Multimodal laparoscopic coincidence gamma imaging system for near-infrared fluorescence guided surgery: a preclinical study.

Purpose: Minimally invasive surgery has advantages in terms of quality of life and patient outcomes. Recently, near-infrared (NIR) fluorescence guided surgery has widely used for preclinical and clinical trials. However, NIR fluorescence has a maximum penetration capability of 10 mm. Radiographic imaging can be a solution to overcome the depth issue of NIR fluorescence. For this reason, the performance of the multimodal imaging system, which integrates annihilation gamma (511 keV) rays, NIR fluorescence, and color images, was evaluated. Approach: The multimodal imaging system consisted of a laparoscopic module, containing an internal detector for annihilation gamma events and cameras for optical imaging, and a flat module for coincidence detection with the internal detector. The acquired images were integrated by an algorithm with post image processing and registration. To evaluate the performance of the proposed multimodal imaging system, the images of a resolution target, a square bar target filled with a fluorescence dye, and a sodium-22 point source were analyzed. A preclinical test for axillary sentinel lymph node (SLN) biopsy with a rat model was conducted. Results: The spatial resolution of color images was equivalent to 4 lp/mm. The modulation transfer function of NIR fluorescence at 1 lp/mm was 0.83. The 511 keV gamma sensitivity and spatial resolution of the point source were 0.54 cps/kBq and 2.1 mm, respectively. The image of 511 keV gamma rays showed almost the same intensity regardless of the thickness of the tissue phantom. In the preclinical test, an integrated image of the SLN sample of the rat model was obtained with the proposed multimodal imaging system. Conclusions: With the proposed laparoscopic system, a merged image of the sample was obtained with the rat model. The annihilation gamma rays showed penetration capability with the tissue-mimicking phantom superior to that of NIR fluorescence.

SiPM-based gamma detector with a central GRIN lens for a visible/NIRF/gamma multi-modal laparoscope.

Intraoperative imaging has been studied using conventional devices such as near infrared (NIR) optical probes and gamma probes. However, these devices have limited depth penetration and spatial resolution. In a previous study, we realized a multi-modal endoscopic system. However, charge-coupled device (CCD)-based gamma imaging required long acquisition times and lacked gamma energy information. A silicon photomultiplier (SiPM)-based gamma detector is implemented in a multi-modal laparoscope herein. A gradient index (GRIN) lens and CCD are used to transfer and readout visible and NIR photons. The feasibility of in-vivo sentinel lymph node (SLN) mapping was successfully performed with the proposed system.

Crystal surface and reflector optimization for the SiPM-based dual-ended readout TOF-DOI PET detector.

Silicon photomultipliers (SiPMs) are now widely used for positron emission tomography (PET) applications because of their high gain and low noise characteristics. The PET image quality has been improved with the advancement of time-of-flight (TOF) and depth-of-interaction (DOI) measurement techniques. For brain-dedicated PET systems, both TOF and DOI information are beneficial for enhancing the reconstructed PET image quality. In a previous study, we proposed SiPM-based dual-ended readout PET detectors that used a mean time method to achieve coincidence timing resolution (CTR) of 349 ps and DOI resolution of 2.9 mm. However, the coincidence timing resolution (CTR) was worse than 300 ps since the crystal surface and the reflector type were not optimized. This study aimed at investigating the optimal crystal surface treatment and the reflector material to achieve a sub-200 ps CTR and sub-3 mm DOI resolution with a dual-ended readout PET detector using an LYSO crystal (2.9 × 2.9 × 20 mm3). The scintillation light inside the LYSO crystal was read out by two SiPMs using the dual-ended readout method. The CTR and DOI resolution were measured with two different crystal surfaces (polished and saw-cut) and three different reflector material scenarios of ESR without grease (i.e., air coupling), ESR with optical grease and Teflon. We digitized the timing and energy signals by using a V775N TDC module (35 ps bit-1) and V965 QDC module, respectively. The combination of the saw-cut LYSO crystal and the ESR with air coupling resulted in the best CTR (188 ± 32 ps) and DOI resolution (2.9 ± 0.2 mm) with the dual-ended readout configuration. We concluded the dual-ended readout method in combination with the saw-cut crystal and the ESR reflector with air coupling can provide a sub-200 ps CTR and sub-3.0 mm DOI resolution simultaneously.

Proof-of-concept of a multimodal laparoscope for simultaneous NIR/gamma/visible imaging using wavelength division multiplexing.

An optical/nuclear hybrid surgical technique using ICG-99mTc-nanocolloid can improve lesion detectability by detecting both fluorescence and gamma signals. However, a hybrid multimodal laparoscope that can obtain both NIR and gamma images is not available yet. In this work, we present a proof-of-concept study of a prototype multimodal laparoscope that can provide simultaneous NIR/gamma/visible imaging using wavelength division multiplexing. The performances of optical and gamma imaging were evaluated using a USAF 1951 negative resolution target and 99mTc-filled tumor-like sources, respectively. Simultaneous NIR/gamma/visible images of two Eppendorf tubes containing a mixture of 99mTc-ICG are presented.

Lens implementation on the GATE Monte Carlo toolkit for optical imaging simulation.

Optical imaging techniques are widely used for in vivo preclinical studies, and it is well known that the Geant4 Application for Emission Tomography (GATE) can be employed for the Monte Carlo (MC) modeling of light transport inside heterogeneous tissues. However, the GATE MC toolkit is limited in that it does not yet include optical lens implementation, even though this is required for a more realistic optical imaging simulation. We describe our implementation of a biconvex lens into the GATE MC toolkit to improve both the sensitivity and spatial resolution for optical imaging simulation. The lens implemented into the GATE was validated against the ZEMAX optical simulation using an US air force 1951 resolution target. The ray diagrams and the charge-coupled device images of the GATE optical simulation agreed with the ZEMAX optical simulation results. In conclusion, the use of a lens on the GATE optical simulation could improve the image quality of bioluminescence and fluorescence significantly as compared with pinhole optics.

A feasibility study of an integrated NIR/gamma/visible imaging system for endoscopic sentinel lymph node mapping.

PURPOSE: The aim of this study is to integrate NIR, gamma, and visible imaging tools into a single endoscopic system to overcome the limitation of NIR using gamma imaging and to demonstrate the feasibility of endoscopic NIR/gamma/visible fusion imaging for sentinel lymph node (SLN) mapping with a small animal. METHODS: The endoscopic NIR/gamma/visible imaging system consists of a tungsten pinhole collimator, a plastic focusing lens, a BGO crystal (11 × 11 × 2 mm3 ), a fiber-optic taper (front = 11 × 11 mm2 , end = 4 × 4 mm2 ), a 122-cm long endoscopic fiber bundle, an NIR emission filter, a relay lens, and a CCD camera. A custom-made Derenzo-like phantom filled with a mixture of 99m Tc and indocyanine green (ICG) was used to assess the spatial resolution of the NIR and gamma images. The ICG fluorophore was excited using a light-emitting diode (LED) with an excitation filter (723-758 nm), and the emitted fluorescence photons were detected with an emission filter (780-820 nm) for a duration of 100 ms. Subsequently, the 99m Tc distribution in the phantom was imaged for 3 min. The feasibility of in vivo SLN mapping with a mouse was investigated by injecting a mixture of 99m Tc-antimony sulfur colloid (12 MBq) and ICG (0.1 mL) into the right paw of the mouse (C57/B6) subcutaneously. After one hour, NIR, gamma, and visible images were acquired sequentially. Subsequently, the dissected SLN was imaged in the same way as the in vivo SLN mapping. RESULTS: The NIR, gamma, and visible images of the Derenzo-like phantom can be obtained with the proposed endoscopic imaging system. The NIR/gamma/visible fusion image of the SLN showed a good correlation among the NIR, gamma, and visible images both for the in vivo and ex vivo imaging. CONCLUSION: We demonstrated the feasibility of the integrated NIR/gamma/visible imaging system using a single endoscopic fiber bundle. In future, we plan to investigate miniaturization of the endoscope head and simultaneous NIR/gamma/visible imaging with dichroic mirrors and three CCD cameras.

An engagement factor for caregiver radiation dose assessment with radioiodine treatment.

This study aims to suggest ways to better manage thyroid cancer patients treated with high- and low-activity radioiodine ((131)I) by assessing external radiation doses to family members and caregivers and the level of radiation in the surrounding environment. The radiation doses to caregivers of 33 inpatients (who were quarantined in the hospital for 2-3 d after treatment) and 31 outpatients who received radioiodine treatment after thyroidectomy were measured using passive thermoluminescence dosemeters. In this study, 33 inpatients were administered high-activity (100-200 mCi) (131)I, and 31 outpatients were administered low-activity (30 mCi) (131)I. The average doses to caregivers were measured at 0.61 mSv for outpatients and 0.16 mSv for inpatients. The total integrated dose of the recovery (recuperation) rooms where the patients stayed after release from hospital was measured to be 0.83 mSv for outpatients and 0.23 mSv for inpatients. To reflect the degree of engagement between the caregiver and the patient, considering the duration and distance between two during exposure, the authors used the engagement factor introduced by Jeong et al. (Estimation of external radiation dose to caregivers of patients treated with radioiodine after thyroidectomy. Health Phys 2014; 106: :466-474.). This study presents a new engagement factor (K-value) of 0.82 obtained from the radiation doses to caregivers of both in- and out-patients treated with high- and low-activity radioiodine, and based on this new value, this study presented a new predicted dose for caregivers. A patient treated with high-activity radioiodine can be released after 24 h of isolation, whereas outpatients treated with low-activity radioiodine should be isolated for at least 12 h.

SiPM-PET with a short optical fiber bundle for simultaneous PET-MR imaging.

For positron emission tomography (PET) inserts to magnetic resonance imaging (MRI) applications, optical fibers have been used for some time to transfer scintillation photons to photomultiplier tubes positioned outside the fringe magnetic field. We previously proposed a novel utilization of an optical fiber for good radio frequency (RF) transmission from body coils to an imaging object. Optical fiber bundles between silicon photomultipliers (SiPM) and scintillation crystals provide an increased spacing between RF-shielded electronics boxes, facilitating RF passage from the body RF coils to imaging objects. In this paper, we present test results of a SiPM-PET system with a short optical fiber bundle for simultaneous PET-MR imaging. We built the SiPM-PET system which consisted of 12 SiPM-PET modules; each module was assembled with a lutetium yttrium oxyorthosilicatecrystal block, a 31 mm optical fiber bundle, a Hamamatsu multi-pixel photon counter S11064-050P and a signal processing box shielded with copper. The SiPM-PET system, with a face-to-face distance of 71 mm, was placed inside a 3 T MRI. A small surface coil placed inside the SiPM-PET system was used to receive the signal from phantoms while the body RF coil transmitted the RF pulses. The SiPM-PET system showed little performance degradation during the simultaneous PET-MR imaging and it caused no significant degradation of MR images with turbo spin echo (TSE), gradient echo or 3D spoiled gradient recalled sequences. Echo planar imaging MR images with and without the SiPM-PET inside the MR scanner were significantly worse than the images obtained with the TSE sequence.

Initial results of simultaneous PET/MRI experiments with an MRI-compatible silicon photomultiplier PET scanner.

UNLABELLED: The most investigated semiconductor photosensor for MRI-compatible PET detectors is the avalanche photodiode (APD). However, the silicon photomultiplier (SiPM), also called the Geiger-mode APD, is gaining attention in the development of the next generation of PET/MRI systems because the SiPM has much better performance than the APD. We have developed an MRI-compatible PET system based on multichannel SiPM arrays to allow simultaneous PET/MRI. METHODS: The SiPM PET scanner consists of 12 detector modules with a ring diameter of 13.6 cm and an axial extent of 3.2 cm. In each detector module, 4 multichannel SiPM arrays (with 4 × 4 channels arranged in a 2 × 2 array to yield 8 × 8 channels) were coupled with 20 × 18 Lu(1.9)Gd(0.1)SiO(5):Ce crystals (each crystal is 1.5 × 1.5 × 7 mm) and mounted on a charge division network for multiplexing 64 signals into 4 position signals. Each detector module was enclosed in a shielding box to reduce interference between the PET and MRI scanners, and the temperature inside the box was monitored for correction of the temperature-dependent gain variation of the SiPM. The PET detector signal was routed to the outside of the MRI room and processed with a field programmable gate array-based data acquisition system. MRI compatibility tests and simultaneous PET/MRI acquisitions were performed inside a 3-T clinical MRI system with 4-cm loop receiver coils that were built into the SiPM PET scanner. Interference between the imaging systems was investigated, and phantom and mouse experiments were performed. RESULTS: No radiofrequency interference on the PET signal or degradation in the energy spectrum and flood map was shown during simultaneous PET/MRI. The quality of the MRI scans acquired with and without the operating PET showed only slight degradation. The results of phantom and mouse experiments confirmed the feasibility of this system for simultaneous PET/MRI. CONCLUSION: Simultaneous PET/MRI was possible with a multichannel SiPM-based PET scanner, with no radiofrequency interference on PET signals or images and only slight degradation of the MRI scans.

A novel compensation method for the anode gain non-uniformity of multi-anode photomultiplier tubes.

The position-sensitive multi-anode photomultiplier tube (MA-PMT) is widely used in high-resolution scintillation detectors. However, the anode gain nonuniformity of this device is a limiting factor that degrades the intrinsic performance of the detector module. The aim of this work was to develop a gain compensation method for the MA-PMT and evaluate the resulting enhancement in the performance of the detector. The method employs a circuit that is composed only of resistors and is placed between the MA-PMT and a resistive charge division network (RCN) used for position encoding. The goal of the circuit is to divide the output current from each anode, so the same current flows into the RCN regardless of the anode gain. The current division is controlled by the combination of a fixed-value series resistor with an output impedance that is much larger than the input impedance of the RCN, and a parallel resistor, which detours part of the current to ground. PSpice simulations of the compensation circuit and the RCN were performed to determine optimal values for the compensation resistors when used with Hamamatsu H8500 MAPMTs. The intrinsic characteristics of a detector module consisting of this MA-PMT and a lutetium-gadolinium-oxyorthosilicate (LGSO) crystal array were tested with and without the gain compensation method. In simulation, the average coefficient of variation and max/min ratio decreased from 15.7% to 2.7% and 2.0 to 1.2, respectively. In the flood map of the LGSO-H8500 detector, the uniformity of the photopeak position for individual crystals and the energy resolution were much improved. The feasibility of the method was shown by applying it to an octagonal prototype positron emission tomography scanner.

Development of small-animal PET prototype using silicon photomultiplier (SiPM): initial results of phantom and animal imaging studies.

UNLABELLED: Silicon photomultiplier (SiPM; also called a Geiger-mode avalanche photodiode) is a promising semiconductor photosensor in PET and PET/MRI because it is intrinsically MRI-compatible and has internal gain and timing properties comparable to those of a photomultiplier tube. In this study, we have developed a small-animal PET system using SiPMs and lutetium gadolinium oxyorthosilicate (LGSO) crystals and performed physical evaluation and animal imaging studies to show the feasibility of this system. METHODS: The SiPM PET system consists of 8 detectors, each of which comprises 2 × 6 SiPMs and 4 × 13 LGSO crystals. Each crystal has dimensions of 1.5 × 1.5 × 7 mm. The crystal face-to-face diameter and axial field of view are 6.0 cm and 6.5 mm, respectively. Bias voltage is applied to each SiPM using a finely controlled voltage supply because the gain of the SiPM strongly depends on the supply voltage. The physical characteristics were studied by measuring energy resolution, sensitivity, and spatial resolution. Various mouse and rat images were obtained to study the feasibility of the SiPM PET system in in vivo animal studies. Reconstructed PET images using a maximum-likelihood expectation maximization algorithm were coregistered with animal CT images. RESULTS: All individual LGSO crystals within the detectors were clearly distinguishable in flood images obtained by irradiating the detector using a (22)Na point source. The energy resolution for individual crystals was 25.8% ± 2.6% on average for 511-keV photopeaks. The spatial resolution measured with the (22)Na point source in a warm background was 1.0 mm (2 mm off-center) and 1.4 mm (16 mm off-center) when the maximum-likelihood expectation maximization algorithm was applied. A myocardial (18)F-FDG study in mice and a skeletal (18)F study in rats demonstrated the fine spatial resolution of the scanner. The feasibility of the SiPM PET system was also confirmed in the tumor images of mice using (18)F-FDG and (68)Ga-RGD and in the brain images of rats using (18)F-FDG. CONCLUSION: These results indicate that it is possible to develop a PET system using a promising semiconductor photosensor, which yielded reasonable PET performance in phantom and animal studies.

Design and simulation of a novel method for determining depth-of-interaction in a PET scintillation crystal array using a single-ended readout by a multi-anode PMT.

PET detectors with depth-of-interaction (DOI) encoding capability allow high spatial resolution and high sensitivity to be achieved simultaneously. To obtain DOI information from a mono-layer array of scintillation crystals using a single-ended readout, the authors devised a method based on light spreading within a crystal array and performed Monte Carlo simulations with individual scintillation photon tracking to prove the concept. A scintillation crystal array model was constructed using a grid method. Conventional grids are constructed using comb-shaped reflector strips with rectangular teeth to isolate scintillation crystals optically. However, the authors propose the use of triangularly shaped teeth, such that scintillation photons spread only in the x-direction in the upper halves of crystals and in the y-direction in lower halves. DOI positions can be estimated by considering the extent of two-dimensional light dispersion, which can be determined from the multiple anode outputs of a position-sensitive PMT placed under the crystal array. In the main simulation, a crystal block consisting of a 29x29 array of 1.5 mmx1.5 mmx20 mm crystals and a multi-anode PMT with 16x16 pixels were used. The effects of crystal size and non-uniform PMT output gain were also explored by simulation. The DOI resolution estimated for 1.5x1.5x20 mm3 crystals was 2.16 mm on average. Although the flood map was depth dependent, each crystal was well identified at all depths when a corner of the crystal array was irradiated with 511 keV gamma rays (peak-to-valley ratio approximately 9:1). DOI resolution was better than 3 mm up to a crystal length of 28 mm with a 1.5x1.5 mm2 or 2.0x2.0 mm2 crystal surface area. The devised light-sharing method allowed excellent DOI resolutions to be obtained without the use of dual-ended readout or multiple crystal arrays.