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To detect a small amount of Period1 (Per1) expression, we developed a micro-photomultiplier tube (μPMT) system which can be used both in vivo and in vitro. Using this system, we succeeded in detecting Per1 gene expression in the skin of freely moving mice over 240 times higher compared with that of the tissue contact optical sensor (TCS) as previously reported. For in vitro studies, we succeeded in detecting elevated Per1 expression by streptozotocin (STZ) treatment in the scalp hairs at an early stage of diabetes, when glucose content in the blood was still normal. In addition, we could detect elevated Per1 expression in a single whisker hair at the time of diabetes onset. These results show that our μPMT system responds to minute changes in gene expression in freely moving mice in vivo and in mice hair follicles in vitro. Furthermore, Per1 in the hair can be used for a marker of diabetic aggravation.

The utilization of gold nanoparticles (GNPs) as a radiation sensitizer has received broad attention. Although GNPs form clusters in living cells, most previous simulation studies have assumed a homogeneous distribution of GNPs. In this study, a GNP cluster was constructed for simulations and the impact of cluster formation on dose enhancement was examined. Energy absorption by the GNPs was compared between clustered and homogeneous distributions for several different GNP concentrations and diameters under 100 keV X-ray irradiations. Our simulations showed that clusters more efficiently absorbed the secondary electrons and photons produced by GNPs themselves. Furthermore, the impact of cluster formation on dose enhancement was more significant for smaller GNPs and higher concentrations. Our results suggest that previous simulations assuming a homogeneous GNP distribution have overestimated the dose enhancement, especially for smaller GNPs and higher concentrations. These findings should guide the selection of GNP size and concentration for effectively optimizing dose enhancement in future studies.

PURPOSE/OBJECTIVE(S) Apparent diffusion coefficient (ADC) values extractable by diffusion-weighted imaging (DWI) are reported as useful in predicting the outcome of surgery and radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). However, their relationship with local tumor control (LC) after proton beam therapy (PBT) has not been fully evaluated. This study aimed to investigate interobserver variability in ADC histogram metrics and their usefulness in predicting LC in HCC patients who underwent PBT. MATERIALS/METHODS The ADC maps of the liver of HCC patients who underwent PBT between 2015 and 2020 were reviewed. The inclusion criteria were imaging DWI at 1.5T within 6 weeks before PBT and the largest tumor dimension between 2 and 10 cm. Twenty-nine patients and 32 tumors were eligible. Axial DWI was acquired using a single-shot spin-echo echo-planar sequence and the b values of 0 and 1000 s mm-2. The ADC maps generated were transferred to a workstation. Five board-certified radiation oncologists (ROs) contoured the whole tumor regions-of-interest (ROIs) on these maps, using anatomical images obtained together as reference. For each ROI, the minimum (ADCmin), mean (ADCmean), maximum (ADCmax), and the 5th (ADC5), 25th (ADC25), 50th (ADC50), 75th (ADC75), and 95th (ADC95) percentiles were extracted. The intraclass correlation coefficient (2,1) (ICC) was calculated to determine interobserver reproducibility: ICC of 0.75 - 0.90 was considered good and > 0.90 excellent. The ADC metrics were averaged among 5 ROs. The optimal cut-off values that determined LC, i.e., non-progressive disease (PD) based on the modified RECIST, were identified using receiver-operating characteristics (ROC) analysis. The LC rates were calculated using the Kaplan-Meier method, and statistical significance was assessed by log-rank test. RESULTS The median calculated biologically effective dose (α / β = 10) was 97 GyE. With a median follow-up of 39 months (5 - 62), 5 tumors had local PD. The ADCmin, ADCmean, ADCmax, ADC5, ADC25, ADC50, ADC75, and ADC95 of all tumors ranged between 0 - 1131, 748 - 1726, 1566 - 3149, 396 - 1430, 600 - 1566, 723 - 1719, 858 - 1874, and 1166 - 2426 (×10-6 mm 2 s-1), respectively. The ICC were 0.761, 0.969, 0.513, 0.864, 0.978, 0.983, 0.974, and 0.859, respectively. For ADCmean, ADC25, ADC50, and ADC75 which showed excellent reproducibility, the optimal cut-off values to determine LC were 1025, 1005, 1156, and 1132 (×10-6 mm 2 s-1), respectively. The tumors with higher ADC metrics had higher 2-year LC rates than their counterparts (100 % vs 40 %, P = 0.002; 100% vs 74%, P = 0.011; 100% vs 76%, P = 0.024; 100% vs 25%, P < 0.001, respectively). CONCLUSION ADCmean, ADC25, ADC50, and ADC75 showed excellent interobserver reproducibility. Pre-treatment ADC histogram metrics may be useful in predicting LC after PBT in HCC.

Gold nanoparticles (GNPs) have been recognized as a promising candidate for a radiation sensitizer. A proton beam incident on a GNP can produce secondary electrons, resulting in an enhancement of the dose around the GNP. However, little is known about the spatial distribution of dose enhancement around the GNP, especially in the direction along the incident proton. The purpose of this study is to determine the spatial distribution of dose enhancement by taking the incident direction into account. Two steps of calculation were conducted using the Geant4 Monte Carlo simulation toolkit. First, the energy spectra of 100 and 195 MeV protons colliding with a GNP were calculated at the Bragg peak and three other depths around the peak in liquid water. Second, the GNP was bombarded by protons with the obtained energy spectra. Radial dose distributions were computed along the incident beam direction. The spatial distributions of the dose enhancement factor (DEF) and subtracted dose (Dsub) were then evaluated. The spatial DEF distributions showed hot spots in the distal radial region from the proton beam axis. The spatial Dsub distribution isotropically spread out around the GNP. Low energy protons caused higher and wider dose enhancement. The macroscopic dose enhancement in clinical applications was also evaluated. The results suggest that the consideration of the spatial distribution of GNPs in treatment planning will maximize the potential of GNPs.

The neuropathological features of Creutzfeldt-Jakob disease are known to vary substantially in distribution and severity among different cases of the disease and also within an individual brain. In order to assess this variability a novel image analysis system has been developed to measure spongiform change, astrocytosis and prion protein deposition. Within the analysis protocol detailed in this paper are descriptions of the three image analysis software modules which have been designed to perform these different tasks. The sampling protocol also lists the different tissue blocks taken for examination. The validation of the computer system has been performed by comparison with a neuropathologist. A number of repetitions of the field selection and image intensity thresholding stages of the algorithm have been performed in order to assess the likely level of error introduced from these sources. The overall feasibility of the analysis protocol has been established by the successful sampling and analysis of one case of Creutzfeldt-Jakob disease. It is anticipated that this system of analysis will provide a method of quantifying the variations in pathology observed among different sub-groups of this disease.

Materials/Methods: Intra-fractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study. Prostate motion has been monitored with the Calypso System: systematic and random prostate motion was largest in the anterior-posterior direction (AP) with S = 2.3 mm and s = 2.9 mm for all trajectories. An industrial Mitsubishi robot moved a cylindrical prostate phantom on these 3D trajectories, this motion was detected via an infrared camera system (Polaris system, NDI) and the robotic HexaPOD (Medical Intelligence) treatment couch was used for real-time correction. Residual phantom motion with and without real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of step-and-shoot intensity-modulated radiotherapy (IMRT) for the three prostate trajectories with the largest random and systematic prostate motion. Results: Without motion compensation, the displacement of the prostate phantom was larger than 1 mm and 5 mm (3D error vector) in 83.3% ± 11.5% and 25% ± 19.8% during the 15 treatment fractions, respectively. No predictive algorithms were used and no post-processing of motion data was performed; measured phantom motion was intended to be fully compensated by couch countersteering. Real-time couch tracking reduced the proportion of the treatment fractions with displacements larger than 1 mm and 5 mm to 6.1% ± 4.6% and 0.3% ± 0.4%, respectively. Couch tracking reduced systematic and random phantom motion in AP direction to S = 0 mm and s = 0.55 mm. Maximum speed and acceleration of the couch during real-time tracking was 9.9 mm/s and 39.3 mm/s 2 (3D vector), respectively. Delay of the whole tracking system was 0.7s. If the moving average of the measured phantom motion (over 1s and 2s) was used as tracking command, residual phantom motion was slightly worse without resulting in smother couch motion. Compared to IMRT delivery to a static phantom, gamma values (2%/2 mm) of