High-resolution Animal Positron Emission Tomography Research Articles

Scatter correction for large non-human primate brain imaging using microPET

The baboon is well suited to pre-clinical evaluation of novel radioligands for positron emission tomography (PET). We have previously demonstrated the feasibility of using a high resolution animal PET scanner for this application in the baboon brain. However, the non-homogenous distribution of tissue density within the head may give rise to photon scattering effects that reduce contrast and compromise quantitative accuracy. In this study, we investigated the magnitude and distribution of scatter contributing to the final reconstructed image and its variability throughout the baboon brain using phantoms and Monte Carlo simulated data. The scatter fraction is measured up to 36% at the centre of the brain for a wide energy window (350–650 keV) and 19% for a narrow (450–650 keV) window. We observed less than 3% variation in the scatter fraction throughout the brain and found that scattered events arising from radioactivity outside the field of view contribute less than 1% of measured coincidences. In a contrast phantom, scatter and attenuation correction improved contrast recovery compared with attenuation correction on its own and reduced bias to less than 10% at the expense of the reduced signal-to-noise ratio. We conclude that scatter correction is a necessary step for ensuring high quality measurements of the radiotracer distribution in the baboon brain with a microPET scanner, while it is not necessary to model out of field of view scatter or a spatially variant scatter function.

Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model

As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2-7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq (mean) [(18)F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [(18)F]fluoride PET by virtue of decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.

Application of PET with feedback injection control system for quantification of drug-induced effects on the brain function

Positron emission tomography (PET) measurement with continuous infusion method, which achieves an equilibrium stage of time activity curve (TAC) in the region of interest (ROI), is expected to assess the drug-induced effects with a single scan. We developed a new system that combined a feedback-controlled injection with a high-resolution animal PET scanner (SHR-7700, Hamamatsu, Japan). A syringe containing labeled ligand solution was set on the injection system and then multi-frame scan with PET was simultaneously started with start of bolus injection to the subject. Based on the previous TAC information of promptly reconstructed PET data, the computer calculated injection speed to maintain equilibrium stage of ligand binding to the target. Then the drug to be assessed was administered. The interaction between cocaine and [ 18F]FE-CFT, which has specificity for dopamine transporters, was evaluated in the conscious monkey brain, showing cocaine-induced dose dependent reduction of [ 18F]FE-CFT binding in the striatum. In conclusion, we successfully demonstrated that the PET with feedback infusion system was very useful to assess the drug-induced changes in ligand-target binding in the living brain.

Detector development for microPET II: a 1 μl resolution PET scanner for small animal imaging

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 × 12 array of 1 × 1 × 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 μm diameter Na-22 point source. Using a 330 μm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.

Studies with a prototype high resolution PET scanner based on LSO-APD modules

Lutetium oxyorthosilicate (LSO) scintillation crystals coupled to avalanche photodiodes (APDs) have been proven to be an interesting detector module for high resolution positron emission tomography (PET). Compact detector modules were built to test their performance in a prototype tomograph. Each detector module consisted of sixteen 3.7/spl times/3.7/spl times/12.0 mm/sup 3/ LSO crystals, which are one-to-one coupled to a two dimensional APD array (2/spl times/8 diodes, 3 mm O, 4 mm spacing). The signals were read out by a low noise, fast, charge sensitive preamplifier, a 50 ns shaping amplifier and CAMAC electronic modules. Two detector modules were mounted on a rotatable gantry, to simulate a detector ring. Long term runs over 110 hours have shown that the detector remains stable over a long period of time. The energy resolution (FWHM) was 13.4% for 511 keV gamma rays and the intrinsic spatial resolution was 2.2 mm (FWHM). The gain dependence of the APD on temperature had been determined as 3.5% K. The time resolution was 3.2/spl plusmn/0.1 ns (FWHM). Phantom measurements showed the suitability of the new LSO/APD detector for high resolution animal PET.

Noninvasive measurement of cerebral blood flow and glucose metabolic rate in the rat with high-resolution animal positron emission tomography (PET): a novel in vivo approach for assessing drug action in the brains of small animals.

The cerebral metabolic rate of glucose (CMRglc) and cerebral blood flow (CBF) in rats were estimated noninvasively with a high-resolution animal positron emission tomography (PET) system that we recently developed. Qualifications of CMRglc and CBF were attempted with radiotracers, 18F-2-fluoro-2-deoxyglucose and 15O-water, respectively. From the data obtained with PET, the CMRglc and CBF values under pretreatment conditions were respectively calculated as 51 +/- 14 mumol/min/100 g and 61 +/- 7 ml/min/100 g under pentobarbital-anesthesia. These values were in close agreement with published data obtained with the autoradiographic technique. Moreover, an increase of 69% (mean) in CBF was detected after i.v. acetazolamide administration. The results indicate that this high-resolution animal PET scanner holds great potential for the assessment of drug-related metabolic and circulatory effects in intact and experimental animals.