Yasukazu Kanai

Development of a Si-PM-based high-resolution PET system for small animals

A Geiger-mode avalanche photodiode (Si-PM) is a promising photodetector for PET, especially for use in a magnetic resonance imaging (MRI) system, because it has high gain and is less sensitive to a static magnetic field. We developed a Si-PM-based depth-of-interaction (DOI) PET system for small animals. Hamamatsu 4 × 4 Si-PM arrays (S11065-025P) were used for its detector blocks. Two types of LGSO scintillator of 0.75 mol% Ce (decay time: ∼45 ns; 1.1 mm × 1.2 mm × 5 mm) and 0.025 mol% Ce (decay time: ∼31 ns; 1.1 mm × 1.2 mm × 6 mm) were optically coupled in the DOI direction to form a DOI detector, arranged in a 11 × 9 matrix, and optically coupled to the Si-PM array. Pulse shape analysis was used for the DOI detection of these two types of LGSOs. Sixteen detector blocks were arranged in a 68 mm diameter ring to form the PET system. Spatial resolution was 1.6 mm FWHM and sensitivity was 0.6% at the center of the field of view. High-resolution mouse and rat images were successfully obtained using the PET system. We confirmed that the developed Si-PM-based PET system is promising for molecular imaging research.

Interference between PET and MRI sub-systems in a silicon-photomultiplier-based PET/MRI system

The silicon-photomultiplier (Si-PM) is a promising photodetector, especially for integrated PET/MRI systems, due to its small size, high gain, and low sensitivity to static magnetic fields. The major problem using a Si-PM-based PET system within the MRI system is the interference between the PET and MRI units. We measured the interference by combining a Si-PM-based PET system with a permanent-magnet MRI system. When the RF signal-induced pulse height exceeded the lower energy threshold level of the PET system, interference between the Si-PM-based PET system and MRI system was detected. The prompt as well as the delayed coincidence count rates of the Si-PM-based PET system increased significantly. These noise counts produced severe artifacts on the reconstructed images of the Si-PM-based PET system. In terms of the effect of the Si-PM-based PET system on the MRI system, although no susceptibility artifact was observed on the MR images, electronic noise from the PET detector ring was detected by the RF coil and reduced the signal-to-noise ratio (S/N) of the MR images. The S/N degradation of the MR images was reduced when the distance between the RF coil and the Si-PM-based PET system was increased. We conclude that reducing the interference between the PET and MRI systems is essential for achieving the optimum performance of integrated Si-PM PET/MRI systems.

Simultaneous imaging using Si-PM-based PET and MRI for development of an integrated PET/MRI system

The silicon photomultiplier (Si-PM) is a promising photo-detector for PET for use in magnetic resonance imaging (MRI) systems because it has high gain and is insensitive to static magnetic fields. Recently we developed a Si-PM-based depth-of-interaction PET system for small animals and performed simultaneous measurements by combining the Si-PM-based PET and the 0.15 T permanent MRI to test the interferences between the Si-PM-based PET and an MRI. When the Si-PM was inside the MRI and installed around the radio frequency (RF) coil of the MRI, significant noise from the RF sequence of the MRI was observed in the analog signals of the PET detectors. However, we did not observe any artifacts in the PET images; fluctuation increased in the count rate of the Si-PM-based PET system. On the MRI side, there was significant degradation of the signal-to-noise ratio (S/N) in the MRI images compared with those without PET. By applying noise reduction procedures, the degradation of the S/N was reduced. With this condition, simultaneous measurements of a rat brain using a Si-PM-based PET and an MRI were made with some degradation in the MRI images. We conclude that simultaneous measurements are possible using Si-PM-based PET and MRI.

A temperature-dependent gain control system for improving the stability of Si-PM-based PET systems

The silicon-photomultiplier (Si-PM) is a promising photodetector for the development of new PET systems due to its small size, high gain and relatively low sensitivity to the static magnetic field. One drawback of the Si-PM is that it has significant temperature-dependent gain that poses a problem for the stability of the Si-PM-based PET system. To reduce this problem, we developed and tested a temperature-dependent gain control system for the Si-PM-based PET system. The system consists of a thermometer, analog-to-digital converter, personal computer, digital-to-analog converter and variable gain amplifiers in the weight summing board of the PET system. Temperature characteristics of the Si-PM array are measured and the calculated correction factor is sent to the variable gain amplifier. Without this correction, the temperature-dependent peak channel shifts of the block detector were -55% from 20 °C to 35 °C. With the correction, the peak channel variations were corrected within ±8%. The coincidence count rate of the Si-PM-based PET system was measured using a Na-22 point source while monitoring the room temperature. Without the correction, the count rate inversely changed with the room temperature by 10% for 1.5° C temperature changes. With the correction, the count rate variation was reduced to within 3.7%. These results indicate that the developed temperature-dependent gain control system can contribute to improving the stability of Si-PM-based PET systems.

Can Complementary 68Ga-DOTATATE and 18F-FDG PET/CT Establish the Missing Link Between Histopathology and Therapeutic Approach in Gastroenteropancreatic Neuroendocrine Tumors?

Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare 68Ga-DOTATATE and 18F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients. Methods: The relation between complementary 68Ga-DOTATATE and 18F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33–79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%–9%) and G2b (10%–20%) according to Ki67 indices. Results: The sensitivity of 68Ga-DOTATATE and 18F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for 68Ga-DOTATATE and 40%, 28%, 28%, and 75% for 18F-FDG, respectively. Statistically significant differences were found between grades 1–2, 2a–2b, and 1–2b with respect to 68Ga-DOTATATE PET/CT as well as between 1–2a and 1–2b with respect to 18F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for 68Ga-DOTATATE and 2a and 2b (P = 0.484) for 18F-FDG. The impact of the combined 18F-FDG and 68Ga-DOTATATE PET/CT on the therapeutic decision was 59%. Conclusion: Combined 68Ga-DOTATATE and 18F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs.

Development of an ultrahigh resolution Si-PM based PET system for small animals

Since a high resolution PET system is needed for small animal imaging, especially for mouse studies, we developed a new small animal PET system that decreased the size of the scintillators to less than 1 mm. Our developed PET system used 0.5 × 0.7 × 5 mm(3) LYSO pixels arranged in an 11 × 13 matrix to form a block with a 0.1 mm BaSO4 reflector between the pixels. Two LYSO blocks were optically coupled to two optical fiber based angled image guides. These LYSO blocks and image guides were coupled to a Si-PM array (Hamamatsu MPPC S11064-050P) to form a block detector. Eight block detectors (16 LYSO blocks) were arranged in a 34 mm inner diameter ring to form a small animal PET system. The block detector showed good separation for the 22 × 13 LYSO pixels in the two-dimensional position histogram. The energy resolution was 20% full-with at half-maximum (FWHM) for 511 keV gamma photons. The transaxial resolution reconstructed by filtered backprojection was 0.71 to 0.75 mm FWHM and the axial resolution was 0.70 mm. The point source sensitivity was 0.24% at the central axial field-of-view. High resolution mouse images were obtained using our PET system. The developed ultrahigh resolution PET system showed attractive images for small animal studies and has a potential to provide new findings in molecular imaging researches.

Development of a high-resolution Si-PM-based gamma camera system.

A silicon photomultiplier (Si-PM) is a promising photodetector for PET, especially for PET/MRI combined systems, due to its high gain, small size, and lower sensitivity to static magnetic fields. However, these properties are also promising for gamma camera systems for single-photon imaging. We developed an ultra-high-resolution Si-PM-based compact gamma camera system for small animals. Y(2)SiO(5):Ce (YSO) was selected as scintillators because of its high light output and no natural radioactivity. The gamma camera consists of 0.6 mm × 0.6 mm × 6 mm YSO pixels combined with a 0.1 mm thick reflector to form a 17 × 17 matrix that was optically coupled to a Si-PM array (Hamamatsu multi-pixel photon counter S11064-050P) with a 2 mm thick light guide. The YSO block size was 12 mm × 12 mm. The YSO gamma camera was encased in a 5 mm thick gamma shield, and a parallel hole collimator was mounted in front of the camera (0.5 mm hole, 0.7 mm separation, 5 mm thick). The two-dimensional distribution for the Co-57 gamma photons (122 keV) was almost resolved. The energy resolution was 24.4% full-width at half-maximum (FWHM) for the Co-57 gamma photons. The spatial resolution at 1.5 mm from the collimator surface was 1.25 mm FWHM measured using a 1 mm diameter Co-57 point source. Phantom and small animal images were successfully obtained. We conclude that a Si-PM-based gamma camera is promising for molecular imaging research.

Crossed cerebellar diaschisis: a positron emission tomography study withl-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-d-glucose

Objective: Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whetherl-[methyl-11C]methionine (MET) uptake is affected in CCD.Methods: In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[18F]fluoroe-d-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively.Results: Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017±0.023 and 0.014±0.039, respectively).Conclusions: Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity.

Development of a flexible optical fiber based high resolution integrated PET/MRI system

PURPOSE The simultaneous measurement of PET and magnetic resonance imaging (MRI) is an emerging field for molecular imaging research. Although optical fiber based PET∕MRI systems have advantages on less interference between PET and MRI, there is a drawback in reducing the scintillation light due to the fiber. To reduce the problem, the authors newly developed flexible optical fiber bundle based block detectors and employed them for a high resolution integrated PET∕MRI system. METHODS The flexible optical fiber bundle used 0.5 mm diameter, 80 cm long double clad fibers which have dual 12 mm × 24 mm rectangular inputs and a single 24 mm × 24 mm rectangular output. In the input surface, LGSO scintillators of 0.025 mol.% (decay time: ∼31 ns: 0.9 mm × 1.3 mm × 5 mm) and 0.75 mol.% (decay time: ∼46 ns: 0.9 mm × 1.3 mm × 6 mm) were optically coupled in depth direction to form depth-of-interaction detector, arranged in 11 × 13 matrix and optically coupled to the fiber bundle. The two inputs of the bundle are bent for 90°, bound to one, and are optically coupled to a Hamamatsu 1-in. square position sensitive photomultiplier tube. RESULTS Light loss due to the fiber bundle could be reduced and the performance of the block detectors was improved. Eight optical fiber based block detectors (16 LGSO blocks) were arranged in a 56 mm diameter ring to form a PET system. Spatial resolution and sensitivity were 1.2 mm full-width at half-maximum and 1.2% at the central field-of-view, respectively. Sensitivity change was less than 1% for 2 °C temperature changes. This PET system was integrated with a 0.3 T permanent magnet MRI system which has 17 cm diameter hole at the yoke area for insertion of the PET detector ring. There was no observable interference between PET and MRI. Simultaneous imaging of PET and MRI was successfully performed for small animal studies. CONCLUSIONS The authors confirmed that the developed high resolution PET∕MRI system is promising for molecular imaging research.

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: 15O-Labeled Gas Inhalation PET with MRI Fusion

PET with 15O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the 15O gas steady-state inhalation method for normal anesthetized rats. Methods: Eight normal male Sprague–Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by 15O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm3; frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with 15O-CO2 and 15O-O2 gases delivered through the radioactive gas stabilizer. CBV was measured by 15O-CO gas inhalation and corrected for the intravascular hemoglobin-bound 15O-O2. Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images. Results: The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68–85) min. In both the 15O-CO2 and the 15O-O2 studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 ± 4.5 mL/100 mL/min; CMRO2, 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% ± 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL. Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO2 using the original steady-state inhalation method of 15O-CO2 and 15O-O2 gases and measurement of CBV using the 15O-CO gas inhalation method in the brain of normal anesthetized rats.