Imaging molecolare ad alta risoluzione spaziale ed alta efficienza F. Garibaldi 09-02-04 - CV INFN - perche’ - come cosa occorre richiesta

Functional Molecular Imaging Large collaboration is needed What is needed Submillimetric spatial resolution -High efficiency collimation is a key parameter standard parallel hole collimator pinhole multipinhole Small animal imaging, important area of bio-medical research - studying new radiopharmaceuticals - animal such mice serve as models for many studies (neural function, coronary diseases, cancer, stem cells etc.) Some example Challenging detectors Models of bone dismetabolism(osteoporosys)(h) Drug metabolism (m) Brain tumors ( for example, neuroblastoma in children) (h) Studying specific vs aspecific uptake of radiopharmaceuticals (m) Studying Annexin V peptide (it is taken up in apopotosys) (m) Brain activity measurements (m) Stem cells (d,w) Techniques - PET - intrinsic limitations - expensive - Single Photon Emission simpler technique tradeoff spatial resolution vs sensitivity and FOV complementarity Large collaboration is needed (physicist and M.D.)

changing L,d Collimator better res. small FOV lower eff. Pinhole PET Thin Line Collimator Thin Cone Pinhole Coded Aperture Thin Cones Compton Cone Surface better res. small FOV lower eff. w - results similar to pinhole higher efficiency > L < d changing L,d efficiency vs sp.res. 0 – 20 mm 1 – 0.009 %

parallel hole pin hole spatial resolution efficiency g = de2/16xb2 a = pin hole - detector distance b = pin hole - object distance d = hole aperture a = pin hole angle efficiency g = de2/16xb2

R3292 (5 inch) or H8500 (Flat panel) FOV=20 mm FOV=10 mm R3292 (5 inch) or H8500 (Flat panel)

Scintillator arrays

starting point simple desktop detector Understanding limitations - spatial resolution - sensitivity what can be improved ? intrinsic detector performances FOV sensitivity .pinhole collimator .array od pixellated scintillator (NaI(Tl))(1.25x1.25x5 mm3) and (1.8 x1.8 x6 mm3) . PSPMT (R2486 (3”) (Hamamatsu) Not independent

H8500 H9500 3 mm 6 mm

Comparison pin-hole parallel hole collimator NaI(Tl), 1.8 x 1.8 mm pixel size 57Co source 1 mm diameter at 5 mm distance 140 keV high resolution parallel hole collimator FWHM= 2.8 mm pin hole collimator I = 3 FWHM = 1.7 mm efficiency - Parallel hole : ~ 15.9 counts/mCixs - Pinhole : ~ 3 counts/mCixs (1mm aperture) “only” a factor ~ 5

Resolution doesn’t improve, pixels identification not so good NaI(Tl), 1.8 x 1.8x 5 mm3 Pinhole aperture : 1mm Source diameter: ~ 1.0 mm Pinhole aperture: 0.67 mm d= 17 mm (I=3) FWHM = 1.1 mm FWHM = 1.7 mm d = 7 mm (I=~7) FWHM = 1.3 mm NaI(Tl), 1.25x1.25x 5 mm3 I = 7 FWHM = 1.3 mm Resolution doesn’t improve, pixels identification not so good --> photodetector limitation

Let’s improve the pixel identification (better sampling at anode level (M16 (4 x 4 mm2 and M64 (2x2 mm2)) Source diameter: ~ 1.0 mm, I ~ 7 NaI(Tl), 1.8 mm pixel size, M64 NaI(Tl), 1.8 mm pixel size, M16 1.0 mm FWHM 1.1 mm FWHM NaI(Tl), 1.25 mm pixel size, M64 NaI(Tl), 1.25 mm pixel size, M16 1.1 mm FWHM 1.0 mm FWHM

CsI(Tl) arrays Hamamatsu PSPMT’s C8,M16,M64 (different anode) 4.2x4.2 mm2 2.5x2.5 mm2 1.5x1.5 mm2

Improving sampling -> better pixel identification (more pixel in the image) M16, 1.8 mm pixel R2486, 1.8 mm pixel M64, 1.8 mm pixel M16, 1.2 mm pixel M64, 1.25 mm pixel R2486, 1.2 mm pixel

small anode pixel ->better sampling ->better performances - pin hole aperture dominates the spatial resolution - apertures = 0.5 mm (or 0.3 mm) would improve spatial resolution but lowering counting rates small anode pixel ->better sampling ->better performances M16 and M64 have small area (~20 x 20 mm2) arrays possible solution but dead area --> not the best H8500 (50 x 50 mm2, 64 channels (anode sampling 6 x 6 mm2) - H9500 (50 x 50 mm2, 256 channels (anode sampling 3x3 mm2) available

catene resistive vs multiwire

To be done - fixing FOV according to the particular research - fixing the area (50 x 50 mm2 to 100 x 100 mm2) seems to best solution ---> FOV = ~ 15 x 15 mm2 to 50 x 50 mm2 (according to the detector area and magnification) - maximizing the number of pixel - trying to improve sensitivity - reading out all the channels

How Pin hole (tungsten) collimator (0.3,0.5,0.7,1) mm better photodetector NaI 1.8 x 1.8 mm2 *(and 1.25 x 1.25 mm2)-H8500 64 channels(6x6 mm2 anode pixel) Improving detector peformances (more pixel, better indentification, improved spatial resolution) NaI 1.25 x 1.25 mm2 H9500 256 channels (3x3 mm2 anode pixel) Improving the efficiency - bigger detector area - better collimation (coded aperture) Next step: smaller scintillator pixel size? CsI (Tl) (or Na? ) or NaI(Tl)

(Pin hole 0.7 mm tungsten, H8500 64 ch) Flood Field irradiation New Detector (Pin hole 0.7 mm tungsten, H8500 64 ch) (1.8 x 1.8 mm2) (1.25 x 1.25 mm2) Good pixel identification For 1.8 x 1.8 not so good for 1.25 x 1. 25 -> better anode sampling is needed --> H8500 256 channels Flood Field irradiation Eg = 122 keV

Read-out electronics

High resolution preserving high SNR ? coded apertures Ideal pinhole +perfect resolution -zero transmitted power Real pinhole +some signal through -degraded resolution Coded Aperture +signal of finite pinhole +resolution of ideal pinhole

Coded apertures I (Image) = O (object) x A (aperture) A  G = d then Figure adapted from:Fenimore and Cannon, Optical Engineering, 19, 3, 283-289, 1980. Example of apertures with known decoding pattern I (Image) = O (object) x A (aperture) There are decoding patterns G allowing: A  G = d then A  G = Ô, in fact Ô = R  G = ( O × A )  G = O * (A  G) = O * PSF

coded aperture collimators simulation for our desktop detector 10Ci in 10 s 4444 pixels 1.25 x 1.25 mm2 FoV 22 cm2. Mask NTHT MURA 2222, =2, 1% transparent, thickness 1.5 mm W. Pitch 0.68 mm. Line source 10Ci in 10 s 2D source 10Ci in 10 s sensitivity improved by a factor 30! coded aperture collimators

Submillimeter spatial resolution Reconstruction of a 122 keV point-like source using the coded apertures Submillimeter spatial resolution High sensitivity (factor ~ 30) FWHM=0.93 mm Sensitivity=145 cps /MBq 5 cps/MBq with pinhole

Image of a mouse head Top view of a mouse injected with 3 mCi of 99Tc-MDP (image time 25 min; FOV = 16 x16 mm2)

Conclusioni Rilevanza Perche’ Come Cosa occorre Imaging funzionale, mediante radionuclidi ad alta risoluzione ed efficienza, signle photon (planare e tomografico) Come Scintillatore(i) pixellato, fototubo(i), DAQ “veloce” per ~ 1000 ch, collimatori pinhole e/o aperture codificate Cosa occorre