In-vivo correlations of fluorescent or radioisotope glucose-analogs in imaging cancer metabolism.

OBJECTIVE: To investigate the impact of different tracer modifications on the imaging of cancer metabolism, focusing on the comparison of fluorescent glucose-analog tracers (2-NBDG and 2-DG-750) and the radiolabeled tracer 18F-FDG in both in-vitro and in-vivo settings. METHODS: We conducted an in-vitro comparative study using four cancer cell lines, each with unique glucose uptake characteristics. The study involved direct comparison of three tracers: 2-NBDG, 2-DG-750 and 18F-FDG, examining their internalization behaviors, metabolic functionality and localization effects in cancer metabolism imaging. RESULTS: The study revealed that each tracer exhibits distinct internalization behaviors correlated with imaging label size and type. 18F-FDG showed the highest uptake efficiency. Fluorescent molecules were found to accumulate in tumors primarily due to hydrophobic interactions and possible aggregation, indicating inefficiency in metabolism and suitability for imaging metabolic phenomena when compared to radiolabeled biomolecules. CONCLUSION: Our findings demonstrate that despite certain impracticalities, nuclear imaging, particularly using radiolabeled biomolecules like 18F-FDG, offers significant potential for accurately capturing biological phenomena. This is crucial for future advancements in both clinical and research settings. The study emphasizes the limitations of fluorescent molecules in imaging metabolic activities due to their inefficient metabolism and aggregation tendencies.

Path-Planning System for Radioisotope Identification Devices Using 4π Gamma Imaging Based on Random Forest Analysis.

We developed a path-planning system for radiation source identification devices using 4π gamma imaging. The estimated source location and activity were calculated by an integrated simulation model by using 4π gamma images at multiple measurement positions. Using these calculated values, a prediction model to estimate the probability of identification at the next measurement position was created by via random forest analysis. The path-planning system based on the prediction model was verified by integrated simulation and experiment for a 137Cs point source. The results showed that 137Cs point sources were identified using the few measurement positions suggested by the path-planning system.

Periodic sea-level oscillation in Tokyo Bay detected with the Tokyo-Bay seafloor hyper-kilometric submarine deep detector (TS-HKMSDD).

Meteorological-tsunami-like (or meteotsunami-like) periodic oscillation was muographically detected with the Tokyo-Bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) deployed in the underwater highway called the Trans-Tokyo Bay Expressway or Tokyo Bay Aqua-Line (TBAL). It was detected right after the arrival of the 2021 Typhoon-16 that passed through the region 400 km south of the bay. The measured oscillation period and decay time were respectively 3 h and 10 h. These measurements were found to be consistent with previous tide gauge measurements. Meteotsunamis are known to take place in bays and lakes, and the temporal and spatial characteristics of meteotsunamis are similar to seismic tsunamis. However, their generation and propagation mechanisms are not well understood. The current result indicates that a combination of muography and trans-bay or trans-lake underwater tunnels will offer an additional tool to measure meteotsunamis at locations where tide gauges are unavailable.

First results of undersea muography with the Tokyo-Bay Seafloor Hyper-Kilometric Submarine Deep Detector.

Tidal measurements are of great significance since they may provide us with essential data to apply towards protection of coastal communities and sea traffic. Currently, tide gauge stations and laser altimetry are commonly used for these measurements. On the other hand, muography sensors can be located underneath the seafloor inside an undersea tunnel where electric and telecommunication infrastructures are more readily available. In this work, the world's first under-seafloor particle detector array called the Tokyo-bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) was deployed underneath the Tokyo-Bay seafloor for conducting submarine muography. The resultant 80-day consecutive time-sequential muographic data were converted to the tidal levels based on the parameters determined from the first-day astronomical tide height (ATH) data. The standard deviation between ATH and muographic results for the rest of a 79-day measurement period was 12.85 cm. We anticipate that if the length of the TS-HKMSDD is extended from 100 m to a full-scale as large as 9.6 km to provide continuous tidal information along the tunnel, this muography application will become an established standard, demonstrating its effectiveness as practical tide monitor for this heavy traffic waterway in Tokyo and in other important sea traffic areas worldwide.

Simultaneous in vivo imaging with PET and SPECT tracers using a Compton-PET hybrid camera.

Positron-emission tomography (PET) and single-photon-emission computed tomography (SPECT) are well-established nuclear-medicine imaging methods used in modern medical diagnoses. Combining PET with 18F-fluorodeoxyglucose (FDG) and SPECT with an 111In-labelled ligand provides clinicians with information about the aggressiveness and specific types of tumors. However, it is difficult to integrate a SPECT system with a PET system because SPECT requires a collimator. Herein, we describe a novel method that provides simultaneous imaging with PET and SPECT nuclides by combining PET imaging and Compton imaging. The latter is an imaging method that utilizes Compton scattering to visualize gamma rays over a wide range of energies without requiring a collimator. Using Compton imaging with SPECT nuclides, instead of the conventional SPECT imaging method, enables PET imaging and Compton imaging to be performed with one system. In this research, we have demonstrated simultaneous in vivo imaging of a tumor-bearing mouse injected with 18F-FDG and an 111In-antibody by using a prototype Compton-PET hybrid camera. We have succeeded in visualizing accumulations of 18F-FDG and 111In-antibody by performing PET imaging and Compton imaging simultaneously. As simultaneous imaging utilizes the same coordinate axes, it is expected to improve the accuracy of diagnoses.

Simultaneous measurements of single gamma ray of 131I and annihilation radiation of 18F with Compton PET hybrid camera.

In internal 131I therapy for thyroid cancer, a decision to continue treatment is made by comparing 131I scintigraphy and [18F]FDG-PET. However, with current SPECT and PET systems, simultaneous imaging of diagnostic PET nuclides and therapeutic 131I nuclides has not been achieved so far. Therefore, we demonstrated that the recently developed Compton PET hybrid camera with Ce:Gd3(Al,Ga)5O12 (GAGG)- Silicon Photomultiplier(SiPM) scintillation detectors can be used to simultaneously image 131I Compton image and 18F PET image.

Simultaneous multi-nuclide imaging via double-photon coincidence method with parallel hole collimators.

Multi-tracer imaging can provide useful information in the definitive diagnosis and research of medical, biological, and pharmaceutical sciences. Single-photon emission computed tomography (SPECT) is one of the nuclear medicine imaging modalities widely used for diagnosis or medical research and has a multi-tracer imaging capability. One of the drawbacks of multi-tracer imaging is crosstalk from other gamma rays, which affects the reconstructed image. Scattering correction methods, such as the dual- and triple-energy window methods, are used for conventional SPECT imaging to reduce the background caused by the crosstalk. This study proposes another crosstalk reduction method. Some nuclides emit two or more gamma rays through intermediate levels. Thus, detecting these gamma rays with the coincidence method allows us to distinguish a true gamma ray signal and a background signal. The nuclide position can be estimated at the intersection of two gamma rays using collimators. We demonstrate herein simultaneous 111In and 177Lu imaging via the double-photon coincidence method using GAGG detectors and parallel hole collimators. The double-photon coincidence method greatly reduces the background caused by other gamma rays and offers higher-quality images than does conventional imaging.

Evaluation of dual-ended readout GAGG-based DOI-PET detectors with different surface treatments.

PURPOSE: Parallax error is a major issue in small animal positron emission tomography (PET) scanners which are used in preclinical studies or detailed scanning of human organs. Several methods have been proposed and investigated to reduce this radial artifact in PET images by estimating the depth of interaction (DOI) of 511-keV photons in the crystal. Among all, the dual-ended readout method seems to be very simple and effective as it does not have any fabrication and readout complications. In the past, some studies suggested that increasing the roughness of crystal lateral surfaces improves DOI resolution. In this paper, this was experimentally examined for four Ce:GAGG crystals with different surface structures. METHODS: Four 1.2 × 1.2 × 20 mm3 GAGG crystals with following surface treatment were examined: polished with optical finishing, fine grinding (using a fine surface grinding machine), fine cutting (no treatment), and coarse cutting (no treatment). These crystals were coupled individually to two SiPMs for dual-ended readout and placed in a coincidence detection circuit for electronic collimation of 511 keV incidents. The crystals were compared in terms of energy response and DOI estimation capability. RESULTS: DOI function for each crystal was extracted and FWHM DOI resolution was calculated. DOI resolution for the polished crystal varied in the range of 0.54-4.14 mm throughout the length of the crystal due to its nonlinear DOI function. The fine grinding crystal showed a linear DOI function within the dynamic range of (-0.75, 0.75), and its DOI resolution varied in the range of 1.24-1.50 mm (1.37 ± 0.13 mm DOI resolution). The fine-cut crystal had almost a linear DOI function and a wider dynamic range of (-0.85, 0.85) and therefore the best performance with 1.2 ± 0.08 mm DOI resolution. However, for the crystal with the roughest surface (coarse-cut crystal), even though the dynamic range expanded to (-0.95, 0.95), its DOI function became nonlinear resulting in 1.24 ± 0.28 mm DOI resolution. This means there is an optimum surface roughness to provide the crystal with the best DOI capability. The pulse-height spectrum measured at each depth was used as a measure to compare the energy performance of the four crystals. The photopeak of 511 keV was observed for all depths, all crystals. The photopeak position for the coarse-cut crystal had extensive depth dependency which results in poorer energy resolution unless the energy window is calibrated for each depth. This variation of photopeak for the fine-cut and fine grinding crystals was comparable with that of polished crystal. CONCLUSION: This paper reports 1.2 ± 0.08 mm FWHM DOI resolution for a fine-cut unpolished crystal. This resolution is as narrow as the crystal width, resulting in the complete elimination of parallax error in PET images. Results suggest that there is an optimum roughness for the best performance of the dual-ended method and further increase in the roughness, degrades DOI resolution. Thanks to the high light yield of GAGG, the energy performance of the fine-cut crystal is acceptable, and the depth dependency of the spectrum is negligible.

Development and evaluation of a prototype detector for an intraoperative laparoscopic coincidence imaging system with PET tracers.

PURPOSE: Conventional positron emission tomography can be used only preoperatively to identify lymph node metastases, and hence, these growths are difficult to locate intraoperatively. Previously, an intraoperative laparoscopic coincidence imaging system, with an external fixed detector array and a detector probe that can be moved and inserted into the stomach, was proposed to identify lymph node metastases during stomach cancer surgery. This paper proposes a prototype detector for this system. METHODS: GAGG:Ce (Gd3Al2Ga3O12:Ce) scintillator crystals, one to one coupled with silicon photomultipliers (SiPMs), were used to identify 511 keV photons. An optical tracking system followed the position and orientation of the movable detector. SiPM outputs were read out by time-over-threshold (TOT)-based application-specific integrated circuits, which converted the electrical charges into digital pulses. To identify the arrival time, channel number, and pulse width, which indicate the energy information of each TOT output, a data acquisition system was developed based on a field-programmable gate array. RESULTS: The spatial resolution of the reconstructed images in lateral direction was better than 7 mm, but that of depth direction was limited, owing to inadequate projections. The prototype successfully reconstructed 44 kBq 18F-fluorodeoxyglucose sources during a 2-min scan. CONCLUSION: We developed a prototype detector for an intraoperative laparoscopic coincidence imaging system. The prototype detector was evaluated successfully, and the produced images were similar to those obtained in the simulation results, thereby suggesting that this method offers a new possibility of imaging lymph node metastases intraoperatively.

A PET detector prototype based on digital SiPMs and GAGG scintillators.

Silicon Photomultipliers (SiPM) are interesting light sensors for Positron Emission Tomography (PET). The detector signal of analog SiPMs is the total charge of all fired cells. Energy and time information have to be determined with dedicated readout electronics. Philips Digital Photon Counting has developed a SiPM with added electronics on cell level delivering a digital value of the time stamp and number of fired cells. These so called Digital Photon Counters (DPC) are fully digital devices. In this study, the feasibility of using DPCs in combination with LYSO (Lutetium Yttrium Oxyorthosilicate) and GAGG (Gadolinium Aluminum Gallium Garnet) scintillators for PET is tested. Each DPC module has 64 channels with 3.2 × 3.8775 mm(2), comprising 3200 cells each. GAGG is a recently developed scintillator (Zeff = 54, 6.63 g cm(-3), 520 nm peak emission, 46 000 photons MeV(-1), 88 ns (92%) and 230 ns (8%) decay times, non-hygroscopic, chemically and mechanically stable). Individual crystals of 2 × 2 × 6 mm(3) were coupled onto each DPC pixel. LYSO coupled to the DPC results in a coincidence time resolution (CTR) of 171 ps FWHM and an energy resolution of 12.6% FWHM at 511 keV. Using GAGG, coincidence timing is 310 ps FWHM and energy resolution is 8.5% FWHM. A PET detector prototype with 2 DPCs equipped with a GAGG array matching the pixel size (3.2 × 3.8775 × 8 mm(3)) was assembled. To emulate a ring of 10 modules, objects are rotated in the field of view. CTR of the PET is 619 ps and energy resolution is 9.2% FWHM. The iterative MLEM reconstruction is based on system matrices calculated with an analytical detector response function model. A phantom with rods of different diameters filled with (18)F was used for tomographic tests.

EGS5 simulations to design a Ce:GAGG scintillator based Compton camera.

Ce(+3): Gd3Al2Ga3O12 (Ce:GAGG) is expected to be promising scintillator for PET, SPECT, and gamma camera applications because of its attractive properties. We designed a Compton camera based on Ce:GAGG, both as scatterer and absorber, for imaging and radioactivity measurement of point sources. The two important parameters sensitivity and spatial resolution are determined for 4 × 4 pixels, each pixel of size 1 × 1 cm(2), for both scatterer and absorber. Our main focus in this paper is to image a distant source for which sensitivity is of prime importance. High sensitivity and light weight are two important advantages of Compton camera for distant source imaging and the availability of Ce:GAGG 3 × 3 mm(2) pixel size is expected to give a spatial resolution of ~ 5 mm for medical applications as well.

Measurement of radioactivity concentration in blood by using newly developed ToT LuAG-APD based small animal PET tomograph.

In order to obtain plasma time activity curve (PTAC), input function for almost all quantitative PET studies, patient blood is sampled manually from the artery or vein which has various drawbacks. Recently a novel compact Time over Threshold (ToT) based Pr:LuAG-APD animal PET tomograph is developed in our laboratory which has 10% energy resolution, 4.2 ns time resolution and 1.76 mm spatial resolution. The measured value of spatial resolution shows much promise for imaging the blood vascular, i.e; artery of diameter 2.3-2.4mm, and hence, to measure PTAC for quantitative PET studies. To find the measurement time required to obtain reasonable counts for image reconstruction, the most important parameter is the sensitivity of the system. Usually small animal PET systems are characterized by using a point source in air. We used Electron Gamma Shower 5 (EGS5) code to simulate a point source at different positions inside the sensitive volume of tomograph and the axial and radial variations in the sensitivity are studied in air and phantom equivalent water cylinder. An average sensitivity difference of 34% in axial direction and 24.6% in radial direction is observed when point source is displaced inside water cylinder instead of air.