γ-PARCEL: Control of Molecular Release Using γ-Rays.

We previously have developed the photoresponsive tetra-gel and nanoparticles for controlling the function of the encapsulated substance by UV irradiation. However, the penetration ability of the UV is not high enough. Here, we developed a radiation-responsive tetra-gel and nanoparticle based on γ-ray-responsive X-shaped polyethylene glycol (PEG) linker with a disulfide bond. The nanoparticle could retain small molecules and biomacromolecules. γ-Rays were used as a trigger signal because of their higher penetrating ability. This allowed a spatiotemporal release and control of the encapsulated substances from the nanoparticle in the deeper region, which is impossible by using light exposure (ultraviolet, visible, and near-infrared).

PET detectors with depth-of-interaction and time-of-flight capabilities.

In positron emission tomography (PET), measurements of depth-of-interaction (DOI) information and time-of-flight (TOF) information are important. DOI information reduces the parallax error, and TOF information reduces noise by measuring the arrival time difference of the annihilation photons. Historically, these have been studied independently, and there has been less implementation of both DOI and TOF capabilities because previous DOI detectors did not have good TOF resolution. However, recent improvements in PET detector performance have resulted in commercial PET scanners achieving a coincidence resolving time of around 200 ps, which result in an effect even for small objects. This means that TOF information can now be utilized even for a brain PET scanner, which also requires DOI information. Therefore, various methods have been proposed to obtain better DOI and TOF information. In addition, the cost of PET detectors is also an important factor to consider, since several hundred detectors are used per PET scanner. In this paper, we review the latest DOI-TOF detectors including the history of detector development. When put into practical use, these DOI-TOF detectors are expected to contribute to the improvement of imaging performance in brain PET scanners.

Optical crosstalk of protective cover on MPPC array for TOF PET detector.

Objective. Time-of-flight (TOF) is an important factor that directly affects the image quality of PET systems, and various attempts have been made to improve the coincidence resolving time (CRT) of PET detectors. For independent readout detectors, the timing is acquired for each silicon photomultiplier (SiPM), so they are less sensitive to diffused scintillation light, resulting in a better CRT. Further improvement can be expected if the light can be focused on a single SiPM. However, existing SiPM arrays have a thin protective cover on the SiPM and the gap between the SiPMs is filled with either air or the protective cover, so the light must diffuse through the cover. In this work, we investigated optical crosstalk in the protective cover to improve the CRT.Approach. We used 3.1 × 3.1 × 20 mm3fast LGSO crystals and 3 mm square 8 × 8 multi pixel photon counter (MPPC) arrays. Pitch of the MPPCs was 3.2 mm and thickness of the protective cover on them was 150µm. To reduce diffusion of scintillation light in the protective cover, the part of the inactive areas on the MPPC array were optically separated using reflective material. Specifically, 50, 100, 150, and 350µm deep grid-shaped slits were made along the inactive area of the MPPCs and they were filled with BaSO4powder as the reflective material.Main results. Coincidence counts were measured with a pair of TOF detectors, and the CRT was shorter with a deeper slit depth. The CRT before improvement was 235 ps, and using the cover having the 350µm deep slits filled with reflective material lowered the CRT to 211 ps.Significance. Up to 10% of the scintillation light was diffused to other MPPCs by the protective cover, and the CRT was degraded by 10% due to optical crosstalk of the cover. The proposed method promises to improve the CRT of the TOF detector.

Two-step optimization for accelerating deep image prior-based PET image reconstruction.

Deep learning, particularly convolutional neural networks (CNNs), has advanced positron emission tomography (PET) image reconstruction. However, it requires extensive, high-quality training datasets. Unsupervised learning methods, such as deep image prior (DIP), have shown promise for PET image reconstruction. Although DIP-based PET image reconstruction methods demonstrate superior performance, they involve highly time-consuming calculations. This study proposed a two-step optimization method to accelerate end-to-end DIP-based PET image reconstruction and improve PET image quality. The proposed two-step method comprised a pre-training step using conditional DIP denoising, followed by an end-to-end reconstruction step with fine-tuning. Evaluations using Monte Carlo simulation data demonstrated that the proposed two-step method significantly reduced the computation time and improved the image quality, thereby rendering it a practical and efficient approach for end-to-end DIP-based PET image reconstruction.

Study on the radiofrequency transparency of partial-ring oval-shaped prototype PET inserts in a 3 T clinical MRI system.

The purpose of this study is to evaluate the RF field responses of partial-ring RF-shielded oval-shaped positron emission tomography (PET) inserts that are used in combination with an MRI body RF coil. Partial-ring PET insert is particularly suitable for interventional investigation (e.g., trimodal PET/MRI/ultrasound imaging) and intraoperative (e.g., robotic surgery) PET/MRI studies. In this study, we used electrically floating Faraday RF shield cages to construct different partial-ring configurations of oval and cylindrical PET inserts and performed experiments on the RF field, spin echo and gradient echo images for a homogeneous phantom in a 3 T clinical MRI system. For each geometry, partial-ring configurations were studied by removing an opposing pair or a single shield cage from different positions of the PET ring. Compared to the MRI-only case, reduction in mean RF homogeneity, flip angle, and SNR for the detector opening in the first and third quadrants was approximately 13%, 15%, and 43%, respectively, whereas the values were 8%, 23%, and 48%, respectively, for the detector openings in the second and fourth quadrants. The RF field distribution also varied for different partial-ring configurations. It can be concluded that the field penetration was high for the detector openings in the first and third quadrants of both the inserts.

Feasibility Study for a Microstrip Transmission Line RF Coil Integrated with a PET Detector Module in a 7T Human MR Imaging System.

PURPOSE: The purpose of this study was to do a feasibility study on a microstrip transmission line (MS) RF coil for a positron emission tomography (PET) insert in a 7 Tesla human MRI system. The proposed MS coil integrated the RF shield of the PET detector as the ground conductor of the coil. We called the integrated module "MS PET coil." METHODS: A single-channel MS PET coil was developed with an integrated RF-shielded PET detector module. For comparison, we also studied a conventional MS coil with a single-layer ground conductor. A lutetium fine silicate (LFS) scintillation crystal block (14 × 14 × 4-layer) with a silicon photomultiplier (Hamamatsu Photonics K.K., Shizuoka, Japan) and a front-end readout circuit board were mounted inside the shield cage of the MS PET coil. The MS PET coil was studied with and without PET detectors. All three coil configurations were studied with a homogeneous phantom in a 7T MRI system (Siemens Healthineers, Erlangen, Germany). PET data measurements were conducted using a Cesium-137 radiation point source. RESULTS: The MR images were similar for the MS coil and the empty MS PET coil, as well as for the cases of MS PET coil with and without PET measurements. Compared to the empty MS PET coil (without PET detector and cable RF shield), decreases in SNR, increases in image noise and RF power, and a slight decrease in resonance frequency were seen for the case of the MS PET coil with the detector and cable shield. Differences in the PET energy histograms or in the crystal identification maps with and without MRI measurements were negligible. CONCLUSIONS: Both the MRI and PET performances of the MS PET coil showed responses that matched the MS coil responses. The performance variations of MRI data with and without PET measurement and PET data with and without MR imaging were negligible.

MRI compatibility study of a prototype radiofrequency penetrable oval PET insert at 3 T.

PURPOSE: To perform an MRI compatibility study of an RF field-penetrable oval-shaped PET insert that implements an MRI built-in body RF coil both as a transmitter and a receiver. METHODS: Twelve electrically floating RF shielded PET detector modules were used to construct the prototype oval PET insert with a major axis of 440 mm, a minor axis of 350 mm, and an axial length of 225 mm. The electric floating of the PET detector modules was accomplished by isolating the cable shield from the detector shield using plastic tape. Studies were conducted on the transmit (B1) RF field, the image signal-to-noise ratio (SNR), and the RF pulse amplitude for a homogeneous cylindrical (diameter: 160 mm and length: 260 mm) phantom (NaCl + NiSO4 solution) in a 3 T clinical MRI system (Verio, Siemens, Erlangen, Germany). RESULTS: The B1 maps for the oval insert were similar to the MRI-only field responses. Compared to the MRI-only values, SNR reductions of 51%, 45%, and 59% were seen, respectively, for the spin echo (SE), gradient echo (GE), and echo planar (EPI) images for the case of oval PET insert. Moreover, the required RF pulse amplitudes for the SE, GE, and EPI sequences were, respectively, 1.93, 1.85, and 1.36 times larger. However, a 30% reduction in the average RF reception sensitivity was observed for the oval insert. CONCLUSIONS: The prototype floating PET insert was a safety concern for the clinical MRI system, and this compatibility study provided clearance for developing a large body size floating PET insert for the existing MRI system. Because of the RF shield of the insert, relatively large RF powers compared to the MRI-only case were required. Because of this and also due to low RF sensitivity of the body coil, the SNRs reduced largely.

Deep learning-based PET image denoising and reconstruction: a review.

This review focuses on positron emission tomography (PET) imaging algorithms and traces the evolution of PET image reconstruction methods. First, we provide an overview of conventional PET image reconstruction methods from filtered backprojection through to recent iterative PET image reconstruction algorithms, and then review deep learning methods for PET data up to the latest innovations within three main categories. The first category involves post-processing methods for PET image denoising. The second category comprises direct image reconstruction methods that learn mappings from sinograms to the reconstructed images in an end-to-end manner. The third category comprises iterative reconstruction methods that combine conventional iterative image reconstruction with neural-network enhancement. We discuss future perspectives on PET imaging and deep learning technology.

Development of DynamicMC for PHITS Monte Carlo package.

Previously, we have developed DynamicMC for modeling relative movement of Oak Ridge National Laboratory phantom in a radiation field for the Monte Carlo N-Particle package (Health Physics. 2023,124(4):301-309). Using this software, three-dimensional dose distributions in a phantom irradiated by a certain mono-energetic (Mono E) source can be deduced through its graphical user interface. In this study, we extended DynamicMC to be used in combination with the Particle and Heavy Ion Transport code System (PHITS) by providing it with a higher flexibility for dynamic movement for an anthropomorphic phantom. For this purpose, we implemented four new functions into the software, which are (1) to generate not only Mono E sources but also those having an energy spectrum of an arbitrary radioisotope (2) to calculate the absorbed doses for several radiologically important organs (3) to automatically average the calculated absorbed doses along the path of the phantom and (4) to generate user-defined slab shielding materials. The first and third items utilize the PHITS-specific modalities named radioisotope-source and sumtally functions, respectively. The computational cost and complexity can be dramatically reduced with these features. We anticipate that the present work and the developed open-source tools will be in the interest of nuclear radiation physics community for research and teaching purposes.

A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

Objective.To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy.Approach.Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models-binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results.Main results.Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions.Significance.The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy.

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages [Formula: see text]B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector's circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target [Formula: see text]B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.

Experience and new prospects of PET imaging for ion beam therapy monitoring.

Pioneering investigations on the usage of positron-emission-tomography (PET) for the monitoring of ion beam therapy with light (protons, helium) and heavier (stable and radioactive neon, carbon and oxygen) ions started shortly after the first realization of planar and tomographic imaging systems, which were able to visualize the annihilation of positrons resulting from irradiation induced or implanted positron emitting nuclei. And while the first clinical experience was challenged by the utilization of instrumentation directly adapted from nuclear medicine applications, new detectors optimized for this unconventional application of PET imaging are currently entering the phase of (pre)clinical testing for more reliable monitoring of treatment delivery during irradiation. Moreover, recent advances in detector technologies and beam production open several new exciting opportunities which will not only improve the performance of PET imaging under the challenging conditions of in-beam applications in ion beam therapy, but will also likely expand its field of application. In particular, the combination of PET and Compton imaging can enable the most efficient utilization of all possible radiative emissions for both stable and radioactive ion beams, while positronium lifetime imaging may enable probing new features of the underlying tumour and normal tissue environment. Thereby, PET imaging will not only provide means for volumetric reconstruction of the delivered treatment and in-vivo verification of the beam range, but can also shed new insights for biological optimization of the treatment or treatment response assessment.

Calibration method of crosshair light sharing PET detector with TOF and DOI capabilities.

Objective. A crosshair light sharing (CLS) PET detector as a TOF-DOI PET detector with high spatial resolution has been developed. To extend that work, a detector calibration method was developed to achieve both higher coincidence resolving time (CRT) and DOI resolution.Approach. The CLS PET detector uses a three-layer reflective material in a two-dimensional crystal array to form a loop structure within a pair of crystals, enabling a CRT of about 300 ps and acquisition of DOI from multi-pixel photon counter (MPPC) output ratios. The crystals were 1.45 × 1.45 × 15 mm3fast LGSO, and the crystal array was optically coupled to an MPPC array. It is important to reduce as many inter-crystal scattering (ICS) events as possible in advance for the accurate detector calibration. DOI information is also expected to improve the CRT because it can estimate the time delay due to the detection depth of crystals.Main results. Using crystal identification and light collection rate of the highest MPPC output reduces the number of ICS events, and CRT is improved by 26%. In addition, CRT is further improved by 13% with a linear correction of time delay as a function of energy. The DOI is ideally estimated from the output ratio of only the MPPC pairs optically coupled to the interacted crystals, which is highly accurate, but the error is large due to light leakage in actual use. The previous method, which also utilizes light leakage to calculate the output ratio, is less accurate, but the error can be reduced. Using the average of the two methods, it is possible to improve the DOI resolution by 12% while maintaining the smaller error.Significance. By applying the developed calibration method, the CLS PET detector achieves the CRT of 251 ps and the DOI resolution of 3.3 mm.

Tracking the same fast-LGSO crystals by changing surface treatments for better coincidence timing resolution in PET.

Achieving fast coincidence timing resolution (CTR) is an important issue in clinical time-of-flight positron emission tomography (TOF-PET) to improve the reconstructed image quality. One of the major factors affecting the CTR is the crystal surface treatment, which is often parameterized as surface roughness. However, previous studies on the crystal surface treatment optimization had two limitations of crystal-by-crystal variation and worse CTR over 200 ps. Here, we report the effects of the crystal surface treatment on the performance of a 20 mm long fast-LGSO crystal based TOF detector by tracking the same crystals in the sub-180 ps CTR regime. The light collection efficiency (LCE), energy resolution (ER) and CTR of the TOF detector were evaluated with six different crystal surface treatments of chemically polished (C.P), C.P half side roughened (1/2S) treatment, and then the C.P one side roughened (1S) treatment, mechanically polished (M.P) treatment, M.P 1/2S treatment, and M.P 1S treatment. The four lateral surfaces of each crystal were wrapped by using enhanced specular reflector film while the top surface was covered by using Teflon tape. The bottom surface of the crystal was optically coupled to a silicon photomultiplier. The timing and energy signals were extracted by using a custom-made high-frequency readout circuit, and then digitized by using a waveform digitizer. All the experimental conditions were same except the crystal surface treatment. Among the six different crystal surface treatments, the M.P 1S would be the optimal crystal surface treatment which balanced enhancements in the CTR (165 ± 3 ps) and ER (10.5 ± 0.5%). Unlike the M.P 1S, the C.P 1S did not enhance the CTR and ER. Hence, the C.P without roughening would be the second-best optimal crystal surface treatment which balanced the CTR (169 ± 3 ps) and ER (10.5 ± 0.5%).

Current and Future PET Imaging for Multiple Myeloma.

Positron emission tomography (PET) is an imaging modality used for the noninvasive assessment of tumor staging and response to therapy. PET with 18F labeled fluorodeoxyglucose (18F-FDG PET) is widely used to assess the active and inactive lesions in patients with multiple myeloma (MM). Despite the availability of 18F-FDG PET for the management of MM, PET imaging is less sensitive than next-generation flow cytometry and sequencing. Therefore, the novel PET radiotracers 64Cu-LLP2A, 68Ga-pentixafor, and 89Zr-daratumumab have been developed to target the cell surface antigens of MM cells. Furthermore, recent studies attempted to visualize the tumor-infiltrating lymphocytes using PET imaging in patients with cancer to investigate their prognostic effect; however, these studies have not yet been performed in MM patients. This review summarizes the recent studies on PET with 18F-FDG and novel radiotracers for the detection of MM and the resulting preclinical research using MM mouse models and clinical studies. Novel PET technologies may be useful for developing therapeutic strategies for MM in the future.

Optimum selection for multi-interaction events in Compton-PET hybrid reconstruction: a Monte Carlo study.

In Compton PET, that has a scatterer inserted inside a PET ring, there are multi-interaction events that can be treated as both PET and Compton events. A PET event from multi-interaction events that include a Compton event and a photoelectric absorption event or two Compton events can be extracted by applying a PET recovery method. In this study, we aimed to establish a method to maximize image quality by utilizing such redundant events. We conducted brain-scale Monte Carlo simulations of a C-shaped Compton-PET geometry and a whole gamma imaging (WGI) geometry. Images were reconstructed by a hybrid image reconstruction method combining both PET and Compton events. The result showed that the spatial resolution was improved when treated as PET events while keeping the noise level. The effect of improvement was more significant in WGI than in C-shaped Compton PET because the number of events recovered as PET events having more accurate spatial information was much larger in WGI. When the PET-recovered multi-interaction events were also included as Compton events in the hybrid reconstruction, we did not observe any improvement in image quality, while the number of used events was largest. The results suggested that treating events as PET events exclusively was better for image quality.

Discrimination of inter-crystal scattering events by signal processing for the X'tal cube PET detector.

Inter-crystal scattering (ICS) events cause degradation of the contrast in PET images. We developed the X'tal cube PET detector with submillimeter spatial resolution, which consisted of a segmented LYSO scintillator and 96 MPPCs. For this high spatial resolution PET detector, the ICS event was not negligible. In this study, we proposed a method to discriminate the ICS events and showed its feasibility by the following method. For each 96 MPPC, we measured the mean and standard deviation of the peak in the pulse height distribution obtained by the photoabsorption events in a scintillator pixel. Every time a newly detected event was identified as the segment, we monitored the reduced chi-square value that was calculated with the pulse height and the prepared mean and the standard deviation for each 96 MPPC. Since the pulse height caused by the photoabsorption event resulted in a small reduced chi-square value, we could eliminate the ICS events by setting a threshold on the reduced chi-square value. We carried out both a Monte Carlo simulation and a scanning experiment. By the simulation, we confirmed that the threshold of the reduced chi square significantly discriminated the ICS event. We obtained the response function by a scanning experiment with a 0.2 mm slit beam of 511 keV gamma-ray. The standard deviation of the response function was improved from 1.6 to 1.06 mm by eliminating the ICS events. The proposed method could significantly eliminate the ICS events and retain the true events.

Pre-acquired CT-based attenuation correction with automated headrest removal for a brain-dedicated PET system.

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (µ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of µ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (µ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (µ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (µ-map-sameHr). Phantom images by VRAIN using each µ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using µ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the µ-map-noHr and the µ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN.

Fully 3D implementation of the end-to-end deep image prior-based PET image reconstruction using block iterative algorithm.

Objective. Deep image prior (DIP) has recently attracted attention owing to its unsupervised positron emission tomography (PET) image reconstruction method, which does not require any prior training dataset. In this paper, we present the first attempt to implement an end-to-end DIP-based fully 3D PET image reconstruction method that incorporates a forward-projection model into a loss function.Approach. A practical implementation of a fully 3D PET image reconstruction could not be performed at present because of a graphics processing unit memory limitation. Consequently, we modify the DIP optimization to a block iteration and sequential learning of an ordered sequence of block sinograms. Furthermore, the relative difference penalty (RDP) term is added to the loss function to enhance the quantitative accuracy of the PET image.Main results. We evaluated our proposed method using Monte Carlo simulation with [18F]FDG PET data of a human brain and a preclinical study on monkey-brain [18F]FDG PET data. The proposed method was compared with the maximum-likelihood expectation maximization (EM), maximuma posterioriEM with RDP, and hybrid DIP-based PET reconstruction methods. The simulation results showed that, compared with other algorithms, the proposed method improved the PET image quality by reducing statistical noise and better preserved the contrast of brain structures and inserted tumors. In the preclinical experiment, finer structures and better contrast recovery were obtained with the proposed method.Significance.The results indicated that the proposed method could produce high-quality images without a prior training dataset. Thus, the proposed method could be a key enabling technology for the straightforward and practical implementation of end-to-end DIP-based fully 3D PET image reconstruction.