane may act within the principles ofG.B.R. in artificial osseous defects in the rats calvaria. It showsthree remarkable qualities : a perfect tissue integration, a very lowrate of resorption and the capacity of maintaining the spacebeneath the membrane.

Results of the multi-centre study in G.B.R show that Phusiline PLA-98 may promote in a predictable way regeneration as much in alveolar defects around implants as for alveolar crest augmentation.

Results of G.B.R. around implants are permanent in time. Theapplication of G.B.R. techniques does not increase the failure ratioof implants on a period of 5 to 9 years in comparison with controlsites with no bone augmentation. Reconstruction of a buccalbone wall is in a way a guarantee of greater stability of the under-lined gingival tissues that prevents the presence of implant expo-sure in anterior sectors where esthetic demands are important.

The essential clinical quality of this membrane is due to itsthermoplastic properties. With such properties, the membrane

can maintain the space needed for tissue or bone guided rege-neration without the need of a bone screw system, autologousbone grafts or any other substitution material used as a spacemaintainer.

The actual clinical interest of this membrane lies within the indi-cations of G.B.R.


The membrane is a Phusiline PLA-98 from Phusis sa, St Ismier,France

Main Equipment

This was a typical clinical study with the usual methods andequipment from the dental field.


BLASE D., BERCY P. Maintenance of attachment gain throughGTR using a biodegradable polymer membrane : 1 to 5 yearsresults. J. Dent. Res 77 Special Issue B, p. 869, abstract 1899,1999.

BLASE D., BERCY P. Long-term results of implants treatedwith Guided Bone Regeneration., in preparation.

OBEID P., BLASE D., BRUNEL G., BERCY P. G.B.R. using aPhusiline® membrane : a study in the rat calvarium, in prepa-ration.

Partnership

Phusis sa, St Ismier, France.Faculté de Chirurgie Dentaire, Université Louis Pasteur de

Strasbourg, France.Faculté de Médecine (Médecine Dentaire) de Genève.

34

STAFF

Total :6

KEY WORDS FOR R&D

bioabsorbable membranedental implantsguided bone regenerationguided tissue regenerationperiodontitisPLA membrane

SENIOR SCIENTISTS

Pierre [email protected]. 32 (0)2 764 57 14

Didier [email protected]. 32 (0)2 764 5719

WEB SITE

www.md.ucl.ac.be/mden/patd/

www.md.ucl.ac.be/mden/patd

35


Drug delivery systems

SENIOR SCIENTISTS :

� Véronique PREAT� Rita VANBEVER

D 5


The laboratory aims at developing new drug delivery systems. Ofparticular interest are delivery systems for biotech drugs. Low oralbioavailability and short biological half-life are indeed limiting fac-tors in the development of protein drugs and gene therapeutics.

Three different approaches are investigated :transdermal drug deliverybiodegradable polymeric systemspulmonary drug delivery.

The research on transdermal drug delivery is focused on methodsto enhance macromolecule delivery, more particularly electricallyenhanced transdermal drug delivery (iontophoresis and electropo-ration) methods. Based on previous studies of the parametersaffecting drug permeation and mechanisms of drug transport,application to peptide, protein, vaccine, oligonucleotide and DNAdelivery are investigated. New devices are developed.

Biodegradable polymeric drug carrier, i.e., micelles for the deliveryof poorly water soluble drugs, as well as nanoparticles and micro-particles for the delivery of proteins and nucleic acids are assessed.Novel polymers are formulated. Their toxicity, efficacy and themechanisms of drug delivery are investigated.

The research on pulmonary drug delivery focuses on new formu-lations of dry powder aerosols that serve as carriers for proteinsand vaccines. The fate of drug molecules in the lungs is investiga-ted following pulmonary administration. The understanding ofthe elimination processes allows to develop formulation strategiesto increase pulmonary absorption or local efficacy.


Drug delivery : feasibility and optimisation studies.

Main Equipment

Transdermal drug delivery : diffusion cells, iontophoresis, elec-troporation.

Polymeric micelles, nanoparticles and microparticles.Pulmonary drug delivery : spray-dryer, cascade impactors,

Harvard ventilator, tissue chopper.Measurement of particle size : photon correlation spectroscopy,

laser diffraction in the wet and dry states.


JADOUL A., DOUCET J., DURAND D., and PREAT V.Modifications induced on stratum corneum structure after in vitroiontophoresis. ATR-FTIR and X-ray scattering studies. J. ControlledRelease, 42 : 165-173, 1996.

JADOUL A., MESENS J., CAERS W., de BEUKELAAR F., CRABBER., PREAT V. Transdermal Permeation of Alniditan by iontophore-sis : in vitro optimization and human pharmacokinetic data.Pharmaceutical Research, 13 : 1348-1353, 1996.

LEMOINE D., FRANCOTTE M. and PREAT V. Nasal vaccines :from fundamental concepts to vaccine development. STP PharmaSciences, special issue Mucosal Immunisation, 8 : 5-18, 1998.

LEMOINE D., PREAT V. Polymeric nanoparticles as delivery sys-tem for influenza virus glycoproteins. Journal of ControlledRelease, 54 : 15-27, 1998.

PREAT V. Transdermal delivery of peptides and proteins. In :Peptide and Protein Drug Delivery, Frokjaer S., Christup L. &Krogsgaard-Larsen P. ed., Munksgaard, Copenhagen, 175-182,1998.

REGNIER V., PREAT V. Localization of a FITC-labeled phospho-rothiote oligodeoxynucleotide in the skin after topical delivery byiontophoresis and electroporation. Pharmaceutical Research, 15 : 1596-1602, 1998.

JADOUL A., BOUWSTRA J. and PREAT V. Effects of iontophore-sis and electroporation on the strateum corneum. Review of thebiophysical studies. Adv. Drug Del. Rev., 35 : 89-105, 1999.

BOSQUILLON C., LOMBRY C., PREAT V., VANBEVER R. Influenceof formulation excipients and physical characteristics of inhalationdry powders on their aerosolization performance. Journal ofControlled Release, 70 : 329-339, 2001.

LOMBRY C., BOSQUILLON C., PREAT V., VANBEVER R. Confocalimaging of rat lungs following intratracheal delivery of dry pow-ders or solutions of fluorescent probes. Journal of ControlledRelease, 83 : 331-341, 2002.

36

CODRONS V., VANDERBIST F., VERBEECK R.K., ARRAS M. LISOND., PREAT V., VANBEVER R. Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats. Journal ofPharmaceutical Sciences, 92 : 938-950, 2003.

PREAT V., VANBEVER R. Skin electroporation for transdermaland topical drug delivery. Transdermal drug delivery, Drugs andthe pharmaceutical sciences 123, ed R. Guy, J. Hadgraft, MarcelDekker, 227-254, 2003.

LOMBRY C., MARTELEUR A., ARRAS M., LISON D., LOUAHEDJ., RENAULD J.-C., PREAT V., VANBEVER R. Local and systemicimmune responses to intratracheal instillation of antigen and DNAvaccines in mice. Pharmaceutical Research, 21 : 127-135, 2004.

CODRONS V., VANDERBIST F., UCAKAR B., PREAT V.,VANBEVER R. Impact of formulation and methods of pulmonarydelivery on absorption of parathyroid hormone (1-34) from ratlungs. Journal of Pharmaceutical Sciences, 93 : 1241-1252, 2004.

LOMBRY C., EDWARDS D.A., PREAT V. and VANBEVER R.Alveolar macrophages are a primary barrier to pulmonary absorp-tion of macromolecules. American Journal of Physiology LungCellular and Molecular Physiology 286 : L1002-L1008, 2004.

Patents

Vanbever R., Edwards D.A., Lombry C., Préat V., Chemical andphysical modulators of bioavailability of inhaled compositions. USpatent, filed May 19, 2003.

Awards

Rita Vanbever, Prize of the Vth section of the Royal BelgianAcademy of Medicine, PhD thesis, 1998.

Rita Vanbever Biennial Prize of the Belgian Society ofPharmaceutical Sciences, PhD thesis, 1999.

Valérie Codrons, Award for Graduate Student of the AmericanAssociation of Pharmaceutical Scientists, Optimization of systemichuman parathyroid hormone (1-34) delivery using inhalation drypowders in rats, 2002.

Rita Vanbever, Named one of the world's top young innovatorsby Technology Review, Massachusetts Institute of Technology’smagazine of innovation, 2003.

Partnership

Alkermes, IncEli LillyGlaxoSmithKline BiologicalsSMB-Technology

STAFF

Total : 18

KEY WORDS FOR R&D

antigen, vaccinebiomedical science, engineeringbiotechnologydrug carrierdrug delivery, pulmonarydrug delivery, transdermaldry powders aerosolselectroporationencapsulationiontophoresisnucleic acidspeptidespharmaceutical productspharmaceutical technologypharmacophysicsproteinstechnology progress

SENIOR SCIENTISTS

Véronique [email protected]. 32 (0)2 764 73 09

Rita [email protected]. 32 (0)2 764 73 25

WEB SITES

www.md.ucl.ac.be/pharma/intro_engl.htmwww.farg.ucl.ac.be

www.md.ucl.ac.be/pharma/intro_engl.htm

www.farg.ucl.ac.be

37


Biomaterials surface and interface

SENIOR SCIENTISTS :

� Patrick BERTRAND� Arnaud DELCORTE� Claude POLEUNIS

D 6


The research activities concern the physical chemistry of solid sur-faces and interfaces. The objective is to develop surface treat-ments and modifications in order to provide new surface proper-ties in view of specific applications in materials science.To reach this goal, our approach is based on a control of the sur-face atomic and molecular composition and structure. The first step required in this way is to be able to characterize thesolid surfaces in terms of chemical and functional compositionand structure at the nanometer scale. For that purpose, our mainexpertise has been the development and the use of surface ana-lytical methods based on the ion-solid interaction (Secondary IonMass Spectrometry and Ion Scattering Spectrometry - ISS andRBS), in combination with other surface techniques such as AES,XPS and the Near Field Microscopies (AFM, STM).More specifically, for ten years, we were contributing to the deve-lopment of the static SIMS technique for the molecular characte-rization of surfaces, with a special emphasis for the organic mate-rials such as polymers. The surface properties of interest are biocompatibility, specificcatalytic activity, gas/molecule permeability and adhesive proper-ties. The methods used to modify the surface are based on che-mical and physical treatments : plasma treatments, ion beam irra-diation, chemical grafting, thin (organic/ metallic) layer adsorption.We have studied the surface modifications in order to improveadhesive properties and biocompatibility. A special attention waspaid to protein adsorption in view of controlling cell adhesion onmicro-patterned polymer surfaces or to prevent biofouling.The group has a long experience of collaboration with partnersfrom university and industry research centers.


Service provided to companies for practical surface characteri-zation and imaging.

Main Equipment

Equipments for surface characterization :Ion Scattering Spectrometry (ISS)Secondary Ion Mass Spectrometry

� quadrupole mass spectrometer (static and dynamic SIMS)� static imaging time-of-flight mass spectrometer (ToF-SIMS)Rutherford Backscattering Spectrometry (using a VDG accelera-

tor) RBSScanning Auger Microprobe (AES–SAM)Access to AFM, STM, XPS-ESCA, SEM, TEM, XRD, Ellipsometry,

static and dynamic contact angles, IR, Raman


J.B. LHOEST, E. DETRAIT, P. VAN DEN BOSCH DE AGUILAR andP. BERTRAND. Fibronectin adsorption, conformation and orienta-tion on polystyrene substrates studied by radiolabelling, XPS andToF SIMS. J. Biomed. Mat. Res. 41, 1998, 95-103.

E. DETRAIT, J.B. LHOEST, B. KNOOPS, P. BERTRAND and P. VANDEN BOSCH DE AGUILAR. Orientation of cell adhesion andgrowth on patterned heterogeneous polystyrene surface. J. Neuroscience Methods 84, 1998, 193-204.

J.L. DEWEZ, J.B. LHOEST, E. DETRAIT, V. BERGER, C. DUPONT-GILLAIN, L.M. VINCENT, Y.J. SCHNEIDER, P. BERTRAND, P.G.ROUXHET. Adhesion of mammalian cells to polymer surfaces :from physical chemistry of surfaces to selective adhesion ondefined patterns. Biomaterials 19, 1998, 1441-1445.

E. DETRAIT, J.B. LHOEST, P. BERTRAND and P. VAN DEN BOSCHDE AGUILAR. Fibronectin-pluronic co-adsorption on polystyrenewith increasing hydrophobicity : relationship with cell adhesion. J. Biomed. Mat. Res. 45, 1999, 404-413.

L. ROUXHET and P. BERTRAND. Albumin adsorption on poly-carbonate : correlation between XPS and TOF-SIMS analyses. In “Secondary Ion Mass Spectrometry, SIMS XII”, Eds; A. Benninghoven, P. Bertrand, H.-N. Migeon and H. Werner,Elsevier Science Publ., 2000, 907-910.

C.M. PRADIER, P. BERTRAND, M.N. BELLON-FONTAINE, C. COMPÈRE, D. COSTA, P. MARCUS, C. POLEUNIS, B. RONDOT,M.G. WALLS. Adsorption of proteins on an AISI 316 stainless steelsurface in natural sea water. Surf. Interface. Anal.,30, 2000, 420-424.

C. COMPÈRE, M.N. BELLON-FONTAINE, P. BERTRAND, D. COSTA, P. MARCUS, C. POLEUNIS, C.M. PRADIER, B. RONDOTand M.G. WALLS. Kinetics of conditioning layer formation onstainless steel immersed in seawater. Biofouling, 17, 2001, 129-145.

38

C. POLEUNIS, C. COMPÈRE and P. BERTRAND. Time-of-flightsecondary ion mass spectrometry : characterization of stainlesssteel surfaces immersed in natural seawater. J. MicrobiologicalMethods 48, 2002, 195-205.

C. POLEUNIS, C. RUBIO, C. COMPÈRE and P. BERTRAND. Roleof salts on the BSA adsorption on stainless steel in aqueoussolutions : II) ToF-SIMS spectral and chemical mapping study.Surf. Interface Anal. 34, 2002, 55-58.

C. POLEUNIS, C. RUBIO, C. COMPÈRE, P. BERTRAND. ToF-SIMS chemical mapping study of protein adsorption onto stain-less steel surfaces immersed in saline aqueous solutions. Appl.Surf. Sc. 203-204, 2003, 693-697.

M. HENRY, C. DUPONT–GILLAIN and P. BERTRAND.Conformation change of albumin adsorbed on polycarbonatemembranes as revealed by ToF-SIMS. in Langmuir, 2003.

Patents

Biomaterial and method for obtaining it, J.L. DEWEZ, J.B. LHOEST, E. DETRAIT, P. BERTRAND, P. VAN DEN BOSCH DE AGUILAR, P. G. ROUXHET, Belgian Patent n° 09401022, Nov. 14, 1994; International Patent Application PCT / BE95/00104,Nov. 14, 1995; United states Patent n° 5, 962,136, 1999.

Membrane pour chambre d'encapsulation de cellules pro-duisant au moins une substance biologiquement active et organebio-artificiel comprenant une telle membrane, A. BELCOURT, P. BERTRAND, G. LEGEAY, L. KESSLER, demande de brevet françaisn°0101248 du 30/01/2001, PCT/FR02/00347

Awards

Prof. at University of Houston, Texas (USA), 1992

Partnership

Action de Recherche Concertée, Belgium, “Interaction électron-vibration dans les nanostructures”.

WALEO programme, Belgium, OLIGONIC Project, collab. withUniversities of Namur and Liège, “Systèmes automatisés de diag-nostic moléculaire par manipulations microfluidiques et détectionélectronique”.

Programme “Réseaux” Région Wallonne, SENSOTEM, collab.with University of Liège, Bio senseurs pour diagnostic de maladiesvirales.

6th European framework programmes STREP andNANOBEAMS.

Research Group on “Etude de l’adhésion du biofilm etrecherche de voies nouvelles d’inhibition de la fixation des salissures marines”, with IFREMER, CNRS, INP & Univ. Toulouse III,Univ. Pierre et Marie Curie, Univ. Bretagne sud, Min. français de laDéfense, Ecole nat. de chimie Paris.

Research group on “Encéphalopathies spongiformes subaigüestransmissibles”, with Ecole Centrale de Lyon, Univ. Lyon et sociétéANIOS.

STAFF

Total : 9

KEY WORDS FOR R&D

biomaterialsion spectrometriesprotein adsorptionsurface characterizationsurface modifications

SENIOR SCIENTISTS

Patrick [email protected]. 32 (0)10 47 35 81

Arnaud [email protected]. 32 (0)10 47 35 82

Claude [email protected]. 32 (0)10 47 35 82

WEB SITE

www.pcpm.ucl.ac.be

www.pcpm.ucl.ac.be

39


Biomaterial interfaces

SENIOR SCIENTISTS :

� Michèle DEBATTY-MESTDAGH� Christine DUPONT� Yves DUFRENE� Paul ROUXHET

D 7


The laboratory is dedicated to the physical chemistry of dispersedsystems and surfaces, and to the application of this discipline,particularly to material science and bioengineering. The researchis organized along three major streams :

physical chemistry of soft matter (aqueous solutions of macro-molecules, gels);

interfaces between materials and biosystems (composition andorganisation, molecular interactions, interfacial processes);

biosystems on the nanometer scale (biomolecules, biomem-branes, living cells).

Recent achievements concern : the probing of biosurfaces by atomic force microscopy (physi-

co-chemical and specific interactions, mechanical properties;mapping);

the relation between chemical composition, nanometer-scaleorganization and properties of biosurfaces (microorganisms, lipidmembranes, adsorbed protein layers);

the adhesion of microbial cells and formation of biofilms;the creation of nanopatterned surfaces; the influence of surface patterning on adhesion of mammalian

cells.

Topics of current interest aim at : developing atomic force microscopy for the study of living cells

and biological membranes; designing surfaces with specific properties (nanopatterned

adsorbed protein layers, targeted mammalian cell response,antifouling properties) and understanding of the processesinvolved;

improving the hemocompatibility of polymer surfaces;fabrication of nanobiomimetic devices for pharmacological

testing; optimizing the use of polymers in dental care.


EPR : transition metal ions and free radicals.Viscosimetry.Chemical composition of surfaces.Wetting properties of surfaces.Electrical properties of surfaces and colloids (zeta potential).

Supramolecular organization of surfaces.

Main Equipment

Atomic force microscope (AFM)Bioadhesion devicesContact angle measurementsDynamic wettingElectron paramagnetic resonance (EPR)Image analysisLangmuir balancethroughMicroelectrophoretic measurementsRheometerStreaming potential measurementsSurface tension measurementsX-ray photoelectron spectrometer (XPS)


DEWEZ J.L., LHOEST J.B., DETRAIT E., BERGER V., DUPONT-GILLAIN C.C., VINCENT L.M., SCHNEIDER Y.J., BERTRAND P.,ROUXHET P.G. Adhesion of mammalian cells to polymer surfaces :from physical chemistry of surfaces to selective adhesion on definedpatterns. Biomaterials, 1998, 19, 1441-1445.

DEWEZ J.L., DOREN A., SCHNEIDER Y.J., ROUXHET P.G.Competitive adsorption of proteins : key of the relationshipbetween substratum surface properties and adhesion of epithelialcells. Biomaterials, 1999, 20, 547-559.

DUPONT-GILLAIN C.C., NYSTEN B., ROUXHET P.G. Collagenadsorption on poly(methyl methacrylate) : net-like structure forma-tion upon drying. Polymer Int., 1999, 48, 271-276.

DUFRENE Y.F., MARCHAL T.G., ROUXHET P.G. Probing the organ-ization of adsorbed protein layers : complementarity of atomicforce microscopy, X-ray photoelectron spectroscopy and radiolabel-ing. Applied Surface Science, 1999, 144-145, 638-643.

DUPONT-GILLAIN C., ADRIAENSEN Y., DERCLAYE S., ROUXHETP.G. Plasma-oxidized polystyrene : wetting properties and surfacereconstruction. Langmuir, 2000, 16, 8194-8200.

LEE G.U., METZGER S., NATESAN M., YANAVICH C., DUFRENEY.F. Implementation of force differentiation in the immunoassay.Anal. Biochem., 2000, 287, 261-271.

DUFRENE Y.F., LEE G.U. Advances in the characterization of sup-

40

ported lipid films with the atomic force microscope. Biochim.Biophys. Acta, 2000, 1509, 14-41.

VAN DER AA B.C., MICHEL R.M., ASTHER M., ZAMORA M.T.,ROUXHET P.G., DUFRENE Y.F. Stretching cell surface macromole-cules by atomic force microscopy. Langmuir, 2001, 17, 3116-3119.

ALAERTS J.A., DE CUPERE V.M., MOSER S., VAN DEN BOSCH DEAGUILAR P., ROUXHET P.G. Surface characterization of poly(methylmethacrylate) microgrooved for contact guidance of mammaliancells. Biomaterials, 2001, 22, 1635-1642.

DUPONT-GILLAIN C., ROUXHET P.G. AFM study of the interactionof collagen with polystyrene and plasma-oxidized polystyrene.Langmuir, 2001, 17, 7261-7266.

DENIS F.A., HANARP P., SUTHERLAND D.S., GOLD J., MUSTINCH., ROUXHET P.G. and DUFRENE Y.F. Protein adsorption on modelsurfaces with controlled nanotopography and chemistry. Langmuir,2002, 18, 819-828.

HILLS B.P., GODWARD J., DEBATTY-MESTDAGH M.M., BARAS L.,SATURIO C.P., OUWERX C. NMR studies of calcium induced algi-nate gelation. Part II. The internal bead structure. Magn. Reson.Chem., 2000, 38, 719-728.

DUFRENE Y.F. Atomic force microscopy, a powerful tool in micro-biology. J. Bacteriol., 2002, 184, 5205-5213.

AHIMOU F., DENIS F.A., TOUHAMI A., DUFRENE Y.F. Probingmicrobial cell surface charges by atomic force microscopy.Langmuir, 2002, 18, 9937-9941.

DENIS F.A., HANARP P., SUTHERLAND D.S., DUFRENE Y.F.Fabrication of nanostructured polymer surfaces using colloidallithography and spin-coating. Nanoletters, 2002, 12, 1419-1425.

TOUHAMI A., HOFFMANN B., VASELLA A., DENIS F.A., DUFRENEY.F. Probing specific lectin-carbohydrate interactions using atomicforce microscopy imaging and force measurements. Langmuir,2003, 19, 1745-1751.

TRUFFIER-BOUTRY D., LELOUP G., DEMOUSTIER-CHAMPAGNES., GALLEZ X. A., DEVAUX J., MESTDAGH M., CHAMPAGNE B.Identification of free radicals trapped in solid methacrylated resins.J. of Polymer Science, A. Polymer chemistry, in press.

Patents

DEWEZ J.L., LHOEST J.B., DETRAIT E., ROUXHET P.G., BERTRAND P.,

VAN DEN BOSCH DE AGUILAR Ph. Biomaterial and method forobtaining it. Belgian Patent n° 09401022, Nov. 14, 1994;International Patent Application PCT/BE 95/00104, Nov. 14, 1995.

DUPONT-GILLAIN Ch. C., ROUXHET P.G. Method for controlling themorphology of a polymer surface and said obtained polymer surfa-ce. European Patent Application n° 00870308.4, Dec. 19, 2000.

STAFF

Total : 20

KEY WORDS FOR R&D

biomaterialsbiomedical, engineering, sciencesbiophysicscolloid, chemistrygelshemocompatibilitylipids, membranesnanotechnologypharmacologyproteinssurfaces and interfaces, chemistry

SENIOR SCIENTISTS

Michèle [email protected]. 32 (0)10 47 36 61

Christine [email protected]. 32 (0)10 47 35 92

Yves [email protected]. 32 (0)10 47 36 00

Paul [email protected]. 32 (0)10 47 35 87

WEB SITES

www.cifa.ucl.ac.bewww.cermin.ucl.ac.be

www.cifa.ucl.ac.be

www.cermin.ucl.ac.be

41


Microsensors and microelectronic circuits integrated on silicon and silicon-on-insulator (SOI) substrates

SENIOR SCIENTIST :

� Denis FLANDRE

E 1


The activities of the Microelectronics Lab are included in theCeRMiN (UCL Research Center on Micro and Nanoscopic mate-rials and electronic devices). They focus on the integration of newmaterials and concepts on semiconductor substrates, using micro-electronics fabrication techniques in view of realizing new high-performance integrated sensors, MEMS, analog/digital/RF circuitsand hence microsystems.

Highlights of previous works include :the design of high-precision and low-power interface circuits

for integrated sensors and their realization in SOI CMOS techno-logy for battery-operated applications (for example, a sense chan-nel amplifier for an implantable cardiac pacemaker consumingonly 110 nA);

the design and realization of optical (UV), magnetic, tempera-ture, humidity, pressure, flow and DNA sensors, and of a microhot-plate for gas sensors, with state-of-the art or record performance(for example, our present DNA microchip has a detection capabil-ity down to 0.1 nM of hybridized DNA);

the study, optimization, modelling and application of many newhigh-performance SOI semiconductor devices (intrinsic MOSFETs,gradual-channel or base MOS and bipolar transistors, dynamicthreshold MOSFETs, high-voltage LDMOS, RF MOSFETs (>40GHz);

the design and realization of communication circuits (amplifiers,mixers, filters, VCO, PLL, turbo coders…) in SOI CMOS technolo-gy (for example, for wireless portable devices in the medical ISMfrequency band at 433 MHz);

the fabrication techniques for thin-film silicon structures forMEMS or double-gate MOSFETs.


Design, fabrication and test of specific sensors and electroniccircuits integrated in silicon-on-insulator wafers.

Main Equipment

Complete pilot fabrication line on silicon/SOI substrates of

about 400 m2 for the rapid prototyping and validation of newfabrication steps and integrated devices, sensors and microsys-tems.

Physical and electrical characterization tools available in a largerange of frequencies and temperatures.

Industry-standard simulation softwares for processes, devicesand circuits on silicon.


D. FLANDRE. Part 1 : Design of low-voltage low-power CMOSanalog building blocks and OTAs using EKV modelling and gm/IDmethodology in bulk and SOI technologies. in the book “Lowpower techniques and neural applications in microelectronics”,Ed. by J. Oliver, ISBN : 84-922529-6-0, 2000, pp. 3-99.

D. FLANDRE. Process alternative : SOI for heterogeneous sys-tems. Microelectronic Engineering, 2000, 54, 49-62, selectedpaper.

D. LEVACQ, L. VANCAILLIE, and D. FLANDRE. Top-down designof an UHF (433 MHz) fully integrated low-voltage, low-powerSOI/CMOS voltage controlled oscillator. 9th URSI Forum, Louvain-la-Neuve, Belgium, p. 39, December 2001.

D. FLANDRE et al. Intelligent SOI CMOS Integrated Circuits andSensors for Heterogeneous Environments and Applications. IEEE Sensors Conf., Orlando, USA, June 2002.

C. DUPONT, D. FLANDRE, J.P. RASKIN. SOI CMOS compatiblelow-power microheater optimization and fabrication for smart gassensor implementations. J. Laconte, Proc. of IEEE SensorsConference, June 12-14-2002, Orlando, USA, p. 1395-1400.

F. SILVEIRA, D. FLANDRE. A 110 nA pacemaker sensing channelin CMOS on silicon-on-insulator. Circuits and Systems, ISCAS2002, IEEE International Symposium, Volume : 5, 2002, Page(s) :181–184.

D. FLANDRE, J.P. RASKIN, D. VANHOENACKER. SOI CMOSTransistors for RF and Microwave Applications. in the book“CMOS RF modeling, characterization and applications”, pub-lished in «Selected Topics in Electronics and Systems» by WorldScientific Publishing Co, Ed. M.J. Dean and T.A. Fjeldly, 2002 (ISBN981-02-4905-5) pp. 273-362.

P.E. LOBERT, D. BOURGEOIS, R. PAMPIN, A. AKHEYAR, L.M.

42

HAGELSIEB, D. FLANDRE and J. REMACLE. Immobilization of DNA on CMOS compatible materials. Sensors and Actuators B : Chemical, vol. 92, Issues 1-2, 1 July 2003, Pages 90-97.

Patents

V. DESSARD, D. FLANDRE. Differential amplifier with gain sub-stantially independent of temperature. European Patentn°00110707.7-2215, 19.05.2000.

V. DESSARD, S. ADRIAENSEN, D. FLANDRE. Ultra Low PowerAnalog Basic Blocks. European application n° 00870313.4-2203,21.12.2000. Granted.

D. FLANDRE, J.P. RASKIN, A. NEVE. Semiconductor fabricationtechnique. European application 26.03.01., Int. PatentApplication PCT/BE02/00043 March 25th 2002.

D. FLANDRE, R. PAMPIN, L. MORENO, D. BOURGEOIS, J.REMACLE, P.E. LOBERT. Method and device for high sensitivitydetection of the presence of DNA and other probes. First deposi-tion June 24th 2002.

Awards

Siemens biennal award FNRS 1992.“Best Paper” award 1994, IEEE International SOI Conference,

USA.Wernaers prize 1997.Scientific prize CEN*SCK Prof Roger Van Geen 1999.

Partnership

HITEN (High Temperature Electronics Network).NEXUS, User-Supplier club on MEMS for geophysics and aero-

nautics.EUROSOI thematic network.SINANO “Silicon-based nano-devices” network of excellence.European programs EURIMUS, MEDEA, ESPRIT, IST, GROWTH,

ESA.Région Wallonne (CAVIMA project).

Industrial partners : IBM, Motorola, STM, Schlumberger, X-FAB,CRF-Fiat, Alcatel, SwatchS, Crouzet, EM Marin.

Research centers CNM, IMEC, CEA-LETI, EPFL.

STAFF

Total : 12

KEY WORDS FOR R&D

biomedical engineeringelectronicsintegrated circuitsmicroelectronics technologynucleic acidssemiconductorssensors and peripherals

SENIOR SCIENTIST

Denis [email protected]. 32 (0)10 47 25 40

WEB SITE

www.dice.ucl.ac.be

www.dice.ucl.ac.be

43


Nano-biosensors for biomedical assays

SENIOR SCIENTISTS :

� Vincent BAYOT� Sophie DEMOUSTIER-CHAMPAGNE� Alain M. JONAS� Bernard NYSTEN

E 2


The activities of our laboratories in this field aim at the applica-tion of nanotechnologies and nanomaterials for the develop-ment of bio-sensors.

In this framework, we develop nano-bio-sensors for the simul-taneous detection of an ensemble of 20 to 100 proteins (anti-bodies and antigens in a first approach) in real time, on verysmall sample volumes, while keeping the same, or enhancing,the sensitivity of the tests presently available on the market.These sensors should also enable the measurement in a largerange of concentrations while maintaining low cost and redu-ced amount of equipment. Ideally, the analysis equipmentshould be integrated in a laptop computer.

The heart of the sensor consists in nano-electrodes coveredwith the specific receptors corresponding to the protein thathas to be detected. These electrodes are placed on a simpleelectronic system enabling the detection of the presence of theprotein. The device fabrication is based on nanotechnologiesand self-assembly of organic molecule.

Presently, mono-analyte sensors are developed and are testedon the following molecules :

thyroid stimulating hormone, TSH (thyrotropin);an antibody characteristic of those produced by a human

organism after vaccination;specific IgE of allergens.

Then the technology will be extended to multi-analytes sensors.The targeted applications are the fabrication of diagnosis kitsfor the detection of a series of antigens associated with a specific pathology, the detection of antibodies associated witha given vaccination, the detection of the specific IgE from theensemble of the allergens of a given allergenic species.

Main Equipment

Clean-rooms facilitiesE-beam nanolithography

Electrochemical analysis & synthesis (chronoamperometry,voltametry, …)

High-resolution scanning electron microscopy (FE-SEM withEDX)

Nano-imprint lithographyScanning probe microscopies (STM, AFM)Spectroscopies : FTIR, Raman, UV-visibleTransmission electron microscopy (TEM with EELS & EDX)X-ray diffraction (X-ray reflectometry)Access to surface analysis facilities (XPS, ToF-SIMS, contact

angle)

Partnership

The Research Center on Micro- and Nano-Materials andElectronic Devices (CerMin) of the Université catholique deLouvain.

The Center of Numerical Molecular Biophysics of the Facultéd’Agronomie de Gembloux (Prof. C. Brasseur).

The Service of Applied Genetics of the Université Libre deBruxelles.

44

STAFF

Total : 9

KEY WORDS FOR R&D

antibodies, antigensbiosensorsinstrumentationmicro- & nano-electronicsmolecular self-assemblynano-imprintnanolithographynanotechnologiesproteinssurfacesthin films

SENIOR SCIENTISTS

Vincent [email protected]. 32 (0)10 47 25 57

Sophie [email protected]. 32 (0)10 47 40 15

Alain M. [email protected]. 32 (0)10 47 37 65


WEB SITES

www.cermin.ucl.ac.bewww.dice.ucl.ac.bewww.poly.ucl.ac.be

www.cermin.ucl.ac.be

www.dice.ucl.ac.be

www.poly.ucl.ac.be

45


Spectrophotometric sensors for biomedical diagnosis and control

SENIOR SCIENTIST :

� Marc MEURENS

E 3


The team named SPECTROLAB is studying the applications ofspectrophotometry in fast and non-destructive chemical analy-sis of food and biological products. The research is focused ontwo problems encountered with the infrared (IR) absorptionspectrometry : the lack of sensitivity and the difficulty to cali-brate the IR spectrophotometers for the accurate determinationof low level constituents embedded in complex matrices.

A first solution has been found in the sample presentation forthe near infrared (NIR) as well as for the mid infrared spectro-metry of aqueous liquids. We have conceived and developed adry extract system for infrared (DESIR) using glass fiber filters assample substrates to accumulate the analytes in solid phase andamplify their NIR spectra. This concept of solid phase extractsupport has been extended to the mid infrared spectroscopywith two kinds of sample supports.

1. A special teflon membrane of microfiltration which allowsisolating individual living cells from a liquid culture medium topresent them in the best conditions for the Fourier transformmid infrared (FTIR) transmission measurement. 2. A hydrophobic film coating the attenuated total reflection(ATR) accessories used in analysis of aqueous liquids by FTIRspectroscopy.

Thereby, non-polar substances such as hydrocarbons can becontinuously extracted from the aqueous phase of the samplesto be accumulated at the interface with the ATR accessory (crys-tal or fiber). So the FTIR spectrometers can monitor the part permillion (ppm) concentrations of non-polar analytes such as lipi-dic substances in liquid samples circulating in flow-through ATRprobes (determination of the substrate in the mg/l range ofconcentration).

We are developing the measurement of short wave NIR (700-1100 nm) transmission spectra across very large samples, suchas whole apples or pieces of meat, whose thickness is aroundor more than 10 centimeters.

Our research is also open to the fluorescence and Raman scat-

tering spectroscopy in order to find sensitive analytical toolsoffering the advantage of automatic non-destructive determi-nations. Laser induced fluorescence and Raman spectrometersare tested with success in applications of food analysis as wellas of medical diagnosis.

In the chemometric data treatments necessary for the calibra-tion of the instruments in quantitative determinations, the teamproposes new methods of automatic stepwise multiple linearregression (SMLR) and artificial neural network (ANN). Thesemethods present the advantage of a higher precision than theusual principal component regression (PCR) and partial leastsquares (PLS) methods.


Databases of NIR, FTIR, fluorescence, and Raman spectra ofbiomolecules.

Design of optical probes and spectrophotometric sensors forfood analysis and medical diagnosis.

Multivariate calibration of spectrophotometric sensors by linear (SMLR) and non-linear methods (ANN).

Main Equipment

UV-Vis-NIR spectrometers with fiber optics, CCD or InGaAsdiode array detectors.

FTIR spectrometers with ZnSe and Ge ATR crystals and flow-through-cell.

FT and dispersive (CCD) Raman spectrometers with micro-scope.

Titanium–Sapphire tunable laser (700 mw) pumped by argoncontinuous wave laser (7W).


MEURENS M., ALFARO G. and BIRTH G.S. Liquid analysis bydry extract NIR reflectance on fiberglass. Applied Spectroscopy,44, 1990, 979 - 986.

46

BARTL F., DELGADILLO I., DAVIES A.N., MEURENS M. andWILSON R.H. An interlaboratory comparison of sample presen-tation in FTIR spectroscopy. Fresenius Journal of AnalyticalChemistry, 354, 1996, 1-5.

MEURENS M., WALLON J., TONG J., NOËL H., and HAOT J.Breast cancer detection by Fourier transform infrared spec-trometry. Vibrational Spectroscopy, 10, 1996, 341-346.

MEURENS M., ACHA V. and NAVEAU H. Extractive samplingto improve the sensitivity of FTIR spectroscopy in analysis ofaqueous liquids. Analysis, 25, 1998, 157-163.

Patent

Meurens M. Device of sample preparation for infrared spectroscopy of dry extract (DESIR), World Patent PCTWO90/15981.

Awards

“ShootOut-1998 Session”, 9th International Diffuse Reflectanceconference, Chambersburg, USA, 1988.

Partnership

Centre de recherche Agronomique, Gembloux, BelgiumRégion Wallonne, BelgiumEurofins Scientific, Nantes, FranceUniversita di Udine, ItalyAPLIGEER Company

STAFF

Total : 7

KEY WORDS FOR R&D

biomedical controlbiomedical diagnosisinfrared spectrometry raman spectrometryspectrofluorimetry

SENIOR SCIENTIST

Marc MEURENS [email protected]. 32 (0)10 47 37 26

WEB SITE

www.bnut.ucl.ac.be

www.bnut.ucl.ac.be

47


Electrophysiological exploration of the pain system

SENIOR SCIENTIST :

� Léon PLAGHKI

E 4


The team is dedicated to the application of cutaneous CO2laser stimulation for the exploration of the pain system inhumans.Topics of current interest :

Laser evoked brain potentials (LEPs) in normal subjects andtheir modulation by affective and cognitive factors.

Time-frequency analysis of LEPs by wavelet transforms.Laser evoked brain potentials in patients with chronic neuro-

pathic pain.Nociceptive motor reflexes (RIII) in normal and chronic pain

states.Psychophysics of the pain system.


Electrophysiological exploration of the pain system in chronicpain patients.

Mathematical analysis of evoked brain potentials : waveletanalysis, brain electrical source analysis.

Electronic recording of neurophysiological and psychophysi-cal data in relation to the pain system.

Main Equipment

Laser skin stimulatorsEEGEMG


PLAGHKI L., BRAGARD D., LE BARS D., WILLER J.Cl., GOD-FRAIND J.-M. Facilitation of a nociceptive flexion reflex by non-noxious laser radiant heat. J. NeuroPhysiol., 79 : 2557-2567,1998.

CHEN A.C.N., ARENDT-NIELSEN L., PLAGHKI L. Laser evokedpotentials in human pain : I. use and possible misuse. PainForum – J. Am. Pain Soc., 7(4) : 174-184, 1998.

CHEN A.C.N., ARENDT-NIELSEN L., PLAGHKI L. Under-standing of cerebral processing of human pain (II) by sourcemodeling of laser evoked potentials in conjunction with neuroimaging : an integration. Pain Forum – J. Am. Pain Soc.,7(4) : 221-230, 1998.

GRISART J. & PLAGHKI L. Impaired selective attention inchronic pain patients. E. J. Pain 3 : 325-333, 1999.

OPSOMMER E., MASQUELIER E., PLAGHKI L. Determinationof nerve conduction velocity of C-Fibres in humans from ther-mal thresholds to contact heat (Thermode) and from evokedbrain potentials to radiant heat (CO2 laser). Neurophysiol. Clin.,29 : 411-422, 1999.

DETREMBLEUR C., PLAGHKI L. Quantitative assessment ofspasticity : effect of intrathecally administered baclofen. Arch.Phys. Med. Rehabil., 81 : 279-284, 2000.

OPSOMMER E., WEISS T., MILTNER W.H.R., PLAGHKI L. Scalptopography of ultralate (C-fibres) evoked potentials followingThulium YAG laser stimuli to tiny skin surface areas in humans.Clin. Neurophysiol., 112 (10) : 1868-1874, 2001.

OPSOMMER E., WEISS T., MILTNER W.H.R., PLAGHKI L.Dipole analysis of ultralate (C-fibres) evoked potentials afterlaser stimulation of tiny cutaneous surface areas in humans.Neurosc. Letters 298 : 41-44, 2001.

OPSOMMER M., PLAGHKI L. Maturational changes in thethermoalgesic system from childhood to adulthood revealed byCO2 laser evoked brain potentials following cutaneous heatstimuli. Neurosc. Letters 316(3) : 137-140, 2001.

LEGRAIN V., GUERIT J.M., BRUYER R., PLAGHKI L. Attentionalmodulation of the nociceptive processing into the humanbrain : selective spatial attention, probability of stimulus occur-rence, and target detection effects on laser evoked potentials.Pain 99 : 21-39, 2002.

LEGRAIN V., BRUYER R., GUERIT J.M., PLAGHKI L. Nociceptiveprocessing in the human brain of infrequent task-relevant andtask-irrelevant noxious stimuli. A study with ERPs elicited byCO2 laser radiant heat stimuli. Pain 103 : 237-248, 2003.

PLAGHKI L., MOURAUX A. How do we selectively activateskin nociceptors with a high power infrared laser? Physiologyand biophysics of laser stimulation. Clin. Neurophysiol., 33 : 269-277, 2003.

WUNSCH A., PHILIPOT P., PLAGHKI L. Affective associative

48

learning modifies the sensory perception of nociceptive stimuliwithout participant’s awareness. Pain 102 : 27-38, 2003.

LEGRAIN V., GUERIT J.M., BRUYER R., PLAGHKI L.Electrophysiological correlates of attentional orientation inhumans to strong intensity deviant nociceptive stimuli, insideand outside the focus of spatial attention. Neurosc. Let.,303 :107-110, 2003.

NAHRA H., PLAGHKI L. The effects of A-fiber pressure blockon perception and neurophysiological correlates of brief non-painful and painful CO2 laser stimuli in humans. Europ. J. Pain,7 : 189-199, 2003.

NAHRA H., PLAGHKI L. Modulation of perception and neuro-physiological correlates of brief CO2 laser stimuli in humansusing concurrent large fiber stimulation. Sensory and MotorRes., 20 : 139-147, 2003.

MOURAUX A., GUERIT J.M., PLAGHKI L. Non-phase lockedEEG responses to CO2 laser skin stimulations reflect centralinteractions between A-delta- and C-fiber afferent volleys. Clin.Neurophysiol., 114 : 710-722, 2003.

OPSOMMER M., GUERIT J.M., PLAGHKI L. Exogenous andendogenous components of ultralate (C-fibres) evoked poten-tials following CO2 laser stimuli to tiny skin surface areas inhealthy subjects. Neurophysiol. Clin., 33 : 78-85, 2003.

STAFF

Total : 4

KEY WORDS FOR R&D

data analysismedical instrumentationneuropathologyneurophysiologyneuropsychologyneurosciencespsychophysics

SENIOR SCIENTIST

Léon PLAGHKI [email protected]. 32 (0)2 764 16 82

WEB SITE

www.read.ucl.ac.be

www.read.ucl.ac.be

49


Development of a microarray allowing the study of the genic expression in prostatic cancers

SENIOR SCIENTIST :

� Jean-Luc GALA

E 5


Prostatic cancer (PC) is a major problem of public health becauseof its frequency and the associated therapeutic problems.

The aim of the study is to establish the molecular profile of pro-static cell line and tumors by a multigenic analysis expression usinga DNA microarray. We need to assess the effect of therapeuticagents (hormono-, radio-therapy, kinase inhibitors), to predict pro-state cells response to these agents and to better understandwhat are the genetic mechanisms of apoptosis or resistance toapoptosis in this setting. The DNA microarray technique is cur-rently being developed in collaboration with Eppendorf ArrayTechnologies. The capchips microarray will monitor the expressionprofile of genes that are known to influence prostate cell respon-se to xenobiotics.

In parallel, protein chips will be used to monitor the effect of newdrugs on phosphorylation process.

The results must allow us to better understand the oncogenesmechanisms in prostatic gland and determine new prognostic andpredictive criteria for the therapeutic response of the patients andmay be the base-line for new and more selective therapeutics.

Another field of investigation is the detection and quantificationof prostate circulating cells in cancer patients. This translationalresearch has to develop a clinical application that is now routinelyperformed as a prognostic indicator in patient after radical pro-statectomy (see ref.).


Detection and quantification of prostate circulating cellsDevelopment of capchips microarrayDevelopment of protein chips (MAPkinase)DNA Sequencing DNA Cloning

Main Equipment

P2 facilitiesReal time PCR (Taqman®)DNA sequencerMicroarray facilities (colorimetric and fluorescent reader,

spotter, software for datamining and quantification); some ofthese facilities are provided by Eppendorf Array Technologies ascooperation agreement.


J.L. GALA, M. HEUSTERSPREUTE, S. LORIC, F. HANON, B. TOMBAL, P. VAN CANGH, Ph. DE NAYER, M. PHILIPPE.Expression of the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) in blood cells : implicationsfor the detection of hematogenous prostate cells and stan-dardization. Clin. Chem., 3, 1998, 472-481.

P. BERTEAUX, F. DUMAS, S. LORIC, P. ESCHWEGE, J.L. GALA.Reverse transcriptase polymerase chain reaction for prostatespecific antigen in the management of prostate cancer [Letterto the Editor]. J. of Urology, 158, 1998, 1649.

J.L. GALA and S. LORIC. Sensitivity or specificity of RT-PCRassays : The real challenge for molecular staging of prostaticcarcinomas. Int. J. Cancer, 77, 1998, 161-163.

J.L. GALA. Despite its name, PSMA doesn’t appear to beprostate specific. Urology Times, page 8, September, 1998.

P.J. VAN CANGH, B. TOMBAL, J.L. GALA. Intermittentendocrine treatment. World Journal of Urology 18, 2000, 183-189.

J.L. GALA, S. LORIC, Y. GUIOT, F. BRASSEUR, M. HEUSTER-SPREUTE, P. ESCHWEGE, G. BENOIT, F. HANON, P. VAN CANGH,P. DE NAYER, B. TOMBAL. Expression of Prostate SpecificMembrane Antigen in Transitional Cell Carcinoma of theBladder : prognostic value. Clinical Cancer Research 6, 2000,4049-4054.

B. TOMBAL, P.J. VAN CANGH, S. LORIC, J.L. GALA.Prognostic value of circulating prostate cells in patients with a rising PSA after radical prostatectomy. Prostate, 17, 2003, 163-170.

50

Patents

Genetic sequences, methods and diagnostic and/or quantifi-cation methods for the identification of staphylococci. BrevetPCT/BE98/00141, 28.09.1998.

Partnership

Eppendorf Array Technologies (EAT), Namur, Belgiumgrant First Europe Capchips

STAFF

Total : 6

KEY WORDS FOR R&D

cancercapchipsgenesmicroarrayprostate

SENIOR SCIENTIST

Jean-Luc [email protected]. 32 (0)2 764 31 65

WEB SITE

www.lbcm.ucl.ac.be

www.lbcm.ucl.ac.be

51


Development of microarray for genotyping bacteria and mycobacteria

SENIOR SCIENTIST :

� Jean-Luc GALA

E 6


The Laboratory of Applied Molecular Technologies (AMT) hostsuniversity and military molecular research activities on infectiousdiseases. Specialized equipment is available as the own proper-ty of the laboratory. Regarding the development of microarray,the equipment required for spotting and reading fluorescenceis available through active and official cooperation withEppendorf Array Technologies company. Collaboration withfederal laboratories is also active on the topic of identificationof pathogenic agents (CODA/CERVA; Institut Pasteur). Activities focus on molecular investigations of microorganisms(bacteria, mycobacteria and antibiotic resistance). The aim is todevelop clinical molecular assays allowing rapid and specificdiagnosis of infections in humans and animals. Activities of thelaboratory focus on the development of new diagnostic assaysand tools. The development of molecular tools aims at impro-ving the clinical diagnosis of infectious diseases affectinghuman beings and animals. This is achieved by combining gen-der and species-specific consensus regions of microorganisms.Achievements can therefore be summarized as follows :1. Patents : identification, characterization and cloning of newgenomic targets laboratory. This has led to two patents for newstaphylococcal and mycobacterial targets (see below : patents).We are currently proceeding with a third patent for a molecu-lar target characterizing gram–positive bacteria. 2. Clinical validation : the specificity and sensitivity of the newtargets are being tested in the laboratory on human and ani-mals samples. Specificity and sensitivity of the molecular mar-kers are tested and compared to conventional microbiologicmethods. This has been successfully performed for staphylo-cocci and mycobacteria. Other clinical validations are ongoing(spondylodiscitis and infection of prosthetic devices in humans;mycobacteria in human and animals – gorillas, deers, etc… incollaboration with CODA/CERVA). Quantitative assessment ofMycobacterium paratuberculosis using the Taqman technologyis under development (Grant PARADIAG from the RégionWallonne).3. Bacterial resistance is also under the scope of the laboratory.Currently, the laboratory is assessing the resistance of staphylo-cocci species through the characterization of the mecA and staphylococcal cassette chromosome (according to the type and

the calls of the mecA resistance). A new project sponsored bythe Ministry of Defence and started January 2004 will extendthe scope to the bacterial resistance to aminoglycosides andpenicillins. 4. Microarray : the aim of the laboratory is to use the new tar-gets as genotypic markers on microarray. Accordingly, Pr. Gala,head of the laboratory, has started the joined interuniversityspin off Advanced Array Technology (AAT) in July 1999. Thespin off became Eppendorf Array Technologies (EAT) in July2002. The laboratory has actively cooperated with AAT and EATto develop new microrarrays for genotyping infectious agents.The new targets identified and characterized in the laboratoryare currently used for these purposes. Clinical relevance of thisdevice is currently assessed in the clinical setting. 5. DNA and bacteria bank : a bank is actively being build up.The bank is used to validate the specificity of new or conven-tional molecular targets. For each bacteria of this collection,bacterial DNA is characterized by sequence analysis for16srDNa, 16s-23s spacer and new patented targets.


Bacterial DNA typing with biochips (Staphychip®; Mycochips®)Development of other biochipsIdentification of DNA genomic targetsBacterial DNA typing by multiplex procedure DNA Sequencing DNA Cloning

Main Equipment

P2 and P3 facilitiesReal time PCR (Taqman®)DNA sequencerMicroarray facilities (colorimetric and fluorescent reader,

spotter, software for datamining and quantification); some ofthese facilities are provided by Eppendorf Array Technologies ascooperation agreement

52


P. VANNUFFEL, J. GIGI, H. EZZIDINE, B. VANDERCAM, M. DELMEE,G. WAUTERS, J.L. GALA. Specific detection of methicillin-resistantstaphylococci species using multiplex PCR. J. Clin. Microb., 1995, 33 : 2864-2867.

J.L. GALA. Specific detection of methicillin-resistant staphylococcispecies using multiplex PCR. J. Clin. Microb., 1996, 34 : 1599.

J.L. GALA, A.T. VANDENBROUCKE, B. VANDERCAM, J.P. PIRNAY,N. DELFERRIERE, G. BURTONBOY. HIV-1 detection by nested-PCRand viral culture in fresh or cryopreserved postmortem skin : poten-tial implications for skin handling and allografting. J. Clin. Pathol.,1997, 50 : 481- 484.

P. VANNUFFEL, M. HEUSTERSPREUTE, M. BOUYER, M. PHILIPPE,J.L. GALA. Molecular characterization of femA from Staphyloccushominis and Staphylococcus saprophyticus and the use of the femA-based discrimination of staphylococcal species. Research inMicrobiology, 1999, 150 : 129-141.

C. COETSIER, P. VANNUFFEL, N. BLONDEEL, J.F. DENEF, C. COCI-TO, J.L. GALA. Duplex PCR for differential identification ofMycobacterium bovis, M. avium, and M. avium subsp.Paratuberculosis in formalin-fixed embedded tissue from cattle.J. Clin. Microbiology, 2000, 38 : 3048-3054.

I. ALEXANDRE, S. HAMELS, S. DUFOUR, J. COLLET, N. ZAMMAT-TEO, F. DE LONGUEVILLE, J.L. GALA, J. REMACLE. Colorimetric silverdetection of DNA Microarrays. Analytical Biochemistry, 2001, 295 :1-8.

S. HAMELS, J.L. GALA, S. DUFOUR, P. VANNUFFEL, N. ZAM-MATTEO, J. REMACLE. Consensus PCR and microarray for diagnosisof the genus Staphylococcus, species, and methicillin resistance.Biotechniques, 2001, 31; 1364-1372.

N. ZAMMATTEO, S. HAMELS, F. DE LONGUEVILLE, I. ALEXANDRE,J.L. GALA, F. BRASSEUR, J. REMACLE. New chips for molecular biology and diagnostics. Tome Volume 8, 85-101. BiotechnologyAnnual Review - M. Raafat El-Gewely, Ed. Elsevier, 2002.

I. ALEXANDRE, Y. HOUBION, J. COLLET, S. HAMELS, J. DEMARTEAU, J.L. GALA, J. REMACLE. Compact disc with bothnumeric and genomic information as DNA microarray platform.Biotechniques, 2002, 33 : 435-439.

Patents

Genetic sequences, methods and diagnostic and/or quantifi-cation methods for the identification of staphylococci.PCT/BE98/00141, 28.09.1998.

Genetic sequences, methods and diagnostic and/or quantifi-cation methods for the identification of mycobacteria. US appli-cation 60/269.848 and US application 60/292.509; Europeanapplication n°002447026.2 filed on February 15, 2002.

Genetic sequences, methods and diagnostic and/or quantifi-cation methods for the identification of gram-positive bacteria.Ongoing process, October 2003.

Partnership

Eppendorf Array Technologies (EAT)CODA/CERVAInstitut PasteurMinistry of Defence, Belgium

STAFF

Total : 6.

KEY WORDS FOR R&D

bacteriagenotypingmicroarrayresistance

SENIOR SCIENTIST


WEB SITE

www.lbcm.ucl.ac.be

www.lbcm.ucl.ac.be

53


Multigenotypic identification of pathogenic bacteria andtheir resistance determinant using biochip technology

SENIOR SCIENTIST :

� Jean-Luc GALA

E 7


While many tools exist for manipulation, cloning, sequencing,transfection, and expression of genes, there is still a need formultigenotypic device allowing a quick identification and a spe-cific detection of human or bacterial genomic specific targets inbiological samples or environment. In this respect, biochip holds great promises, being one of themost powerful tools for multiple, rapid and simultaneous ana-lysis of genes and DNA or RNA sequences. It appears as anessential component allowing to exploit the ever expandinggenomic database.

The DNA microarrays or biochips are made of a surface onwhich are covalently linked multiple capture probes, each onebeing specific for the binding and detection of one DNA target.The advantage of the chips is to allow the detection of multiplegenomic sequences in a single assay rather than performingthese one by one.

New genomic targets are identified, characterized and clonedin our laboratory, whereas development of the biochip toolitself is performed by Prof. José Remacle, Facultés Notre Damede la Paix in Namur.

On the basis of a joined interuniversity start up, we have deve-loped and totally completed our first application, aStaphychip®. This biochip allows molecular identification ofstaphylococci genus and species through only one duplex PCRamplification. Amplicons are hybridized on a set of genomicprobes linked on the chips :

1. A consensus genus specific probe allows the detection ofstaphylococci in clinical samples or environment, regardless ofthe species.2. Various species-specific probes allow a specific identificationof 5 among the most common staphylococci species in humanpathology (S. aureus, S. epidermidis, S. hominis, S. haemolyti-cus, S. saprophyticus).3. Detection of mecA-specific probe, the main staphylococcalresistance determinant responsible for cross resistance towardsall beta-lactam antibiotics among the staphylococcal species.

Clinical relevance of this device is currently assessed in a rangeof applications. Bacterial chips are also being further developed. They target awide range of other human or animal pathogenic bacteria. Cancer biochips are under development as well, either basedon RNA (gene expression) or DNA (detection of gene families).


Bacterial DNA typing with biochip Staphychip®Development of other biochipsIdentification of DNA genomic targetsBacterial DNA typing by multiplex procedure DNA SequencingDNA Cloning

Main Equipment

P2 facilitiesReal time PCR (Taqman®)DNA sequencer


P. VANNUFFEL, J. GIGI, H. EZZIDINE, B. VANDERCAM, M. DELMEE, G. WAUTERS, J.L. GALA. Specific detection ofmethicillin-resistant staphylococci species using multiplex PCR.J. Clin. Microb., 33 : 2864-2867, 1995.

J.L. GALA. Specific detection of methicillin-resistant staphylo-cocci species using multiplex PCR. J. Clin. Microb., 34 : 1599,1996.

J.L. GALA, A.T. VANDENBROUCKE, B. VANDERCAM, J.P. PIRNAY, N. DELFERRIERE, G. BURTONBOY. HIV-1 detectionby nested-PCR and viral culture in fresh or cryopreserved post-mortem skin : potential implications for skin handling and allografting. J. Clin. Pathol., 50 : 481- 484, 1997.

P. VANNUFFEL, M. HEUSTERSPREUTE, M. BOUYER, M. PHILIPPE, J.L. GALA. Molecular characterization of femAfrom Staphylococcus hominis and Staphylococcus saprophyti-

54

cus and the use of the femA-based discrimination of staphylo-coccal species. Research in Microbiology, 150 : 129-141, 1999.

C. COETSIER, P. VANNUFFEL, N. BLONDEEL, J.F. DENEF, C. COCITO, J.L. GALA. Duplex PCR for differential identificationof Mycobacterium bovis, M. avium, and M. avium subsp.Paratuberculosis in formalin-fixed embedded tissue from cattlepathogenic mycobacteria. J. Clin. Microbiology, May, 2000.

J.L. GALA. Orthopaedic prostheses and bacterial infection.Ann. Med. Mil. Belg., 14 : 53-62, 2000.

P. VANNUFFEL, M. BOUYER, O. CORNU, M. MOREAU, O. WENANU, B. VANDERCAM, J.-L. GALA. Molecular strategiesfor identification of infected prostheses. Ann. Med. Mil. Belg.,14 : 63-64, 2000.

Patents

Genetic sequences, methods and diagnostic and/or quantifi-cation methods for the identification of staphylococci. BrevetPCT/BE98/00141, 28.09.1998

Partnership

Eppendorf Array Technologies (EAT), Namur, BelgiumFacultés Notre Dame de la Paix, Namur, Belgium.

STAFF

Total : 6

KEY WORDS FOR R&D

bacteriabiochips cancerdiagnosisepidemiology molecular typingmultigenotypic identification

SENIOR SCIENTIST


WEB SITE

www.lbcm.ucl.ac.be

www.lbcm.ucl.ac.be

55


Pharmacogenetics of cytochrome p450, thiopurine-methyl-transferase and multidrug resistance

SENIOR SCIENTIST :

� Jean-Luc GALA

E 8


Some genes are known to play a major role in the metabolismof drugs (cytochrome p450 gene or CYP, TPMT, etc…). Thegenetic status defined by polymorphisms determines the meta-bolism of active drugs (efficacy and toxicity).

We are currently developing genetic screening of some of themost clinically important polymorphisms affecting CYP 450(2C9, 2C19, 2D6), MDR-1 and TPMT.

The goal is to establish a genomic bank containing the mostinteresting alleles within this family of genes. To do so, we arescreening Caucasian and African individuals. We are correlatingthe genotypic status with pharmacodynamic data in collaborationwith the UCL faculty unit of gastroenterology (Prof.Y. Horsmans).

In collaboration with Eppendorf Array Technologies, we are alsodeveloping the microarray detection system for SNP genotypingof the most clinically relevant alleles.

For the TPMT gene, we are already implementing clinical appli-cations in order to guide the therapy of patients receivingAzathioprine.

We are also studying the enzymatic activity of recently discove-red alleles in the Belgian population. This study is performed incollaboration with Prof. Broly (Hôpital Calmette, Lille).


Identification of DNA genomic polymorphismDNA Sequencing Quantification of gene expression

Main Equipment

P2 facilitiesReal time PCR (Taqman®)DNA sequencerMicroarray facilities (colorimetric and fluorescent reader,

spotter, software for datamining and quantification). Some ofthese facilities are provided by Eppendorf Array Technologies ascooperation agreement.


A.C. ALLABI, J.L. GALA (corresponding author), J.P.DESAGER, M. HEUSTERSPREUTE, Y. HORSMANS. Genetic poly-morphisms of CYP2C9 and CYP2C19 in the Beninese andBelgian populations. Br. J. Clin. Pharm., 2003.

C. GALANT, J.L. GALA, V. VAN DEN BERGE, M. BERLIERE, E. HAUMONT, Y. HORSMANS. Immunolocalisation ofCytochrome P 450 3A enzymes in human breast carcinoma :relationship with tumor differentiation and steroid receptors.Pharmacol. Toxicol., 88, 2001, 142-146.

V. HAUFROID, F. TOUBEAU, A. CLIPPE, M. BUYSSCHAERT, J.L. GALA, D. LISON. Real-time quantification of cytochromeP4502E1 (CYP2E1) mRNA in human peripheral blood lympho-cytes by RT-PCR : method and practical application. ClinicalChemistry, 47, 2001, 1126-1129.

R. HAMDAN-KHALILA, D. ALLORGE, J.M. LO-GUIDICEA, C. CUAFFIEZA, D. CHEVALIERA, N. HOUDRETA, C. LIBERSAB,M. LHERMITTEA, J.F. COLOMBEL., J.L. GALA, F. BROLY. In vitrocharacterization of four novel non-functional variants of the thiopurine S-methyltransferase (TPMT). Biochemical andBiophysical Research Communication, 2003.

Partnership

Prof.Y. Horsmans, GAEN, UCLEppendorf Array Technologies (grant WALEO from the

Région Wallonne)Prof. Broly, Hôpital Calmette, Lille, France

56

STAFF

Total : 7

KEY WORDS FOR R&D

cytochrome p450multidrug resistance (MDR-1)pharmacogeneticsthiopurine-methyl-transferase (TPMT)

SENIOR SCIENTIST


WEB SITE

www.lbcm.ucl.ac.be

www.lbcm.ucl.ac.be

57


Interfaces for respiratory monitoring in emergency care

SENIOR SCIENTISTS :

�Frédéric THYS�Franck VERSCHUREN �Jean ROESELER �Marc S. REYNAERT

E 9


This team is dedicated to the clinical application of informationtechnologies (simulation, monitoring and data analysis) to therespiratory system.

The research is organised along two main streams :

1. Work of breathing and non-invasive ventilation. Topic of current interest is developing a dedicated device withnon-invasive sensors for the monitoring and integration of thework of breathing (ECG recording, oxymetry, thoracic andabdominal respiratory movements by plethysmography, electro-myogram of accessory respiratory muscles activity) and the ven-tilators output signals. This monitoring should be efficient in the particular environ-ment of the Emergency Department. The use of monitoring signals to predict the fate of non-invasi-ve ventilation should certainly be among the future steps inimprovement of care in patients with acute respiratory failure.

2. Volumetric capnography in the non-intubated critically illpatient.

Topics of current interest are :developing a dedicated device with non-invasive sensors for

the monitoring of volumetric capnography (integration ofdetermination of the slope of phase 3 of CO2 expirogram,adjunct of the late deadspace fraction, computerized neuralnetwork analysis of CO2 and spirometry data)

evaluation of clinical application in several diseases : diagno-sis of pulmonary disease, monitoring of thrombolytic efficacy inpulmonary embolism, differential diagnosis in acute respiratorydiseases and non-invasive evaluation of cardiac output.


Sensors to monitor work of breathingSensors to monitor volumetric capnographyAnalysis of all data recorded

Main Equipment

Workstations


THYS F., ROESELER J., DELAERE S. and al. Two-level non inva-sive positive pressure ventilation (Nippv) in the initial treatmentof acute respiratory failure (ARF) in an emergency department (ED).European Journal of Emergency Medicine, 1999, 6 : 207-214.

THYS F., ELAMLY A., MARION E. and al. Arterial ETCO2/CO2gradient : early indicator of thrombolysis efficacy in the massivepulmonary embolism. Resuscitation, 2001, 49, 105-108, IF 2001, 1.774.

THYS F., LIISTRO G., DOZIN O., MARION E., RODENSTEIND.O. Determinants of Fi O2 with O2 supplementation duringnon invasive two-level positive pressure ventilation. EuropeanRespiratory Journal, 2002, 19 : 653-657.

THYS F., ROESELER J., REYNAERT M.S., LIISTRO G., RODEN-STEIN D.O. Non invasive ventilation for acute respiratory failure : a prospective randomized placebo-controlled trial.European Respiratory Journal, 2002, 20 : 545-555.

VERSCHUREN F., THYS F. Steady-state end-tidal alveolar deadspace measure and D-Dimer. Chest, 2002, 121 (4) : 1373.

VERSCHUREN F., THYS F., LIISTRO G. Volumetric capnographyin the non intubated critical ill patient. Yearbook for the 22ndInternational Symposium on Intensive Care and EmergencyMedicine, 2002, 564-578.

VERSCHUREN F., LIISTRO G., COFFENG R., THYS F., ROESEL-ER J, ZECH F., REYNAERT M. Volumetric capnography as ascreening test for pulmonary embolism at the emergencydepartment, (in press).

THYS F., ROESELER J., REYNAERT M., LIISTRO G., RODEN-STEIN D.O. Respiratory rate and sternocleidomastoid activity areearly predictors of success of non invasive ventilation for acuterespiratory failure, (in press).

Patents

European patent : 99870119.7-2305

58

STAFF

Total : 8

KEY WORDS FOR R&D

biomaterialsbiomedical engineeringbiomedical sciencesdata analysisemergencymedical instrumentationmonitoring pneumology

SENIOR SCIENTISTS

Frédéric [email protected] Tel. 32 (0)2 764 16 13

Franck [email protected]. 32 (0)2 764 16 13

Jean ROESELER [email protected]. 32 (0)2 764 16 13

Marc S. [email protected] Tel. 32 (0)2 764 27 11

WEB SITE

www.rean.ucl.ac.be

www.rean.ucl.ac.be

59


Biomedical physiopathology : blood gas and inert gas modeling

SENIOR SCIENTISTS :

� Daniel RODENSTEIN� Giuseppe LIISTRO� Thierry CLERBAUX

F 1


The laboratory is dedicated to the physiological properties ofthe blood oxygen transport (simulation, data analysis and moni-toring) and to the determination of ventilation-perfusion ratiosof the lung by multiple inert-gas elimination technique (MIGET).

The research is organized around three poles : Analysis of the oxyhemoglobin dissociation curve (ODC) and

the modulation of this curve, by means of chemical and physi-cal factors in order to enhance the oxygen transport and deliv-ery to the tissues. We investigate the factors acting on thehemoglobin affinity for oxygen of the human, animal and arti-ficial blood.

Measurement of the continuous distribution of ventilation-perfusion relationships of the lung by the MIGET. The ventila-tion-perfusion inequality is the major cause of hypoxemia.

Complete measurement of the lung mechanics, during spon-taneous and mechanically assisted breathy, including the analy-sis of the patient-ventilator interactions.

Finally, all the above-mentioned techniques are applied inhumans and in an animal model of bronchial asthma.


Assessment of the factors acting on the affinity of hemoglo-bin for oxygen (drugs, ions, biochemical agents,…).

Measurement of the ventilation-perfusion relationship of thelung, in combination with the lung mechanics analysis, inhuman and animals.

Main Equipment

Blood gas analyzerChromatograph (gas phase) FID and ECDDetector for MIGET techniqueLung mechanics workstationOxygen dissociation curve analyzer (ODC)


CLERBAUX T., DETRY B., REYNAERT M., KREUZER F., FRANSA. Reestimation of the effects of inorganic phosphates on theequilibrium between oxygen and hemoglobin. Intensive CareMed., 1992; 18(4) : 222-5.

CLERBAUX T., HENRY P., VERITER C., NULLENS W., DETRY B.,CAO M.L., RAPHAEL D. The effect of inhaled salbutanol on pul-monary gas exchange in patients with chronic obstructive bron-chopneumopathy. Rev. Mal. Respir., 1992; 9(2) : 171-7.

CLERBAUX T., GUSTIN P., DETRY B., CAO M.L., FRANS A.Comparative study of the oxyhemoglobin dissociation curve offour mammals : man, dog, horse and cattle. Comp. Biochem.Physiol., 1993 Dec;106(4) : 687-94.

GUSTIN P., DETRY B., CAO M.L., CHENUT F., ROBERT A.,ANSAY M., FRANS A. Chloride and inorganic phosphate modu-late binding of oxygen to bovine red blood cells. J. Appl.Physiol., 1994 Jul; 77(1) : 202-8.

CLERBAUX T., DETRY B., REYNAERT M., FRANS A. Right shiftof the oxyhemoglobin dissociation curve in acute respiratorydistress syndrome. Pathol. Biol. (Paris), 1997 Apr;45(4) : 269-73.

GUSTIN P., DETRY B., ROBERT A., CAO M.L., LESSIRE F.,CAMBIER C., KATZ V., ANSAY M., FRANS A. Influence of ageand breed on the binding of oxygen to red blood cells of bovinecalves. J. Appl. Physiol., 1997, 82(3) 784-90.

FRANS A., LERBAUX T., DETRY B., ROBERT A., LATERRE P.F.,POCHET J.M., REYNAERT M. Effect of inorganic ions on theoxyhemoglobin dissociation curve of severely ill patients.Pathol.Biol. (Paris), 1998 Jan;46(1) : 8-14.

CAMBIER C., DETRY B., BEERENS D., FLORQUIN S., ANSAYM., FRANS A., CLERBAUX T., GUSTIN P. Effects of hyper-chloremia on blood oxygen binding in healthy calves. J. Appl.Physiol., 1998; 85(4) : 1267-72.

CAMBIER C., CLERBAUX T., AMORY H., DETRY B., FLORQUINS., MARVILLE V., FRANS A., GUSTIN P. Mechanisms controllingthe oxygen consumption in experimentally inducedhypochloremic alkalosis in calves. Vet. Res., 2002, 33, 697-708.

WATREMEZ C., ROESELER J., DE KOCK M., CLERBAUX T.,DETRY B., VERITER C., REYNAERT M., GIANELLO P., JOLLIET P.,LIISTRO G. An improved porcine model of stable methacholine-

60

induced bronchospasm. Int. Car. Med., 2003, 29, 119-125.

DETRY B., CAMBIER C., FRANS A., GUSTIN P., CLERBAUX T.Calculation of bovine hemoglobin oxygen saturation by algo-rithms integrating age, hemoglobin content, blood pH, oxygenblood pressure, carbon dioxide blood pressure and tempera-ture. The Veterinary Journal, 2003, 165-3, 258-265.

Awards

Boerhinger Ingelheim prize, Société belge de pneumologie,1982.

Partnership

Universities of Grenoble (France), Amiens (France), Belo Horizonte (Bresil), Barcelone (Spain)

Hospital of Palma de Mallorca (Spain)

STAFF

Total : 10

KEY WORDS FOR R&D

biomedical engineeringbiomedical sciencesdata analysisgas exchangesinert gas elimination techniqueinternal medicinelung mechanicsmodelingoxyhemoglobinpneumology

SENIOR SCIENTISTS

Daniel [email protected]. 32 (0)2 764 28 32

Giuseppe [email protected]. 32 (0)2 764 28 43

Thierry [email protected]. 32 (0)2 764 94 47

WEB SITE

www.pneu.ucl.ac.be

www.pneu.ucl.ac.be

61


Modeling in neuroscience

SENIOR SCIENTIST :

� Philippe LEFEVRE

F 2


Our aim is to study and model the mechanisms underlying the neu-ral control of movement, interacting with vision. The oculomotor system is characterized by the interaction betweenperipheral reflexes and central motor commands of visual origin. The dynamical properties of the oculomotor plant are very simple,thus it is a good testing bench for studying interfaces between sen-sory and motor systems in the brain. Moreover, in gaze orientation,combined eye and head motions are good examples of the controlof imbedded platforms.

In addition, the neural control of gaze in natural conditions requi-res the interaction between different strategies of oculomotorcontrol. In particular, some eye movements are controlled by visualfeedback (smooth pursuit : slow movements) whereas others arecontrolled in open loop with respect to vision (saccades : fast move-ments).

Within this context, we are currently involved in the followingresearch subjects :

Visual tracking of moving targets in two dimensions. Interaction between smooth and saccadic eye movements in

visual tracking.Role played by position error and velocity error (retinal slip) in the

prediction of target motion during smooth and saccadic pursuit.Importance of prediction and anticipation in smooth pursuit and

how this relates to the localization of targets in space.Clinical study of eye movements in patients showing different

types of pathologies (e.g. Duane syndrome). Influence of micro-gravity on eye-hand coordination.Comparison of human performance with theoretical predictions

from systems theory in simple rhythmic tasks (juggling).

Main Equipment

Magnetic coil for 3D eye recording (Skalar).Set of galvanometers for the presentation of simple visual

stimuli in closed loop.Video system for 3D eye recording (Chronos, Skalar).Optotrak system for 3D recording of the kinematics of limb

movements.

Cambridge visual stimulator for the real-time presentation ofcomplex visual stimuli.


LEFÈVRE P., QUAIA C., OPTICAN L.M. Distributed model ofcontrol of saccades by superior colliculus and cerebellum.Neural Networks, 1998, 11, 1175-1190.

QUAIA C., LEFÈVRE P., OPTICAN L.M. Model of the control ofsaccades by Superior Colliculus and Cerebellum. Journal ofNeurophysiology, 1999, 82, 999-1018.

COIMBRA A., LEFÈVRE P., MISSAL M., OLIVIER E. Differencebetween visually and electrically evoked gaze saccades dis-closed by altering the head moment of inertia. Journal ofNeurophysiology, 2000, 83, 1103-1107.

MISSAL M., DE BROUWER S., LEFÈVRE P., OLIVIER E. Activityof mesencephalic vertical burst neurons during saccades andsmooth pursuit. Journal of Neurophysiology, 2000, 83, 2080-2092.

DE BROUWER S., MISSAL M., LEFÈVRE P. Role of retinal slip inthe prediction of target motion during smooth and saccadicpursuit. Journal of Neurophysiology, 2001, 86, 550-558.

DE BROUWER S., YUKSEL D., BLOHM G., MISSAL M.,LEFÈVRE P. What triggers catch-up saccades during visual track-ing? Journal of Neurophysiology, 2002, 87, 1646-1650.

DE BROUWER S., MISSAL M., BARNES G.R., LEFÈVRE P.Quantitative analysis of catch-up saccades during sustainedpursuit. Journal of Neurophysiology, 2002, 87, 1772-1780.

MISSAL M., COIMBRA A., LEFÈVRE P., OLIVIER E. A quantita-tive analysis of the correlations between eye movements andneural activity in the pretectum. Experimental Brain Research,2002, 143, 373-382.

MISSAL M., COIMBRA A., LEFÈVRE P., OLIVIER E. Further evi-dence that separate circuits drive slow eye movements and sac-cades through a shared efferent collicular pathway.Experimental Brain Research, 2002, 147, 344-352.

BLOHM G., MISSAL M., LEFÈVRE P. Interaction betweensmooth anticipation and saccades during ocular orientation indarkness. Journal of Neurophysiology, 2003, 89, 1423-1433.

62

STAFF

Total : 10

KEY WORDS FOR R&D

biomedical engineeringeye-hand coordinationeye movementslimb movementsmicrogravitymodelneurosciencesaccadessimulationsmooth pursuitvision

SENIOR SCIENTIST

Philippe [email protected] Tel. 32 (0)10 47 23 82

WEB SITE

www.auto.ucl.ac.be/~lefevre

www.auto.ucl.ac.be/~lefevre

63


Bio-informatics : analysis of biochemical networks

SENIOR SCIENTISTS :

� Yves DEVILLE� Pierre DUPONT

F 3


The team is dedicated to the applications of artificial intelligen-ce techniques to the analysis of biochemical networks.

The research is done in collaboration with the ULB (Prof.Shoshana Wodak, Molecular Biology & Bioinformatics).

Topics of current interest are :Modelisation of biochemical networksApplication of constraint programming techniques to the

analysis of biochemical networksPattern discovery

Main Equipment

Workstations


C. LEMER, E. ANTEZANA, F. COUCHE, F. FAYS, X.SANTOLARIA, R. JANKY, Y. DEVILLE, J. RICHELLE, S. WODAK.The aMAZE LightBench : a Web interface to a relational data-base of cellular processes. Nucleic Acid Research, DatabaseIssue,32, 2004.

Y. DEVILLE, D. GILBERT, J. VAN HELDEN and S. WODAK. An Overview of Data Models for the Analysis of BiochemicalPathways. Briefings in Bioinformatics, 2003, 4 : 3, pp 246-259,ISSN 1467-5463.

STAFF

Total : 4

KEY WORDS FOR R&D

artificial intelligencebiochemical networksbioinformaticssystem biology

SENIOR SCIENTISTS

Yves [email protected]. 32 (0)10 47 20 67

Pierre [email protected]. 32 (0)10 47 91 14

WEB SITE

www.info.ucl.ac.be

www.info.ucl.ac.be

65


Biological effects of microwaves and their measurement

SENIOR SCIENTISTS :

�André VANDER VORST�Benoît STOCKBROECKX

F 4


For quite a time, a question has regularly been raised : can micro-waves and or millimetre waves induce effects other than thermal? Today, measurements indicate that such effects might exist atmillimetre waves. At microwaves however, no experimental resulthas given a positive answer to the question. The question is quiteimportant. Humans and animals are indeed more and moreimmersed in such fields, in particular with the advent of mobiletelephony.Experimental research has been going on in this area in the labo-ratory since about 1986, more explicitly on the interaction bet-ween microwaves and the nervous system. Several procedureshave been designed, such as a dolormeter yielding quantitativemeasurements of pain threshold; the injection of microwaves intoacupuncture points, proving the efficiency of this antalgic process;measuring the release of neurotransmitters in the centre of painreception in the brain; applying an electric impulse to a superficialnerve of a rabbit, inducing a nerve impulse transmitted to thebrain along the spinal cord.Microwave fields penetrate exposed biological tissues. Althoughcellular mobile phones emit low power, the user head absorbshighly localized microwaves from the phone antenna. The inter-action between handset antenna and human head is of specialinterest. Extensive experiments concerning thermal effects due toGSM exposure from handheld mobile telephone have been per-formed by the team. The temperature evolution of different partsof the human head has been measured as a function of time,when exposed to GSM microwaves.The team is involved in designing and running a one-year experi-ment in which rat populations are submitted to CW as well as pul-sed microwave fields at 1 and 10 GHz, at a level of exposure cal-culated to be equivalent for rats to the ICNIRP recommendationsfor human beings.The team is frequently consulted by public authorities and privatepersons about the assessment of health risk due to microwavefield exposure. It has established guidelines which gave rise to alarge interest by authorities and the public. A comprehensive booklet has been published (in French) on this subject.A spin-off has been founded in 2002 about designing equipmentand methods for calculating and measuring microwave exposure.


Antenna designExposure calculationExposure measurementsHazards evaluationMicrowave measurements

Main Equipment

Microwave exposure


TENG J., CARTON de TOURNAI D., DUHAMEL F., VANDERVORST A. No non-thermal effect observed under microwaveirradiation of spinal cord. IEEE Trans. Microwave Th. and Tech.,Vol. 44, n° 10, October 1996, pp. 1942-1948.

COCHEROVA E., DUHAMEL F., VANDER VORST A. Simulationof the microwave influence on the nerve fibre action potential.Proc. Biological systems and emc field Conf., Prague, 1997, pp. 1-3.

DUHAMEL F., HUYNEN I., VANDER VORST A. Measurementsof complex permittivity of biological and organic liquids up to110 GHz. Proc. MTT-S Symposium, Denver, June 1997, Vol. I,pp. 107-110.

VANDER VORST A., DUHAMEL F. Mobile telephony : recom-mendations vs. biology. Int. Conf. on TelecommunicationsICT’98, Porto Carras, June 1998, Vol. III, pp. 356-360.

VANDER VORST A. What about safety when using mobiletelephony? Proc. MICROCOLL’99, Budapest, March 1999, pp. 35-39, (invited paper).

GERIN A., STOCKBROECKX B., VANDER VORST A. Champsmicro-ondes et santé. Louvain-la-Neuve, Hyperfréquences UCL,1999, 56 p.

TAURISANO D., VANDER VORST A. Measurements of thermaleffects induced on a human head exposed to 900 MHz mobilephone. Proc. IMS 2000, Boston, Jun. 2000, pp. 1017-1020.

VANDER VORST A., TAURISANO D., STOCKBROECKX B.Cellular telephones : hazards or not? Proc. IMS 2000, Boston,

66

Jun. 2000, pp. 937-940.ROSEN A., VANDER VORST A., KOTSUKA Y. Editorial Special

Issue on Medical Application and Biological Effects ofRF/Microwaves. IEEE Trans. Microwave Th. and Tech., vol. 48,no 11, Nov. 2000, pp. 1781-1782 and 1977-1978.

TAURISANO M., VANDER VORST A. Experimental thermo-graphic analysis of thermal effects induced on a human headexposed to 900 MHz fields of mobile phones. IEEE Trans.Microwave Th. and Tech., Special Issue, vol. 48, no 11, Nov.2000, pp. 2022-2032.

STOCKBROECKX B., MOREAU B., VANDER VORST A.Measured ELF components of radio-communication systems.Proc. 2nd Intl. Workshop Biol. Eff. Electrom. Fields, Rhodes, Oct.2002, pp. 260-265.

AZANZA M., PEREZ BRUZON R., LEDERER D., CALVO A., delMORAL L., VANDER VORST A. Reversibility of the effectsinduced on the spontaneous bioelectric activity of neuronsunder exposure to 8.3 and 217.0 Hz low intensity magneticfields. Proc. 2nd Intl. Workshop Biol. Eff. Electrom. Fields,Rhodes, Oct. 2002, pp. 651-659.ROSEN A., STUCHLY M., VANDER VORST A. Applications ofRF/Microwaves in Medicine. IEEE Trans. Microwave Th. andTech., 50th Ann. Special Issue, vol. 50, no 7, Mar. 2002, pp.963-974 (invited paper).

Awards

Fellow of the IEEE, Institute of Electrical and ElectronicsEngineers, since 1985.

Prix de la Société Belge des Ingénieurs de Télécommuni-cations et d’Electronique (SITEL), 1986.

Meritorious Service Award, Microwave Theory and TechniquesSociety (MTT), IEEE, 1994.

EEE Millenium Medal, 2000.Microwave career award, MTT, IEEE, 2004.Member of Academia Europaea and Electromagnetics

Academy.

Patents

STOCKBROECKX B., VANDER VORST A., PLATTEBORZE R.Method and device for measuring electric field strength. L2395-EP.

Partnership

Military Hospital, BelgiumDrexel University, USATechnical Committee Biological Effects and MedicalApplications, IEEE - Microwave Theory and Techniques

Society, USA

STAFF

Total : 7

KEY WORDS FOR R&D

acupuncturebiomedical sciencesbiotechnologydielectricselectric conductivityepidemiologyhertzian linksinstrumentationmicrowavespublic healthradartelecommunicationsthermodynamics

SENIOR SCIENTISTS

André VANDER [email protected]. 32 (0)10 47 23 05


WEB SITE

www.emic.ucl.ac.be

www.emic.ucl.ac.be

67


3D cephalometry A.1

3D reconstruction A.1

acupuncture F.4

adhesion, mammalian cells D.2

allografts D.1

analytical system A.3

anatomopathology D.1

anatomy A.1

angiogenesis C.2

antibodies, antigens E.2

antigen, vaccine D.5

application software A.1

artificial intelligence F.3

artificial neural networks C.3

artificial organ B.1

auditory plasticity B.1

autologous cell therapy D.1

bacteria E.6, E.7

bacteriology D.1

bioabsorbable membrane D.4

biochemical networks F.3

biochips E.7

biocompatibility C.2, D.2

bioinformatics F.3

biologically active compounds D.2

biomaterials C.2 D.1, D.2, D.3, D.6, D.7, E.9

biomechanics B.1, D.1

biomedical control E3

biomedical diagnosis E.3

biomedical, engineering, sciences A.1, B.1, B.2, C.1, C.2,

C.3, C.4, D.1, D.5, D.2, D.3, D.7, E.1, E.9, F.1, F.2, F.4

biometry A.1

biophysics C.2, E.5

biosensors C.2, F.2

biotechnology E.1, G.4

bone induction D.1

bone remodeling D.1

cancer C.2, E.5, E.7

capchips E.5

chemotherapy C.2

cochlear implant B.1

colloid, chemistry D.7

craniomaxillofacial surgery A.1

cytochrome p450 E.8

data analysis C.3, E.4, E.9, F.1

deafness B.1

dental implants D.4

diagnosis E.7

dielectrics F.4

diffusion imaging C.1

drug carrier D.5

drug delivery, pulmonary D.5

drug delivery system A.2

drug delivery, transdermal D.5

drugs A.3

dry powders aerosols D.5

electric conductivity F.4

electrocardiograms C.3

electroencephalograms C.3

electron beams A.3

electronics E.1

electroporation D.5

embryology (human) A.1

emergency E.9

encapsulation D.5

enzyme inhibitors D.2

epidemiology E.7, F.4

EPR C.2

eye movements F.2

eye-hand coordination F.2

free radicals C.2

functional brain imaging C.4

functional evaluation B.3

functional imaging B.2, C.1, C.2

gamma rays A.3

gas exchanges F.1

Key Words Index

68

gastro-enterology C.1

gels D.7

genes E.5

genotyping E.6

growth and development (human) A.1

guided bone regeneration D.4

guided tissue regeneration D.4

handheld computers B.3

health-care financing B.3

hearing aid B.1

hearing loss B.1

hemocompatibility D.2, D.7

hemodynamics C.2

hertzian links F.4

histomorphology D.1

imaging A.1, C.1, C.2, C.4

implant B.1

implantable pump A.2

inert gas elimination technique F.1

informatics A.1

infrared spectrometry E.3

instrumentation E.2, F.4

integrated circuits E.1

internal medicine F.1

ion spectrometries D.6

iontophoresis D.5

joint tribology D.1

language development B.1

legionnella A.3

limb movements F.2

lipids, membranes D.7

lung mechanics F.1

macromolecular chemistry D.3

magnetic resonance C.1

medical informatics C.4

medical instrumentation A.1, B.1, E.4, E.9

medicinal chemistry D.2

micro- & nano-electronics E.2

microarray E.5, E.6

microelectronics technology E.1

microgravity F.2

micro-hydraulic A.2

micro-motors A.2

micropump A.2

microwaves F.4

model F.2

modeling F.1

molecular self-assembly E.2

molecular typing E.7

monitoring E.9

MRI C.2

multidrug resistance (MDR-1) F.8

multigenotypic identification E.7

nanoimprint E.2

nanolithography E.2

nanotechnology D.7, E.2

nephrology C.1

neurology C.1

neuropathology E.4

neurophysiology E.4

neuroprostheses B.2

neuropsychology E.4

neurosciences B.2, E.4, F.2

nitric oxide C.2

NMR C.2

nucleic acids D.5, E.1

organic synthesis D.2

orthognathic surgery A.1

orthopaedic D.1

otorhinolaryngology B.1

oxygen C.2

oxyhemoglobin F.1

paleo anthropology A.1

paperless medical record B.3

peptides D.5

peptidomimetics D.2

69


periodontitis D.4

perfusion imaging C.1

pharmaceutical products D.5

pharmaceutical technology D.5

pharmacogenetics E.8

pharmacology C.1, C.2, D.7

pharmacophysics D.5

physiological modeling C.1

PLA membrane D.4

plastic and aesthetic surgery A.1

pneumology E.9, F.1

polymer chemistry D.2

prostate E.5

protein adsorption D.6

proteins D.5, D.7, E.2

psychophysics E.4

public health E.4

radar E.4

radiology A.1, C.1, C.4

radiosensitivity C.2

radiosterilization A.3

radiotherapy C.2

raman spectrometry E.3

Rasch measurement B.3

rehabilitation engineering B.2

rehabilitation medicine B.3

resistance E.6

robot A.1

saccades F.2

semiconductors E.1

sensors and peripherals E.1

sensory substitution B.2

signal processing C.1, C.3

simulation F.2

smooth pursuit F.2

software A.1

spectrofluorimetry E.3

spectroscopy C.2

spin trapping C.2

stereophony B.1

stereovision glasses A.1

stomatology-odontology D.3

stroke C.1

surface characterization D.6

surface modifications D.6

surfaces and interfaces chemistry D.2, D.7

surfaces E.2

surgery A.1, D.1

system biology F.3

technology progress D.5

telecommunications F.4

thermodynamics F.4

thin films E.2

thiopurine-methyl-transferase (TPMT) E.8

tomography A.1, C.4

toxicity D.1

transplantation D.1

tumor C.1, C.2

virtual reality A.1

vision F.2

visual prosthesis B.2, C.3

waste waters A.3

biomedical engineering at ucl 2004 - université ... · pdf filebiomedical engineering...

Documents