Using inverse Laplace transform in positronium lifetime imaging.

Positronium (Ps) lifetime imaging is gaining attention to bring out additional biomedical information from positron emission tomography (PET). The lifetime of Psin vivocan change depending on the physical and chemical environments related to some diseases. Due to the limited sensitivity, Ps lifetime imaging may require merging some voxels for statistical accuracy. This paper presents a method for separating the lifetime components in the voxel to avoid information loss due to averaging. The mathematics for this separation is the inverse Laplace transform (ILT), and the authors examined an iterative numerical ILT algorithm using Tikhonov regularization, namely CONTIN, to discriminate a small lifetime difference due to oxygen saturation. The separability makes it possible to merge voxels without missing critical information on whether they contain abnormally long or short lifetime components. The authors conclude that ILT can compensate for the weaknesses of Ps lifetime imaging and extract the maximum amount of information.

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture.

BACKGROUND: Angiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the 'VELOUR' trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL. Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action. We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment. AIM: To determine and compare the efficacy and safety profiles of AFL in the second-line and salvage therapy settings. METHODS: Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan (FOLFIRI) regimen were collected retrospectively from six institutions in Japan, for the period from May 2017 to March 2019. Patient characteristics collected included age, sex, tumor location, RAS and RAF status, metastatic sites, number of previous treatment cycles, therapeutic response, adverse events, duration of previous AI treatment, and survival time. The end points were time to AFL treatment failure (aTTF) and median survival time post-AFL (aMST). Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting, which was defined as the days since the end of second-line therapy. RESULTS: All 41 patients who received AFL + FOLFIRI for advanced CRC had metastatic or unresectable cancer. Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting. The patient characteristics were similar in the two groups, except for two factors. The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients (144 d vs 323 d, P = 0.006). In the second-line and salvage therapy groups, the objective response rates were 11% and 0%, respectively (P = 0.50), and the disease control rates were 53% and 50%, respectively (P = 1.00). In the second-line and salvage therapy groups, the aTTF (123 d vs 71 d, respectively), aMST (673 d vs 396 d, respectively), and incidence of adverse events of grade 3 [8 (36%) vs 9 (47%)] were not significantly different between the two groups. CONCLUSION: AFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

Optical observation of energy loss distribution and practical range of positrons from a 18F water solution in a water-equivalent phantom.

The energy loss distribution of beta+ particles is closely related to their maximum penetration depth distribution and annihilation point distribution. The latter is of practical importance for positron emission tomography. Experimental data related to the energy loss distribution are important for comprehensive validation of physics and simulation models of beta+ interactions. In this paper the authors present a new experimental approach that allows them to visually observe the beta+ energy loss distribution of a solution of nuclear medicine radioisotopes in a plastic scintillator using an optical camera. The authors also report a set of the first experimental results. A water solution of 18F was localized in a small hole in a plastic scintillator (BC430). Optical imaging of the scintillator yielded visual images of the energy loss distribution with a submillimeter resolution. The radial dependence in the energy distribution was quantitatively measured by analysis of the images, and exponential fitting parameters were obtained. The authors observed that the results of Monte Carlo simulation with EGS5 (version 1.0.2) and GEANT4 (version 4.9.01.p01) were consistent with those obtained experimentally. The results of the Monte Carlo simulation indicated that for a linear scale, the energy loss distribution in the scintillator was approximately the same as that in water, and the relative shape of the energy loss distribution was close to those of the maximum penetration depth distribution and annihilation point distribution. This paper also presents discussions about the further possibilities of this optical imaging approach. Thus, optical observation of the beta+ energy loss distribution in a scintillator is a promising technique for visual and quantitative experimental studies of beta+ emission from a solution of radioisotopes that are used in nuclear medicine.

Simulation studies of a new 'OpenPET' geometry based on a quad unit of detector rings.

We have proposed an 'OpenPET' geometry which consists of two detector rings of axial length W each axially separated by a gap G. In order to obtain an axially continuous field-of-view (FOV) of 2W+G, the maximum limit for G must be W. However, two valleys of sensitivity appear, one on each side of the gap. In practice, the gap should be G

Preliminary study on potential of the jPET-D4 human brain scanner for small animal imaging.

OBJECTIVE: One trend in positron emission tomography (PET) instrumentation over the last decade has been the development of scanners dedicated to small animals such as rats and mice. Thicker crystals, which are necessary to obtain higher sensitivity, result in degraded spatial resolution in the peripheral field-of-view (FOV) owing to the parallax error. On the other hand, we are developing the jPET-D4, which is a dedicated human brain PET scanner that has a capability for depth-of-interaction (DOI) measurement. Although its crystal width is about twice that of commercially available small animal PET scanners, we expect the jPET-D4 to have a potential for small animal imaging by making full use of the DOI information. In this article, we investigate the jPET-D4's potential for small animal imaging by comparing it with the microPET Focus220, a state-of-the-art PET scanner dedicated to small animals. METHODS: The jPET-D4 uses four-layered GSO crystals measuring 2.9 mm x 2.9 mm x 7.5 mm, whereas the microPET Focus220 uses a single layer of LSO crystals measuring 1.5 mm x 1.5 mm x 10.0 mm. First, the absolute sensitivity, counting rate performance and spatial resolution of both scanners were measured. Next a small hot-rod phantom was used to compare their imaging performance. Finally, a rat model with breast tumors was imaged using the jPET-D4. RESULTS: Thanks to the thicker crystals and the longer axial FOV, the jPET-D4 had more than four times higher sensitivity than the microPET Focus220. The noise equivalent counting-rate performance of the jPETD4 reached 1,024 kcps for a rat-size phantom, whereas that of the microPET Focus220 reached only 165 kcps. At the center of the FOV, the resolution was 1.7 mm for the microPET Focus220, whereas it was 3.2 mm for the jPET-D4. On the other hand, the difference of resolution became smaller at the off-center position because the radial resolution degraded faster for the microPET Focus220. The results of phantom imaging showed that the jPET-D4 was comparable to the microPET Focus220 at the off-center position even as the microPET Focus220 outperformed the jPET-D4 except for the peripheral FOV. CONCLUSIONS: The jPET-D4 human brain PET scanner, which was designed to achieve not only high resolution but also high sensitivity by measuring DOI information, was proven to have a potential for small animal imaging.

Imaging simulations of an "OpenPET" geometry with shifting detector rings.

We have proposed a new "OpenPET" geometry consisting of two detector rings of axial length W each separated by a gap G. For obtaining an axially continuous field of view (FOV) of 2W + G, the maximum limit for G must be W. However, two valleys of sensitivity appear on both sides of the gap. Setting a more limited range for the gap as G < W, which is desirable for filling in the sensitivity valleys, results in not only a shortened gap, but also a shortened axial FOV. In this paper, we propose an alternative method for improving the uniformity of sensitivity by shifting two detector rings axially closer or further apart at the same velocity to each other. In addition, image reconstruction of the OpenPET is an incomplete problem, and low-frequency components are missing in the gap. Therefore, the proposed method is also expected to improve the conditions for the inverse problem. We simulated an OpenPET scanner which measures events simultaneously by shifting the detector rings. The results showed that the right and left peaks of the sensitivity approach each other upon shifting of the detector rings, and these valleys of sensitivity are effectively recovered. The results also showed that distortion, which is observed for objects containing low-frequency components, is reduced. Larger detector shifts allow a more uniform axial distribution of sensitivity and a higher image quality, but at the cost of a smaller minimum gap. Therefore, an appropriate detector-shifting pattern should be determined based on the desired scanner application.

Poly[bis(phenethyl-ammonium) [di-bromido-plumbate(II)]-di-µ-bromido]].

Crystals of the title compound, {(C(6)H(5)C(2)H(4)NH(3))(2)[PbBr(4)]}(n), were grown at room temperature from a solution in N,N-dimethyl-formamide (DMF) using nitro-methane as the poor solvent. This perovskite-type organic-inorganic hybrid compound consists of well ordered sheets of corner-sharing disordered PbBr(6) octa-hedra separated by bilayers of phenethyl-ammonium cations. The octa-hedra are rotated and tilted due to N-H⋯Br hydrogen bonds with the ammonium groups, generating a superstructure in the unit cell similar to that of the tetra-chloridoplumbate (C(6)H(5)C(2)H(4)NH(3))(2)[PbCl(4)].

A proposal of an open PET geometry.

The long patient port of a PET scanner tends to put stress on patients, especially patients with claustrophobia. It also prevents doctors and technicians from taking care of patients during scanning. In this paper, we proposed an 'open PET' geometry, which consists of two axially separated detector rings. A long and continuous field-of-view (FOV) including a 360 degrees opened gap between two detector rings can be imaged enabling a fully 3D image reconstruction of all the possible lines-of-response. The open PET will become practical if iterative image reconstruction methods are applied even though image reconstruction of the open PET is analytically an incomplete problem. First we implemented a 'masked' 3D ordered subset expectation maximization (OS-EM) in which the system matrix was obtained from a long 'gapless' scanner by applying a mask to detectors corresponding to the open space. Next, in order to evaluate imaging performance of the proposed open PET geometry, we simulated a dual HR+ scanner (ring diameter of D = 827 mm, axial length of W = 154 mm x 2) separated by a variable gap. The gap W was the maximum limit to have axially continuous FOV of 3W though the maximum diameter of FOV at the central slice was limited to D/2. Artifacts, observed on both sides of the open space when the gap exceeded W, were effectively reduced by inserting detectors partially into unnecessary open spaces. We also tested the open PET geometry using experimental data obtained by the jPET-D4. The jPET-D4 is a prototype brain scanner, which has 5 rings of 24 detector blocks. We simulated the open jPET-D4 with a gap of 66 mm by eliminating 1 block-ring from experimental data. Although some artifacts were seen at both ends of the opened gap, very similar images were obtained with and without the gap. The proposed open PET geometry is expected to lead to realization of in-beam PET, which is a method for an in situ monitoring of charged particle therapy, by letting the beams pass through the gap. The proposed open PET geometry will also allow simultaneous PET/CT measurements of the same PET FOV as the CT FOV, in contrast to the conventional PET/CT where each FOV is separated by several tens of centimeters.

Performance evaluation for 120 four-layer DOI block detectors of the jPET-D4.

The jPET-D4 is a brain positron emission tomography (PET) scanner that we have developed to meet user demands for high sensitivity and high spatial resolution. For this scanner, we developed a four-layer depth-of-interaction (DOI) detector. The four-layer DOI detector is a key component for the jPET-D4, its performance has great influence on the overall system performance. Previously, we reported the original technique for encoding four-layer DOI. Here, we introduce the final design of the jPET-D4 detector and present the results of an investigation on uniformity in performance of the detector. The performance evaluation was done over the 120 DOI crystal blocks for the detectors, which are to be assembled into the jPET-D4 scanner. We also introduce the crystal assembly method, which is simple enough, even though each DOI crystal block is composed of 1,024 crystal elements. The jPET-D4 detector consists of four layers of 16 x 16 Gd(2)SiO(5) (GSO) crystals and a 256-channel flat-panel position-sensitive photomultiplier tube (256ch FP-PMT). To identify scintillated crystals in the four-layer DOI detector, we use pulse shape discrimination and position discrimination on the two-dimensional (2D) position histogram. For pulse shape discrimination, two kinds of GSO crystals that show different scintillation decay time constants are used in the upper two and lower two layers, respectively. Proper reflector arrangement in the crystal block then allows the scintillated crystals to be identified in these two-layer groupings with two 2D position histograms. We produced the 120 DOI crystal blocks for the jPET-D4 system, and measured their characteristics such as the accuracy of pulse shape discrimination, energy resolution, and the pulse height of the full energy peak. The results show a satisfactory and uniform performance of the four-layer DOI crystal blocks; for example, misidentification rate in each GSO layer is <5% based on pulse shape discrimination, the averaged energy resolutions for the central four crystals of the first (farthest from the FP-PMT), second, third, and 4th layers are 15.7 +/- 1.0, 15.8 +/- 0.6, 17.7 +/- 1.2, and 17.3 +/- 1.4%, respectively, and variation in pulse height of the full energy peak among the four layers is <5% on average.

Annihilation photon acollinearity in PET: volunteer and phantom FDG studies.

Annihilation photon acollinearity is a fundamental but little investigated problem in positron emission tomography (PET). In this paper, the cause of the angular deviation from 180.00 degrees is described as well as how to evaluate it under conditions of a spatially distributed radiation source and a limited acquisition time for the human body. A relationship between the shape of the photopeak spectrum and the angular distribution is formulated using conservation laws of momentum and energy over the pair annihilation. Then the formula is used to evaluate the acollinearity for a pool phantom and the human body with FDG injected. The angular distribution for the pool phantom agrees well with that for pure water which had been directly measured by Colombino et al in 1965 (Nuovo Cimento 38 707-23), and also with that for the human body determined in this study. Pure water can be considered as a good approximation of the human body regarding the angular deviation. The blurring coefficient to be multiplied by the ring diameter in calculations of the PET spatial resolution is experimentally determined for the first time as 0.00243 +/- 0.00014; this is 10% larger than the value widely used by investigators.

Application of accelerators for the research and development of scintillators.

We introduce experimental systems which use accelerators to evaluate scintillation properties such as scintillation intensity, wavelength, and lifetime. A single crystal of good optical quality is often unavailable during early stages in the research and development (R&D) of new scintillator materials. Because of their beams' high excitation power and/or low penetration depth, accelerators facilitate estimation of the properties of early samples which may only be available as powders, thin films, and very small crystals. We constructed a scintillation spectrum measurement system that uses a Van de Graaff accelerator and an optical multichannel analyzer to estimate the relative scintillation intensity. In addition, we constructed a scintillation time profile measurement system that uses an electron linear accelerator and a femtosecond streak camera or a microchannel plate photomultiplier tube followed by a digital oscilloscope to determine the scintillation lifetimes. The time resolution is approximately 10 ps. The scintillation spectra or time profiles can be obtained in a significantly shorter acquisition time in comparison with that required by conventional measuring systems. The advantages of the systems described in this study can significantly promote the R&D of novel scintillator materials.

Evaluation of static physics performance of the jPET-D4 by Monte Carlo simulations.

The jPET-D4 is the first PET scanner to introduce a unique four-layer depth-of-interaction (DOI) detector scheme in order to achieve high sensitivity and uniform high spatial resolution. This paper compares measurement and Monte Carlo simulation results of the static physics performance of this prototype research PET scanner. Measurement results include single and coincidence energy spectra, point and line source sensitivities, axial sensitivity profile (slice profile) and scatter fraction. We use GATE (Geant4 application for tomographic emission) as a Monte Carlo radiation transport model. Experimental results are reproduced well by the simulation model with reasonable assumptions on characteristic responses of the DOI detectors. In a previous study, the jPET-D4 was shown to provide a uniform spatial resolution as good as 3 mm (FHWM). In the present study, we demonstrate that a high sensitivity, 11.3 +/- 0.5%, is provided at the FOV centre. However, about three-fourths of this sensitivity is related to multiple-crystal events, for which some misidentification of the crystal cannot be avoided. Therefore, it is crucial to develop a more efficient way to identify the crystal of interaction and to reduce misidentification in order to make use of these high performance values simultaneously. We expect that effective sensitivity can be improved by replacing the GSO crystals with more absorptive crystals such as BGO and LSO. The results we describe here are essential to take full advantage of the next generation PET systems that have DOI recognition capability.