“From man to mouse” … Human PET microPET human mouse rat rat infant monkey mouse

.. and back again

Molecular(?) Imaging Modalities Ultrasound Optical (Bioluminescence, fluorescence) Structure Tissue Density, Z A Topography H Concentration F Doppler BOLD, DCE Radiotracer M ~1-2 mm <10-12 mole = quantitative -galactocidase 0.1 µmole H / µmole 31P ~103 cells  quantitative 20-50 µm 0.1 mm µm to mm CT                                                                                   PET/SPECT Aujourd’hui, en altérant le génome nous pouvons manipuler le métabolisme et recréer les conditions qui mènent au développement de différentes maladies. L’intérêt ici est de pouvoir suivre l’expression de ces gènes dans le temps et au travers de différentes conditions. C ’est dans des cas ici que les méthodes d ’imagerie prennent toute leur importance car elles permettent de visualiser ce qui se passe dans l’animal d ’une manière non invasive et non létale. Presque toute les méthodes d’imagerie clinique sont maintenant disponibles pour l’imagerie animale, ce qui permet de faire des parallèles entre les études cliniques et les études animales.   MRI

Mechanic Collimation Parallel Holes Pinhole Coded Aperture b a Parallel Holes b a Pinhole b a Coded Aperture Better Resolution Little Field of View Low Efficiency Better Resolution High Efficiency Complicated Reconstruction L d t Resolution & Efficiency inversely related

Normal Myocardial Perfusion Single Vessel Coronary Artery Disease Cardiac SPECT Images Normal Myocardial Perfusion at stress and rest Single Vessel Coronary Artery Disease at stress and rest SPECT image exhibits full perfusion (bright, donut shape) both at rest and under stress SPECT image shows limited perfusion (horseshoe shape rather than donut) especially under stress.

Trying to Image apoptosis by proper tracer (e.g.99mTcINIC-Annexin-V) Performances not good enough for imaging biological process in vivo in small animals (mice) Man Rat Mouse Body weight ~70 kg ~200 g ~20 g Brain ~105 mm ~10 mm ~6 mm Heart ~300 g ~1 g ~0.1 g Aorthic cannula ~ 30 mm 1.5 – 2.2 mm 0.9-1.3 mm (0.5 mm) man rat Trying to Image apoptosis by proper tracer (e.g.99mTcINIC-Annexin-V) Geant 4 simulation detector area: 100 x 100 mm2 aorta: ~ 2 mm diameter plaque size: 0.5 x 1 x 4 mm3 - pixellated CsI(Tl) (0.8 - 0.4 mm pitch) LaBr3 continuous (3 mm thick, different surface(s) treatment(diffusive vs absorptive) 6 x 6 mm2, 3 x 3 mm2, 1.5 x 1.5 mm2 (PMT anode pixel size) spatial resolution: ~ 500 m system sensitivity: ~ 10 cps/Ci 1000 counts/view/resol.elem. 1 plaque = 10 mCi,10 resol.elem.

Sample projection image Preliminary pinhole SPECT reconstruction results from the CsI detector Images are displayed as MIP (maximum-intensity-re-projections) animations 2 point sources APOE mouse (kidneys shown) Flood image Sample projection image Fig. 28 APOE mice

(cortex apex-temporal lobe) Caratteristiche insufficienti per l’imaging di processi biologici in piccoli animali (topi). E’ necessario migliorare la risoluzione spaziale e l’efficienza Man Rat Mouse Body weight ~70 kg ~200 g ~20 g Brain (cortex apex-temporal lobe) ~105 mm ~10 mm ~6 mm Heart ~300 g ~1 g ~0.1 g Aorthic cannula () ~ 30 mm 1.5 – 2.2 mm 0.9-1.3 mm (0.5 mm) Human Rat Required spatial resolution: Small size detectors (high pixellization) Individual detectors or “perfect” coding 6 mm FWHM (200 mm3) 2 mm FWHM (8 mm3)  1 mm FWHM ( 1 mm3)