molecular genetics neurosciences interface physique biologie group oncology optibase dna sequencing...
Post on 19-Dec-2015
216 views
TRANSCRIPT
Molecular genetics
Neurosciences
Interface Physique Biologie group
Oncology
OPTIBASE
DNA Sequencing Per-operative Imaging
In Vivo Quantificationfor small animals
POCI I and II TOHR, SIC
Study of the glucose metabolism by the SIC-NMR coupling
in animal models of neurodegenerative diseases
Context of nuclear imaging of small animals
¤ detection principle of SIC
¤ model of Sokoloff : kinetics implicated in glucose metabolism Glucose metabolism : interest of the SIC-NMR coupling
Use of Geant4
tracer
Radioactive isotope
molecule
Having information on physiological or biochemical functions
inject in the organism
Follow the evolution of the molecules
Follow the effect of a treatment
Radiodetectors for in vivo study in small animals :
Context and Stakes
Ex vivo Imaging on Tissue Slices
In vivo Measurements
High resolution tomograph : TOHR
(TomographeHaute Résolution)
Intracerebralradiosensitiveprobe : SIC
(SondeIntraCérébrale
)
1 cm
TOHR
123I-Epidepride
SIC
0
2
4
6
8
10
12
0 5 10 15 20 25 30 35 40 45 50 55 60 65
Time (min.)
nC
i/m
l
Malonate-injected striatum
Intact striatum
nCi x 10000/ml of plasma
FDG injection:42.25 MBq
Malonate + FDG
Study of the striatum
28mm
PM Low noise
SIC : Intracerebral radiosensitive probe
Scintillating plastic Fiber =500m or 250m
Clear Fiber
Optical fiber
Counting electronics
1cm
Evaluation of the detection volume
Radioisotopes used for labeling
structures of interest
11C18F
Optic Guide
cerebellumstriatum
Isotope
18F
11C
Type
+
+
Emax(keV)
634
960
Range(mm)
2,3
3,5
Radius(mm)
0,8
1,0
15mm
Intracellular Accumulation
[18]-FDG
circulatingblood
Cs
[18]-FDG
free(tissue)
Ct
K1
K2
[18]-FDG6-
phosphate
(tissue)K4
K3
hexokinase
Fructose-6-phosphate
Model of Sokoloff : kinetics of the glucose modelisation
sample rate of 1 s perform the dynamic modelling
dCsdt
= - K1 Cs + K2 Ct
Study of the glucose metabolism thanks to the SIC-NMR coupling
GLUCOSE
GLUCOSE
glucose 6-phosphate
pyruvate
Kreb ’sCycle
Acetyl CoA
Kreb’s cycle turn-over NMR Spectroscopy [13C]-glucose
hexokinase activity SIC FDG
[13C] glutamate[13C] glutamine
hexokinase
Physiological data in healthy and pathological animal models
First : studies on control animals injection of [18]-FDG and [13C]-glucose
electric stimulation of the leg : study of the somatosensory cortex activation mechanisms of the rat
variation of the cerebral activity level with/without anaesthesia level
To set up the relation between the hexokinase activity level measured by the model of Sokoloff and the Kreb ’s Cycle turn-over
To check experimentally if the hexokinase activity is the limiting step
Subsequently : studies on animal models of neurodegenerative disease
rats treated with 3-Nitropropionic acid (inhibitor of the Kreb ’s cycle)
Differences between control rats and treated rats
Conclusion Use of Geant4 : influence of a magnetic field on the positrons low energy electromagnetic processes relatively easy visualisation of the events utilisation of an intense magnetic field
Objective :
complete the study of the magnetic field influence define the possibilities of Geant4 in a biological or medical context particularly for TOHR and POCI
develop a competence to make simulations for other detectors
3T 7T
B B
0T
18F beta spectrum in water
Group IPB/IPN Orsay
R. Mastrippolito, P. Lanièce, F. Pain, H. Gurden, A. Desbrée, L. Pinot, F. Lefebvre, L. Valentin.
Collaboration « Service Hospitalier Frédéric Joliot » CEA/CNRS Orsay
P. Hantraye, L. Besret, V. Lebon, M.C. Grégoire, G. Bloch.