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Varese, 28 Febbraio 2008 Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal.

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Presentazione sul tema: "Varese, 28 Febbraio 2008 Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal."— Transcript della presentazione:

1 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Functional imaging and Instrumentation Group – Univ. Pisa Department of Physics E.Fermi University of Pisa Advances in PET technology for molecular imaging Alberto Del Guerra Professor of Medical Physics, Faculty of Medicine Head, and Director Specialty School in Medical Physics Head Functional Imaging and Instrumentation Group Department of Physics "E.Fermi' University of Pisa, Pisa, Italy Center of Excellence AmbiSEN - Univ. Pisa INFN - Pisa Varese, 28 Febbraio 2008

2 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments CONTENTS Molecular Imaging The Physics of PET The small animal scanner YAP-(S)PET Applications of the YAP-(S)PET scanner in molecular imaging Conclusions Acknowledgments

3 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Imaging molecolare Rappresentazione visuale, caratterizzazione e quantificazione dei processi biologici che avvengono in un essere vivente a livello cellulare e sub-cellulare

4 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Risorse ed obiettivi dellimaging molecolare Risorse Sviluppo delle tecniche di biologia cellulare e molecolare Disponibilità di nuovi farmaci e probes ad alta specificità Sviluppo di strumentazione per imaging di piccoli animali Obiettivi: Sviluppo di metodi di imaging non invasivi che riflettano i processi cellulari e molecolari, (es. espressione genica o interazioni proteina-proteina) Visualizzazione di trafficking e targeting cellulare Ottimizzazione di terapie farmacologiche e geniche Follow-up delle malattie da un punto di vista molecolare... e soprattutto=> Ottenere tali obiettivi in modo Rapido, Quantitativo e Riproducibile

5 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Imaging molecolare: Interdisciplinare! Anatomia Fisiologia Molecolare Ottico MN RMN US TAC Convergenza di varie metodologie di imaging, di biologia cellulare e molecolare, chimica, medicina e farmacologia, matematica e informatica e di varie tecnologie di fisica

6 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Concetto di probe György Hevesy ( ) Premio Nobel per la Chimica (1943) per il suo lavoro nellutilizzo di isotopi come traccianti nello studio dei processi chimici 1924: Principio del radiotracciante La sostituzione di un atomo in una molecola con il suo analogo radioattivo (radioisotopo) non cambia significativamente il suo comportamento biologico Conseguenza: il movimento, la distribuzione e la concentrazione di una molecola può essere misurata con rivelatori per radiazione Estensione del concetto in imaging molecolare Si utilizzano opportuni probes molecolari come sorgente di contrasto per limmagine. Questi sono solitamente ottenuti a partire da un composto affine che interagisce con il target di interesse con laggiunta di una componente che produce un segnale.

7 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Varie tecniche di imaging molecolare per piccoli animali A. Imaging PET di un ratto utilizzando 18 F-FDG che mostra il metabolismo del glucosio B. Imaging TAC delladdome di un topo dopo liniezione di un mezzo di contrasto iodato. C. Imaging SPECT delladdome di un topo tramite 99m Tc-methylene diphosphonate che mostra laccumulo nelle ossa. D. Imaging ottico di un topo (D) che mostra la fluorescenza GFP dal fegato, addome, colonna vertebrale e cervello dovuta alla presenza di cellule tumorali E. immagine RMN pesata T2 del cervello di topo. F. Imaging ottico in bioluminescenza di un topo sovrapposta ad una fotografia dellanimale.

8 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Principio della Tomografia a Emissione di Positroni (PET)

9 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Formazione delle immagini a emissione di positroni Principio della tecnica PET –I due rivelatori (fotomoltiplicatori e scintillatori) rivelano i due misurando lenergia rilasciata ed il punto di impatto nel rivelatore –Il circuito di coincidenza (AND in una certa finestra temporale) stabilisce se i due provengono dallannichilazione del positrone (coincidenza) –Le posizioni di rivelazione nei rivelatori stabiliscono la linea lungo la quale è avvenuta lannichilazione (linea di risposta o LOR).

10 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Tipici radiotraccianti in PET Radioisotopi – 11 C(t 1/2 = 20.4 min) sostituzione isotopica – 13 N(t 1/2 = 10.4 min) sostituzione isotopica – 15 O(t 1/2 = 2.5 min) sostituzione isotopica – 18 F(t 1/2 = min) sostituzione di un atomo di H Tracciante a-specifico: segue un processo biochimico – 18 F-FDG tracciante di metabolismo ( Misura dellattività metabolica: ricerca di processi anormali ) - 15 O-H 2 O tracciante di flusso sanguigno cerebrale Tracciante specifico: interagisce direttamente con un sito ricettore –Segue uno specifico processo fisiologico o biochimico Es.: 11 C-flumazenil ricettori della benzodiazepina: » Analisi di disturbi neurologici » Misura dellefficacia degli psicofarmaci In imaging molecolare si utilizzano principalmente traccianti specifici.

11 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments » Dipende dal radioisotopo 180° ± 0.25° Limiti della tecnica PET Errori intrinseci (MeV) in acqua FWHM (mm) 18 F mm C mm Ga mm1.35 Range del positroneDeviazione angolare » Dipende dal raggio dellanello (1.8 mm per 40 cm di raggio)

12 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Spatial resolution requirements

13 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments PET Spatial resolution limitations * Derenzo & Moses, "Critical instrumentation issues for resolution <2mm, high sensitivity brain PET", in Quantification of Brain Function, Tracer Kinetics & Image Analysis in Brain PET, ed. Uemura et al, Elsevier, 1993, pp :degradation due to tomographic reconstruction d:crystal size b:systematic inaccuracy of positioning scheme (range: 0-2 mm) D:coincident detector separation (~gantry diameter) r:effective source size, including positron range 0.55mm w/ 18 F) p:Parallax error (radial elongation) Non- colinearity Positron range CrystalCoding Intrinsic Parallax error How to achieve high spatial resolution? Individual detectors or perfect coding High granularity detectors (e.g. small crystal pixels) Parallax error reduction

14 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Sensitivity requirements Imaging of low activity sources low uptake processes such as in gene research Possibility to study fast metabolic processes with characteristic time comparable with the scanning time Utilization of radionuclides with a very high specific activity such as PET short half-life radioisotopes: 15 O (122 s), 13 N (10 min), 11 C (20 min), 18 F (110min) High geometry efficiency (large solid angle covered by detectors) High detection efficiency (e.g. for crystals: high/medium Z, high density) Solutions Requirements Brain receptor saturation usually a maximum of 100 Ci can be injected to a mouse Limitation on the volume a maximum of 300 l can be injected to a mouse Limitations

15 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Strumentazione per small animal PET Tipicamente basata su rivelatori a scintillazione(LSO) e fotomoltiplicatori. La tecnologia più recente è orientata alla massimizzazione della sensibilità pur mantenendo una buona risoluzione. Lalta sensibilità si ottiene con cristalli scintillatori ad alta densità (alta probabilità di interazione) e alto Z (alta probabilità di interazione fotoelettrica). Sono necessarie tecnologie per limitare lerrore dovuto alla profondità di interazione nel cristallo (effetto di parallasse).

16 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments YAP-(S)PET II small animal scanner Scanner configuration Configuration:Four rotating heads Scintillator:YAlO 3 :Ce (YAP:Ce) Crystal size:27 x 27 (1.5 x 1.5 x 20 mm 3 each) Photodetector:Position Sensitive PMT Readout method:Resistive chain (4 channels) FoV size:40.5 mm axial 40.5 mm Ø Collimators: (SPECT)Lead (parallel holes) Head-to-head distance: cm Scanner installed at the Institute of Clinical Physiology (IFC-CNR) within the framework of the Center of Excellence AmbiSEN of the University of Pisa, Italy

17 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: system sensitivity The PET system sensitivity is measured with a linear source placed inside a metal tubes. The measure is repeated five times with increasing wall thickness. The system sensitivity at 125 mm head-to-head distance, averaged over the whole axial FOV, extrapolated from the accumulated sleeve measurements, is 1.25% per pair 2.50% per the four head scanner

18 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: absolute sensitivity Measured sensitivity PET: Measured with 18 F-FDG High sensitivity energy window: ~25 CFOV ( keV) (2.5%) High resolution energy window: ~12 CFOV ( keV) (1.2%) SPECT: Measured with 99m Tc: 37 cps/MBq ( keV) Absolute sensitivity curve along the scanner axis in PET mode. The sensitivity is measured after energy cuts. The results are plotted against the actual position of the source along the axis. Two different curves are produced for different energy windows: keV (high sensitivity) and keV (high resolution).

19 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: PET spatial resolution Comparison of the radial, tangential, and axial FWHM of the reconstructed images, obtained with the FBP-2D (top left) using Single Slice (SSRB) and Fourier (FORE) rebinning ( keV energy window). The spatial resolution is plotted against the radial offset. FBP Volume resolution obtained for two axial positions (central plane and 10 mm axial offset using FORE+FBP). We have used a 22 Na point source of about 100 kBq.

20 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: transaxial resolution Derenzo Phantom (PET) 1.2 mm 3.0 mm 1.5 mm 2.0 mm FORE+FBP keV 3D-OSEM keV The rods of the Derenzo phantom were filled with 18 F solution. Both FBP+FORE (ramp filter) and 3D- OSEM reconstructions were used on a mm 3 voxel space. A high sensitivity energy window ( keV) was used. 2.5 mm 1.2 mm 3.0 mm 1.5 mm 2.0 mm 2.5 mm 1.2 mm 3.0 mm 1.5 mm 2.0 mm 2.5 mm mm thick slices

21 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: Axial resolution Defrise Phantom (PET) Slice thickness 4 mm Volume view The Defrise phantom were filled with 18 F solution. 3D-OSEM reconstructions was used on a mm 3 voxel space. A high sensitivity energy window ( keV) was used.

22 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: Transaxial resolution Derenzo Phantom (SPECT) The rods of the Derenzo phantom were filled with a 99m Tc solution. FBP (ramp filter) reconstruction was used on a mm 3 voxel space. Sinograms were build using keV energy window. 1.5 mm thick slices 1.2 mm 3.0 mm 1.5 mm

23 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: Image quality NEMA I.Q. Phantom 8 mm 1 mm 2 mm 4 mm 3 mm 5 mm 30 mm Drawing and picture of the NEMA Image Quality phantom for small animal PET scanners. The interior is has been filled with: PET mode: 300 Ci of a 18 F solution and scanned for 20 min. SPECT mode: 5 mCi of a 99m Tc solution and scanned for 60 min.

24 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: Image quality NEMA I.Q. Phantom images (PET) 3D ML-EM reconstruction Voxel size mm mm (transaxial) mm (axial) (E.W keV)

25 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Uniformity and quantitation (PET) Activity concentration 20:1 10:1 1:1 Uniformity (std dev / mean) = 6%

26 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: Image quality NEMA I.Q. Phantom images (PET) Recovery coefficients obtained from hot bars in the IQ phantom Recovery coefficient = avg(max ROI )/mean UNIFORM ROI size = twice the rod diameter slice thickness (10 consecutive ROIs were considered in the calculation)

27 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Performance: Image quality NEMA I.Q. Phantom images (SPECT) FBP (E.W keV)EM coll. (50 it.)

28 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Small animal Imaging with the YAP-(S)PET scanner Brain Metabolism in Rats Heart Metabolism in Rats and Mice Heart Perfusion In Rats and Mice Bone metabolism in Rats and Mice Tumor Imaging in Rats and Mice Tumor Models in Mice (Breast Cancer) Neurology in Rats Myocardial Models in Rats

29 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Harderian glands Cerebral cortex Neostriatum Thalamus Olfactory bulbs Salivary glands Inferior colliculus Cerebellum Eye ball Transaxial sections (0.25 mm x 0.25 mm x 2.0 mm) Brain metabolism in rat with 18 F-FDG (PET)

30 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Brain metabolism in rat Ipotyroidism study with 18 F-FDG (PET) Rat with induced Ipotyroidism Normal Rat Normal rats (Wistar) were compared with rats with induced Ipotyroidism in terms of brain glucose consumption (FDG). The effect of the threatment with T3 has been also studied. The rats with induced Ipotyroidism shows a strongly reduced uptake in the harderian glands

31 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Rat and mouse heart metabolism with 18 F-FDG (PET) The rat (Sprague-Dawley, 236 g) has been injected with 37 MBq (1 mCi) of 18 F-FDG and scanned after 2h for 40min. Heart section details (contrast enhancement) RAT (Pisa) MOUSE (Dijon) Heart section details (contrast enhancement) The mouse, 24 g has been injected with 30 MBq (0.8 mCi) of 18 F-FDG and scanned after 25min for 33min.

32 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Rat heart perfusion with 99m Tc-Myoview (SPECT) Weight: 204 g Injected activity 8 mCi of 99m Tc Myoview Acquisition start: 180 min post injection Scan time: 80 min Voxel 0.5 x 0.5 x 0.5 mm 3

33 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Mouse heart perfusion with 99m Tc-Myoview (SPECT) Weight: 33 g Injected activity 4 mCi of 99m Tc Myoview Acquisition start: 90 min post injection Scan time 80 min. Voxel 0.5 x 0.5 x 0.5 mm 3 Voxel 0.5 x 0.5 x 2.0 mm 3

34 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Bone metabolism in rats with PET and SPECT The rat (Sprague-Dawley, 200 g) has been injected with 480 MBq (13 mCi) of 99m Tc-MDP and scanned after 2 h for 82 min (3 bed positions) The rat (200 g) has been injected with 48 MBq (1.3 mCi) of 18 F- and scanned after 30 min for 30 min (2 bed positions) PET (Mainz) SPECT (Ferrara)

35 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Bone metabolism in mice with PET and SPECT NaF 18 F - Transaxial slices (2 mm thick) Voxel size (0.25 x 0.25 x 1 mm) Voxel size (0.25 x 0.25 x 2 mm) PET (Mainz) PET (Dijon) Longitudinal slices 99m Tc - MDP SPECT (Ferrara)

36 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Tumour imaging in mice with 18 F-FDG and 18 F-Choline PET FDG F-Choline Tumor model: MAT-Ly-Lu – Prostatic tumor (subcutaneous) Body weight: 250g – Position: prone/left side down, head forward

37 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Liver and kidney imaging in mice with 18 F-Choline (PET) Transaxial sections (0.5 x 0.5 x 2 mm voxel) Horizontal sections (0.5 x 1 x 0.5 mm voxel) 3D rendering (maximum projections)

38 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Tumor imaging: Human glioma in rat with 18 F-FDG (PET) Rat with brain glioma Normal Rat Controls animals (Wistar) were compared with implanted rats using 18 F-FDG. F98 Glioma model has been selected as tumor with infiltrative pattern. The methodology was able to image the tumor and giving the requested information on the position and dimension of the lesion.

39 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Brain histological slice: tumors and surrounding normal brain tissues were removed and treated following conventional preparative histological protocols to fixation and subsequent criosectioning. Tumor bearing rat (F98 line) injected with 37MBq of 18 F-FDG. Uptake time 45 minutes, acquisition time 60 minutes. Coronal sections (0.5 x 0.5 x 2 mm voxel) Tumor Imaging: Human glioma in rat with 18 F-FDG (PET)

40 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments S. Del Vecchio et al., Universita degli Studi di Napoli Federico II ed Istituto di Biostrutture e Bioimmagini CNR Tumor model: Nude mice model of carcinoma breast cancer with 99m Tc-Sestamibi (SPECT) Nude mice with subcutaneous carcinoma breast cancer. The studies were performed before (Basal) and after (Post-therapy) the administration of citotoxic drugs. The SPECT acquisition were performed 1 hour after the injection of 99m Tc- Sestamibi. Bladder Post-therapy Basal Bladder Tumor Bladder

41 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Tumor model : Mice model of breast cancer with 99m Tc-Annexin V(SPECT) The RIII female mouse represents a model of genetically modified breast cancer induced by a virus (RIII virus, murine mammary tumor virus, MuMTV) which is transmitted from mother to daughter through breast feeding. The effect of Taxol ® was evaluated at different time points after the drug administration (1, 3, 6 and 24 hours), trying to understand when the highest uptake of 99m Tc-Annexin V occurs, as indicator of Taxol induced apoptosis. The animals were i.v. injected in one of the caudal veins with a single dose of Taxol (0.02 mg/g, about 6mg/animal). After 1,3,6 and 24 hours from Taxol administration MBq ( mCi) of 99m Tc- Annexin V. One hour after radiotracer injection the animals were anaesthetized with intra-peritoneal injection of a mix of ketamine (60 mg/kg and 4.4 mg/kg) and fenobarbital (50 mg/kg). coronal transaxial sagittal Nuclear Medicine Department, University of Pisa

42 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Neurology in rats: Striatal D2 receptors study with 18 F-Fallypride (PET) Normal rats were compared with rats with receptor blocking (pre-treated with intraperitoneal injection of 50 mg/(kg body weight) of Haloperidol). All the animals were anesthetized with chloralhydrate 7% and injected via a lateral tail vein with 37 MBq of a high-affinity dopamine D2 receptor ligand 18-F-Fallypride: the acqusition started immediately and the activity in the striatum was monitored (performed at Mainz University). EM reconstruction: 40 iterations. Rat threated with receptor blocking Normal Rat Transaxial section Horizontal section Transaxial section Horizontal section A. Bartoli et al Preliminary assessment of the imaging capability of the YAP–(S)PET small animal scanner in neuroscience, NIM A 569, (2006) 488–491

43 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Neurology in rats: 18 F-MPPF 5HT1a receptors study at the University Hospital of Geneva Sprague-Dawley male rats underwent 18 F-MPPF multiple injections: at o time: 1.5 mCi (55 MBq) of 18 F-MPPF after 60 minutes: 1.5 mCi (55 MBq) of 18 F-MPPF and 10 mg/kg of unlabeled MPPF after 115 minutes: 1.5 mCi (55 MBq) of 18 F-MPPF and 110 mg/kg of unlabedeled MPPF. P. Millet et al In vivo quantification of 5-HT- 1A -[ 18 ]F]MPPF interactions in rats using the YAP-(S)PET scanner and a β-microprobe, JCBFM, 2008, in press.

44 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Neurology in rats: 18 F-MPPF 5HT1a receptors study at the University Hospital of Geneva Results for this region: P. Millet et al In vivo quantification of 5-HT- 1A -[ 18 ]F]MPPF interactions in rats using the YAP-(S)PET scanner and a β-microprobe, JCBFM, 2008, in press

45 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Neurology in rats: Receptor study with 11 C-Raclopride at San Raffaele Hospital, Milano, Italy CoronalAxial Rat model of Huntingtons desease: monolateral lesion QA induced Male Wistar rats weighting 300 g were injected icv in the left striatum with 210 nmol of QA solution and in the right striatum with PBS 0.1 mol/l. Stereotaxic coordinates: AP=+ 1.5, L=+ 2.6, V=-7.0 mm from the Bregma, according to the atlas of Paxinos and Watson. Day 0 - control 169 mCi (~6.2 MBq) injected, uptake time: 16 min, acquisition time: 45 minutes Day 8 after QA injection 108 Ci (~4.0 MBq) injected, uptake time: 26 min, acquisition time: 30 minutes Day 30 after QA injection 173 Ci (~6.4 MBq) injected, uptake time: 29 min, acquisition time: 30 minutes S. Belloli et al Evaluation of three quinoline-carboxamide derivatives as potential radioligands for the in vivo pet imaging of neurodegeneration, Neurochemistry International 44 (2004) 433–440

46 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Myocardial studies of a rat model of ischemia and reperfusion Myocardial perfusion evaluation: 99m Tc-Myoview 13 N-Ammonia Glucose metabolism: 18 F-FDG Apoptosis: 99m Tc-Annexin V Acute necrosis: 99m Tc-Glucarate Assessment of the imaging capability of the YAP-(S)PET small animal scanner in a rat model of ischemia and reperfusion, Bartoli A., Lionetti V., Erba P.A., Fabbri S., Belcari N., Del Guerra A., Recchia F., Mariani G., Salvadori P. ESMI Naples (I), June 14-15, 2007

47 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Rat myocardium perfusion studies with 99m Tc-Myoview (SPECT) Rat injected with ~ 5 mCi of 99m Tc-Myoview, 60 minutes uptake time, acquisition time 60 minutes, EM reconstruction

48 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Blood Flow with 13 N-Ammonia Rat injected with ~ 1 mCi of 13 N-NH 3, no uptake time, acquisition time 30 minutes, 3D-OSEM reconstruction

49 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Rat injected with ~ 1 mCi of 18 F-FDG, 5 ml of glucosate at 5% min before injection time, uptake time 45 minutes, acquisition time 45 minutes, EM reconstruction 10 iterations Glucose consumption with 18 F-FDG coronal transaxial sagittal

50 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Tracer comparison study Myoview vs. Annexin on rat heart 99m Tc-Myoview (high uptake in the heart) 99m Tc-Annexin (low uptake in the heart) Fusion (feasible)

51 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Model of rat heart with ischemia and subsequent re-perfusion w/ Dept Nuclear Medicine, Pisa Short axisVertical long axisHorizontal long axis Injection: 300 MBq (8 mCi) of 99m Tc-Myoview uptake time180 min, acquisition 48 min, reconstruction EM algorithm Injection: 300 MBq (8 mCi) of 99m Tc-Annexin uptake time 90 min, acquisition 1 hour and half, reconstruction EM algorithm Fusion

52 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Rat injected with ~ 5-6 mCi of 99m Tc-glucarate, uptake time 1 hour and half, acquisition time 1 hour and half, EM reconstruction 50 iterations with collimator model 3D rendering (maximum intensity projection) Acute necrosis with 99m Tc-Glucarate coronal transaxial sagittal

53 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Small animal CT: technology Circular orbit (A) CT or Spiral CT (B) Rotating sample or rotating detectors Linear or flat panel detectors

54 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Small animal CT Department of Physics, University of Pisa X-ray source Fixed tungsten anode Maximum voltage: 60 kV Maximum power: 10 W Measured focus size: 7 m FWHM Beam aperture: 32° X-ray detector 1024 x 2048 pixels (48 m each) 5 cm x 10 cm active area Maximum frame rate 2.7 fps Measured focus size: 7 m FWHM 10lp/mm resolution

55 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Applicazioni tipiche small animal TAC 40 mm 3 mm 0.75 mm » 40 kVp, 1 mm Al, High-Speed continuous rotation protocol (5 00) » 500 views, full-scan, magnificazione 4x. Binning 2x2 vertebra Organo malattia - ossa - Denti - Vasi sanguigni - tumori Campione/animale Biopsie Tessuti Piccoli animali (ratti / topi) in vitro e in vivo Immagini ottenute con il prototipo dellUniversità di Pisa

56 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Conclusions Our experience with the YAP-(S)PET II indicates that its spatial resolution and sensitivity are adequate for molecular imaging investigation in both PET and SPECT modalities. The good image uniformity and linearity permit quantitative studies once the partial volume effect has been taken into account. The availability of both emission techniques on the same gantry allows multimodality study in a very easy and effective way. The future installation of an integrated CT will be a critical improvement for a better visualization of anatomical repere, attenuation correction and morphological characterization.

57 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Acknowledgements #1 - FIIG Francesca Attanasi (PhD student) Antonietta Bartoli (PhD student) Nicola Belcari (Res Assistant) Valter Bencivelli (Ass Professor) Laura Biagi (Post-doc) Maria G. Bisogni (Res Assistant) Manuela Camarda(PhD Student) Serena Fabbri (PhD Student) Alberto Del Guerra (Full Professor) Sebnem Erturk (PhD Student) Judy Fogli (PhD student) Gabriela Llosá (Marie Curie Fellow) Sara Marcatili (PhD Student) Sascha Moehrs (Post-Doc) Daniele Panetta (PhD Student) Michela Tosetti (Researcher) Valeria Rosso (Associate Professor) Sara Vecchio (PhD Student) Functional Imaging and Instrumentation Group Department of PhysicsE.Fermi University of Pisa, Pisa, Italy

58 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Acknowledgments #2 In alphabetical order: AdAcAp / Oncodesign (Dijon) Centro di Eccellenza AmbiSEN, University of PISA Istituto di Fisiologia Clinica del CNR, Pisa (Prof. Luigi Donato) ISE – Ingegneria dei Sistemi Elettronici, Pisa Ospedale S. Raffaele, Milano (Prof. F. Fazio) University of Ferrara University of Mainz (Prof. Frank Roesch) University of Pisa (dept of Endocrinology, dept of Nuclear Medicine) University of Napoli Federico II (Prof. Marco Salvatore) University Hospital Geneva (Prof. P. Millet) EMIL (European Molecular Imaging Laboratory) [FP6 NoE]

59 Varese, 28 Febbraio Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal CT Conclusions Acknowledgments Thank you!


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