Estimating blurless and noise-free Ir-192 source images from gamma camera images for high-dose-rate brachytherapy using a deep-learning approach.

Objective. Precise monitoring of the position and dwell time of iridium-192 (Ir-192) during high-dose-rate (HDR) brachytherapy is crucial to avoid serious damage to normal tissues. Source imaging using a compact gamma camera is a potential approach for monitoring. However, images from the gamma camera are affected by blurring and statistical noise, which impact the accuracy of source position monitoring. This study aimed to develop a deep-learning approach for estimating ideal source images that reduce the effect of blurring and statistical noise from experimental images captured using a compact gamma camera.Approach. A double pix2pix model was trained using the simulated gamma camera images of an Ir-192 source. The first model was responsible for denoising the Ir-192 images, whereas the second model performed super resolution. Trained models were then applied to the experimental images to estimate the ideal images.Main results. At a distance of 100 mm between the compact gamma camera and the Ir-192 source, the difference in full width at half maximum (FWHM) between the estimated and actual source sizes was approximately 0.5 mm for a measurement time of 1.5 s. This difference has been improved from approximately 2.7 mm without the use of DL. Even with a measurement time of 0.1 s, the ideal images could be estimated as accurately as in the 1.5 s measurements. This method consistently achieved accurate estimations of the source images at any position within the field of view; however, the difference increased with the distance between the Ir-192 source and the compact gamma camera.Significance. The proposed method successfully provided estimated images from the experimental images within errors smaller than 0.5 mm at 100 mm. This method is promising for reducing blurring and statistical noise from the experimental images, enabling precise real-time monitoring of Ir-192 sources during HDR brachytherapy.

Urethral identification using three-dimensional magnetic resonance imaging and interfraction urethral motion evaluation for prostate stereotactic body radiotherapy.

Prostatic urethra identification is crucial in prostate stereotactic body radiotherapy (SBRT) to reduce the risk of urinary toxicity. Although computed tomography (CT) with a catheter is commonly employed, it is invasive, and catheter placement may displace the urethral position, resulting in possible planning inaccuracies. However, magnetic resonance imaging (MRI) can overcome these weaknesses. Accurate urethral identification and minimal daily variation could ensure a highly accurate SBRT. In this study, we investigated the usefulness of a three-dimensional (3D) T2-weighted (T2W) sequence for urethral identification, and the interfractional motion of the prostatic urethra on CT with a catheter and MRI without a catheter for implementing noninvasive SBRT. Thirty-two patients were divided into three groups. The first group underwent MRI without a catheter to evaluate urethral identification by two-dimensional (2D)- and 3D-T2W sequences using mean slice-wise Hausdorff distance (MSHD) and Dice similarity coefficient (DSC) of the contouring by two operators and using visual assessment. The second group provided 3-day MRI data without a catheter using 3D-T2W, and the third provided 3-day CT data with a catheter to evaluate the interfractional motion using MSHD, DSC, and displacement distance (Dd). The MSHD and DSC for the interoperator variability in urethral identification and visual assessment were superior in 3D-T2W than in 2D-T2W. Regarding interfractional motion, the Dd value for prostatic urethra was smaller in MRI than in CT. These findings indicate that the 3D-T2W yielded adequate prostatic urethral identification, and catheter-free MRI resulted in less interfractional motion, suggesting that 3D-T2W MRI without a catheter is a feasible noninvasive approach to performing prostate SBRT.

Shifting-field-of-view technique enhancing the inflow effect for identifying tumor/vessel boundaries in MRI for radiotherapy treatment planning.

This study presents two cases of tumors in contact with the inferior vena cava during radiotherapy, and introduces a clinically useful technique for identifying tumor boundaries adjacent to blood vessels by adjusting the position of the field-of-view (FOV) to enhance the inflow effect in magnetic resonance imaging. We named this technique "Shifting-FOV." This method consists of three steps: (1) remove the upper and lower saturation pulses outside the FOV, (2) align the FOV to position the lower edge of the imaging slab as close to the tumor as possible, and (3) manually adjust the table position to locate the tumor at the center of the magnetic field. The proposed method allowed for accurate identification of the tumor/vessel boundaries in both cases. This is a useful technique that can be readily applied to other facilities. Furthermore, images obtained using this technique may enable accurate tumor contouring in radiotherapy treatment planning.

Optimization of the energy window setting in Ir-192 source imaging for high-dose-rate brachytherapy using a YAP(Ce) gamma camera.

PURPOSE: Although real-time imaging of the high-activity iridium-192 (Ir-192) source position during high-dose-rate (HDR) brachytherapy using a high-energy gamma camera system is a promising approach, the energy window was not optimized for spatial resolution or scatter fraction. METHODS: By using a list-mode data-acquisition system that can acquire energy information of a cerium-doped yttrium aluminum perovskite (YA1O3: YAP(Ce)) gamma camera, we tried to optimize the energy window's setting to improve the spatial resolution and reduce scatter fraction. RESULTS: The spatial resolution was highest for the central energy of the window at ∼300 keV. The scatter fraction was also smallest for the central energy of the window at ∼300 keV, and the scatter fraction was more than 48 % smaller than that for the full energy window. CONCLUSIONS: We clarified that the spatial resolution can be improved and the scatter fraction can be reduced through optimizing the energy window of the YAP(Ce) gamma camera by setting the central energy of the window to ∼300 keV for HDR brachytherapy.

Technical note: Short-time sequential high-energy gamma photon imaging using list-mode data acquisition system for high-dose-rate brachytherapy.

PURPOSE: Measurement of the dwell time and moving speed of a high-activity iridium-192 (Ir-192) source used for high-dose-rate (HDR) brachytherapy is important for estimating the precise dose delivery to a tumor. For this purpose, we used a cerium-doped yttrium aluminum perovskite (YA1O3 :YAP(Ce)) gamma camera system, combined with a list-mode data acquisition system that can acquire short-time sequential images, and measured the dwell times and moving speeds of the Ir-192 source. METHODS: Gamma photon imaging was conducted using the gamma camera in list mode for the Ir-192 source of HDR brachytherapy with fixed dwell times and positions. The acquired list-mode images were sorted to millisecond-order interval time sequential images to evaluate the dwell time at each position. Time count rate curves were derived to calculate the dwell time at each source position and moving speed of the source. RESULTS: We could measure the millisecond-order time sequential images for the Ir-192 source. The measured times for the preset dwell times of 2 s and 10 s were 1.98 to 2.00 s full width at half maximum (FWHM) and 10.0 s FWHM, respectively. The dwell times at the first dwell position were larger than those at other positions. We also measured the moving speeds of the source after the dwells while moving back to the afterloader and found the speed increased with the distance from the edge of the field of view to the last dwell position. CONCLUSION: We conclude that millisecond-order time sequential imaging of the Ir-192 source is possible by using a gamma camera and is useful for evaluating the dwell times and moving speeds of the Ir-192 source.

Hybrid 3D T1-weighted gradient-echo sequence for fiducial marker detection and tumor delineation via magnetic resonance imaging in liver stereotactic body radiation therapy.

PURPOSE: Gold fiducial markers are used to guide liver stereotactic body radiation therapy (SBRT) and are hard to detect by magnetic resonance imaging (MRI). In this study, the parameters of the three-dimensional T1-weighted turbo gradient-echo (3D T1W-GRE) sequence were optimized for gold marker detection without degrading tumor delineation. METHODS: Custom-made phantoms mimicking tumor and normal liver parenchyma were prepared and embedded with a gold marker. The 3D T1W-GRE was scanned by varying echo time (TE), bandwidth (BW), flip angle (FA), and base matrix size. The signal-to-noise ratio (SNR), contrast ratio (CR), and relative standard deviation (RSD) of the signal intensity in the area including the gold marker were evaluated, and the parameters were optimized accordingly. The modified 3D T1W-GRE (called HYBRID) was compared with the conventional T1W-GRE- and T2*-sequences in both phantom and clinical studies. In the clinical study of six patients with primary liver tumors, two observers visually assessed marker detection, tumor delineation, and overall image quality on a four-point scale. RESULTS: In the phantom study, HYBRID showed significantly higher SNR and RSD than those of conventional T1W-GRE (P < 0.001). In the clinical study, HYBRID yielded significantly higher scores than conventional T1W-GRE did in terms of marker detection (P < 0.001). The scores of both sequences were not statistically different in terms of tumor delineation and overall image quality (P = 0.56 and P = 0.32). CONCLUSIONS: The proposed HYBRID sequence improved gold fiducial marker detection without degrading tumor delineation in MRI for SBRT of primary liver tumor.

Source position measurement by Cherenkov emission imaging from applicators for high-dose-rate brachytherapy.

PURPOSE: We developed a novel and simple method to measure the source positions in applicators directly for high-dose-rate (HDR) brachytherapy based on Cherenkov emission imaging, and evaluated the performance. METHODS: The light emission from plastic applicators used in cervical cancer treatments, irradiated by an 192 Ir γ-ray source, was captured using a charge-coupled device camera. Moreover, we attached plastics of different shapes, including tapes, tubes, and plates to a metal applicator, to use as screens for the Cherenkov imaging. We determined the source positions and dwell intervals from the light profiles along with the applicator and compared these with preset values and dummy marker measurements. RESULTS: The source positions and dwell intervals measured from the light images were comparable to the dummy marker measurements and preset values. The distance from the applicator tip to the first source positions agreed with the dummy marker measurements within 0.2 mm for the plastic tandem. The dwell intervals measured using the Cherenkov method agreed with the preset values within 0.6 mm. The distances measured with three plastic types on the metal applicator also agreed with the dummy marker measurements within 0.2 mm. The dwell intervals measured using the plastic tape agreed with the preset values within 0.7 mm. CONCLUSIONS: The proposed method should be suitable for rapid and easy quality assurance (QA) investigations in HDR brachytherapy, as it enables source position using a single image. The method allows for real-time, filmless measurements of the source positions to be obtained and is useful for rapid feedback in QA procedures.

Indoleamine 2,3-dioxygenase 1 in corneal endothelial cells limits herpes simplex virus type 1-induced acquired immune response.

BACKGROUND: Corneal endothelial cells are known to be targets of herpes simplex virus type 1 (HSV-1) infection; however, the pathogenesis of HSV infections of the endothelial cells has not been definitively determined. The purpose of this study was to examine an unrecognised strategy of corneal endothelial cells to protect themselves from HSV-1 infection. METHODS: Immortalised human corneal endothelial cells (HCEn) were infected with HSV-1. Based on the global transcriptional profile, the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was determined using real-time PCR and western blots. To examine whether IDO1 has any antiviral role, we tested whether viral replication was affected by blocking the activity of IDO1. The immune modulatory role of IDO1 was analysed to determine whether IDO1 might contribute to modulating the recall responses of HSV-1-sensitised CD4(+) T cells. RESULTS: IDO1 was strongly expressed in HCEn cells after HSV-1 infection. IDO1 blockade did not significantly restrict viral transcription or replication, arguing against a previously recognised antiviral role for IDO1. When HCEn cells were examined for antigen-presenting function, HSV-1-primed HCEn cells stimulated the proliferation of allogeneic CD4(+) T cells and interleukin 10 (IL-10) secretion. When the recall response to HSV-1 was measured by the mixed lymphocyte reaction, the HCEn-stimulated CD4(+) T cells modulated and limited the recall response. When IDO1 was silenced in HCEn cells, the HCEn-mediated immune modulatory activity and regulatory T-cell activation were reduced. Overexpression of IDO1 promoted immune modulatory activity, which was partly conveyed by IL-10. CONCLUSIONS: IDO1 induced by HSV-1 infection limits and dampens excessive acquired immune responses in corneal endothelial cells.

Associations of inflammatory cytokines with choroidal neovascularization in highly myopic eyes.

PURPOSE: To determine the relationships between the levels of intraocular inflammatory cytokines and the clinical characteristics of myopic choroidal neovascularization (mCNV) in eyes with myopic maculopathy. METHODS: One hundred eyes of 100 cases, including 51 mCNV eyes, 14 highly myopic eyes without choroidal neovascularization, and 35 normal subjects, were studied. The intraocular levels of choroidal neovascularization-related cytokines, like vascular endothelial growth factor, MCP-1, IL-8, IL-10, and IL-23, were determined. RESULTS: The levels of vascular endothelial growth factor and IL-8 were significantly higher in eyes with mCNV than in high myopia eyes without mCNV with significant odds ratio of 2.00 and 2.25 per quartile, respectively (P < 0.05). When myopic lesions of patients with mCNV were classified into 3 categories based on the severity, IL-8 and MCP-1 were significantly elevated depending on the presence of maculopathy (P < 0.05). Vascular endothelial growth factor was significantly elevated in eyes of Category 2. An advancement of the maculopathy category was significantly associated with the need for multiple treatment of intravitreal bevacizumab (P < 0.05). In 12 eyes that required multiple intravitreal bevacizumab, the MCP-1 level was significantly elevated. CONCLUSION: The significant associations of mCNV in highly myopic eyes with elevated levels of vascular endothelial growth factor or inflammatory cytokines and maculopathy lesions strongly suggest an involvement of inflammation in the etiology of mCNVs.

Inhibition of iron uptake by ferristatin II is exerted through internalization of DMT1 at the plasma membrane.

Ferristatin II, discovered as an iron transport inhibitor, promotes the internalization and degradation of transferrin receptor 1 (TfR1). DMT1, which mediates iron transport across cell membranes, is located at the plasma membrane of enterocytes and imports dietary iron into the cytosol. TfR1 is not directly engaged in the intestinal absorption of free iron, and iron uptake by DMT1 is attenuated by ferristatin II treatment. In this study, we found another function for ferristatin II in iron uptake. Ferristatin II did not cause degradation of DMT1 but did induce DMT1 internalization from the plasma membrane. Dynasore, a small molecule inhibitor of dynamin, did not inhibit this internalization by ferristatin II, which might occur via a clathrin-independent pathway.

Comparison of toxicities of moxifloxacin, cefuroxime, and levofloxacin to corneal endothelial cells in vitro.

PURPOSE: To evaluate and compare the toxic effects of moxifloxacin, cefuroxime, and levofloxacin on human corneal endothelial cells in vitro and determine the safe intracameral concentrations for them. SETTING: Tottori University, Tottori, Japan. DESIGN: Experimental study. METHODS: Human corneal endothelial cells in culture were exposed to moxifloxacin, cefuroxime, and levofloxacin at concentrations up to 2000 µg/mL. Evaluation of membrane damage was determined by ethidium homodimer-1 uptake and cell viability, by intrinsic esterase activity. The inhibitory effects of the 3 antibiotics on the constitutive secretion of interleukin-6 (IL-6) by human corneal endothelial cells were determined by enzyme-linked immunosorbent assay. RESULTS: The acute effects (6 hour) of the 3 antibiotics on membrane damage and cell death were dose-dependent for moxifloxacin and levofloxacin (≥ 500 µg/mL). For cefuroxime, membrane damage was not observed at 6 hours and only slight damage was detected at 24 hours at concentrations higher than 500 µg/mL. The half maximum inhibitory concentrations on cell viability of moxifloxacin, levofloxacin, and cefuroxime were 487 µg/mL, 578 µg/mL, and 1600 µg/mL, respectively. The inhibitory effects of the 3 antibiotics on the constitutive secretion of IL-6 were observed at 15.6 µg/mL or higher, indicating the antibiotics can impair the secretion of the protective cytokine even at low concentrations. CONCLUSIONS: Moxifloxacin at more than 500 µg/mL caused damage to the cell membranes of corneal endothelial cells; even higher concentrations decreased cell viability. Considering the lower minimum inhibitory concentration for inhibiting 90% growth by moxifloxacin, intracameral moxifloxacin at 500 µg/mL or less is recommended for prophylactic use. FINANCIAL DISCLOSURE: Dr. Inoue is a medical advisor to Alcon Japan Ltd. No author has a financial or proprietary interest in any material or method mentioned.

Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2.

BACKGROUND: Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter. METHODS: Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 µg/mouse, i.c.v.), respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. RESULTS: Repeated administration of betaine (0.163 mmol/kg, s.c.) prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection) and acute administration (1 hr after LPS injection) of betaine also prevented LPS-induced memory impairment in the Y-maze test. CONCLUSIONS: These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.