focus line overview - smart hub vlaams-brabant · roadmap/challenges: lmtc brief outline q3-2014 +...

Focus Line overview

2 LMTC brief outline Q3-2014 + Focus Line Overview

Objectives of L-MTC

• Increase the efficiency of interdisciplinary

collaboration in Med Tech R&D within KU Leuven and

the Association;

• Support Technology Transfer of research results;

• Increase external visibility of Med Tech R&D within KU

Leuven;

• Support the new Master in Biomedical Technology (Fac.

Engineering) and the Master of Biomedical Sciences (Fac.

Medicine);

• Promote Biomedical Technology R&D at the level of

Association KU Leuven.


Coordinator

Siegfried Jaecques

Int’l affairs

Luc Mortelmans

Chairman

Jos Vander Sloten

Medical Imaging

• Medical Imaging Research Center

Robotics and Automation in Health Care

Controlled Release

Biomaterials & Tissue Regeneration

• Prometheus (Skeletal Tissue Engineering Leuven)

Biomonitoring & Control

Co-chairman

Frank Luyten

Focus themes LMTC


– Integration biological systems – artificial systems

– Personalised approach (« service » approach) =

procedures instead of products, optimisation by functional

simulation

– Scale-up & industrialisation

– New disciplines: biomedical engineer, tissue engineer,

developmental engineer

– Paradigm shift:

• from ‘hospital centric care’ to ‘patient centric care’

• from curative medicine to integrative medicine:

prevention – screening – diagnostics – treatment –

management

(« patient centric care cycle »)

Roadmap/Challenges:


• 40 member groups, 800+ researchers and clinicians

• Distributed center concept

• Full time co-ordinator

• Workshops

• Representation at international events

• Matchmaking internally and externally

• Major grants (EIT, TTC, EC programmes, …)

LMTC facts


– Computational Medicine (12/09/2011)

– Molecular imaging, a platform for translational medicine (10/10/2011)

– Regenerative medicine in the post-genomic era (28/11/2011)

– Point of Care Diagnostics (14/02/2012)

– Controlled release technologies for drug development (23/04/2012)

– “Large Animal Models in clinical research and training” (07/02/2013)

– European Surgical Robotics Demonstration Day (27/03/2014)

– “The evolutionary path for clinical studies”, 13/5/2014

– Visionary Seminar Assistive Robotics Technology (02/10/2014)

– Spin-off day “Health(y) Entrepreneurship” (06/11/2014)

– Ageing with a Healthy Brain EIT workshops (19-20/01 & 28-

29/04/2015)

– CRAS (Computer/Robot Assisted Surgery) workshop (10-12/09/2015)

(co) Organized Events 2011-2014 (selection)


• Health for Growth & Leuven Health Metropolis

• Flanders Smart Hub Development (FSH-D) / Sports.Tech

• Care Innovation platform/ “Living Lab” InnovAGE

• Health Axis Europe

Starting Up:

• KIC EIT Health

Strategic Networking and BDS


EIT – Health network spans across Europe

Co-location centre

EIT Health InnoStars

countries

International Headquarters

Coordinator: Roche

Diagnostics GmbH


Loco-regional to International

EU/Int’l

Cross-border

Leuven

• EIT Health

• Accelerator/Projects/Campus

• H2020

• Interreg NWE, EU

• RegMed 2.0

• BuSyBee, CrossCare

• RegMed

• HealthHouse, Leuven.Inc, Gezondheidsmetropool Leuven

• InnovAge


Relation with industry & spin-offs

Academic programmes driven by evolution in the field

MSc Biomedical Engineering

Human-Machine synergy as a key concept (~Human Health Engineering)

Opportunitities for industry and spin-offs

Instrumen

http://www.custom8.com/index.php

http://www.biorics.com/

http://www.formacpharma.com/

http://www.ziscoat.com/

http://www.tigenix.com/

http://www.silicos.be/

http://www.medicim.com/en/home

http://www.amtbe.com/

http://www.eyetronics.com/

http://www.layerwise.com/

http://www.mech.kuleuven.be/vesalius/index.php


1. MEDICAL IMAGING


• Exploring and exploiting the potential of novel imaging

technology in medicine and biomedical research:

from “seeing” to “understanding”

1. Medical imaging


• Radiology

• Nuclear Medicine

• Cardiology

• Radiation Oncology

• ESAT – Medical Image Computing

• > 20 faculty

• > 80 researchers

• engineers, physicians, physicists

• fundamental and applied research

in a clinical setting

Medical Imaging Research Center


• Radiopharmacy

• Molecular Medicine

• Clinical and Experimental Neurology

• Laboratory of Neuro- and Psychophysiology

• Oral Imaging Center

• Forensic Medicine

• ESAT - SCD - Biomedical Data Processing group

• …

Collaborating groups


• Centralized research facility

– Core location in the hospital itself (‘Louvre’)

• State of the art clinical imaging equipment

– 3T MRI, 4D & dual energy CT, PET/CT, CBCT, US, …

– Inter-connected via DICOM, PACS, HIS

• Small animal imaging center (SAIC)

– 9T microMRI, microPET, microCT, BLI, dedicated US

– Pre-clinical imaging in animal models (rodents)

• Molecular Imaging Research and Clinic Leuven (MIRACLE)

– Molecular imaging for drug development and clinical trials

– GMP lab in collaboration with industry

• High-performance computing cluster

– Inside the hospital (fire wall)

Facilities


• Optimization of imaging protocols

– Anatomical, functional and molecular imaging

• Image reconstruction

– Cone beam CT, PET/MRI

• Image quality enhancement

– Resolution, contrast, SNR, artifact reduction

• Imaging probes:

– Contrast agents (CT, MRI)

– Radio-labeled tracers (PET, SPECT)

– (Nano-) particles (MRI, US)

– Reporter genes (pre-clinical imaging)

Image acquisition


• Registration (‘image fusion’)

• Segmentation (‘object delineation’)

• Quantification (‘image measurements’)

– Contrast

– Structure

– Changes over time

– Inter-subject differences

• Visualization

– Interpretation

– Interaction

Image computing


2. ROBOTICS AND AUTOMATION

IN HEALTH CARE


Advanced mechatronic & automation technology for

- increased patient safety

- patient-specific medical devices

- surgical simulators

- better mobility and home care

- logistics in health care

Robotics and automation in health care


1. Increased patient safety

Smart instrumentation

– Instruments that sense interaction with tissue and

- measure

- analyse

- react

Example 1: pulling aside the renal vein

Example 2: clamping the renal artery


Experimental results

Stress and damage pattern after 1 N of clamping load for both clamp designs:

Famaey, Sommer, Vander Sloten, Holzapfel (2012) Arterial clamping: finite element simulation

and in vivo validation Mechanical Behaviour of Biological Materials

Detail of an H&E-stained sample crushed

with a mosquito clamp. Stretching of the

fibres is noticed at the edge.

Boxplot of the endothelial cell count.


Advanced surgical robotics

Follows the surgeon in the

safe zone

Increases the resistance in the

boundary zone

Activates a virtual wall in the

forbidden zone

The teleoperation control:

Willaert (2012) Ph.D. thesis KU Leuven


2. Custom made devices and procedures

(Corten et al. ORS 2011)


3. Surgical simulators

Lack of real life representation:

- visual

- haptic, tactile

- bio-response


4. Smart devices for rehabilitation

• Orthotics to treat spasticity

• Intelligent and adaptive orthotics


5. Logistics in health care

Patient safety and technical management of medical devices in

hospitals

→ focus on risk assessment

Home care and medical devices:

→ focus on weak user profile, having an impact on risk assessment


Robotics and automation in health care – member groups

• Experimental Cardiac Surgery

• Abdominal Transplant Surgery

• Mobilab (KHKempen)

• Ergonomics & Occupational Biomechanics

• Orthopaedic Surgery

• Traumatology

• Experimental Urology

• Experimental Neurosurgery and Neuroanatomy

• Endoscopic surgery

• Production Engineering, Machine Design and Automation

(PMA – RAS)

• Industrial Management – Logistics in Health Care


3. CONTROLLED RELEASE


3. Controlled release

The study of drug delivery systems that enable controlled release of a

pharmacologically active compound (API) during a specified time

The release kinetics are reproducable and predictable

Controlled release ? slow and prolonged, delayed, pulsed, targeting

increased release rate and extent

Advantages:

1. Reduced intake (advantageous in case of low t1/2)

2. Improved patient compliance and comfort

3. Reduced side effects

4. Controllable release kinetics: less fluctuation in plasma API levels and

uniform therapeutic effect


Highlights of recent projects

1. Development of a binary polymer matrix system for the prolonged release

of poorly soluble compounds for parenteral administration

2. Understanding the influence of compression forces on the phase

behavior of amorphous solid dispersions

3. Down stream processing evaluation of mesoporous silica

4. Amorphous microporous silica (AMS) for prolonged drug release


Examples of recent projects

... Down stream processing evaluation of mesoporous silica

Man (n=12)

0 4 8 12 16 20 240.0

0.5

1.0

1.5

2.0

2.5

Time (h)

Pla

sm

a c

on

cen

trati

on

(µ

g/m

l)

Man (n=12)Dose-normalized

0 4 8 12 16 20 240

1

2

3

4

Time (h)

Pla

sm

a c

on

cen

trati

on

(µ

g/m

l)

33.5 mg Formac capsule

67 mg Lipanthyl (micronized fenofibrate)

silica

Micronized powder

KU Leuven spin off (2007)

Silica drug delivery company

Fenofibrate release (powder in capsules)

Silica typically has/is:

- Poor flow properties (large scale)

- Poor compactibility (tablet)

- Hygroscopic

(commercial product)

Solid dosage form development is challenging!!



...Amorphous microporous silica (AMS) for prolonged drug release

AMS180

AMS280

AMS1800

Control of Chlorhexidine release from AMS

Particle size

Release rate

Pore size

Release rate

Oral controlled release

Dental implants


Controlled release – member groups

• Laboratory of Pharmacotechnology and Biopharmacy

• Centre for Surface Chemistry and Catalysis

• Physical Metallurgy and Materials Engineering

• Applied Rheology and Polymer Processing

Ph.D. projects

• J. Meeus

• Z. Worku

• A. Paudel

• M. Vialpando

• E. Verraedt


4. BIOMATERIALS AND

TISSUE REGENERATION


• Prometheus – Interdisciplinary research platform

– Incubator for TE technology

• Rheumatology

• Orthopedics

• BIOMAT Research Cluster

• Abdominal wall tissue engineering

• Laboratory of experimental medicine

and endocrinology

• Biomechanics (BMe)

• Groep T Biomedical Engineering

4. Biomaterials and Tissue Regeneration


Tissue Regeneration – Prometheus

• Mission statement: Development of consistent and

clinically relevant Tissue Engineering concepts for

skeletal applications

• Participating of other focus line members

• Rheumatology

• Orthopedics

• BIOMAT Research Cluster

• Legendo

• Biomechanics (BMe)

• Groep T Biomedical Engineering

• Blueprint for other tissues

• Link to abdominal wall TE via SCIL Clinical


Preclinical bone regeneration


Personalised regenerative therapy

Prof. Eric Legius

Laboratory for

Neurofibromatosis Research

YES ?


• Large soft tissue regeneration challenges

• Limited experience with expensive biological

meshes, both clinically and preclinically

• No match prosthesis degradation & tissue

regeneration

• Stimulate site specific tissue remodelling

• Addition of growth factors - stem cells -

fibroblasts to the biological scaffolds

• SCIL Clinical as discussion forum

• Projects

• Prospective EU registry biological prostheses

• Treatment of large abdominal wall defects

using collagen prostheses

• Genetic and tissue examination from patients

with inguinal and incisional hernias

Abdominal wall reconstruction & TE


a ba ba ba bunloaded loaded

unloaded loaded

• Mechanobiology of implant osseointegration

BIOMAT Research Cluster

Low

frequency

bone

chamber

High

frequency

whole body

vibration


• Optimisation of implant osseointegration in compromised bone

conditions (osteoporosis)

Highlights BIOMAT Research Cluster


Prometheus biomaterial ‘spin-off’ actions

• Scaffold design

• Ti scaffolds

• Design

• Production

• Surface treatment & characterisation

• Interest biomedical companies

• Testing new biomaterials

• FP7 BioTiNet project

• Novel Ti alloys

• Hydrogel technology

• EPFL - Hubbell technology

• Tenure Track Prof. J. Patterson


5. BIOMONITORING & CONTROL


Current trends in technology

• Design of new sensors

• Miniaturisation (micro, nano)

• Wireless communication

• Ubiquitous computing

5. Biomonitoring and control


Current trends in biomedicine

• Poor data rich data

• Standard treatments individually tailored treatments

• Curing prevention

• Fragmented care integrated care

Need

• ‘Intelligence’ in healthcare monitoring and control systems



Bioresponses

(e.g. heart

rate)

Process

inputs

(e.g. drug)

(2) Analyses

& models

(3) Controller/

monitor Desired/expected

output

(1) Sensors (1) Sensors

Actuators



1. Measure bio-responses

– Microsystem technology

• Micro-electronics (e.g. MEMS)

• Micro-mechanics

(e.g. accelerometers)

• Biotelemetry

• Nanotechnology

– Medical imaging

– Biomedical expertise

• Neurology & physiology

(e.g. epilepsy)

• Pneumology (e.g. COPD)

• Oto-rhino-laryngology (ORL)



2. Analyse & model bio-responses

– Biomedical data analysis

• Signal processing

• Bioinformatics

• Medical imaging

– Understand human behaviour

• Audiology

• Psychology

• …



3. Manage bio-responses

– Monitor and control responses

• Monitoring implant fixation

• Body Area Networks

• Cochlear implants

• Telemedicine

• COPD monitoring

• …

Integrate intelligence in daily life of patients/users




Neonatal Non-invasive Monitoring

• Non-invasive measurement of the neonatal cerebral circulation and

oxygenation

• Continuous measurement of the cerebral autoregulation

• Non-invasive measurement of the lung function

• Pharmacodynamic measurements


Epilepsy research

• Collaboration KUL-UZ, KUL-ESAT and IMEC

• Validation of wireless 8ch EEG system

• Use of a wireless monitoring system of autonomic nervous system

(ECG, respiration, galvanic skin response and temperature) in

epilepsy research

Participation in the NeoGuard project

• wireless neonatal EEG monitor with real-time bedside data

visualisation in a realistic head model

• collaboration KUL-UZ and ESAT in automated background analysis

and automated seizure detection


Developmental Neurophysiology



iMinds/Stadius (fka SISTA-BioMed)



• TOPICS: in collaboration with UZ Leuven and EU partners

• EMG & HRV signal processing for stress monitoring

• MR Spectroscopic quantitation & brain tumor recognition using MRS(I)

• (Functional) Near-Infrared Spectroscopy & neonatal brain monitoring

• Cardiovascular dynamics, fetal ECG extraction & HRV analysis

• Preoperative cancer diagnosis & prognosis: ovarian, prostate, brain, breast

• EEG based signal processing for epileptic monitoring and ERP analysis

• Video/accelerometry for epileptic seizure monitoring

• Osseoperception, prediction of ectopic pregnancies, renography, …


Blood glucose control in the Intensive Care Unit

• Tight Glycaemic Control in critically ill patients lowers mortality and

morbidity

• LOGIC-Insulin = algorithm/software that advises the nurse on insulin dose

and time interval for the next blood sample

LOGIC-Insulin

Insulin pump Glucose sensor



• Engineering

– Design of algorithm

– Design of graphical user interface

• Clinical validation (Randomized Controlled Trial)

– Comparison LOGIC-Insulin vs. nurse

– 300 patients

• Team (UZ Leuven ~ ESAT-SCD)

– Dr. Ing. Tom Van Herpe ([email protected])

– Prof. Dr. Dieter Mesotten

– Prof. Dr. Greet Van den Berghe

– Prof. Dr. Ir. Bart De Moor


Blood glucose control in the Intensive Care Unit


Highlights of recent projects – Experimental Oto-rhino-

laryngology & speech processing

• Speech and music processing for cochlear implants

• Noise reduction for improved speech reception with hearing

instruments in adverse and noisy listening environments

• Binaural hearing: signal processing schemes and evaluation

procedures for bilateral acoustical and/or electrical hearing

instruments

• New electrical pulse-waveforms for optimal neural stimulation in

cochlear implants

• Temporal neural processing in the auditory system


• Activity monitoring for patients with COPD and lung transplantation

to relate daily activity to complications and co-morbid disease

• New surgical techniques to improve pulmonary function for the

treatment of COPD patients

• Tissue bank for relating clinical variables and structural

abnormalities in lung diseases such as COPD

• D-base of lung cancer patients to analyse the effects of treatment on

survival in patients

• Flow-volume characterisation for monitoring COPD evolution (in

collaboration with M3-BIORES)

Highlights of recent projects - Pneumology


Design, development and evaluation of brain stimulation and recording probes

Rigid probes for recording in the

brain in collaboration with IMEC

(W Eberle, M Welkenhuysen, et al)

Flexible probes for cortex or brain

lesions in collaboration with ESAT - MICAS (B Puers,

F Ceyssens)

In vivo bio- and MRI-compatibility

testing in collaboration with MoSAIC

Highlights of recent projects – Neurosurgery and Neuroanatomy


Deep brain stimulation in psychiatric disorders

Neuroimaging in collaboration with MoSAIC

Local field potential recording and

single cell recording for closed-

loop stimulation in collaboration with ESAT (S Van Huffel) and

M3-BIORES (JM Aerts)



Deep brain stimulation in lesion cavities

Brain lesions induce functional

impairment

concept of treatment with recording and

stimulation with electrode contacts

covering the lesion cavity wall

Recording and stimulation in ex-vivo

slices with brain lesions in collaboration with IMEC (W Eberle) and ESAT

(S Van Huffel)

0

.

1

m

V

2

0

m

s

C

A

3

D

G

C

A

1

Recording and stimulation in-vivo in

rats with brain lesions

epilepsy, chronic pain, motor deficits in collaboration with M3-BIORES (JM Aerts)



• Early warning infection and inflammation monitoring in

the ICU (in collaboration with UZ Leuven – G. Van den Berghe)

• Monitoring and prediction of nephropathia epidemica

outbreaks caused by bankvoles (in collaboration with UZ

Leuven – M. Van Ranst)

• Reverse engineering of synaptic plasticity in the

hippocampus (in collaboration with D. Balschun)

Time (minutes)

-50 0 50 100 150

Ce

ll re

sp

on

se

40

60

80

100

120

Highlights of recent projects – Measure, Model & Manage Bioresponses


• Monitoring and control of cell growth in perfusion bioreactors for

bone tissue engineering (in collaboration with Prometheus – J. Schrooten, F.

Luyten)

• Behaviour monitoring and brain signal analysis in rat models for

obsessive-compulsive disorders and anorexia (in collaboration with B.

Nuttin)

0 5 10 15 20 25 30Loca

tion o

f ra

t in

cage in

y-d

irect

ion (

cm)

0

5

10

15

20

25

30

Travelled distance: 7827 cmNumber of drinking sessions: 55

Location of rat in cage in x-direction (cm)



• Physical condition monitoring for athletes (in collaboration with FABER and

P. Clarys)

• Sleep monitoring (in collaboration with a.o. R. Cluydts,

J. Vander Sloten)



Highlights of recent projects - Sensors and Biotelemetry group

Min. linewidth of Pt wires: 5 mm

Electrode diameter: 15 – 80 mm

Insulation thickness: 3 mm

Embeddded in porous chitosan

Highly flexible neural implants for monitoring and stimulation


Inductive powering

Image compression

•High-resolution

monitoring of the GI tract

Swallowable camera pill

Highlights of recent projects - Sensors and Biotelemetry group


Highlights of recent projects – Mechatronics, Biostatistics and Sensors

Microfluid lab-on-a-chip for high-throughput analysis

Glucose monitoring system based on optical sensors


Biomonitoring and control – member groups

• Neonatal Non-Invasive Monitoring (Gunnar Naulaers)

• Epilepsy research (Wim Van Paesschen)

• Developmental Neurophysiology (Lieven Lagae)

• Biomedical Data Processing (SISTA-BIOMED) (Sabine Van Huffel)

• Bioinformatics (SISTA-Bioi) (Bart De Moor)

• Speech processing (Marc Moonen)

• Experimental oto-rhino-laryngology (Jan Wouters)

• Pneumology (Marc Decramer)

• Neurosurgery and Neuroanatomy (Bart Nuttin)

• Measure, Model & Manage Bioresponses (M3-BIORES) (Jean-Marie Aerts)

• Sensors and Biotelemetry group (Bob Puers)

• Mechatronics, Biostatistics and Sensors (MeBioS) (Bart Nicolaï)


• www.kuleuven.be/lmtc

• Interested in a joint project? First contact:

Dr. ir. Siegfried Jaecques, IOF fellow

Coordinator Leuven Medical Technology Centre (LMTC)

p.a. Celestijnenlaan 300, bus 2419, 3001 Heverlee, Belgium

tel. +32-16-327056 or +32-16-327096 (secr. BMe)

tel. +32-16-326500 or +32-16-326525 (secr. LRD)

fax +32-16-327994

GSM +32-486-498345

[email protected]

More info

http://www.kuleuven.be/lmtc



focus line overview - smart hub vlaams-brabant · roadmap/challenges: lmtc brief outline q3-2014 +...

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