Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology.

Intestinal epithelial cell (IEC) damage by T cells contributes to graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis. But little is known about the target cell-intrinsic features that affect disease severity. Here we identified disruption of oxidative phosphorylation and an increase in succinate levels in the IECs from several distinct in vivo models of T cell-mediated colitis. Metabolic flux studies, complemented by imaging and protein analyses, identified disruption of IEC-intrinsic succinate dehydrogenase A (SDHA), a component of mitochondrial complex II, in causing these metabolic alterations. The relevance of IEC-intrinsic SDHA in mediating disease severity was confirmed by complementary chemical and genetic experimental approaches and validated in human clinical samples. These data identify a critical role for the alteration of the IEC-specific mitochondrial complex II component SDHA in the regulation of the severity of T cell-mediated intestinal diseases.

Uridine-derived ribose fuels glucose-restricted pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox balance, survival and proliferation in glucose-restricted PDA cells. In PDA, UPP1 is regulated by KRAS-MAPK signalling and is augmented by nutrient restriction. Consistently, tumours expressed high UPP1 compared with non-tumoural tissues, and UPP1 expression correlated with poor survival in cohorts of patients with PDA. Uridine is available in the tumour microenvironment, and we demonstrated that uridine-derived ribose is actively catabolized in tumours. Finally, UPP1 deletion restricted the ability of PDA cells to use uridine and blunted tumour growth in immunocompetent mouse models. Our data identify uridine utilization as an important compensatory metabolic process in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy.

Harmonic field extension for QSM with reduced spatial coverage using physics-informed generative adversarial network.

Quantitative susceptibility mapping (QSM) is frequently employed in investigating brain iron related to brain development and diseases within deep gray matter (DGM). Nonetheless, the acquisition of whole-brain QSM data is time-intensive. An alternative approach, focusing the QSM specifically on areas of interest such as the DGM by reducing the field-of-view (FOV), can significantly decrease scan times. However, severe susceptibility value underestimations have been reported during QSM reconstruction with a limited FOV, largely attributable to artifacts from incorrect background field removal in the boundary region. This presents a considerable barrier to the clinical use of QSM with small spatial coverages using conventional methods alone. To mitigate the propagation of these errors, we proposed a harmonic field extension method based on a physics-informed generative adversarial network. Both quantitative and qualitative results demonstrate that our method outperforms conventional methods and delivers results comparable to those obtained with full FOV. Furthermore, we demonstrate the versatility of our method by applying it to data acquired prospectively with limited FOV and to data from patients with Parkinson's disease. The method has shown significant improvements in local field results, with QSM outcomes. In a clear illustration of its feasibility and effectiveness in real clinical environments, our proposed method addresses the prevalent issue of susceptibility underestimation in QSM with small spatial coverage.

Alterations in the multilayer network in patients with rapid eye movement sleep behaviour disorder.

This study aimed to reveal the pathophysiology of isolated rapid eye movement sleep behaviour disorder (RBD) in patients using multilayer network analysis. Participants eligible for isolated RBD were included and verified via polysomnography. Both iRBD patients and healthy controls underwent brain MRI, including T1-weighted imaging and diffusion tensor imaging. Grey matter matrix was derived from T1-weighted images using a morphometric similarity network. White matter matrix was formed from diffusion tensor imaging-based structural connectivity. Multilayer network analysis of grey and white matter was performed using graph theory. We studied 29 isolated RBD patients and 30 healthy controls. Patients exhibited a higher average overlap degree (27.921 vs. 23.734, p = 0.002) and average multilayer clustering coefficient (0.474 vs. 0.413, p = 0.002) compared with controls. Additionally, several regions showed significant differences in the degree of overlap and multilayer clustering coefficient between patients with isolated RBD and healthy controls at the nodal level. The degree of overlap in the left medial orbitofrontal, left posterior cingulate, and right paracentral nodes and the multilayer clustering coefficients in the left lateral occipital, left rostral middle frontal, right fusiform, right inferior posterior parietal, and right parahippocampal nodes were higher in patients with isolated RBD than in healthy controls. We found alterations in the multilayer network at the global and nodal levels in patients with isolated RBD, and these changes may be associated with the pathophysiology of isolated RBD. Multilayer network analysis can be used widely to explore the mechanisms underlying various neurological disorders.

Three-dimensional heavily T2-weighted FLAIR in the detection of blood-labyrinthine barrier leakage in patients with sudden sensorineural hearing loss: comparison with T1 sequences and application of deep learning-based reconstruction.

OBJECTIVE: Blood-labyrinthine barrier leakage has been reported in sudden sensorineural hearing loss (SSNHL). We compared immediate post-contrast 3D heavily T2-weighted fluid-attenuated inversion recovery (FLAIR), T1 spin echo (SE), and 3D T1 gradient echo (GRE) sequences, and heavily T2-weighted FLAIR (hvT2F) with and without deep learning-based reconstruction (DLR) in detecting perilymphatic enhancement. METHODS: Fifty-four patients with unilateral SSNHL who underwent ear MRI with three sequences were included. We compared asymmetry scores, confidence scores, and detection rates of perilymphatic enhancement among the three sequences and obtained 3D hvT2F with DLR from 35 patients. The above parameters and subjective image quality between 3D hvT2F with and without DLR were compared. RESULTS: Asymmetry scores and detection rate of 3D hvT2F were significantly higher than 3D GRE T1 and SE T1 (respectively, 1.37, 0.11, 0.19; p < 0.001). Asymmetry scores significantly increased with DLR compared to 3D hvT2F for experienced and inexperienced readers (respectively, 1.77 vs. 1.40, p = 0.036; 1.49 vs. 1.03, p = 0.012). The detection rate significantly increased only for the latter (57.1% vs. 31.4%, p = 0.022). Patients with perilymphatic enhancement had significantly higher air conduction thresholds on initial (77.96 vs. 57.79, p = 0.002) and 5 days after presentation (63.38 vs. 41.85, p = 0.019). CONCLUSION: 3D hvT2F significantly increased the detectability of perilymphatic enhancement compared to 3D GRE T1 and SE T1. DLR further improved the conspicuity of perilymphatic enhancement in 3D hvT2F. 3D hvT2F and DLR are useful for evaluating blood-labyrinthine barrier leakage; furthermore, they might provide prognostic value in the early post-treatment period. CLINICAL RELEVANCE STATEMENT: Ten-minute post-contrast 3D heavily T2-weighed FLAIR imaging is a potentially efficacious sequence in demonstrating perilymphatic enhancement in patients with sudden sensorineural hearing loss and may be further improved by deep learning-based reconstruction. KEY POINTS: • 3D heavily T2-weighted FLAIR (3D hvT2F) is a sequence sensitive in detecting low concentrations of contrast in the perilymphatic space. • 3D hvT2F sequences properly demonstrated perilymphatic enhancement in sudden sensorineural hearing loss compared to T1 sequences and were further improved by deep learning-based reconstruction (DLR). • 3D hvT2F and DLR are efficacious sequences in detecting blood-labyrinthine barrier leakage and with potential prognostic information.

Anti-seizure medication response and the glymphatic system in patients with focal epilepsy.

BACKGROUND AND PURPOSE: We aimed to evaluate (i) glymphatic system function in patients with focal epilepsy in comparison with healthy controls, and (ii) the association between anti-seizure medication (ASM) response and glymphatic system function by using diffusion tensor image analysis along the perivascular space (DTI-ALPS). METHODS: We retrospectively enrolled 100 patients with focal epilepsy who had normal brain magnetic resonance imaging (MRI) findings, and classified them as "poor" or "good" ASM responders according to their seizure control at the time of brain MRI. We also included 79 age- and sex-matched healthy controls. All patients and healthy controls underwent conventional brain MRI and diffusion tensor imaging. The DTI-ALPS index was calculated using the DSI studio program. RESULTS: Of the 100 patients with focal epilepsy, 38 and 62 were poor and good ASM responders, respectively. The DTI-ALPS index differed significantly between patients with focal epilepsy and healthy controls and was significantly lower in patients with focal epilepsy (1.55 vs. 1.70; p < 0.001). The DTI-ALPS index also differed significantly according to ASM response and was lower in poor ASM responders (1.48 vs. 1.59; p = 0.047). Furthermore, the DTI-ALPS index was negatively correlated with age (r = -0.234, p = 0.019) and duration of epilepsy (r = -0.240, p = 0.016) in patients with focal epilepsy. CONCLUSION: Our study is the first to identify, in focal epilepsy patients, a greater reduction in glymphatic system function among poor ASM responders compared to good responders. To confirm our results, further prospective multicenter studies with large sample sizes are needed.

Structural connectivity as a predictive factor for responsiveness to levetiracetam treatment in epilepsy.

PURPOSE: To investigate whether structural connectivity or glymphatic system function is a potential predictive factor for levetiracetam (LEV) response in patients with newly diagnosed epilepsy. METHODS: We enrolled patients with newly diagnosed epilepsy who were administered LEV as initial monotherapy and underwent diffusion tensor imaging (DTI) at diagnosis. We categorized the patients into drug response. We used graph theory to calculate the network measures for structural connectivity based on the DTI scans in patients with epilepsy. Additionally, we evaluated glymphatic system function by calculating the DTI analysis along the perivascular space (DTI-ALPS) index based on DTI scans. RESULTS: We enrolled 84 patients with epilepsy. The clinical factors and DTI-ALPS index did not differ between the groups. However, some of the structural connectivity measures significantly differ between the groups. The poor responders exhibited a higher mean clustering coefficient, global efficiency, and small-worldness index than the good responders (p = 0.003, p = 0.048, and p = 0.038, respectively). In the receiver operating characteristic curve analysis, the mean clustering coefficient exhibited the highest performance in predicting the responsiveness to LEV (area under the curve of 0.677). In the multiple logistic regression analysis, the mean clustering coefficient of the structural connectivity measures was the only significant predictor of LEV response (p = 0.014). Furthermore, in the survival analysis, the mean clustering coefficient was the only significant predictor of LEV response (p = 0.026). CONCLUSION: We demonstrated that structural connectivity is a potential predictive factor for responsiveness to LEV treatment in patients with newly diagnosed epilepsy.

Multilayer network analysis in patients with juvenile myoclonic epilepsy.

INTRODUCTION: We conducted a multilayer network analysis in patients with juvenile myoclonic epilepsy (JME) and healthy controls, to investigate the gray matter layer using a morphometric similarity network and analyze the white matter layer using structural connectivity. METHODS: We enrolled 42 patients with newly diagnosed JME and 53 healthy controls. Brain magnetic resonance imaging (MRI) using a three-tesla MRI scanner, including T1-weighted imaging and diffusion tensor imaging (DTI) were performed. We created a gray matter layer matrix with a morphometric similarity network using T1-weighted imaging, and a white matter layer matrix with structural connectivity using the DTI. Subsequently, we performed a multilayer network analysis by applying graph theory. RESULTS: There were significant differences in network at the global level in the multilayer network analysis between the groups. The average multiplex participation of patients with JME was lower than that of healthy controls (0.858 vs. 0.878, p = 0.007). In addition, several regions showed significant differences in multiplex participation at the nodal level in the multilayer network analysis. Multiplex participation in the right entorhinal cortex was lower, whereas multiplex participation in the right supramarginal gyrus was higher at the nodal level in the multilayer network analysis of patients with JME compared to healthy controls. CONCLUSION: We demonstrated differences in network at the global and nodal levels in the multilayer network analysis between patients with JME and healthy controls. These features may be associated with the pathophysiology of JME and could help us understand the complex brain network in patients with JME.

Alteration of multilayer network perspective on gray and white matter connectivity in obstructive sleep apnea.

PURPOSE: The objective of this research was to examine changes in the neural networks of both gray and white matter in individuals with obstructive sleep apnea (OSA) in comparison to those without the condition, employing a comprehensive multilayer network analysis. METHODS: Patients meeting the criteria for OSA were recruited through polysomnography, while a control group of healthy individuals matched for age and sex was also assembled. Utilizing T1-weighted imaging, a morphometric similarity network was crafted to represent gray matter, while diffusion tensor imaging provided structural connectivity for constructing a white matter network. A multilayer network analysis was then performed, employing graph theory methodologies. RESULTS: We included 40 individuals diagnosed with OSA and 40 healthy participants in our study. Analysis revealed significant differences in various global network metrics between the two groups. Specifically, patients with OSA exhibited higher average degree overlap and average multilayer clustering coefficient (28.081 vs. 23.407, p < 0.001; 0.459 vs. 0.412, p = 0.004), but lower multilayer modularity (0.150 vs. 0.175, p = 0.001) compared to healthy controls. However, no significant differences were observed in average multiplex participation, average overlapping strength, or average weighted multiplex participation between the patients with OSA and healthy controls. Moreover, several brain regions displayed notable differences in degree overlap at the nodal level between patients with OSA and healthy controls. CONCLUSION: Remarkable alterations in the multilayer network, indicating shifts in both gray and white matter, were detected in patients with OSA in contrast to their healthy counterparts. Further examination at the nodal level unveiled notable changes in regions associated with cognition, underscoring the effectiveness of multilayer network analysis in exploring interactions across brain layers.

Cerebellar volumes and the intrinsic cerebellar network in patients with obstructive sleep apnea.

PURPOSE: This research aimed to explore changes in both cerebellar volume and the intrinsic cerebellar network in patients with obstructive sleep apnea (OSA). METHODS: Newly diagnosed OSA patients and healthy controls were included in the study. All participants underwent three-dimensional T1-weighted imaging using a 3-T MRI scanner. Cerebellar volumes, both overall and subdivided, were quantified using the ACAPULCO program. The intrinsic cerebellar network was assessed using the BRAPH program, which applied graph theory to the cerebellar volume subdivision. Comparisons were drawn between the patients with OSA and healthy controls. RESULTS: The study revealed that the 26 patients with OSA exhibited a notably lower total cerebellar volume compared to the 28 healthy controls (8.330 vs. 9.068%, p < 0.001). The volume of the left lobule VIIB was reduced in patients with OSA compared to healthy controls (0.339 vs. 0.407%, p = 0.001). Among patients with OSA, there was a negative correlation between the volume of the left lobule X and apnea-hypopnea index during non-rapid eye movement sleep (r = - 0.536, p = 0.005). However, no significant differences were observed in the intrinsic cerebellar network between patients and healthy controls. CONCLUSION: This study established that patients with OSA exhibited decreased total cerebellar volumes and particularly reduced volumes in subdivisions such as the left lobule VIIB compared to healthy controls. These findings suggest potential involvement of the cerebellum in the underlying mechanisms of OSA.

A redox cycle with complex II prioritizes sulfide quinone oxidoreductase-dependent H2S oxidation.

The dual roles of H2S as an endogenously synthesized respiratory substrate and as a toxin raise questions as to how it is cleared when the electron transport chain is inhibited. Sulfide quinone oxidoreductase (SQOR) catalyzes the first step in the mitochondrial H2S oxidation pathway, using CoQ as an electron acceptor, and connects to the electron transport chain at the level of complex III. We have discovered that at high H2S concentrations, which are known to inhibit complex IV, a new redox cycle is established between SQOR and complex II, operating in reverse. Under these conditions, the purine nucleotide cycle and the malate aspartate shuttle furnish fumarate, which supports complex II reversal and leads to succinate accumulation. Complex II knockdown in colonocytes decreases the efficiency of H2S clearance while targeted knockout of complex II in intestinal epithelial cells significantly decreases the levels of thiosulfate, a biomarker of H2S oxidation, to approximately one-third of the values seen in serum and urine samples from control mice. These data establish the physiological relevance of this newly discovered redox circuitry between SQOR and complex II for prioritizing H2S oxidation and reveal the quantitatively significant contribution of intestinal epithelial cells to systemic H2S metabolism.

In vitro modeling of liver fibrosis with 3D co-culture system using a novel human hepatic stellate cell line.

Hepatic stellate cells (HSCs) play an important role in liver fibrosis; however, owing to the heterogeneity and limited supply of primary HSCs, the development of in vitro liver fibrosis models has been impeded. In this study, we established and characterized a novel human HSC line (LSC-1), and applied it to various types of three-dimensional (3D) co-culture systems with differentiated HepaRG cells. Furthermore, we compared LSC-1 with a commercially available HSC line on conventional monolayer culture. LSC-1 exhibited an overall upregulation of the expression of fibrogenic genes along with increased levels of matrix and adhesion proteins, suggesting a myofibroblast-like or transdifferentiated state. However, activated states reverted to a quiescent-like phenotype when cultured in different 3D culture formats with a relatively soft microenvironment. Additionally, LSC-1 exerted an overall positive effect on co-cultured differentiated HepaRG, which significantly increased hepatic functionality upon long-term cultivation compared with that achieved with other HSC line. In 3D spheroid culture, LSC-1 exhibited enhanced responsiveness to transforming growth factor beta 1 exposure that is caused by a different matrix-related protein expression mechanism. Therefore, the LSC-1 line developed in this study provides a reliable candidate model that can be used to address unmet needs, such as development of antifibrotic therapies.

Structural brain network analysis in occipital lobe epilepsy.

BACKGROUND: This study aimed to analyze the structural brain network in patients with occipital lobe epilepsy (OLE) and investigate the differences in structural brain networks between patients with OLE and healthy controls. METHODS: Patients with OLE and healthy controls with normal brain MRI findings were enrolled. They underwent diffusion tensor imaging using a 3.0T MRI scanner, and we computed the network measures of global and local structural networks in patients with OLE and healthy controls using the DSI studio program. We compared network measures between the groups. RESULTS: We enrolled 23 patients with OLE and 42 healthy controls. There were significant differences in the global structural network between patients with OLE and healthy controls. The assortativity coefficient (-0.0864 vs. -0.0814, p = 0.0214), mean clustering coefficient (0.0061 vs. 0.0064, p = 0.0203), global efficiency (0.0315 vs. 0.0353, p = 0.0086), and small-worldness index (0.0001 vs. 0.0001, p = 0.0175) were lower, whereas the characteristic path length (59.2724 vs. 53.4684, p = 0.0120) was higher in patients with OLE than those in the healthy controls. There were several nodes beyond the occipital lobe that showed significant differences in the local structural network between the groups. In addition, the assortativity coefficient was negatively correlated with the duration of epilepsy (r=-0.676, p = 0.001).

Involvement of the default mode network in patients with transient global amnesia: multilayer network.

INTRODUCTION: We aimed to investigate the alterations in the multilayer network in patients with transient global amnesia (TGA). METHODS: We enrolled 124 patients with TGA and 80 healthy controls. Both patients with TGA and healthy controls underwent a three-teslar brain magnetic resonance imaging (MRI). A gray matter layer matrix was created using a morphometric similarity network derived from the T1-weighted imaging, and a white matter layer matrix was constructed using structural connectivity based on the diffusion tensor imaging. A multilayer network analysis was performed by applying graph theoretical analysis. RESULTS: There were no significant differences in global network measures between the groups. However, several regions, related to the default mode network, showed significant differences in nodal network measures between the groups. Multi-richness in the left pars opercularis, multi-rich-club degree in the right posterior cingulate gyrus, and weighted multiplex participation in the right posterior cingulate gyrus were higher in patients with TGA compared with healthy controls (15.47 vs. 12.26, p = 0.0005; 41.68 vs. 37.16, p = 0.0005; 0.90 vs. 0.80, p = 0.0005; respectively). The multiplex core-periphery in the left precuneus was higher (0.96 vs. 0.84, p = 0.0005), whereas that in the transverse temporal gyrus was lower in patients with TGA compared with healthy controls (0.00 vs. 0.02, p = 0.0005). CONCLUSION: We newly find the alterations in the multilayer network in patients with TGA compared with healthy controls, which shows the involvement of the default mode network. These changes may be related to the pathophysiology of TGA.

Cerebellar Volume Reduction in Patients with Isolated REM Sleep Behavior Disorder: Evidence of a Potential Role of the Cerebellum.

INTRODUCTION: In this study, we aimed to investigate changes in the total cerebellar volume, subdivisions of the cerebellar volume, and intrinsic cerebellar network in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) compared to healthy controls. METHODS: We enrolled patients with newly diagnosed iRBD and healthy controls who had no structural lesions according to their brain MRI. All participants underwent three-dimensional T1-weighted imaging. We obtained the total cerebellar volume and subdivisions of the cerebellar volume using the ACAPULCO program and calculated the intrinsic cerebellar network using a BRAPH program based on the subdivisions of the cerebellar volume by applying a graph theory. We compared the cerebellar volumes and intrinsic cerebellar network between the patients with iRBD and healthy controls. RESULTS: In total, we enrolled 43 patients with iRBD and 47 healthy controls. Total cerebellar volume in patients with iRBD was lower than that in the healthy controls (8.4637 vs. 9.0863%, p = 0.0001). There were significant differences in the subdivisions of cerebellar volume between the groups. The volumes of the right and left lobule VIIB in the patients with iRBD were lower than those in the healthy controls (right, 0.3495 vs. 0.4025%, p = 0.0009; left, 0.3561 vs. 0.4293%, p < 0.0001). However, the other cerebellar volumes, such as the corpus meullare and vermis, were not different between the groups. The intrinsic cerebellar network was not different between the patients with iRBD and healthy controls. CONCLUSION: We found decreased total cerebellar volumes and subdivisions of the cerebellar volume, particularly in the right and left lobule VIIB, in patients with iRBD compared to healthy controls. The present results suggest that the cerebellum may play a potential role in the pathogenesis of iRBD.

Comparison of deep learning-based reconstruction of PROPELLER Shoulder MRI with conventional reconstruction.

OBJECTIVE: To compare the image quality and agreement among conventional and accelerated periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) MRI with both conventional reconstruction (CR) and deep learning-based reconstruction (DLR) methods for evaluation of shoulder. MATERIALS AND METHODS: We included patients who underwent conventional (acquisition time, 8 min) and accelerated (acquisition time, 4 min and 24 s; 45% reduction) PROPELLER shoulder MRI using both CR and DLR methods between February 2021 and February 2022 on a 3 T MRI system. Quantitative evaluation was performed by calculating the signal-to-noise ratio (SNR). Two musculoskeletal radiologists compared the image quality using conventional sequence with CR as the reference standard. Interobserver agreement between image sets for evaluating shoulder was analyzed using weighted/unweighted kappa statistics. RESULTS: Ninety-two patients with 100 shoulder MRI scans were included. Conventional sequence with DLR had the highest SNR (P < .001), followed by accelerated sequence with DLR, conventional sequence with CR, and accelerated sequence with CR. Comparison of image quality by both readers revealed that conventional sequence with DLR (P = .003 and P < .001) and accelerated sequence with DLR (P = .016 and P < .001) had better image quality than the conventional sequence with CR. Interobserver agreement was substantial to almost perfect for detecting shoulder abnormalities (κ = 0.600-0.884). Agreement between the image sets was substantial to almost perfect (κ = 0.691-1). CONCLUSION: Accelerated PROPELLER with DLR showed even better image quality than conventional PROPELLER with CR and interobserver agreement for shoulder pathologies comparable to that of conventional PROPELLER with CR, despite the shorter scan time.

Automated Brain Volumetry in Patients With Memory Impairment: Comparison of Conventional and Ultrafast 3D T1-Weighted MRI Sequences Using Two Software Packages.

BACKGROUND. Isotropic 3D T1-weighted imaging has long acquisition times, potentially leading to motion artifact and altered brain volume measurements. Acquisition times may be greatly shortened using an isotropic ultrafast 3D echo-planar imaging (EPI) T1-weighted sequence. OBJECTIVE. The purpose of this article was to compare automated brain volume measurements between conventional 3D T1-weighted imaging and ultrafast 3D EPI T1-weighted imaging. METHODS. This retrospective study included 36 patients (25 women, 11 men; mean age, 68.4 years) with memory impairment who underwent 3-T brain MRI. Examinations included both conventional 3D T1-weighted imaging using inversion recovery gradient-recalled echo sequence (section thickness, 1.0 mm; acquisition time, 3 minutes 4 seconds) and, in patients exhibiting motion, an isotropic ultrafast 3D EPI T1-weighted sequence (section thickness, 1.2 mm; acquisition time, 30 seconds). The 36-patient sample excluded five patients in whom severe motion artifact rendered the conventional sequence of insufficient quality for volume measurements. Automated brain volumetry was performed using NeuroQuant (version 3.0, CorTechs Laboratories) and FreeSurfer (version 7.1.1, Harvard University) software. Volume measurements were compared between sequences for nine regions in each hemisphere. RESULTS. Volumes showed substantial to almost perfect agreement between the two sequences for most regions bilaterally. However, most regions showed significant mean differences between sequences, and Bland-Altman analyses showed consistent systematic biases and wide limits of agreement (LOA). For example, for the left hemisphere using NeuroQuant, volume was significantly greater for the ultrafast sequence in four regions and significantly greater for the conventional sequence in three regions, whereas standardized effect size between sequences was moderate for four regions and large for one region. Using NeuroQuant, mean bias (ultrafast minus conventional) and 95% LOA were greatest in cortical gray matter bilaterally (-50.61 cm3 [-56.27 cm3, -44.94 cm3] for the left hemisphere; -50.02 cm3 [-54.88 cm3, -45.16 cm3] for the right hemisphere). The variation between the two sequences was observed in subset analyses of 16 patients with and 20 patients without Alzheimer disease. CONCLUSION. Brain volume measurements show significant differences and systematic biases between the conventional and ultrafast sequences. CLINICAL IMPACT. In patients in whom severe motion artifact precludes use of the conventional sequence, the ultrafast sequence may be useful to enable brain volume-try. However, the current conventional 3D T1-weighted sequence remains preferred in patients who can tolerate the standard examination.

Image Quality and Diagnostic Performance of Accelerated Shoulder MRI With Deep Learning-Based Reconstruction.

BACKGROUND. Shoulder MRI using standard multiplanar sequences requires long scan times. Accelerated sequences have tradeoffs in noise and resolution. Deep learning-based reconstruction (DLR) may allow reduced scan time with preserved image quality. OBJECTIVE. The purpose of this study was to compare standard shoulder MRI sequences and accelerated sequences without and with DLR in terms of image quality and diagnostic performance. METHODS. This retrospective study included 105 patients (45 men, 60 women; mean age, 57.6 ± 10.9 [SD] years) who underwent a total of 110 3-T shoulder MRI examinations. Examinations included standard sequences (scan time, 9 minutes 23 seconds) and accelerated sequences (3 minutes 5 seconds; 67% reduction), both including fast spin-echo sequences in three planes. Standard sequences were reconstructed using the conventional pipeline; accelerated sequences were reconstructed using both the conventional pipeline and a commercially available DLR pipeline. Two radiologists independently assessed three image sets (standard sequence, accelerated sequence without DLR, and accelerated sequence with DLR) for subjective image quality and artifacts using 4-point scales (4 = highest quality) and identified pathologies of the subscapularis tendon, supraspinatus-infraspinatus tendon, long head of the biceps brachii tendon, and glenoid labrum. Interobserver agreement and agreement between image sets for the evaluated pathologies were assessed using weighted kappa statistics. In 27 patients who underwent arthroscopy, diagnostic performance was calculated using arthroscopic findings as a reference standard. RESULTS. Mean subjective image quality scores for readers 1 and 2 were 10.6 ± 1.2 and 10.5 ± 1.4 for the standard sequence, 8.1 ± 1.3 and 7.2 ± 1.1 for the accelerated sequence without DLR, and 10.7 ± 1.2 and 10.5 ± 1.6 for the accelerated sequence with DLR. Mean artifact scores for readers 1 and 2 were 9.3 ± 1.2 and 10.0 ± 1.0 for the standard sequence, 7.3 ± 1.3 and 9.1 ± 0.8 for the accelerated sequence without DLR, and 9.4 ± 1.2 and 9.8 ± 0.8 for the accelerated sequence with DLR. Interobserver agreement ranged from kappa of 0.813-0.951 except for accelerated sequence without DLR for the supraspinatus-infraspinatus tendon (κ = 0.673). Agreement between image sets ranged from kappa of 0.809-0.957 except for reader 1 for supraspinatus-infraspinatus tendon (κ = 0.663-0.700). Accuracy, sensitivity, and specificity for tears of the four structures were not different (p > .05) among image sets. CONCLUSION. Accelerated sequences with DLR provide 67% scan time reduction with similar subjective image quality, artifacts, and diagnostic performance to standard sequences. CLINICAL IMPACT. Accelerated sequences with DLR may provide an alternative to standard sequences for clinical shoulder MRI.

Normal glymphatic system function in patients with migraine: A pilot study.

OBJECTIVE: No studies have evaluated the glymphatic system function in patients with migraine. In this pilot study, we evaluated and compared the alterations in the glymphatic system function in patients with migraine with healthy controls using a diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) method. We also investigated the differences in the glymphatic system function table between patients with migraine with and without aura using the ALPS method. METHODS: This field study used a cross-sectional study design. We prospectively enrolled patients with migraine and healthy controls. All brain magnetic resonance imaging (MRI), including DTI, in participants, patients with migraine, and healthy controls were obtained using the same MRI scanner. We calculated and compared the ALPS index between patients with migraine and healthy controls, and between patients with migraine with and without aura. In addition, we investigated the association between the glymphatic system function and the clinical characteristics of migraine. RESULTS: We enrolled 92 patients with migraine and 80 healthy controls. There were no significant differences in the ALPS index between patients with migraine and healthy controls (1.655 ± 0.335 [patients with migraine] vs. 1.713 ± 0.297 [controls], difference = 0.058, 95% confidence interval [CI] of difference = -0.037 to 0.154, p = 0.233), and between patients with migraine with and without aura (1.690 ± 0.380 [with aura] vs. 1.645 ± 0.323 [without aura], difference = -0.044, 95% CI of difference = -0.213 to 0.124, p = 0.601). There was no significant correlation between the ALPS index and clinical characteristics of migraine, including age (r = -0.07, p = 0.507), age at onset (r = 0.07, p = 0.552), disease duration (r = -0.12, p = 0.306), attack frequency (r = -0.05, p = 0.668), and headache intensity (r = 0.00, p = 0.976). CONCLUSIONS: There was no glymphatic system dysfunction in patients with migraine. Moreover, there were no differences in the glymphatic system function between patients with migraine with and without aura. We also demonstrated the feasibility of the ALPS method, which can be used for research on various neurological diseases. Further studies are needed to confirm our findings.

Glymphatic dysfunction in isolated REM sleep behavior disorder.

OBJECTIVES: This study aimed to evaluate glymphatic-system function in patients with isolated rapid eye movement sleep behavior disorder (iRBD) in comparison with healthy controls by using diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) method. We hypothesized that patients with iRBD may show glymphatic-system dysfunction. METHODS: We retrospectively enrolled 18 patients with iRBD and 18 age- and sex-matched healthy controls. All participants underwent DTI magnetic resonance imaging (MRI) using the same 3T MRI scanner, and the DTI-ALPS index was calculated using DTI data. We evaluated the differences in the DTI-ALPS index between patients with iRBD and healthy controls. In addition, we evaluated the correlation between the DTI-ALPS index and demographic and polysomnographic characteristics. RESULTS: The DTI-ALPS index was significantly different between the groups; it was significantly lower in patients with iRBD than in healthy controls (1.5647 vs. 1.7612, p = .0157). The index did not correlate with demographic and polysomnographic characteristics, including age, Epworth Sleepiness Scale score, total sleep time, sleep efficiency, sleep stage N1 ratio, stage N2 ratio, stage N3 ratio, stage R ratio, and total apnea-hypopnea index. CONCLUSION: The DTI-ALPS index was significantly lower in patients with iRBD than in healthy controls, indicating the presence of glymphatic-system dysfunction in patients with iRBD. Our study also suggests that the DTI-ALPS index could serve as a biomarker for evaluating glymphatic-system function in neurological disorders.