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Background: "Batch effect" in MR images, due to vendor‐specific features, MR machine generations, and imaging parameters, challenges image quality and hinders deep learning (DL) model generalizability. Purpose: We aim to develop a DL model using contrast adjustment and super‐resolution to reduce diffusion‐weighted images (DWIs) diversity across magnetic field strengths and imaging parameters. Study Type: Retrospective. Subjects: The DL model was built using an open dataset from one individual. The MR machine identification model was trained and validated on a dataset of 1134 adults (54% females, 46% males), with 1050 subjects showing no DWI abnormalities and 84 with conditions like stroke and tumors. The 21,000 images were divided into 80% for training, 20% for validation, and 3500 for testing. Field Strength/Sequence: Seven MR scanners from four manufacturers with 1.5 T and 3 T magnetic field strengths. DWIs were acquired using spin‐echo sequences and high‐resolution T2WIs using the T2‐SPACE sequence. Assessment: An experienced, board‐certified radiologist evaluated the effectiveness of restoring high‐resolution T2WI and harmonizing diverse DWI with metrics such as PSNR and SSIM, and the texture and frequency attributes were further analyzed using gray‐level co‐occurrence matrix and 1‐dimensional power spectral density. The model's impact on machine‐specific characteristics was gauged through the performance metrics of a ResNet‐50 model. Comprehensive statistical tests were employed for statistical robustness, including McNemar's test and the Dice index. Results: Our DL protocol reduced DWI contrast and resolution variation. ResNet‐50 model's accuracy decreased from 0.9443 to 0.5786, precision from 0.9442 to 0.6494, recall from 0.9443 to 0.5786, and F1 score from 0.9438 to 0.5587. The t‐SNE visualization indicated more consistent image features across multiple MR devices. Autoencoder halved learning iterations; Dice coefficient >0.74 confirmed signal reproducibility in 84 lesions. Conclusion: This study presents a DL strategy to mitigate batch effects in diffusion MR images, improving their quality and generalizability. Evidence Level: 3 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Background and Objectives: Integrating large language models (LLMs) such as GPT-4 Turbo into diagnostic imaging faces a significant challenge, with current misdiagnosis rates ranging from 30–50%. This study evaluates how prompt engineering and confidence thresholds can improve diagnostic accuracy in neuroradiology. Methods: We analyze 751 neuroradiology cases from the American Journal of Neuroradiology using GPT-4 Turbo with customized prompts to improve diagnostic precision. Results: Initially, GPT-4 Turbo achieved a baseline diagnostic accuracy of 55.1%. By reformatting responses to list five diagnostic candidates and applying a 90% confidence threshold, the highest precision of the diagnosis increased to 72.9%, with the candidate list providing the correct diagnosis at 85.9%, reducing the misdiagnosis rate to 14.1%. However, this threshold reduced the number of cases that responded. Conclusions: Strategic prompt engineering and high confidence thresholds significantly reduce misdiagnoses and improve the precision of the LLM diagnostic in neuroradiology. More research is needed to optimize these approaches for broader clinical implementation, balancing accuracy and utility. [ABSTRACT FROM AUTHOR]

The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood–brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field. Evidence Level: 3 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV–adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK–SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann–Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10−3, p < 0.001). The MBs volume/TBV ratio correlated with visual memory, as assessed, respectively, by the Rey–Osterrieth Complex Figure test delayed recall (ρ = 0.62, p < 0.001). In conclusion, retired athletes with rmTBI have MB atrophy, potentially contributing to memory impairment linked to the Papez circuit disconnection. [ABSTRACT FROM AUTHOR]

Background: Two‐dimensional synthetic MRI of the breast has limited spatial coverage. Three‐dimensional (3D) synthetic MRI could provide volumetric quantitative parameters that may reflect the immunohistochemical (IHC) status in invasive ductal carcinoma (IDC) of the breast. Purpose: To evaluate the feasibility of 3D synthetic MRI using an interleaved Look–Locker acquisition sequence with a T2 preparation pulse (QALAS) for discriminating the IHC status, including hormone receptor (HR), human epidermal growth factor receptor 2 (HER 2), and Ki‐67 expression in IDC. Study Type: Prospective observational study. Population: A total of 33 females with IDC of the breast (mean, 52.3 years). Field Strength/Sequence: A 3‐T, 3D‐QALAS gradient‐echo and fat‐suppressed T1‐weighted 3D fast spoiled gradient‐echo sequences. Assessment: Two radiologists semiautomatically delineated 3D regions of interest (ROIs) of the whole tumors on the dynamic MRI that was registered to the synthetic T1‐weighted images acquired from 3D‐QALAS. The mean T1 and T2 were measured for each IDC. Statistical Tests: Intraclass correlation coefficient for assessing interobserver agreement. Mann–Whitney U test to determine the relationship between the mean T1 or T2 and the IHC status. Multivariate logistic regression analysis followed by receiver operating characteristics (ROC) analysis for discriminating IHC status. A P value <0.05 was considered statistically significant. Results: The interobserver agreement was good to excellent. There was a significant difference in the mean T1 between HR‐positive and HR‐negative lesions, while the mean T2 value differed between HR‐positive and HR‐negative lesions, between the triple‐negative and HR‐positive or HER2‐positive lesions, and between the Ki‐67 level > 14% and ≤ 14%. Multivariate analysis showed that the mean T2 was higher in HR‐negative IDC than in HR‐positive IDC. ROC analysis revealed that the mean T2 was predictive for discriminating HR status, triple‐negative status, and Ki‐67 level. Data Conclusion: 3D synthetic MRI using QALAS may be useful for discriminating IHC status in IDC of the breast. Evidence Level: 1. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

Background: Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA‐PD) have a more aggressive disease course than those with idiopathic PD (iPD). Objective: The objective of this study was to investigate fiber‐specific white matter (WM) differences in nonmedicated patients with early‐stage GBA‐PD and iPD using fixel‐based analysis, a novel technique to assess tract‐specific WM microstructural and macrostructural features comprehensively. Methods: Fixel‐based metrics, including microstructural fiber density (FD), macrostructural fiber‐bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA‐PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses. Results: Patients with GBA‐PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal‐thalamo‐cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal‐thalamo‐cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA‐PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α‐synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores. Conclusions: We report reduced fiber‐specific WM density and bundle cross‐sectional size in patients with GBA‐PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α‐synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the along the perivascular space (ALPS) index based on the diffusion tensor image ALPS (DTI-ALPS) in corticobasal degeneration with corticobasal syndrome (CBD-CBS) and investigate its correlation with motor and cognitive functions. Materials and methods: The data of 21 patients with CBD-CBS and 17 healthy controls (HCs) were obtained from the 4-Repeat Tauopathy Neuroimaging Initiative and the Frontotemporal Lobar Degeneration Neuroimaging Initiative databases. Diffusion magnetic resonance imaging was performed using a 3-Tesla MRI scanner. The ALPS index based on DTI-ALPS was automatically calculated after preprocessing. The ALPS index was compared between the CBD-CBS and HC groups via a general linear model analysis, with covariates such as age, sex, years of education, and intracranial volume (ICV). Furthermore, to confirm the relation between the ALPS index and the motor and cognitive score in CBD-CBS, the partial Spearman's rank correlation coefficient was calculated with covariates such as age, sex, years of education, and ICV. A p value of < 0.05 was considered as statistically significant in all statistical analyses. Results: The ALPS index of CBD-CBS was significantly lower than that of HC (Cohen's d = − 1.53, p < 0.005). Moreover, the ALPS index had a significant positive correlation with the mini mental state evaluation score (rs = 0.65, p < 0.005) and a significant negative correlation with the unified Parkinson's Disease Rating Scale III score (rs = − 0.75, p < 0.001). Conclusion: The ALPS index of patients with CBD-CBS, which is significantly lower than that of HCs, is significantly associated with motor and cognitive functions. [ABSTRACT FROM AUTHOR]

Purpose: This multisite study aimed to use the COMBined Association Test (COMBAT), a harmonization technique that uses regression of covariates with an empirical Bayesian framework, to harmonize diffusion tensor image analysis along the perivascular space (DTI-ALPS) variations caused by scanner, site, and protocol differences. Materials and methods: This study included multisite diffusion magnetic resonance imaging (dMRI) data of 45 patients with Alzheimer's disease (AD) and 82 cognitively normal (CN) participants from the AD neuroimaging initiative database. The dMRI data were obtained with two b values (0 and 1000 s/mm2) from 27 institutions and three different 3-Tesla MRI scanners (two vendors). The ALPS index was calculated from multisite dMRI data, and COMBAT was used to harmonize the factors causing site variations. Welch's t test was used, Cohen's d was calculated to compare the difference in the ALPS index between AD and CN before and after harmonization, and Pearson's correlation coefficient was calculated to assess the relationships between the ALPS index and the cognitive score, [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET), and [18F] florbetapir (AV45)-PET standardized uptake value ratios (SUVRs). Results: COMBAT harmonized scanner differences and increased Cohen's d of the left and right ALPS indexes between AD and CN from 0.288 to 0.438 and 0.328 to 0.480, respectively. The ALPS indexes were significantly different between AD and CN after harmonization (P < 0.05) but not before it. Moreover, Pearson's correlation coefficients between the ALPS index and cognitive score, FDG-PET, and AV45-PET SUVRs were higher after harmonization than before it. Conclusion: This study demonstrates the application of COMBAT harmonization to eliminate between-scanner, site, and protocol variations in the ALPS index calculated from DTI-ALPS using dMRI and possibly facilitate the use of the ALPS index in multi-center studies. [ABSTRACT FROM AUTHOR]

In automated analyses of brain morphometry, skull stripping or brain extraction is a critical first step because it provides accurate spatial registration and signal-intensity normalization. Therefore, it is imperative to develop an ideal skull-stripping method in the field of brain image analysis. Previous reports have shown that convolutional neural network (CNN) method is better at skull stripping than non-CNN methods. We aimed to evaluate the accuracy of skull stripping in a single-contrast CNN model using eight-contrast magnetic resonance (MR) images. A total of 12 healthy participants and 12 patients with a clinical diagnosis of unilateral Sturge–Weber syndrome were included in our study. A 3-T MR imaging system and QRAPMASTER were used for data acquisition. We obtained eight-contrast images produced by post-processing T1, T2, and proton density (PD) maps. To evaluate the accuracy of skull stripping in our CNN method, gold-standard intracranial volume (ICVG) masks were used to train the CNN model. The ICVG masks were defined by experts using manual tracing. The accuracy of the intracranial volume obtained from the single-contrast CNN model (ICVE) was evaluated using the Dice similarity coefficient [= 2(ICVE ⋂ ICVG)/(ICVE + ICVG)]. Our study showed significantly higher accuracy in the PD-weighted image (WI), phase-sensitive inversion recovery (PSIR), and PD-short tau inversion recovery (STIR) compared to the other three contrast images (T1-WI, T2-fluid-attenuated inversion recovery [FLAIR], and T1-FLAIR). In conclusion, PD-WI, PSIR, and PD-STIR should be used instead of T1-WI for skull stripping in the CNN models. [ABSTRACT FROM AUTHOR]

Purpose: The method of diffusion tensor image analysis along the perivascular space (DTI-ALPS) was gathering attention to evaluate the brain's glymphatic function or interstitial fluid dynamics. However, to the best knowledge, no study was conducted on the reproducibility of these automated methods for ALPS index values. Therefore, the current study evaluated the ALPS index reproducibility based on DTI-ALPS using two major automated calculation techniques in scan and rescan of the same subject on the same day. Materials and methods: This study included 23 participants, including 2 with Alzheimer's disease, 15 with mild cognitive impairment, and 6 with cognitive normals. Scan and rescan data of diffusion magnetic resonance images were obtained, as well as automatically index for ALPS (ALPS index) and ALPS index maintaining tensor vector orientation information (vALPS index) with region of interest on the template fractional anisotropy map calculated by FSL software.These ALPS indices were compared in terms of scan and rescan reproducibility. Results: The absolute difference in ALPS-index values between scan and rescan was larger in the ALPS index than in the vALPS index by approximately 0.6% as the relative difference. Cohen's d for the left and right ALPS indices between methods were 0.121 and 0.159, respectively. Conclusion: The vALPS index based on DTI-ALPS maintaining tensor vector orientation information has higher reproducibility than the ALPS index. This result encourages a multisite study on the ALPS index with a large sample size and helps detect a subtle pathological change in the ALPS index. [ABSTRACT FROM AUTHOR]

Carbonyl stress is a condition featuring increased rich reactive carbonyl compounds, which facilitate the formation of advanced glycation end products including pentosidine. We previously reported the relationship between enhanced carbonyl stress and disrupted white matter integrity in schizophrenia, although which microstructural component is disrupted remained unclear. In this study, 32 patients with schizophrenia (SCZ) and 45 age- and gender-matched healthy volunteers (HC) were recruited. We obtained blood samples for carbonyl stress markers (plasma pentosidine and serum pyridoxal) and multi-modal magnetic resonance imaging measures of white matter microstructures including apparent axonal density (intra-cellular volume fraction (ICVF)) and orientation (orientation dispersion index (ODI)), and inflammation (free water (FW)). In SCZ, the plasma pentosidine level was significantly increased. Group comparison revealed that mean white matter values were decreased for ICVF, and increased for FW. We found a significant negative correlation between the plasma pentosidine level and mean ICVF values in SCZ, and a significant negative correlation between the serum pyridoxal level and mean ODI value in HC, regardless of age. Our results suggest an association between enhanced carbonyl stress and axonal abnormality in SCZ. [ABSTRACT FROM AUTHOR]

White matter bundle segmentation using diffusion magnetic resonance imaging fiber tractography enables detailed evaluation of individual white matter tracts three-dimensionally, and plays a crucial role in studying human brain anatomy, function, development, and diseases. Manual extraction of streamlines utilizing a combination of the inclusion and exclusion of regions of interest can be considered the current gold standard for extracting white matter bundles from whole-brain tractograms. However, this is a time-consuming and operator-dependent process with limited reproducibility. Several automated approaches using different strategies to reconstruct the white matter tracts have been proposed to address the issues of time, labor, and reproducibility. In this review, we discuss few of the most well-validated approaches that automate white matter bundle segmentation with an end-to-end pipeline, including TRActs Constrained by UnderLying Anatomy (TRACULA), Automated Fiber Quantification, and TractSeg. [ABSTRACT FROM AUTHOR]

Background: A new image reconstruction process termed the MUS method (masking process on unsmoothed images) was developed to eliminate artifacts, especially those in the inferior wall. We compared diagnostic performance between the MUS and conventional method in stress myocardial perfusion SPECT (MPS). Methods: Enrolled were 126 patients who underwent stress-rest MPS with 99 m Tc-MIBI. Patients were divided into two groups: 91 with < 50% stenosis in the RCA or LCX (non-ischemia group) and 35 patients with ≥ 90% stenosis or FFR-positive in the RCA (ischemia group), according to coronary CT or coronary angiography within 3 months of MPS. Ischemic heart disease (IHD) was considered positive when the summed difference score of five segments corresponding to the inferior wall region was ≥ 2. Results: Sensitivity was comparable between the MUS method and the conventional method (ordered subset expectation maximization; OSEM) (51% vs 54%, respectively; (p = 0.366), specificity was significantly higher using the MUS method (87% vs 77%, respectively; p < 0.05), and diagnostic performance was higher using the MUS method (area under curve [AUC], conventional 0.61 vs. MUS 0.69, p = 0.138). In evaluation of 87 patients after excluding 39 who received additional prone imaging, sensitivity using the MUS method was 44%, which was comparable to 44% using the conventional method but specificity was 90%, which was significantly higher than 77% using the conventional method (p < 0.05). The diagnostic performance of the MUS method was higher (AUC, conventional 0.60 vs. MUS 0.67, p = 0.185). Conclusion: Use of the MUS method improved specificity in diagnosis of IHD while maintaining sensitivity, compared with the conventional method. The MUS method can achieve an improvement in diagnostic accuracy equivalent to the supine position, particularly in patients who have difficulty performing the prone position, without increasing the patient burden. [ABSTRACT FROM AUTHOR]

The effectiveness and safety of intraoperative magnetic resonance imaging (iMRI) are evident from many reports over the past decade. However, these reports have mainly concerned surgeries for glioma and other intra-axial tumours, and applications of this approach for extra-axial tumours are poorly documented. We retrospectively examined three cases in which iMRI was used to assist in the removal of epidermoid cysts. T2-weighted images and diffusion-weighted images were acquired during the surgeries. The value to surgeons of images generated by iMRI, the length of interruption of surgery, and the safety of the patients were assessed. In this study, the images obtained through iMRI provided were clear representations of remnant tumours, even with a low-field system (0.4 Tesla). These images generated enough information to help surgeons decide whether to use an assistance device, such as an endoscope, to remove remnant tumours and whether further retraction of the brain was safe for patients and useful in tumour removal. Intraoperative MRI has long been thought unnecessary for surgery for tumours that are well demarcated and clearly visible under a surgical microscope; in this study, however, intraoperative MRI proved to be useful and safe for patients undergoing epidermoid cyst resection. [ABSTRACT FROM AUTHOR]

Background: Voxel-based morphometry (VBM) using magnetic resonance imaging (MR) has been used to estimate cortical atrophy associated with various diseases. However, there are mis-segmentations of segmented gray matter image in VBM. Purpose: To study a twofold evaluation of single- and multi-channel segmentation using synthetic MR images: (1) mis-segmentation of segmented gray matter images in transverse and cavernous sinuses; and (2) accuracy and repeatability of segmented gray matter images. Material and Methods: A total of 13 healthy individuals were scanned with 3D quantification using an interleaved Look–Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) sequence on a 1.5-T scanner. Three of the 13 healthy participants were scanned five consecutive times for evaluation of repeatability. We used SyMRI software to create images with three contrasts: T1-weighted (T1W), T2-weighted (T2W), and proton density-weighted (PDW) images. Manual regions of interest (ROI) on T1W imaging were individually set as the gold standard in the transverse sinus, cavernous sinus, and putamen. Single-channel (T1W) and multi-channel (T1W + T2W, T1W + PDW, and T1W + T2W + PDW imaging) segmentations were performed with statistical parametric mapping 12 software. Results: We found that mis-segmentations in both the transverse and cavernous sinuses were large in single-channel segmentation compared with multi-channel segmentations. Furthermore, the accuracy of segmented gray matter images in the putamen was high in both multi-channel T1W + PDW and T1W + T2W + PDW segmentations compared with other segmentations. Finally, the highest repeatability of left putamen volumetry was found with multi-channel segmentation T1WI + PDWI. Conclusion: Multi-channel segmentation with T1WI + PDWI provides good results for VBM compared with single-channel and other multi-channel segmentations. [ABSTRACT FROM AUTHOR]

Simple Summary: This was a multicenter, single-arm, phase II study comprising two protocol treatments. Patients were enrolled after craniotomy or biopsy and initiated the concurrent phase; oral daily temozolomide concomitant with radiation therapy during the first 6 weeks of treatment. Bevacizumab was intravenously administered every other week. The protocol-defined secondary therapy (i.e., BBP regimen) was given as bevacizumab monotherapy or in combination with other chemotherapeutic agents upon first progression or recurrence until further progression or unacceptable toxicity developed. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. Expression profiling using RNA sequencing identified that Cluster 2, enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the MGMT methylation status. We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, n = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the MGMT methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated MGMT. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab. [ABSTRACT FROM AUTHOR]

Objectives: Vorticity calculated using computational fluid dynamics (CFD) could assess the flow disturbance generated by coronary stenosis. The purpose of this study was to investigate whether vorticity would be an underlying cause of functionally significant stenosis assessed by invasive fractional flow reserve (FFR). Methods: This retrospective study included 113 patients who underwent coronary CT angiography showing intermediate stenosis and subsequent invasive FFR between December 2015 and March 2020. Vorticity at the stenosis site was calculated using a mesh-free CFD method. We also evaluated the minimum lumen area (MLA) and diameter stenosis (DS) of the lesion. Invasive FFR of ≤ 0.80 was considered functionally significant. Data were compared using Student's t-test and logistic regression analysis was performed. Results: Of the evaluated 144 vessels, 53 vessels (37%) showed FFR ≤ 0.80. Vorticity of significant stenosis was significantly higher than non-significant stenosis (569 ± 78 vs. 328 ± 34 s−1, p < 0.001). A significant negative relationship was present between vorticity and invasive FFR (R2 = 0.31, p < 0.001). Multivariate logistic regression analysis including MLA and DS showed that vorticity (per 100 s−1, odds ratio: 1.36, 95% confidence interval: 1.21–1.57, p < 0.001) was a statistically significant factor to detect functional significance. The area under the receiver operating characteristic curve statistically significantly increased when vorticity was combined with DS and MLA (0.76 vs. 0.87, p = 0.001). Conclusions: Vorticity had a statistically significant negative relationship with invasive FFR independent of geometric stenosis. Key Points: • Flow disturbance caused by coronary stenosis could be evaluated by calculating vorticity which is defined as the norm of the rotation of the velocity vector. • Vorticity was statistically significantly higher in stenosis with functional significance than stenosis without. • Vorticity has an additive value to detect functionally significant stenosis over geometrical stenosis. [ABSTRACT FROM AUTHOR]

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the influence of magnetic resonance fingerprinting (MRF) dictionary design on radiomic features using in vivo human brain scans. Methods: Scan-rescans of three-dimensional MRF and conventional T1-weighted imaging were performed on 21 healthy volunteers (9 males and 12 females; mean age, 41.3 ± 14.6 years; age range, 22–72 years). Five patients with multiple sclerosis (3 males and 2 females; mean age, 41.2 ± 7.3 years; age range, 32–53 years) were also included. MRF data were reconstructed using various dictionaries with different step sizes. First- and second-order radiomic features were extracted from each dataset. Intra-dictionary repeatability and inter-dictionary reproducibility were evaluated using intraclass correlation coefficients (ICCs). Features with ICCs > 0.90 were considered acceptable. Relative changes were calculated to assess inter-dictionary biases. Results: The overall scan-rescan ICCs of MRF-based radiomics ranged from 0.86 to 0.95, depending on dictionary step size. No significant differences were observed in the overall scan-rescan repeatability of MRF-based radiomic features and conventional T1-weighted imaging (p = 1.00). Intra-dictionary repeatability was insensitive to dictionary step size differences. MRF-based radiomic features varied among dictionaries (overall ICC for inter-dictionary reproducibility, 0.62–0.99), especially when step sizes were large. First-order and gray level co-occurrence matrix features were the most reproducible feature classes among different step size dictionaries. T1 map-derived radiomic features provided higher repeatability and reproducibility among dictionaries than those obtained with T2 maps. Conclusion: MRF-based radiomic features are highly repeatable in various dictionary step sizes. Caution is warranted when performing MRF-based radiomics using datasets containing maps generated from different dictionaries. Key Points: • MRF-based radiomic features are highly repeatable in various dictionary step sizes. • Use of different MRF dictionaries may result in variable radiomic features, even when the same MRF acquisition data are used. • Caution is needed when performing radiomic analysis using data reconstructed from different dictionaries. [ABSTRACT FROM AUTHOR]

Background: Atlas-based volumetry using three-dimensional T1-weighted (3D-T1W) magnetic resonance imaging (MRI) has been used previously to evaluate the volumes of intracranial tissues. Purpose: To evaluate the detectability of volume difference and accuracy for volumetry using smoothed data with an atlas-based method. Material and Methods: Twenty healthy individuals and 24 patients with idiopathic normal-pressure hydrocephalus (iNPH) underwent 3-T MRI, and sagittal 3D-T1W images were obtained in all participants. Signal values (as tissue probability) of voxels in five segmented data types (gray matter, white matter, cerebrospinal fluid [CSF], skull, soft tissue) derived from the 3D-T1W images with SPM 12 software were assigned simulated 3D-T1W signal intensities to each tissue image. The assigned data were termed "reference data." We created a reference 3 D-T1W image that included the reference data of all five tissue types. Standard volumes were measured for the reference CSF data with region of interest of lateral ventricle in native space, and measured volumes were obtained for non-smoothed and smoothed-modulated data. Detectability was evaluated between measured volumes in the healthy control and iNPH groups. Accuracy was evaluated as the difference between the mean measured and standard volumes. Results: In group comparison of measured volumes between the healthy control and iNPH groups, the lowest P value was for smoothed-modulated CSF data. In both groups, the largest difference from the standard volume was found for the mean of the measured volumes for smoothed-modulated CSF data. Conclusion: Our study shows that using smoothed data can improve detectability in group comparison. However, using smoothed data reduces the accuracy of volumetry. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder characterized by various neurological symptoms. Almost all RTT cases are caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, and several mouse models have been established to understand the disease. However, the neuroanatomical abnormalities in each brain region of RTT mouse models have not been fully understood. Here, we investigated the global and local neuroanatomy of the Mecp2 gene-deleted RTT model (Mecp2 -KO) mouse brain using T2-weighted 3D magnetic resonance imaging with different morphometry to clarify the brain structural abnormalities that are involved in the pathophysiology of RTT. We found a significant reduction in global and almost all local volumes in the brain of Mecp2 -KO mice. In addition, a detailed comparative analysis identified specific volume reductions in several brain regions in the Mecp2 -deficient brain. Our analysis also revealed that the Mecp2 -deficient brain shows changes in hemispheric asymmetry in several brain regions. These findings suggest that MeCP2 affects not only the whole-brain volume but also the region-specific brain structure. Our study provides a framework for neuroanatomical studies of a mouse model of RTT. [ABSTRACT FROM AUTHOR]

Moving particle semi-implicit (MPS) method is a mesh-free method to perform computational fluid dynamics (CFD). The purpose of this study was to calculate the simulated fractional flow reserve (sFFR) using a coronary stenosis model, and to validate the MPS-derived sFFR against invasive FFR using clinical coronary CT data. Coronary flow simulation included 21 stenosis models with stenosis ranging 30–70%. Patient coronary analysis was performed in 76 consecutive patients (100 vessels) who underwent coronary CT angiography and subsequent invasive FFR between November 2016 and March 2020. Accuracy of sFFR and CT angiography for diagnosis of invasive FFR ≤ 0.80 was compared. Quantitative morphological stenosis data of CT angiography were also obtained. Area stenosis showed a good correlation to sFFR (R2 = 0.996, p < 0.001) in coronary stenosis models. In the patient study, the mean FFR value was 0.82 ± 0.10, and 37 out of 100 vessels showed FFR ≤ 0.80. FFR and sFFR values showed a good correlation (R2 = 0.59, p < 0.001) with a slight underestimation of sFFR as compared with FFR (mean difference − 0.015 ± 0.096, p = 0.12). The sensitivity, specificity, positive predictive value, and negative predictive value of sFFR to predict FFR ≤ 0.80 was 86%, 89%, 82%, 92%, respectively. The accuracy to predict FFR ≤ 0.80 using sFFR was greater than using diameter stenosis and minimum lumen area (88% vs. 74%, p = 0.008). CFD using the MPS method showed feasible results validated against invasive FFR. The accuracy to predict significant stenosis was higher than morphological stenosis. [ABSTRACT FROM AUTHOR]

Background: Impulse control behaviors (ICBs) in Parkinson's disease (PD) are thought to be caused by an overdose of dopaminergic therapy in the relatively spared ventral striatum, or by hypersensitivity of this region to dopamine. Alterations in brain networks are now also thought to contribute to the development of ICBs. Objective: To comprehensively assess white matter microstructures in PD patients with ICBs using advanced diffusion MRI and magnetization transfer saturation (MT‐sat) imaging. Methods: This study included 19 PD patients with ICBs (PD‐ICBs), 18 PD patients without ICBs (PD‐nICBs), and 20 healthy controls (HCs). Indices of diffusion tensor imaging (DTI), diffusion kurtosis imaging, neurite orientation dispersion and density imaging, and MT‐sat imaging were evaluated using tract‐based spatial statistics (TBSS), regions of interest (ROIs), and tract‐specific analysis (TSA). Results: Compared with HCs, PD‐nICBs had significant alterations in many major white matter tracts in most parameters. In contrast, PD‐ICBs had only partial changes in several parameters. Compared with PD‐ICBs, TBSS, ROI, and TSA analyses revealed that PD‐nICBs had lower axial kurtosis, myelin volume fraction, and orientation dispersion index in the uncinate fasciculus and external capsule, as well as in the retrolenticular part of the internal capsule. These are components of the reward system and the visual and emotional perception areas, respectively. Interpretation: Myelin and axonal changes in fibers related to the reward system and visual emotional recognition might be more prominent in PD‐nICBs than in PD‐ICBs. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesize that myelin is more susceptible to damage over time than axons. We investigated the association between the estimated duration from the onset of multiple sclerosis (MS) plaques and myelin- and axon-related quantitative synthetic magnetic resonance imaging (SyMRI) and neurite orientation dispersion and density imaging (NODDI) metrics. Methods: We analyzed 31 patients with MS with 73 newly appeared plaques. Simple linear regression analysis was performed to assess the association between the estimated duration from the onset of plaques and quantitative MRI metrics. These metrics included the myelin volume fraction (MVF), axon volume fraction, and g-ratio in plaque and normal-appearing white matter. Results: MS plaques with a longer estimated duration from onset were significantly correlated with a lower MVF (slope = − 0.0070, R2 = 0.0970), higher g-ratio (slope = 0.0078, R2 = 0.0842) (all P values < 0.05). Conclusion: These results suggested that myelin in plaques undergoes continuous damage, more so than axons. Myelin imaging with SyMRI and NODDI may be useful for the quantitative assessment of temporal changes in MS plaques. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the water diffusivity changes along the perivascular space after lumboperitoneal shunt (LPS) surgery in idiopathic normal pressure hydrocephalus. Methods: Nine patients diagnosed with idiopathic normal pressure hydrocephalus (iNPH; three men and six women, mean age ± SD = 75.22 ± 5.12 years) according to the guidelines for iNPH in Japan were included in the study. Post-LPS surgery, six patients with iNPH who exhibited improvement in symptoms were defined as responder subjects, while three patients with iNPH who did not were defined as non-responder subjects. We calculated the mean analysis along the perivascular space (ALPS) index of the left and right hemispheres and compared the differences between pre- and post-LPS surgery mean ALPS indices in iNPH patients. In the responder or non-responder subjects, the mean ALPS indices in the pre- and post-operative iNPH groups were compared using Wilcoxon signed-rank tests. Next, correlation analyses between pre- and post-operation changes in the mean ALPS index and clinical characteristics were conducted. Results: The mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.021). In responder subjects, the mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.046). On the other hand, in the non-responder subjects, the mean ALPS index of the post-operative iNPH group was not significantly different compared to the pre-operative iNPH group (p = 0.285). The mean ALPS index change was not significantly correlated with changes in the Mini-Mental State Examination (MMSE) score (r = −0.218, p = 0.574), Frontal Assessment Battery (FAB) score (r = 0.185, p = 0.634), Trail Making Test A (TMTA) score (r = 0.250, p = 0.516), and Evans' index (r = 0.109, p = 0.780). In responder subjects, the mean ALPS index change was significantly correlated with Evans' index in pre-operative patients with iNPH (r = 0.841, p = 0.036). Conclusion: This study demonstrates the improved water diffusivity along perivascular space in patients with iNPH after LPS surgery. This could be indicative of glymphatic function recovery following LPS surgery. [ABSTRACT FROM AUTHOR]

Differentiating corticobasal degeneration presenting with corticobasal syndrome (CBD-CBS) from progressive supranuclear palsy with Richardson's syndrome (PSP-RS), particularly in early stages, is often challenging because the neurodegenerative conditions closely overlap in terms of clinical presentation and pathology. Although volumetry using brain magnetic resonance imaging (MRI) has been studied in patients with CBS and PSP-RS, studies assessing the progression of brain atrophy are limited. Therefore, we aimed to reveal the difference in the temporal progression patterns of brain atrophy between patients with CBS and those with PSP-RS purely based on cross-sectional data using Subtype and Stage Inference (SuStaIn)—a novel, unsupervised machine learning technique that integrates clustering and disease progression modeling. We applied SuStaIn to the cross-sectional regional brain volumes of 25 patients with CBS, 39 patients with typical PSP-RS, and 50 healthy controls to estimate the two disease subtypes and trajectories of CBS and PSP-RS, which have distinct atrophy patterns. The progression model and classification accuracy of CBS and PSP-RS were compared with those of previous studies to evaluate the performance of SuStaIn. SuStaIn identified distinct temporal progression patterns of brain atrophy for CBS and PSP-RS, which were largely consistent with previous evidence, with high reproducibility (99.7%) under cross-validation. We classified these diseases with high accuracy (0.875) and sensitivity (0.680 and 1.000, respectively) based on cross-sectional structural brain MRI data; the accuracy was higher than that reported in previous studies. Moreover, SuStaIn stage correctly reflected disease severity without the label of disease stage, such as disease duration. Furthermore, SuStaIn also showed the genialized performance of differentiation and reflection for CBS and PSP-RS. Thus, SuStaIn has potential for improving our understanding of disease mechanisms, accurately stratifying patients, and providing prognoses for patients with CBS and PSP-RS. [ABSTRACT FROM AUTHOR]

Purpose: The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was developed to evaluate the brain's glymphatic function or interstitial fluid dynamics. This study aimed to evaluate the reproducibility of the DTI-ALPS method and the effect of modifications in the imaging method and data evaluation. Materials and methods: Seven healthy volunteers were enrolled in this study. Image acquisition was performed for this test–retest study using a fixed imaging sequence and modified imaging methods which included the placement of region of interest (ROI), imaging plane, head position, averaging, number of motion-proving gradients, echo time (TE), and a different scanner. The ALPS-index values were evaluated for the change of conditions listed above. Results: This test–retest study by a fixed imaging sequence showed very high reproducibility (intraclass coefficient = 0.828) for the ALPS-index value. The bilateral ROI placement showed higher reproducibility. The number of averaging and the difference of the scanner did not influence the ALPS-index values. However, modification of the imaging plane and head position impaired reproducibility, and the number of motion-proving gradients affected the ALPS-index value. The ALPS-index values from 12-axis DTI and 3-axis diffusion-weighted image (DWI) showed good correlation (r = 0.86). Also, a shorter TE resulted in a larger value of the ALPS-index. Conclusion: ALPS index was robust under the fixed imaging method even when different scanners were used. ALPS index was influenced by the imaging plane, the number of motion-proving gradient axes, and TE in the imaging sequence. These factors should be uniformed in the planning ALPS method studies. The possibility to develop a 3-axis DWI-ALPS method using three axes of the motion-proving gradient was also suggested. [ABSTRACT FROM AUTHOR]

Purpose: Artery contrasted computed tomography (CT) enables accurate observations of the arteries and surrounding structures, thus being widely used for the diagnosis of diseases such as aneurysm. To avoid the complications caused by contrast agent, this paper proposes an aorta-aware deep learning method to synthesize artery contrasted CT volume form non-contrast CT volume. Methods: By introducing auxiliary multi-resolution segmentation tasks in the generator, we force the proposed network to focus on the regions of aorta and the other vascular structures. Then, the segmentation results produced by the auxiliary tasks were used to extract aorta. The detection of abnormal CT images containing aneurysm was implemented by estimating the maximum axial radius of aorta. Results: In comparison with the baseline models, the proposed network with auxiliary tasks achieved better performances with higher peak signal-noise ratio value. In aorta regions which are supposed to be the main region of interest in many clinic scenarios, the average improvement can be up to 0.33dB. Using the synthesized artery contrasted CT, the F score of aneurysm detection achieved 0.58 at slice level and 0.85 at case level. Conclusion: This study tries to address the problem of non-contrast to artery contrasted CT modality translation by employing a deep learning model with aorta awareness. The auxiliary tasks help the proposed model focus on aorta regions and synthesize results with clearer boundaries. Additionally, the synthesized artery contrasted CT shows potential in identifying slices with abdominal aortic aneurysm, and may provide an option for patients with contrast agent allergy. [ABSTRACT FROM AUTHOR]

The Gamma-Ray Astro-Imager with Nuclear Emulsion (GRAINE) project is aimed at the precise observation of astronomical gamma-ray sources in the energy range of 10 MeV–100 GeV using a balloon-borne telescope utilizing a nuclear emulsion, which can help realize precise imaging with high angular resolution (1.0○ at 100 MeV), polarization sensitivity, and large aperture area (10 m2). In 2018, the third balloon experiment was carried out as a demonstration of the detection of the brightest known astronomical gamma-ray source, the Vela pulsar, with an aperture area of 0.38 m2. In these data, some gamma rays were produced by the π0 → 2γ decay, which was caused by the hadronic interactions of cosmic rays in the detector. These could be used to calibrate the reconstructed angle, energy, and so on. In this study, we establish a method of searching for hadronic interactions and concomitant gamma rays with high statistics and purity. Our analysis indicates that the performance of our detector for gamma rays is as expected in wide incidence angle and energy ranges. We plan to commence scientific observations using the proposed system with the verified high angular resolution and largest aperture area in 2022 or later. [ABSTRACT FROM AUTHOR]

Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94–2.48], Low; 1.86 [1.02–3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98–2.02], Low; 1.49 [1.04–2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64–11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk. [ABSTRACT FROM AUTHOR]

Idiosyncratic drug toxicity (IDT) associated with specific human leukocyte antigen (HLA) allotype is a rare and unpredictable life-threatening adverse drug reaction for which prospective mechanistic studies in humans are difficult. Here, we show the importance of immune tolerance for IDT onset and determine whether it is susceptible to a common IDT, HLA-B*57:01-mediated abacavir (ABC)-induced hypersensitivity (AHS), using CD4+ T cell-depleted programmed death-1 receptor (PD-1)-deficient HLA-B*57:01 transgenic mice (B*57:01-Tg/PD-1−/−). Although AHS is not observed in B*57:01-Tg mice, ABC treatment increases the proportion of cytokine- and cytolytic granule-secreting effector memory CD8+ T cells in CD4+ T cell-depleted B*57:01-Tg/PD-1−/− mice, thereby inducing skin toxicity with CD8+ T cell infiltration, mimicking AHS. Our results demonstrate that individual differences in the immune tolerance system, including PD-1highCD8+ T cells and regulatory CD4+ T cells, may affect the susceptibility of humans to HLA-mediated IDT in humans. Using a transgenic mouse model that recapitulates abacavir hypersensitivity syndrome, an idiosyncratic adverse drug reaction, Susukida et al show that individual differences in the immune tolerance system affect the susceptibility to idiosyncratic drug toxicity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether Parkinson's disease (PD) can be differentiated from healthy controls and to identify neural circuit disorders in PD by applying a deep learning technique to parameter-weighted and number of streamlines (NOS)–based structural connectome matrices calculated from diffusion-weighted MRI. Methods: In this prospective study, 115 PD patients and 115 healthy controls were enrolled. NOS-based and parameter-weighted connectome matrices were calculated from MRI images obtained with a 3-T MRI unit. With 5-fold cross-validation, diagnostic performance of convolutional neural network (CNN) models using those connectome matrices in differentiating patients with PD from healthy controls was evaluated. To identify the important brain connections for diagnosing PD, gradient-weighted class activation mapping (Grad-CAM) was applied to the trained CNN models. Results: CNN models based on some parameter-weighted structural matrices (diffusion kurtosis imaging (DKI)–weighted, neurite orientation dispersion and density imaging (NODDI)–weighted, and g-ratio-weighted connectome matrices) showed moderate performance (areas under the receiver operating characteristic curve (AUCs) = 0.895, 0.801, and 0.836, respectively) in discriminating PD patients from healthy controls. The DKI-weighted connectome matrix performed significantly better than the conventional NOS-based matrix (AUC = 0.761) (DeLong's test, p < 0.0001). Alterations of neural connections between the basal ganglia and cerebellum were indicated by applying Grad-CAM to the NODDI- and g-ratio-weighted matrices. Conclusion: Patients with PD can be differentiated from healthy controls by applying the deep learning technique to the parameter-weighted connectome matrices, and neural circuit disorders including those between the basal ganglia on one side and the cerebellum on the contralateral side were visualized. [ABSTRACT FROM AUTHOR]

Despite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells. [ABSTRACT FROM AUTHOR]

Background: Although pathological studies usually indicate pure dopaminergic neuronal degeneration in patients with parkin (PRKN) mutations, there is no evidence to date regarding white matter (WM) pathology. A previous diffusion MRI study has revealed WM microstructural alterations caused by systemic oxidative stress in idiopathic Parkinson's disease (PD), and we found that PRKN patients have systemic oxidative stress in serum biomarker studies. Thus, we hypothesized that PRKN mutations might lead to WM abnormalities. Objective: To investigate whether there are WM microstructural abnormalities in early-onset PD patients with PRKN mutations using diffusion tensor imaging (DTI). Methods: Nine PRKN patients and 15 age- and sex-matched healthy controls were recruited. DTI measures were acquired on a 3T MR scanner using a b value of 1,000 s/mm2 along 32 isotropic diffusion gradients. The DTI measures were compared between groups using tract-based spatial statistics (TBSS) analysis. Correlation analysis was also performed between the DTI parameters and several serum oxidative stress markers obtained in a previously conducted metabolomic analysis. Results: Although the WM volumes were not significantly different, the TBSS analysis revealed a corresponding decrease in fractional anisotropy and an increase in mean diffusivity and radial diffusivity in WM areas, such as the anterior and superior corona radiata and uncinate fasciculus, in PRKN patients compared with controls. Furthermore, 9-hydroxystearate, an oxidative stress marker, and disease duration were positively correlated with several parameters in PRKN patients. Conclusion: This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults. Methods: NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N = 26; 19 males and 7 females; 32.93 ± 9.24 years old) and age- and sex-matched typically developing (TD; N = 25; 17 males and 8 females; 34.43 ± 9.02 years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD. Results: Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67–73%; specificity, 68–80%). Limitations: The absence of histopathological confirmation limit the interpretation of our findings. Conclusions: Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism. [ABSTRACT FROM AUTHOR]

Background: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are useful in determining indications for revascularization of coronary artery disease (CAD). Although the discordance of FFR and iFR was noted in approximately 20%, this cause has not been well established. We investigated patient background and features on coronary CT angiography (CCTA) showing not only FFR- and iFR-positive findings but also discordance between FFR ≤ 0.8 and iFR ≤ 0.89. Methods: Subjects were consecutively treated in 83 cases with 105 vessels in which stenosis of 30–90% was detected at one vessel of at least 2 mm or more in the major epicardial vessels and FFR and iFR was performed within subsequent 90 days, among suspected CAD which underwent CCTA. The factors affecting not only FFR- and iFR-positive findings, respectively, but also discordance between FFR and iFR was evaluated using logistic regression analysis on per-patient and per-vessel basis. Results: FFR- and iFR-positive findings were observed in 42 vessels (40.0%) and 34 vessels (32.3%), respectively. Discordance between FFR ≤ 0.8 and iFR ≤ 0.89 was observed in 22 vessels (21.0%) of 21 patients. In multivariate logistic analysis, LAD (OR 3.55; 95%CI 1.20–11.71; p = 0.0217) and lumen volume/myocardial weight (L/M) ratio (OR 0.93; 0.86–0.99, p = 0.0290) were significant predictors for FFR-positive findings. For iFR-positive findings, LAD (OR 3.86; 95%CI 1.12–13.31; p = 0.0236) was only significant predictor. In FFR ≤ 0.8 and iFR > 0.89 group (15 vessels, 14.3%), positive remodeling (PR) (OR 5.03, 95%CI 1.23–20.48, p = 0.0205) was significant predictor. In FFR > 0.8 and iFR ≤ 0.89 group (7 vessels, 6.7%), there were no significant predictors. Conclusion: On CCTA characteristics, a relevant predictor for FFR-positive findings included low L/M ratio. PR was significant predictor in FFR-positive, iFR-negative patients among those with discordance between the FFR and iFR. [ABSTRACT FROM AUTHOR]