Varese, 28 Febbraio 2008 e-mail: [email protected] Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal

Varese, 28 Febbraio 2008 e-mail: [email protected]

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 GuerraProfessor of Medical Physics, Faculty of Medicine

Head, and Director Specialty School in Medical PhysicsHead Functional Imaging and Instrumentation Group

Department of Physics "E.Fermi'University of Pisa, Pisa, Italy

e-mail: [email protected]://www.df.unipi.it/~fiig/

Center of ExcellenceAmbiSEN - Univ. Pisa

INFN - Pisa

Varese, 28 Febbraio 2008


Molecular Imaging

The Physics of PET

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


Molecular Imaging

The Physics of PET

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”


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Risorse ed obiettivi dell’imaging 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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Imaging molecolare: Interdisciplinare!

Anatomia Fisiologia Molecolare

Ott

ico

M

N

RM

N

U

S

TA

C

Convergenza di varie metodologie di imaging, di biologia cellulare e molecolare, chimica, medicina e farmacologia, matematica e informatica

e di varie tecnologie di fisica


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Concetto di probe

György Hevesy (1885-1966)

Premio Nobel per la Chimica (1943)“per il suo lavoro nell’utilizzo 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 l’immagine.

Questi sono solitamente ottenuti a partire da un composto affine che interagisce con il target di interesse con l’aggiunta di una componente che produce un segnale.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Varie tecniche di imaging molecolare per piccoli animali

A. Imaging PET di un ratto utilizzando 18F-FDG che mostra il metabolismo del glucosio

B. Imaging TAC dell’addome di un topo dopo l’iniezione di un mezzo di contrasto iodato.

C. Imaging SPECT dell’addome di un topo tramite 99mTc-methylene diphosphonate che mostra l’accumulo 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 dell’animale.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Principio della Tomografia a Emissione di Positroni (PET)


Molecular Imaging

The Physics of PET

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 l’energia rilasciata ed il punto di impatto nel rivelatore

– Il circuito di coincidenza (AND in una certa finestra temporale) stabilisce se i due provengono dall’annichilazione del positrone (coincidenza)

– Le posizioni di rivelazione nei rivelatori stabiliscono la linea lungo la quale è avvenuta l’annichilazione (linea di risposta o LOR).


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Tipici radiotraccianti in PET

Radioisotopi

– 11C(t1/2 = 20.4 min) sostituzione isotopica

– 13N(t1/2 = 10.4 min) sostituzione isotopica

– 15O(t1/2 = 2.5 min) sostituzione isotopica

– 18F(t1/2 = 109.6 min) sostituzione di un atomo di H

Tracciante a-specifico: segue un processo biochimico– 18F-FDG tracciante di metabolismo

( Misura dell’attività metabolica: ricerca di processi anormali )

- 15O-H2O tracciante di flusso sanguigno cerebrale

Tracciante specifico: interagisce direttamente con un sito ricettore– Segue uno specifico processo fisiologico o biochimico Es.: 11C-

flumazenil ricettori della benzodiazepina: » Analisi di disturbi neurologici

» Misura dell’efficacia degli psicofarmaci

In imaging molecolare si utilizzano principalmente traccianti specifici.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

» Dipende dal radioisotopo

180° ± 0.25°

Limiti della tecnica PETErrori intrinseci

<Ec >

(MeV)

<Range> in acqua

FWHM(mm)

18F 0.242 1.4 mm 0.22

11C 0.385 1.7 mm 0.28

68Ga 0.740 3.0 mm 1.35

Range del positrone Deviazione angolare

» Dipende dal raggio dell’anello(1.8 mm per 40 cm di raggio)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Spatial resolution requirements


Molecular Imaging

The Physics of PET

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. 25-40.

1.25 : 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/

18F)

p : Parallax error (radial elongation)

Non-colinearity

PositronrangeCrystal Coding

0022.0 2 25.1 22222 prDbdFWHM

Intrinsic

Parallaxerror

How to achieve high spatial resolution?• Individual detectors or “perfect coding”• High granularity detectors (e.g. small crystal pixels)• Parallax error reduction


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Sensitivity requirements

Imaging of low activity sourceslow uptake processes such as in gene research

Possibility to study fast metabolic processeswith characteristic time comparable with the scanning time

Utilization of radionuclides with a very high specific activity such as PET short half-life radioisotopes: 15O (122 s), 13N (10 min), 11C (20 min), 18F (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


Molecular Imaging

The Physics of PET

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.

L’alta 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 l’errore dovuto alla profondità di interazione nel cristallo (effetto di parallasse).


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

YAP-(S)PET II small animal scanner

Scanner configuration

Configuration: Four rotating heads

Scintillator: YAlO3:Ce (YAP:Ce)

Crystal size: 27 x 27 (1.5 x 1.5 x 20 mm3 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: 10-15 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


Molecular Imaging

The Physics of PET

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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: absolute sensitivity

Measured sensitivity

PET: Measured with 18F-FDG

High sensitivity energy window: ~25 cps/kBq @ CFOV (50-850 keV) (2.5%)

High resolution energy window: ~12 cps/kBq @ CFOV (50-420 keV) (1.2%)

SPECT: Measured with 99mTc:37 cps/MBq (140-250 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: 50-850 keV (high sensitivity) and 50-420 keV (high resolution).


Molecular Imaging

The Physics of PET

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 (50-850 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 22Na point source of about 100 kBq.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: transaxial resolutionDerenzo Phantom (PET)

1.2 mm

3.0 mm1.

5 m

m

2.0 mm

FORE+FBP50-850 keV

3D-OSEM50-850 keV

The rods of the Derenzo phantom were filled with 18F solution. Both FBP+FORE (ramp filter) and 3D-OSEM reconstructions were used on a 0.3750.3750.750 mm3 voxel space. A high sensitivity energy window (50-850 keV) was used.

2.5 mm

1.2 mm

3.0 mm1.

5 m

m

2.0 mm 2.5 mm

1.2 mm

3.0 mm1.

5 m

m

2.0 mm 2.5 mm

0.750 mm thick slices


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: Axial resolutionDefrise Phantom (PET)

Slice thickness 4 mm

Volume view

The Defrise phantom were filled with 18F solution. 3D-OSEM reconstructions was used on a 0.3750.3750.750 mm3 voxel space. A high sensitivity energy window (50-850 keV) was used.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: Transaxial resolutionDerenzo Phantom (SPECT)

The rods of the Derenzo phantom were filled with a 99mTc solution. FBP (ramp filter) reconstruction was used on a 0.3750.3751.5 mm3 voxel space. Sinograms were build using 140-250 keV energy window.

1.5 mm thick slices

1.2

mm

3.0 mm

1.5 mm


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: Image qualityNEMA 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: 300Ci of a 18F solution and scanned for 20 min. SPECT mode: 5 mCi of a 99mTc solution and scanned for 60 min.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: Image qualityNEMA I.Q. Phantom images (PET)

3D ML-EM reconstruction

Voxel size 0.375 mm 0.375 mm (transaxial) 0.750 mm (axial)

(E.W. 50-850 keV)


Molecular Imaging

The Physics of PET

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%


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: Image qualityNEMA I.Q. Phantom images (PET)

Recovery coefficients obtained from hot bars in the IQ phantom

Recovery coefficient = avg(maxROI)/meanUNIFORM

ROI size = twice the rod diameter slice thickness

(10 consecutive ROI’s were considered in the calculation)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Performance: Image qualityNEMA I.Q. Phantom images (SPECT)

FBP

FBP

(E.W. 140-250 keV)EM coll. (50 it.)

EM coll. (50 it.)


Molecular Imaging

The Physics of PET

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


Molecular Imaging

The Physics of PET

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 18F-FDG (PET)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Brain metabolism in rat Ipotyroidism study with 18F-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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Rat and mouse heart metabolismwith 18F-FDG (PET)

The rat (Sprague-Dawley, 236 g) has been injected with 37 MBq (1 mCi) of 18F-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 18F-FDG and scanned after 25min for 33min.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Rat heart perfusionwith 99mTc-Myoview (SPECT)

Weight: 204 g

Injected activity 8 mCi of 99mTc Myoview

Acquisition start: 180 min post injection

Scan time: 80 min

Voxel 0.5 x 0.5 x 0.5 mm3 Voxel 0.5 x 0.5 x 0.5 mm3


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Mouse heart perfusion with 99mTc-Myoview (SPECT)

Weight: 33 g

Injected activity 4 mCi of 99mTc Myoview

Acquisition start: 90 min post injection

Scan time 80 min.

Voxel 0.5 x 0.5 x 0.5 mm3

Voxel 0.5 x 0.5 x 2.0 mm3

Voxel 0.5 x 0.5 x 2.0 mm3


Molecular Imaging

The Physics of PET

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 99mTc-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 18F- and scanned after 30 min for 30 min (2 bed positions)

PET(Mainz)

SPECT(Ferrara)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Bone metabolism in mice with PET and SPECT

NaF

18F-

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

99mTc - MDP

SPECT (Ferrara)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Tumour imaging in mice with 18F-FDG and 18F-Choline PET

FDG

F-Choline

Tumor model: MAT-Ly-Lu – Prostatic tumor (subcutaneous)Body weight: 250g – Position: prone/left side down, head forward


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Liver and kidney imaging in mice with 18F-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)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Tumor imaging: Human glioma in rat with 18F-FDG (PET)

Rat with brain glioma

Normal Rat

Controls animals (Wistar) were compared with implanted rats using 18F-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.


Molecular Imaging

The Physics of PET

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 18F-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 18F-FDG (PET)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

S. Del Vecchio et al., 2007. Universita’ degli Studi di Napoli “Federico II”ed Istituto di Biostrutture e Bioimmagini CNR

Tumor model: Nude mice model of carcinoma breast cancer with 99mTc-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 99mTc-Sestamibi.

Bladder

Post-therapyBasal

BladderTumorBladder


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Tumor model: Mice model of breastcancer with 99mTc-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 99mTc-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 37-55 MBq (1- 1.5 mCi) of 99mTc-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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Neurology in rats: Striatal D2 receptors study with 18F-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 blockingNormal 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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Neurology in rats: 18F-MPPF 5HT1a receptors

study at the University Hospital of Geneva

Sprague-Dawley male rats underwent 18F-MPPF multiple injections:• at o time: 1.5 mCi (55 MBq) of 18F-MPPF• after 60 minutes: 1.5 mCi (55 MBq) of 18F-MPPF and 10 mg/kg of unlabeled MPPF• after 115 minutes: 1.5 mCi (55 MBq) of 18F-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)PETscanner and a β-microprobe”, JCBFM, 2008, in press.


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Neurology in rats: 18F-MPPF 5HT1a receptors

study at the University Hospital of Geneva

B'

max = 1.94 ± 0.56 pmol/ml

K1 = 0.306 ± 0.022 min

-1

k2 = 0.257 ± 0.019 min

-1

kon

/VR = 0.024 ml/(pmol min)

koff

= 0.053 min-1

KdV

R = 2.13 pmol/ml

0

2

4

6

8

0 20 40 60 80 100 120 140 160

ModelYAP-(s)PET

Tim

e co

ncen

trat

ion

curv

es (

pmol

/ml)

Time (min)

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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Neurology in rats: Receptor study with 11C-Racloprideat San Raffaele Hospital, Milano, Italy

Coronal Axial

Rat model of Huntington’s 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 - control169 mCi (~6.2 MBq) injected, uptake time: 16 min, acquisition time: 45 minutes

Day 8 after QA injection108 108 Ci (Ci (~4.0~4.0 MBq) injected, MBq) injected, uptake time: 26 min, uptake time: 26 min, acquisition time: 30 minutesacquisition time: 30 minutes

Day 30 after QA injection173 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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Myocardial studies of a rat model of ischemia and reperfusion

Myocardial perfusion evaluation:• 99mTc-Myoview• 13 N-Ammonia

Glucose metabolism: 18F-FDG

Apoptosis: 99mTc-Annexin V

Acute necrosis: 99mTc-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


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Rat myocardium perfusion studies with 99mTc-Myoview (SPECT)

Rat injected with ~ 5 mCi of 99mTc-Myoview, 60 minutes

uptake time, acquisition time 60 minutes, EM reconstruction


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Blood Flow with 13N-Ammonia

Rat injected with ~ 1 mCi of 13N-NH3, no uptake time,

acquisition time 30 minutes, 3D-OSEM reconstruction


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Rat injected with ~ 1 mCi of 18F-FDG, 5 ml of glucosate at 5%10-15 min before injection time, uptake time 45 minutes,

acquisition time 45 minutes, EM reconstruction 10 iterations

Glucose consumption with 18F-FDG

coronal

transaxial sagittal


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Tracer comparison studyMyoview vs. Annexin on rat heart

99mTc-Myoview(high uptake in the heart)

99mTc-Annexin(low uptake in the heart)

Fusion(feasible)


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Model of rat heart with ischemia and subsequent re-perfusion

w/ Dept Nuclear Medicine, PisaShort axis Vertical long axis Horizontal long axis

Injection: 300 MBq (8 mCi) of 99mTc-Myoviewuptake time180 min, acquisition 48 min, reconstruction EM algorithm

Injection: 300 MBq (8 mCi) of 99mTc-Annexin uptake time 90 min, acquisition 1 hour and half, reconstruction EM algorithm

Fusion


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Rat injected with ~ 5-6 mCi of 99mTc-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 99mTc-Glucarate

coronal

transaxial sagittal


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Small animal CT: technology

Circular orbit (A) CT or Spiral CT (B)

cone beam

high voltage

x-ray tube CCD detectorsample

axis of

Rotating sample or rotating detectors

Linear or flat panel detectors


Molecular Imaging

The Physics of PET

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


Molecular Imaging

The Physics of PET

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 dell’Università di Pisa


Molecular Imaging

The Physics of PET

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.


Molecular Imaging

The Physics of PET

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 GroupDepartment of Physics”E.Fermi”

University of Pisa, Pisa, Italy


Molecular Imaging

The Physics of PET

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]


Molecular Imaging

The Physics of PET

The YAP-(S)PET


Small animal CT

Conclusions

Acknowledgments

Thank you!

Documents

Varese, 28 Febbraio 2008 e-mail: [email protected] Molecular Imaging The Physics of PET The YAP-(S)PET Applications of the YAP-(S)PET Small animal