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Objective . Prompt gamma photon, prompt x-ray, and induced positron imaging are possible methods for observing a proton beam's shape from outside the subject. However, since these three types of images have not been measured simultaneously nor compared using the same subject, their advantages and disadvantages remain unknown for imaging beam shapes in therapy. To clarify these points, we developed a triple-imaging-modality system to simultaneously measure prompt gamma photons, prompt x-rays, and induced positrons during proton beam irradiation to a phantom. Approach . The developed triple-imaging-modality system consists of a gamma camera, an x-ray camera, and a dual-head positron emission tomography (PET) system. During 80 MeV proton beam irradiation to a polymethyl methacrylate (PMMA) phantom, imaging of prompt gamma photons was conducted by the developed gamma camera from one side of the phantom. Imaging of prompt x-rays was conducted by the developed x-ray camera from the other side. Induced positrons were measured by the developed dual-head PET system set on the upper and lower sides of the phantom. Main results . With the proposed triple-imaging-modality system, we could simultaneously image the prompt gamma photons and prompt x-rays during proton beam irradiation. Induced positron distributions could be measured after the irradiation by the PET system and the gamma camera. Among these imaging modalities, image quality was the best for the induced positrons measured by PET. The estimated ranges were actually similar to those imaged with prompt gamma photons, prompt x-rays and induced positrons measured by PET. Significance . The developed triple-imaging-modality system made possible to simultaneously measure the three different beam images. The system will contribute to increasing the data available for imaging in therapy and will contribute to better estimating the shapes or ranges of proton beam., (© 2024 Institute of Physics and Engineering in Medicine.)

Objective . Prompt x-ray imaging using a low-energy x-ray camera is a promising method for observing a proton beam's shape from outside the subject. Furthermore, imaging of positrons produced by nuclear reactions with protons is a possible method for observing the beam shape. However, it has not been possible to measure these two types of images with a single imaging system due to the limited imaging capability of existing systems. Imaging of both prompt x-rays and the distribution of positrons may compensate for the shortcomings of each method. Approach . We conducted imaging of the prompt x-ray using a pinhole x-ray camera during irradiation with protons in list mode. Then, after irradiation with protons, imaging of annihilation radiations from the produced positrons was conducted using the same pinhole x-ray camera in list mode. After this imaging, list-mode data were sorted to obtain prompt x-ray images and positron images. Main results . With the proposed procedure, we could measure both prompt x-ray images and induced positron images with a single irradiation by a proton beam. From the prompt x-ray images, ranges and widths of the proton beams could be estimated. The distributions of positrons were slightly wider than those of the prompt x-rays. From the time sequential positron images, we could derive the time activity curves of the produced positrons. Significance . Hybrid imaging of prompt x-rays and induced positrons using a pinhole x-ray camera was achieved. The proposed procedure would be useful for measuring prompt x-ray images during irradiation to estimate the beam structures as well as for measuring the induced positron images after irradiation to estimate the distributions and time activity curves of the induced positrons., (© 2023 Institute of Physics and Engineering in Medicine.)

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

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.

In clinical cardiac positron emission tomography using (15)O-water, significant tracer accumulation is observed not only in the heart but also in the liver and lung, which are partially outside the field-of-view. In this work, we investigated the effects of scatter on quantitative myocardium blood flow (MBF) and perfusable tissue fraction (PTF) by a precise Monte Carlo simulation (Geant4) and a numerical human model. We assigned activities to the heart, liver, and lung of the human model with varying ratios of organ activities according to an experimental time activity curve and created dynamic sinograms. The sinogram data were reconstructed by filtered backprojection. By comparing a scatter-corrected image (SC) with a true image (TRUE), we evaluated the accuracy of the scatter correction. TRUE was reconstructed using a scatter-eliminated sinogram, which can be obtained only in simulations. A scatter-uncorrected image (W/O SC) and an attenuation-uncorrected image (W/O AC) were also constructed. Finally, we calculated MBF and PTF with a single tissue-compartment model for four types of images. As a result, scatter was corrected accurately, and MBFs derived from all types of images were consistent with the MBF obtained from TRUE. Meanwhile, the PTF of only the SC was in agreement with the PTF of TRUE. From the simulation results, we concluded that quantitative MBF is less affected by scatter and absorption in 3D-PET using (15)O-water. However, scatter correction is essential for accurate PTF.

The objective of this study was to evaluate a resolution recovery (RR) method using a variety of simulated human brain [¹¹C]raclopride positron emission tomography (PET) images. Simulated datasets of 15 numerical human phantoms were processed by a wavelet-based RR method using an anatomical prior. The anatomical prior was in the form of a hybrid segmented atlas, which combined an atlas for anatomical labelling and a PET image for functional labelling of each anatomical structure. We applied RR to both 60 min static and dynamic PET images. Recovery was quantified in 84 regions, comparing the typical 'true' value for the simulation, as obtained in normal subjects, simulated and RR PET images. The radioactivity concentration in the white matter, striatum and other cortical regions was successfully recovered for the 60 min static image of all 15 human phantoms; the dependence of the solution on accurate anatomical information was demonstrated by the difficulty of the technique to retrieve the subthalamic nuclei due to mismatch between the two atlases used for data simulation and recovery. Structural and functional synergy for resolution recovery (SFS-RR) improved quantification in the caudate and putamen, the main regions of interest, from -30.1% and -26.2% to -17.6% and -15.1%, respectively, for the 60 min static image and from -51.4% and -38.3% to -27.6% and -20.3% for the binding potential (BP(ND)) image, respectively. The proposed methodology proved effective in the RR of small structures from brain [¹¹C]raclopride PET images. The improvement is consistent across the anatomical variability of a simulated population as long as accurate anatomical segmentations are provided.

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 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.

The silicon photomultiplier (Si-PM) is a promising photodetector for a high-resolution PET scanner due to its small size, high gain and lower sensitivity to magnetic fields. There are several commercially available Si-PM arrays with different pixel sizes and fill factors, and these parameters can affect the performance of a PET block detector read out by these devices. We compared the performance of block detectors using 4 × 4 Si-PM arrays with 25 µm (Hamamatsu S11064-025P) and 50 µm (S11064-050P) pixels combined with the same 15 × 15 matrix LGSO block made of 0.7 × 0.7 × 6 mm(3) scintillator pixels. Evaluated characteristics include photopeak linearity, energy resolution and positioning performance. Although the photopeak linearity and energy resolution are slightly better for the Si-PM with 25 µm pixels, the position performance measured by the separation of the position histogram is significantly better for the Si-PM with 50 µm pixels. We conclude that using the Si-PM with 50 µm pixels will provide a better solution for the development of ultrahigh-resolution PET systems.

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.

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.

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.

Cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating (15)O-labelled water (H(15)(2)O) and oxygen ((15)O(2)). Conventionally, those images are measured with separate scans for three tracers C(15)O for CBV, H(15)(2)O for CBF and (15)O(2) for CMRO(2), and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO(2) rapidly by sequentially administrating H(15)(2)O and (15)O(2) within a short time. Because quantitative CBF and CMRO(2) values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO(2) were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO(2) values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer was larger than half of the first one. Bias and deviation in those values were also compatible to that of the conventional method, when noise was imposed on the arterial TAC. We concluded that the present calculation based methods could be of use for quantitatively calculating CBF and CMRO(2) with the DARG approach.

Pinhole collimation can be used to improve spatial resolution in SPET. However, the resolution improvement is achieved at the cost of reduced sensitivity, which leads to projection images with poor statistics. Images reconstructed from these projections using the maximum likelihood expectation maximization (ML-EM) algorithms, which have been used to reduce the artefacts generated by the filtered backprojection (FBP) based reconstruction, suffer from noise/bias trade-off: noise contaminates the images at high iteration numbers, whereas early abortion of the algorithm produces images that are excessively smooth and biased towards the initial estimate of the algorithm. To limit the noise accumulation we propose the use of the pinhole median root prior (PH-MRP) reconstruction algorithm. MRP is a Bayesian reconstruction method that has already been used in PET imaging and shown to possess good noise reduction and edge preservation properties. In this study the PH-MRP algorithm was accelerated with the ordered subsets (OS) procedure and compared to the FBP, OS-EM and conventional Bayesian reconstruction methods in terms of noise reduction, quantitative accuracy, edge preservation and visual quality. The results showed that the accelerated PH-MRP algorithm was very robust. It provided visually pleasing images with lower noise level than the FBP or OS-EM and with smaller bias and sharper edges than the conventional Bayesian methods.

In quantitative pinhole SPECT, photon penetration through the collimator edges (penetration), and photon scattering by the object (object scatter) and collimator (collimator scatter) have not been investigated rigorously. Monte Carlo simulation was used to evaluate these three physical processes for different tungsten knife-edge pinhole collimators using uniform, hotspot and donut phantoms filled with 201Tl, 99mTc, 123I and 131I solutions. For the hotspot phantom, the penetration levels with respect to total counts for a 1 mm pinhole aperture were 78%, 28% and 23% for 131I, 123I and 99mTc, respectively. For a 2 mm aperture, these values were 65% for 131I, 16% for 123I and 12% for 99mTc. For all pinholes, 201Tl penetration was less than 4%. The evaluated scatter (from object and collimator) with a hotspot phantom for the 1 mm pinhole was 24%, 16%, 18% and 13% for 201Tl, 99mTc, 123I and 131I, respectively. Summation of the object and collimator scatter for the uniform phantom was approximately 20% higher than that for the hotspot phantom. Significant counts due to penetration and object and collimator scatter in the reconstructed image were observed inside the core of the donut phantom. The collimator scatter can be neglected for all isotopes used in this study except for 131I. Object scatter correction for all radionuclides used in this study is necessary and correction for the penetration contribution is necessary for all radionuclides but 201Tl.

We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals 11C-labelled Doxepin, 11C-labelled YM09151-2 and 11C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6 +/- 6.2 and 32.1 +/- 12.0 kBq h MBq-1 respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq-1 with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq-1 respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.