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We have developed an in-house software equipped with partial image phase-only correlation (PIPOC) which can automatically quantify radiographic joint space narrowing (JSN) progression. The purpose of this study was to evaluate the software in phantom and clinical assessments.In the phantom assessment, the software's performance on radiographic images was compared to the joint space width (JSW) difference using a micrometer as ground truth. A phantom simulating a finger joint was scanned underwater. In the clinical assessment, 15 RA patients were included. The software measured the radiological progression of the finger joints between baseline and the 52nd week. The cases were also evaluated with the Genant-modified Sharp score (GSS), a conventional visual scoring method. We also quantitatively assessed these joints' synovial vascularity (SV) on power Doppler ultrasonography (0, 8, 20 and 52 weeks).In the phantom assessment, the PIPOC software could detect changes in JSN with a smallest detectable difference of 0.044 mm at 0.1 mm intervals. In the clinical assessment, the JSW change of the joints with GSS progression detected by the software was significantly greater than those without GSS progression (p = 0.004). The JSW change of joints with positive SV at baseline was significantly higher than those with negative SV (p = 0.024).Our in-house software equipped with PIPOC can automatically and quantitatively detect slight radiographic changes of JSW in clinically inactive RA patients.

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.

Purpose: The real-time tumor tracking radiotherapy (RTRT) system requires periodic quality assurance (QA) and quality control. The goal of this study is to propose QA procedures from the viewpoint of imaging devices in the RTRT system. Methods: Tracking by the RTRT system (equips two sets of colored image intensifiers (colored I.I.s) fluoroscopy units) for the moving gold-marker (diameter 2.0 mm) in a rotating phantom were performed under various X-ray conditions. To analyze the relationship between fluoroscopic image quality and precision of gold marker coordinate calculation, the standard deviation of the 3D coordinate (sigma 3D [mm]) of the gold marker, the mean of the pattern recognition score (PRS) and the standard deviation of the distance between rays (DBR) (sigma DBR [mm]) were evaluated. Results: When tracking with speed of 10-60 mm/s, sigma DBR increased, though the mean PRS did not change significantly (p>0.05). On the contrary, the mean PRS increased depending on the integral noise equivalent quanta (integral NEQ) that is an indicator of image quality calculated from the modulation transfer function (MTF) as an indicator of spatial resolution and the noise power spectrum (NPS) as an indicator of noise characteristic. Conclusion: The indicators of NEQ, MTF, and NPS were useful for managing the tracking accuracy of the RTRT system. We propose observing the change of these indicators as additional QA procedures for each imaging device from the commissioning baseline.

BACKGROUND: Although rheumatoid arthritis (RA) causes destruction of articular cartilage, early treatment significantly improves symptoms and delays progression. It is important to detect subtle damage for an early diagnosis. Recent software programs are comparable with the conventional human scoring method regarding detectability of the radiographic progression of RA. Thus, automatic and accurate selection of relevant images (e.g. hand images) among radiographic images of various body parts is necessary for serial analysis on a large scale. OBJECTIVE: In this study we examined whether deep learning can select target images from a large number of stored images retrieved from a picture archiving and communication system (PACS) including miscellaneous body parts of patients. METHODS: We selected 1,047 X-ray images including various body parts and divided them into two groups: 841 images for training and 206 images for testing. The training images were augmented and used to train a convolutional neural network (CNN) consisting of 4 convolution layers, 2 pooling layers and 2 fully connected layers. After training, we created software to classify the test images and examined the accuracy. RESULTS: The image extraction accuracy was 0.952 and 0.979 for unilateral hand and both hands, respectively. In addition, all 206 test images were perfectly classified into unilateral hand, both hands, and the others. CONCLUSIONS: Deep learning showed promise to enable efficiently automatic selection of target X-ray images of RA patients.

Circadian disturbance of clock gene expression is a risk factor for diseases such as obesity, cancer, and sleep disorders. To study these diseases, it is necessary to monitor and analyze the expression rhythm of clock genes in the whole body for a long duration. The bioluminescent reporter enzyme firefly luciferase and its substrate d-luciferin have been used to generate optical signals from tissues in vivo with high sensitivity. However, little information is known about the stability of d-luciferin to detect gene expression in living animals for a long duration. In the present study, we examined the stability of a luciferin solution over 21 days. l-Luciferin, which is synthesized using racemization of d-luciferin, was at high concentrations after 21 days. In addition, we showed that bioluminescence of Period1 (Per1) expression in the liver was significantly decreased compared with the day 1 solution, although locomotor activity rhythm was not affected. These results showed that d-luciferin should be applied to the mouse within, at most, 7 days to detect bioluminescence of Per1 gene expression rhythm in vivo.

Because the disruption of circadian clock gene is a risk factor in many diseases such as obesity and cancer, it is important to monitor and analyzed the expression of the rhythm of the clock gene throughout the body over a long period of time. Although we previously reported on a new gene expression analysis system tracking a target position on the body surface of freely moving mice, the experimental apparatus required a large space. We have therefore developed an in vivo recording system using a portable photomultiplier tube (PMT) system attached to an optical fibre. Directly connecting the target area with the device, we could easily measure the photon counts in a very small space. However, little information is known about the characteristics of optical fibres when exposed to twisting/looping in association with a moving mouse and the effect of the surface of optical fibre. In the present study, we report on the characteristics of optical fibres to detect gene expression rhythm in freely moving mice. Using this portable optical device directly connected with a target area, we were able to measure the circadian rhythm of clock gene expression over a prolonged period in freely moving mice in a small space.

Purpose Rheumatoid arthritis (RA) causes joint space narrowing (JSN) as a form of joint destruction. We developed an automatic system that can detect joint locations and compute the joint space difference index (JSDI), which was defined as the chronological change in JSN between two radiographs. This study aims to evaluate the application of "machine vision" for radiographic image of the finger joints. Materials and methods Fifteen RA patients with long-term sustained clinical low disease activity were recruited. All patients underwent hand radiography and power Doppler ultrasonography (PDUS). The JSN was evaluated using the Genant-modified Sharp scoring (GSS) method and the automatic system. Synovial vascularity (SV) was assessed quantitatively using ultrasonography. Results There were no significant differences in the JSDI between the joints with JSN and those without JSN on GSS (p = 0.052). The JSDI of the joints with SV was significantly higher than those without SV (p = 0.043). The JSDI of the no therapeutic response group was significantly higher than those of the response group (p < 0.001). Conclusion Our software can automatically evaluate temporal changes of JSN, which might free rheumatologists / radiologists from the burden of scoring hand radiography.

This contribution examines feasting strategies in Early Horizon Nepena (800–200 BC), coastal Ancash, north-central Peru. Through the analysis of volumetric capacities of vessels, we estimate scales...

The purpose of this study was to illustrate the clinical and imaging properties of giant intraosseous cyst-like lesions (GICLs) of the metacarpal bones extending beyond the central diaphysis in rheumatoid arthritis (RA) patients on magnetic resonance (MR) images. A keyword search was conducted to extract GICLs of the metacarpal bones out of MR reports in RA patients. There were nine GICLs extending from the subchondral bone region beyond the central diaphysis of the metacarpal bones on MR images in eight subjects with RA (seven females, one male). The age range was from 60 to 87 years with a median age of 65.5 years. The average disease duration was 13.1 years. As for the disease activity, one was low, six were moderate and one was high. None of the nine lesions were visible on radiography. The Steinbrocker stage distribution was as follows: I (n = 3), II (n = 2), and III (n = 3). Intraosseous cyst-like lesion of the metacarpal bones on MR images is a relatively rare manifestation in patients with long-standing RA. Although the lesion seems to be derived from subcortical bone break, it is not necessarily erosive in nature.

We provide details of the dual-focal 3D tracking and pixel intensity calibration (DuFT) system used to record gene expression in targeted areas on the skin of freely moving mice. The accuracy of the 3D position calculation was determined by placing a scintillator on the calibration disk at various known locations within the recording cage. The height of the disk was varied from the bottom (Z = 0 cm) to the top (Z = 30 cm). The distance from the central axis range from near the center (R = 1 cm) to near to edge (R = 5 cm). The mean deviation between the known and calculated position was .31 ± 0.16 mm. The maximum deviation was less than .86 mm. The results indicate that the location of a scintillator within the recording cage imaged with two cameras can be calculated with submillimeter accuracy. We hope that our methods can be applied to improve automatic (even real-time) tracking of various animals in vivo.

Ultrasonography is useful for assessment of synovitis in the hand of rheumatoid arthritis (RA) patients. The aim of this study was to investigate the predictive value of the quantitative power Doppler (PD) signal assessment in the subchondral bone region of the metacarpophalangeal (MCP) joint in patients with RA showing radiographic progression of the hand by comparing with those of previously reported scoring systems. Twenty-two patients (20 women) with RA who underwent power Doppler ultrasonography (PDUS) of the bilateral one to five MCP joints at baseline were included in the study. Radiography of both hands was performed at baseline and at 1 year. PDUS of the synovial space was evaluated according to semi-quantitative scoring (0–3) and quantitative measurement (0–100%). The PD signal in the subchondral bone region was qualitatively (0, 1) and quantitatively (mm2) assessed. The performance of PDUS assessment was compared using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the risk ratio (RR). As a predictor for radiographic progression, the quantitative PD signal assessment in the subchondral bone region (AUC = 0.842, p

Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity. In the present study, to explore the role of clock genes in developing diabetes, we examined the effect of streptozotocin (STZ)-induced high glucose on Period1 (Per1) gene expression rhythm in the liver and the olfactory bub (OB) in the brain. We found a drastic increase of Per1 expression in both tissues after STZ injection while blood glucose content was low. After a rapid expression peak, Per1 expression showed no rhythm. Associated with an increase of glucose content, behavior became arrhythmic. Finally, we succeeded in detecting an increase of Per1 expression in mice hair follicles on day 1 after STZ administration, before the onset of symptoms. These results show that elevated Per1 expression by STZ plays an important role in the aggravation of diabetes.

In rheumatoid arthritis (RA), the radiographic progression of joint space narrowing (JSN) is evaluated using visual assessments. However, those methods are complicated and time-consuming. We developed an automatic system that can detect joint locations and compute the joint space difference index (JSDI), which was defined as the chronological change in JSN between two radiographs. The purpose of this study was to establish the validity of the software that automatically evaluates the temporal change of JSN. This study consisted of 39 patients with RA. All patients were treated with tocilizumab and underwent hand radiography (left and right hand separately) at 0, 6, and 12 months. The JSN was evaluated using mTSS (modified Total Sharp Score) by one musculoskeletal radiologist as well as our automatic system. Software measurement showed that JSDI between 0 and 12 months was significantly higher than that between 0 and 6 months (p < 0.01). While, there was no significant difference in mTSS between 0, 6, and 12 months. The group with higher disease activity at 0 months had significantly higher JSDI between 0 and 6 months than that with lower disease activity (p = 0.02). The automatic software can evaluate JSN progression of RA patients in the finger joint on X-ray. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10278-020-00390-6) contains supplementary material, which is available to authorized users.

Several visual scoring methods are currently used to assess progression of rheumatoid arthritis (RA) on radiography. However, they are limited by its subjectivity and insufficient sensitivity. We have developed an original measurement system which uses a technique called phase-only correlation (POC). The purpose of this study is to validate the system by using a phantom simulating the joint of RA patients. A micrometer measurement apparatus that can adjust arbitrary joint space width (JSW) in a phantom joint was developed to define true JSW. The phantom was scanned with radiography, 320 multi detector CT (MDCT), high-resolution peripheral quantitative CT (HR-pQCT), cone beam CT (CBCT), and tomosynthesis. The width was adjusted to the average size of a women’s metacarpophalangeal joint, from 1.2 to 2.2 mm with increments of 0.1 mm and 0.01 mm. Radiographical images were analyzed by the POC-based system and manual method, and images from various tomographical modalities were measured via the automatic margin detection method. Correlation coefficients between true JSW difference and measured JSW difference were all strong at 0.1 mm intervals with radiography (POC-based system and manual method), CBCT, 320MDCT, HR-pQCT, and tomosynthesis. At 0.01 mm intervals, radiography (POC-based system), 320MDCT, and HR-pQCT had strong correlations, while radiography (manual method) and CBCT had low correlations, and tomosynthesis had no statistically significant correlation. The smallest detectable changes for radiography (POC-based system), radiography (manual method), 320MDCT, HR-pQCT, CBCT, and tomosynthesis were 0.020 mm, 0.041 mm, 0.076 mm, 0.077 mm, 0.057 mm, and 0.087 mm, respectively. We conclude that radiography analyzed with the POC-based system might sensitively detect minute joint space changes of the finger joint.

Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity and cancer. To understand the mechanism of regulating clock gene expression rhythms in vivo, multiple real time recording systems are required. In the present study, we developed a double recording system of Period1 expression rhythm in peripheral tissue (liver) and the brain. In peripheral tissue, quantification of gene expression in a steadily moving target was achieved by using a photomultiplier tube (PMT) attached to a tissue contact optical sensor (TCS). Using this technique, we were able to analyze circadian rhythms of clock gene expression over a prolonged period in the liver and olfactory bub (OB) of the brain. The present double recording system has no effect on behavioral activity or rhythm. Our novel system thus successfully quantifies clock gene expression in deep areas of the body in freely moving mice for a period sufficient to analyze circadian dynamics. In addition, our double recording system can be widely applied to many areas of biomedical research, as well as applications beyond medicine.

This research aimed to study the application of deep learning to the diagnosis of rheumatoid arthritis (RA). Definite criteria or direct markers for diagnosing RA are lacking. Rheumatologists diagnose RA according to an integrated assessment based on scientific evidence and clinical experience. Our novel idea was to convert various clinical information from patients into simple two-dimensional images and then use them to fine-tune a convolutional neural network (CNN) to classify RA or nonRA. We semi-quantitatively converted each type of clinical information to four coloured square images and arranged them as one image for each patient. One rheumatologist modified each patient’s clinical information to increase learning data. In total, 1037 images (252 RA, 785 nonRA) were used to fine-tune a pretrained CNN with transfer learning. For clinical data (10 RA, 40 nonRA), which were independent of the learning data and were used as testing data, we compared the classification ability of the fine-tuned CNN with that of three expert rheumatologists. Our simple system could potentially support RA diagnosis and therefore might be useful for screening RA in both specialised hospitals and general clinics. This study paves the way to enabling deep learning in the diagnosis of RA.

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.

BACKGROUND Synovitis, which is a hallmark of rheumatoid arthritis (RA), needs to be precisely quantified to determine the treatment plan. Time-intensity curve (TIC) shape analysis is an objective assessment method for characterizing the pixels as artery, inflamed synovium, or other tissues using dynamic contrast-enhanced MRI (DCE-MRI). PURPOSE/HYPOTHESIS To assess the feasibility of our original arterial mask subtraction method (AMSM) with mutual information (MI) for quantification of synovitis in RA. STUDY TYPE Prospective study. SUBJECTS Ten RA patients (nine women and one man; mean age, 56.8 years; range, 38-67 years). FIELD STRENGTH/SEQUENCE 3T/DCE-MRI. ASSESSMENT After optimization of TIC shape analysis to the hand region, a combination of TIC shape analysis and AMSM was applied to synovial quantification. The MI between pre- and postcontrast images was utilized to determine the arterial mask phase objectively, which was compared with human subjective selection. The volume of objectively measured synovitis by software was compared with that of manual outlining by an experienced radiologist. Simple TIC shape analysis and TIC shape analysis combined with AMSM were compared in slices without synovitis according to subjective evaluation. STATISTICAL TESTS Pearson's correlation coefficient, paired t-test and intraclass correlation coefficient (ICC). RESULTS TIC shape analysis was successfully optimized in the hand region with a correlation coefficient of 0.725 (P

Background The quantity and quality of skeletal muscle have been observed to be closely related with post-transplantation mortality in patients undergoing living donor liver transplantation (LDLT). However, the effect of LDLT on skeletal muscle has not been thoroughly investigated. The aim of this study was to investigate the change of trunk muscle mass and adiposity in recipients of LDLT. Methods The study population included LDLT recipients at Hokkaido University Hospital who underwent pre- and post-operative computed tomography (CT) scans (31 recipients; 14 males, and 17 females). The cross-sectional area of the dorsal muscle group at the 12th thoracic vertebra (Th12) was measured with the dorsal muscle group mass index (DMGMI), while the psoas muscle at the upper border of 4th lumber vertebra (L4) was measured with the psoas muscle mass index (PMI). Muscle adiposity of the dorsal muscle group was also measured with the intramuscular adipose tissue content (IMAC). For these data, the correlation between pre-operative values and follow-up changes (post-operative values minus pre-operative values) were analyzed. Each sex was evaluated separately. Results A statistically significant correlation was detected between pre-operative values and follow-up differences in DMGMI for both sexes (male: r=-0.675, P=0.008; female: r=-0.687, P=0.002) and in PMI for both sexes (males: r=-0.739, P=0.003; females: r=-0.641, P=0.006). The correlation of pre-operative values and follow-up differences for IMAC was not statistically significant with r=0.132 (P=0.700) and r=-0.498 (P=0.071) for males and females, respectively. Conclusions Improvement of sarcopenia in recipients of LDLT can be demonstrated regardless of sex using volumetric CT.

In this paper, we compare two radiation effect models: the average surviving fraction (ASF) model and the integral biologically effective dose (IBED) model for deriving the optimal irradiation scheme and show the superiority of ASF. Minimizing the effect on an organ at risk (OAR) is important in radiotherapy. The biologically effective dose (BED) model is widely used to estimate the effect on the tumor or on the OAR, for a fixed value of dose. However, this is not always appropriate because the dose is not a single value but is distributed. The IBED and ASF models are proposed under the assumption that the irradiation is distributed. Although the IBED and ASF models are essentially equivalent for deriving the optimal irradiation scheme in the case of uniform distribution, they are not equivalent in the case of non-uniform distribution. We evaluate the differences between them for two types of cancers: high α/β ratio cancer (e.g. lung) and low α/β ratio cancer (e.g. prostate), and for various distributions i.e. various dose–volume histograms. When we adopt the IBED model, the optimal number of fractions for low α/β ratio cancers is reasonable, but for high α/β ratio cancers or for some DVHs it is extremely large. However, for the ASF model, the results keep within the range used in clinical practice for both low and high α/β ratio cancers and for most DVHs. These results indicate that the ASF model is more robust for constructing the optimal irradiation regimen than the IBED model.

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.

We have developed a refined computer-based method to detect joint space narrowing (JSN) progression with the joint space narrowing progression index (JSNPI) by superimposing sequential hand radiographs. The purpose of this study is to assess the validity of a computer-based method using images obtained from multiple institutions in rheumatoid arthritis (RA) patients. Sequential hand radiographs of 42 patients (37 females and 5 males) with RA from two institutions were analyzed by a computer-based method and visual scoring systems as a standard of reference. The JSNPI above the smallest detectable difference (SDD) defined JSN progression on the joint level. The sensitivity and specificity of the computer-based method for JSN progression was calculated using the SDD and a receiver operating characteristic (ROC) curve. Out of 314 metacarpophalangeal joints, 34 joints progressed based on the SDD, while 11 joints widened. Twenty-one joints progressed in the computer-based method, 11 joints in the scoring systems, and 13 joints in both methods. Based on the SDD, we found lower sensitivity and higher specificity with 54.2 and 92.8%, respectively. At the most discriminant cutoff point according to the ROC curve, the sensitivity and specificity was 70.8 and 81.7%, respectively. The proposed computer-based method provides quantitative measurement of JSN progression using sequential hand radiographs and may be a useful tool in follow-up assessment of joint damage in RA patients.

Background Recent papers suggest that finger joints with positive synovial vascularity (SV) assessed by ultrasonography under clinical low disease activity (CLDA) in rheumatoid arthritis (RA) patients may cause joint space narrowing (JSN) progression. Purpose To investigate the performance of a computer-based method by directly comparing with the conventional scoring method in terms of the detectability of JSN progression in hand radiography of RA patients with CLDA. Material and Methods Fifteen RA patients (13 women, 2 men) with long-term sustained CLDA of >2 years were included. Radiological progression of finger joints was measured or scored using the computer-based method which can detect JSN progression between two radiographic images as the joint space difference index (JSDI), as well as the Genant-modified Sharp score (GSS). We also quantitatively assessed SV of these joints using ultrasonography. Results Out of 270 joints, we targeted 259 finger joints after excluding nine damaged joints (four ankylosis, three complete luxation, and two subluxation) and two improved joints according to the GSS results. The JSDI of finger joints with JSN progression was significantly higher than those without JSN progression ( P = 0.018). The JSDI of finger joints with ultrasonographic SV was significantly higher than those without ultrasonographic SV ( P = 0.004). Progression in JSDI showed stronger associations with ultrasonographic SV than progression in GSS (odds ratio [95% confidence interval]: 7.19 [3.37–15.36] versus 5.84 [2.76–12.33]). Conclusion The computer-based method was comparable to the conventional scoring method regarding the detectability of JSN progression in RA patients with CLDA.

Background Despite the advantages of ultrasound (US) in the management of rheumatoid arthritis (RA) patients, power Doppler (PD) US may be highly dependent on the type of US machine used. Purpose To present a method to calibrate the PD signal of two models of US machines by use of a flow phantom and finger joints of patients with RA. Material and Methods For the phantom study, the PD signal count was measured in the flow phantom perfusing blood mimicking fluid at various injection rates and pulse repetition frequencies (PRFs). The quantitative PD index was calculated with ImageJ. For the clinical study, the second and third metacarpophalangeal joints of five consecutive patients with RA were examined. The quantitative PD index was measured at various PRFs by use of two models of machine (the same models as the phantom study). Results For the phantom and clinical studies, negative correlations were found between the PRF and the quantitative PD index when the flow velocity was constant and positive correlations between flow velocity and the quantitative PD index at constant PRF. There was a significant difference in the depiction performance of synovial blood flow between the two models, which can be calibrated by adjusting the PRF values derived from the phantom study in each model. Conclusion Signal calibration of pannus vascularity between US machines may be possible by adjusting the PRF value according to flow phantom data. Different US machines can thus provide equivalent examination results concerning the pannus vascularity.

The joint space difference index (JSDI) is a newly developed radiographic index which can quantitatively assess joint space narrowing progression of rheumatoid arthritis (RA) patients by using an image subtraction method on a computer. The aim of this study was to investigate the reliability of this method by non-experts utilizing RA image evaluation. Four non-experts assessed JSDI for radiographic images of 510 metacarpophalangeal joints from 51 RA patients twice with an interval of more than 2 weeks. Two rheumatologists and one radiologist as well as the four non-experts examined the joints by using the Sharp-van der Heijde Scoring (SHS) method. The radiologist and four non-experts repeated the scoring with an interval of more than 2 weeks. We calculated intra-/inter-observer reliability using the intra-class correlation coefficients (ICC) for JSDI and SHS scoring, respectively. The intra-/inter-observer reliabilities for the computer-based method were almost perfect (inter-observer ICC, 0.966-0.983; intra-observer ICC, 0.954-0.996). Contrary to this, intra-/inter-observer reliability for SHS by experts was moderate to almost perfect (inter-observer ICC, 0.556-0.849; intra-observer ICC, 0.589-0.839). The results suggest that our computer-based method has high reliability to detect finger joint space narrowing progression in RA patients.

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.

BACKGROUND Postcontrast-enhanced MRI is currently the reference standard for synovial proliferation in rheumatoid arthritis (RA). However, the technique is somewhat invasive due to the use of gadolinium contrast agents, which may cause severe adverse/side effects. Intravoxel incoherent motion (IVIM) simultaneously permits quantification of perfusion as well as diffusion using a single imaging scan. PURPOSE/HYPOTHESIS To test the capability of IVIM MRI for noninvasive discrimination of synovial proliferation in hand arthritis. STUDY TYPE Prospective. SUBJECTS Seven suspected RA patients (three women and four men; mean age, 61 years; range, 26-74 years). FIELD STRENGTH/SEQUENCE 3 T/short tau inversion recovery (STIR), IVIM, postcontrast-enhanced MRI. ASSESSMENT Region of interest (ROI) was identified based on STIR. Contrast-enhanced MRI was evaluated using a 5-point grading scale of 0 (water) to 4 (synovial proliferation) according to the degree of contrast enhancement within the ROI. For each ROI, we calculated the apparent diffusion coefficient (ADC) and IVIM parameters (molecular diffusion coefficient [D], perfusion fraction [f], and perfusion-related diffusion coefficient [D*]). These parameters were subsequently compared with ROI contrast enhancement grades. STATISTICAL TESTS Spearman's rank correlation test and a receiver operating characteristic (ROC) curve. RESULTS A total of 90 ROIs of suspected synovial proliferation and/or joint effusion were identified. ROI grades were correlated with ADC and D values (r S = -0.385, P < 0.001, r S = -0.458, P < 0.0001, respectively), but not with the f and D* values (r S = -0.010, P = 0.936, r S = -0.084, P = 0.505, respectively). The area under the curves (AUCs) of D values (0.708-0.888, P = 0.002-0.0002) were slightly larger than those of ADC values (0.692-0.791, P = 0.013-0.001) when comparing low- vs. high-contrast enhancement grades. DATA CONCLUSION The IVIM parameter D and ADC may be useful for the noninvasive identification of synovial proliferation in hand arthritis. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1199-1206.

Our computer-based method can detect the chronological change in joint space width between baseline and follow-up images as the joint space difference index (JSDI). The aim of this study was to verify the sensitivity and specificity of our computer-based method in assessment of joint space narrowing progression in rheumatoid patients. Twenty-seven patients (24 women and 3 men) with rheumatoid arthritis underwent radiography of the bilateral hand at baseline and at 1 year. The joint space narrowing (JSN) of a total of 252 metacarpophalangeal (MCP) joints and 229 carpal joints was assessed by our computer-based method, setting the Sharp/van der Heijde method as the gold standard. We constructed a receiver operating characteristic curve by using the Sharp/van der Heijde method as the gold standard and set the optimal cutoff on JSDI for MCP, carpal, and MCP/carpal joints. We then calculated the sensitivity and specificity for each cutoff in assessment of JSN progression. At the most discriminant cutoff, the sensitivity and specificity of the computer-based method for MCP joints was 78.6 versus 85.3 %, respectively (AUC = 0.837; P < 0.001). Carpal joints revealed a lower sensitivity and specificity with 64.7 and 86.8 % (AUC = 0.775; P < 0.001). Furthermore, the sensitivity and specificity for MCP/carpal joints was 71.0 versus 83.6 %, respectively (AUC = 0.778; P < 0.001). The computer-based method presented a reliable assessment of JSN progression with high sensitivity and specificity and may be useful in follow-up assessment of the joint damage in rheumatoid patients.

The scintillator with optical fiber (SOF) dosimeter consists of a miniature scintillator mounted on the tip of an optical fiber. The scintillator of the current SOF dosimeter is a 1-mm diameter hemisphere. For a scintillation dosimeter coupled with an optical fiber, measurement accuracy is influenced by signals due to Cerenkov radiation in the optical fiber. We have implemented a spectral filtering technique for compensating for the Cerenkov radiation effect specifically for our plastic scintillator-based dosimeter, using a wavelength-separated counting method. A dichroic mirror was used for separating input light signals. Individual signal counting was performed for high- and low-wavelength light signals. To confirm the accuracy, measurements with various amounts of Cerenkov radiation were performed by changing the incident direction while keeping the Ir-192 source-to-dosimeter distance constant, resulting in a fluctuation of

Purpose: In radiation therapy, gold nanoparticles (GNPs) are regarded as a promising radiosensitizer candidate. Several studies have revealed a dose enhancement by GNPs in X-ray and even proton irradiation. However, these studies have been limited to the depth direction. The dose distribution in both depth and lateral directions is crucial to evaluate the full radio sensitizing effect. The purpose of this study is to estimate the dose distribution around a GNP in terms of ejected electrons. Methods: The Geant4 Monte Carlo simulation toolkit was used to evaluate the energy deposition of electrons produced by a GNP. A 20 nm diameter spherical GNP was located in a water box and proton beams were incident unidirectionally. The energy deposition and location of produced electrons were tallied by 5 nm width water slabs at a variety of depths behind the GNP. The radial dose distribution was obtained in each slab. Results: The largest radial dose was observed in the slab closest to the GNP. At the slabs deeper than 90 nm, the dose in the radial direction within 10 nm from the beam direction was found to be smaller than that without GNP. This is because the presence of a GNP decreases the dose behind the GNP, forming a dose shadow. The dose enhancement both in depth and lateral directions was shown in surrounding areas. The area of distribution became larger as the absorbed dose decreased. Conclusion: The dose distribution around a GNP was estimated by a simulation study. The dose enhancement was observed in both the lateral and depth directions. This study will enable us to make use of GNPs as a radiosensitizer in proton therapy.

Synovitis, which is a hallmark of rheumatoid arthritis (RA), needs to be precisely quantified to determine the treatment plan. Time-intensity curve (TIC) shape analysis is an objective assessment method for characterizing the pixels as artery, inflamed synovium, or other tissues using dynamic contrast-enhanced MRI (DCE-MRI).To assess the feasibility of our original arterial mask subtraction method (AMSM) with mutual information (MI) for quantification of synovitis in RA.Prospective study.Ten RA patients (nine women and one man; mean age, 56.8 years; range, 38-67 years).3T/DCE-MRI.After optimization of TIC shape analysis to the hand region, a combination of TIC shape analysis and AMSM was applied to synovial quantification. The MI between pre- and postcontrast images was utilized to determine the arterial mask phase objectively, which was compared with human subjective selection. The volume of objectively measured synovitis by software was compared with that of manual outlining by an experienced radiologist. Simple TIC shape analysis and TIC shape analysis combined with AMSM were compared in slices without synovitis according to subjective evaluation.Pearson's correlation coefficient, paired t-test and intraclass correlation coefficient (ICC).TIC shape analysis was successfully optimized in the hand region with a correlation coefficient of 0.725 (P 0.01) with the results of manual assessment regarded as ground truth. Objective selection utilizing MI had substantial agreement (ICC = 0.734) with subjective selection. Correlation of synovial volumetry in combination with TIC shape analysis and AMSM with manual assessment was excellent (r = 0.922, P 0.01). In addition, negative predictive ability in slices without synovitis pixels was significantly increased (P 0.01).The combination of TIC shape analysis and image subtraction reinforced with MI can accurately quantify synovitis of RA in the hand by eliminating arterial pixels.2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Purpose: In spot scanning proton therapy, accurate patient positioning before and during treatment is essential. A small gold ball marker is suitable as a fiducial for prostate treatment. However, it has been pointed out that the marker causes dose shadowing because the protons are scattered with their energy quickly diminished. In this research we explore the possibility that the biological effect of dose shadowing can be mitigated with a limited number of fields. Methods: The proton dose distribution in prostate was simulated using Geant4. The simulations include the Hokkaido University spot scanning nozzle and a water phantom positioned isocentrically. The PTV was delineated at the center of the phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV. The plan was created by single‐field optimization and each of the following beam arrangements was investigated; (1) single lateral field (2) two lateral fields (3) two lateral + one anterior fields (4) four‐field box. The dose prescription was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP) were compared for the four beam arrangements. Results: For (1)–(4), the minimum dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The reduction of the TCP values from those in the absence of the gold marker were 50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al. (Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the biological parameters in LevegrA¼n et al. (Int.J.RadiatOncol.Biol.Phys. 51, 2001), respectively. Conclusions: Although dose shadowing by the gold marker is locally non‐negligible, the size of the affected domain is tiny. It was found that with a minimum number of fields, the TCP nearly recovers to the value without the gold marker.

Objective: To demonstrate the superiority of total psoas volume (TPV) over total psoas area (TPA) in terms of predicting post-operative complications in living-donor liver transplantation (LDLT). Methods: The TPA and TPV were assessed in 32 recipients who underwent CT before LDLT. The TPA was measured using an axial CT image at the level of the upper margin of the fourth lumbar vertebral body. The TPV was calculated using all the CT images from the muscle origin through the level of the pubic symphysis. Patients were divided into a sarcopenia group and nosarcopenia group based on the medians of normalized TPA (nTPA) and normalized TPV (nTPV). We calculated the odds ratio (OR) of post-operative respiratory complications in relation to nTPA and nTPV, respectively. Results: Out of 32 recipients, 17 recipients experienced at least 1 post-operative respiratory complication. The OR for males according to nTPV [OR=15.00, 95% confidence interval (CI) =1.03-218.31; p=0.031] was higher than that for nTPA (OR=3.33, 95% CI=0.36-30.70; p=0.280). The OR for females according to nTPV (OR=4.00, 95% CI=0.56-28.40; p=0.16) was the same as that for nTPA (OR=4.00, 95% CI=0.56-28.40; p=0.16). Conclusion: Pre-operative volume of the skeletal muscle might be a better predictor for post-operative risks in LDLT recipients than pre-operative area of the skeletal muscle. Advances in knowledge: Post-operative risks for respiratory complications in LDLT recipients might be evaluated more accurately by using TPV instead of TPA.

The purpose of the study is to validate the semi-automated method using tomosynthesis images for the assessment of finger joint space narrowing (JSN) in patients with rheumatoid arthritis (RA), by using the semi-quantitative scoring method as the reference standard. Twenty patients (14 females and 6 males) with RA were included in this retrospective study. All patients underwent radiography and tomosynthesis of the bilateral hand and wrist. Two rheumatologists and a radiologist independently scored JSN with two modalities according to the Sharp/van der Heijde score. Two observers independently measured joint space width on tomosynthesis images using an in-house semi-automated method. More joints with JSN were revealed with tomosynthesis score (243 joints) and the semi-automated method (215 joints) than with radiography (120 joints), and the associations between tomosynthesis scores and radiography scores were demonstrated (P

In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within +/- 2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction.

The visual assessment of joint space narrowing (JSN) on radiographs of rheumatoid arthritis (RA) patients such as the Genant-modified Sharp score (GSS) is widely accepted but limited by its subjectivity and insufficient sensitivity. We developed a software application which can assess JSN quantitatively using a temporal subtraction technique for radiographs, in which the chronological change in JSN between two radiographs was defined as the joint space difference index (JSDI). The aim of this study is to prove the superiority of the software in terms of detecting fine radiographic progression in finger JSN over human observers. A micrometer measurement apparatus that can adjust arbitrary joint space width (JSW) in a phantom joint was developed to define true JSW. We compared the smallest detectable changes in JSW between the JSDI and visual assessment using phantom images. In a clinical study, 222 finger joints without interval score change on GSS in 15 RA patients were examined. We compared the JSDI between joints with and without synovial vascularity (SV) on power Doppler ultrasonography during the follow-up period. True JSW difference was correlated with JSDI for JSW differences ranging from 0.10 to 1.00 mm at increments of 0.10 mm (R2 = 0.986 and P

Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1−/− Cry2−/− arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice., The circadian rhythms of peripheral clocks are difficult to study. Here the authors demonstrate a technique to image clock gene expression simultaneously in various tissues of freely moving mice, and use it to show that a long duration light pulse resets the rhythms in the olfactory bulb faster than other tissues.

We examined the capability of a gray-scale arterial spin labeling blood flow pattern variation (BFPV) map with two different post labeling delay (PLD) times to discriminate pannus in patients with rheumatoid arthritis (RA) at 3T. There was a statistically significant difference in the BFPV values between artery, pannus, and surrounding tissue. Furthermore, the color-coded BFPV map was able to accurately distinguish pannus from other tissues. These results suggest this approach may be capable of identifying pannus noninvasively.