Decreased diffusivity along the perivascular space and cerebral hemodynamic disturbance in adult moyamoya disease.

Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via 15O-gas positron emission tomography (PET), and all patients underwent cognitive tests. Compared to controls, patients (38.4 (13.2) years old, 35 females) had lower ALPS indices in the left and right hemispheres (1.94 (0.27) vs. 1.65 (0.25) and 1.94 (0.22) vs. 1.65 (0.19), P < 0.001). While the right ALPS index showed no correlation, the left ALPS index was correlated with parenchymal freewater (ρ = -0.47, P < 0.001); perfusion measured with PET (cerebral blood flow, ρ = 0.70, P < 0.001; mean transit time, ρ = -0.60, P = 0.003; and oxygen extraction fraction, ρ = -0.52, P = 0.003); and cognitive tests (trail making test part B for executive function; ρ = -0.37, P = 0.01). Adult patients with MMD may exhibit decreased glymphatic system activity, which is correlated with the degree of hemodynamic disturbance, increased interstitial freewater, and cognitive dysfunction, but further investigation is needed.

Associations between Verbal Fluency and Asymmetry of White Matter Integrity in the Superior Longitudinal Fasciculus in At-Risk Mental States for Psychosis.

Verbal fluency is one of the most severely impaired components of cognitive function in schizophrenia and is also impaired in at-risk mental states (ARMSs) for psychosis. The aim of this study was to explore the markers of disease progression in subjects with ARMSs by comparing the association between the white matter integrity of the superior longitudinal fasciculus (SLF) and verbal fluency in subjects with ARMSs and healthy control (HC) subjects. The correlations of the fractional anisotropy (FA) values on diffusion tensor imaging (DTI) and the laterality index (LI) values of SLF branches I, II, and III with the verbal fluency performance were analyzed in right-handed subjects with ARMSs (ARMS group; n = 18) and HC subjects (HC group; n = 34) aged 18 to 40 years old. In the HC group compared with the ARMS group, the LI values suggested right lateralization of the SLF II and III. Letter fluency was significantly correlated with the LI of the SLF III in both the ARMS and HC groups. The regression coefficient (ß) of this correlation was calculated using the least squares method and yielded a positive number (73.857) in the ARMS group and a negative number (-125.304) in the HC group. The association of the rightward asymmetry of the SLF III with the verbal fluency performance observed in the HC group appeared to be lost in the ARMS group, and this could serve as one of the markers of the pathological progression to psychosis in patients with schizophrenia.

Free-water diffusion magnetic resonance imaging under selegiline treatment in Parkinson's disease.

INTRODUCTION: Monoamine oxidase type B inhibitors, including selegiline, are established as anti-Parkinsonian Drugs. Inhibition of monoamine oxidase type B enzymes might suppress the inflammation because of inhibition to generate reactive oxygen species. However, its effect on brain microstructure remains unclear. The aim of this study is to elucidate white matter and substantia nigra (SN) microstructural differences between Patients with Parkinson's disease with and without selegiline treatment by two independently recruited cohorts. METHODS: Diffusion tensor imaging and free water imaging indices of WM and SN were compared among 22/15 Patients with Parkinson's disease with selegiline (PDselegiline(+)), 33/23 Patients with Parkinson's disease without selegiline (PDselegiline(-)), and 25/20 controls, in the first/second cohorts. Two cohorts were analyzed with different MRI protocols. RESULTS: Diffusion tensor imaging and free-water indices of major white matter tracts were significantly differed between the PDselegiline(-) and controls in both cohorts, although not between the PDselegiline(+) and controls except for restricted areas. Compared with the PDselegiline(+), free-water was significantly higher in the PDselegiline(-) in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and superior and posterior corona radiata (first cohort) and the forceps major and splenium of the corpus callosum (second cohort). There were no significant differences in free-water of anterior or posterior substantia nigra between PDselegiline(+) and PDselegiline(-). CONCLUSIONS: Selegiline treatment might reduce the white matter microstructural abnormalities detected by free-water imaging in Parkinson's disease.

Surface-based Analyses of Diffusional Kurtosis Imaging in Amyotrophic Lateral Sclerosis: Relationship with Onset Subtypes.

PURPOSE: Here, we aimed to characterize the cortical and subcortical microstructural alterations in the brains of patients with amyotrophic lateral sclerosis (ALS). In particular, we compared these features between bulbar-onset ALS (b-ALS) and limb-onset ALS (l-ALS). METHODS: Diffusion MRI data (b = 0, 700, 2000 ms/mm2, 1.7-mm isotropic voxel) from 28 patients with ALS (9 b-ALS and 19 l-ALS) and 17 healthy control subjects (HCs) were analyzed. Diffusional kurtosis imaging (DKI) metrics were sampled at the mid-cortical and subcortical surfaces. We used permutation testing with a nonparametric combination of mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) to assess intergroup differences over the cerebrum. We also carried out an atlas-based analysis focusing on Brodmann Area 4 and 6 (primary motor and premotor areas) and investigated the correlation between MRI metrics and clinical parameters. RESULTS: At both the mid-cortical and subcortical surfaces, b-ALS was associated with significantly greater MD, smaller FA, and smaller MK in the motor and premotor areas than HC. In contrast, the patients with l-ALS showed relatively moderate differences relative to HCs. The ALS Functional Rating Scale-Revised bulbar subscore was significantly correlated with the diffusion metrics in Brodmann Area 4. CONCLUSION: The distribution of abnormalities over the cerebral hemispheres and the more severe microstructural alteration in b-ALS compared to l-ALS were in good agreement with findings from postmortem histology. Our results suggest the feasibility of surface-based DKI analyses for exploring brain microstructural pathologies in ALS. The observed differences between b-ALS and l-ALS and their correlations with functional bulbar impairment support the clinical relevance of DKI measurement in the cortical and juxtacortical regions of patients with ALS.

Advancements in Diffusion MRI Tractography for Neurosurgery.

ABSTRACT: Diffusion magnetic resonance imaging tractography is a noninvasive technique that enables the visualization and quantification of white matter tracts within the brain. It is extensively used in preoperative planning for brain tumors, epilepsy, and functional neurosurgical procedures such as deep brain stimulation. Over the past 25 years, significant advancements have been made in imaging acquisition, fiber direction estimation, and tracking methods, resulting in considerable improvements in tractography accuracy. The technique enables the mapping of functionally critical pathways around surgical sites to avoid permanent functional disability. When the limitations are adequately acknowledged and considered, tractography can serve as a valuable tool to safeguard critical white matter tracts and provides insight regarding changes in normal white matter and structural connectivity of the whole brain beyond local lesions. In functional neurosurgical procedures such as deep brain stimulation, it plays a significant role in optimizing stimulation sites and parameters to maximize therapeutic efficacy and can be used as a direct target for therapy. These insights can aid in patient risk stratification and prognosis. This article aims to discuss state-of-the-art tractography methodologies and their applications in preoperative planning and highlight the challenges and new prospects for the use of tractography in daily clinical practice.

Association between middle cerebral artery morphology and branch atheromatous disease.

INTRODUCTION: Branch atheromatous disease (BAD) is a type of cerebral infarction caused by stenosis or occlusion at the entrance of the penetrating branch due to the presence of plaque. Despite its clinical significance, it is not clear how these plaques are formed. Focal geometrical characteristics are expected to be as important as vascular risk factors in the development of atherosclerosis. This study aimed to analyze the association between middle cerebral artery (MCA) geometric features and the onset of BAD. Shear stress results from the blood flow exerting force on the inner wall of the vessels and places with low wall shear stress may be prone to atherosclerosis. At the curvature of blood vessels, the shear stress is weak on the inside of the curve and plaque is likely to form. When this is applied to the MCA M1 segment, downward type M1 is likely to form plaques on the superior side. Because the lenticulostriate artery usually branches off from the superior side of the MCA M1 segment, in downward type M1, a plaque is likely to be formed at the entrance of the penetrating branch, and for that reason, BAD is likely to onset. METHODS: We retrospectively reviewed hospitalized stroke patients with BAD and investigated the morphology of their MCA using magnetic resonance imaging. The M1 segment was classified as straight or curved. Additionally, we compared the difference between the symptomatic and the asymptomatic side. Data regarding patients' medical history were also collected. RESULTS: A total of 56 patients with lenticulostriate artery infarctions and BAD were analyzed. On the symptomatic side, downward type M1 accounted for the largest proportion at 44%, whereas on the asymptomatic side, it was the lowest, at 16%. CONCLUSION: A downward type MCA may be associated with the onset of BAD and the morphological characteristics might affect the site of plaque formation. J. Med. Invest. 70 : 411-414, August, 2023.

Traveling Subject-Informed Harmonization Increases Reliability of Brain Diffusion Tensor and Neurite Mapping.

Diffusion-weighted magnetic resonance imaging (dMRI) of brain has helped elucidate the microstructural changes of psychiatric and neurodegenerative disorders. Inconsistency between MRI models has hampered clinical application of dMRI-based metrics. Using harmonized dMRI data of 300 scans from 69 traveling subjects (TS) scanning the same individuals at multiple conditions with 13 MRI models and 2 protocols, the widely-used metrics such as diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) were evaluated before and after harmonization with a combined association test (ComBat) or TS-based general linear model (TS-GLM). Results showed that both ComBat and TS-GLM significantly reduced the effects of the MRI site, model, and protocol for diffusion metrics while maintaining the intersubject biological effects. The harmonization power of TS-GLM based on TS data model is more powerful than that of ComBat. In conclusion, our research demonstrated that although ComBat and TS-GLM harmonization approaches were effective at reducing the scanner effects of the site, model, and protocol for DTI and NODDI metrics in WM, they exhibited high retainability of biological effects. Therefore, we suggest that, after harmonizing DTI and NODDI metrics, a multisite study with large cohorts can accurately detect small pathological changes by retaining pathological effects.

Noninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity.

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.

Fiber-specific micro- and macroscopic white matter alterations in progressive supranuclear palsy and corticobasal syndrome.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are characterized by progressive white matter (WM) alterations associated with the prion-like spreading of four-repeat tau, which has been pathologically confirmed. It has been challenging to monitor the WM degeneration patterns underlying the clinical deficits in vivo. Here, a fiber-specific fiber density and fiber cross-section, and their combined measure estimated using fixel-based analysis (FBA), were cross-sectionally and longitudinally assessed in PSP (n = 20), CBS (n = 17), and healthy controls (n = 20). FBA indicated disease-specific progression patterns of fiber density loss and subsequent bundle atrophy consistent with the tau propagation patterns previously suggested in a histopathological study. This consistency suggests the new insight that FBA can monitor the progressive tau-related WM changes in vivo. Furthermore, fixel-wise metrics indicated strong correlations with motor and cognitive dysfunction and the classifiability of highly overlapping diseases. Our findings might also provide a tool to monitor clinical decline and classify both diseases.

Accuracy of skull stripping in a single-contrast convolutional neural network model using eight-contrast magnetic resonance images.

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.

Increased Parenchymal Free Water May Be Decreased by Revascularization Surgery in Patients with Moyamoya Disease.

PURPOSE: Moyamoya disease (MMD) is a cerebrovascular disease associated with steno-occlusive changes in the arteries of the circle of Willis and with hemodynamic impairment. Previous studies have reported that parenchymal extracellular free water levels may be increased and the number of neurites may be decreased in patients with MMD. The aim of the present study was to investigate the postoperative changes in parenchymal free water and neurites and their relationship with cognitive improvement. METHODS: Multi-shell diffusion MRI (neurite orientation dispersion and density imaging and free water imaging using a bi-tensor model) was performed in 15 hemispheres of 13 adult patients with MMD (11 female, mean age 37.9 years) who had undergone revascularization surgery as well as age- and sex-matched normal controls. Parameter maps of free water and free-water-eliminated neurites were created, and the regional parameter values were compared among controls, patients before surgery, and patients after surgery. RESULTS: The anterior and middle cerebral artery territories of patients showed higher preoperative free water levels (P ≤ 0.007) and lower postoperative free water levels (P ≤ 0.001) than those of normal controls. The change in the dispersion of the white matter in the anterior cerebral artery territory correlated with cognitive improvement (r = -0.75; P = 0.004). CONCLUSION: Our study suggests that increased parenchymal free water levels decreased after surgery and that postoperative changes in neurite parameters are related to postoperative cognitive improvement in adult patients with MMD. Diffusion analytical methods separately calculating free water and neurites may be useful for unraveling the pathophysiology of chronic ischemia and the postoperative changes that occur after revascularization surgery in this disease population.

Effect of Temporal Sampling Rate on Estimates of the Perfusion Parameters for Patients with Moyamoya Disease Assessed with Simultaneous Multislice Dynamic Susceptibility Contrast-enhanced MR Imaging.

PURPOSE: The effect of temporal sampling rate (TSR) on perfusion parameters has not been fully investigated in Moyamoya disease (MMD); therefore, this study evaluated the influence of different TSRs on perfusion parameters quantitatively and qualitatively by applying simultaneous multi-slice (SMS) dynamic susceptibility contrast-enhanced MR imaging (DSC-MRI). METHODS: DSC-MRI datasets were acquired from 28 patients with MMD with a TSR of 0.5 s. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and time to maximum tissue residue function (Tmax) were calculated for eight TSRs ranging from 0.5 to 4.0 s in 0.5-s increments that were subsampled from a TSR of 0.5 s datasets. Perfusion measurements and volume for chronic ischemic (Tmax ≥ 2 s) and non-ischemic (Tmax < 2 s) areas for each TSR were compared to measurements with a TSR of 0.5 s, as was visual perfusion map analysis. RESULTS: CBF, CBV, and Tmax values tended to be underestimated, whereas MTT and TTP values were less influenced, with a longer TSR. Although Tmax values were overestimated in the TSR of 1.0 s in non-ischemic areas, differences in perfusion measurements between the TSRs of 0.5 and 1.0 s were generally minimal. The volumes of the chronic ischemic areas with a TSR ≥ 3.0 s were significantly underestimated. In CBF and CBV maps, no significant deterioration was noted in image quality up to 3.0 and 2.5 s, respectively. The image quality of MTT, TTP, and Tmax maps for the TSR of 1.0 s was similar to that for the TSR of 0.5 s but was significantly deteriorated for the TSRs of ≥ 1.5 s. CONCLUSION: In the assessment of MMD by SMS DSC-MRI, application of TSRs of ≥ 1.5 s may lead to deterioration of the perfusion measurements; however, that was less influenced in TSRs of ≤ 1.0 s.

Analysis of synthetic magnetic resonance images by multi-channel segmentation increases accuracy of volumetry in the putamen and decreases mis-segmentation in the dural sinuses.

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.

Automation of a Rule-based Workflow to Estimate Age from Brain MR Imaging of Infants and Children Up to 2 Years Old Using Stacked Deep Learning.

PURPOSE: Myelination-related MR signal changes in white matter are helpful for assessing normal development in infants and children. A rule-based myelination evaluation workflow regarding signal changes on T1-weighted images (T1WIs) and T2-weighted images (T2WIs) has been widely used in radiology. This study aimed to simulate a rule-based workflow using a stacked deep learning model and evaluate age estimation accuracy. METHODS: The age estimation system involved two stacked neural networks: a target network-to extract five myelination-related images from the whole brain, and an age estimation network from extracted T1- and T2WIs separately. A dataset was constructed from 119 children aged below 2 years with two MRI systems. A four-fold cross-validation method was adopted. The correlation coefficient (CC), mean absolute error (MAE), and root mean squared error (RMSE) of the corrected chronological age of full-term birth, as well as the mean difference and the upper and lower limits of 95% agreement, were measured. Generalization performance was assessed using datasets acquired from different MR images. Age estimation was performed in Sturge-Weber syndrome (SWS) cases. RESULTS: There was a strong correlation between estimated age and corrected chronological age (MAE: 0.98 months; RMSE: 1.27 months; and CC: 0.99). The mean difference and standard deviation (SD) were -0.15 and 1.26, respectively, and the upper and lower limits of 95% agreement were 2.33 and -2.63 months. Regarding generalization performance, the performance values on the external dataset were MAE of 1.85 months, RMSE of 2.59 months, and CC of 0.93. Among 13 SWS cases, 7 exceeded the limits of 95% agreement, and a proportional bias of age estimation based on myelination acceleration was exhibited below 12 months of age (P = 0.03). CONCLUSION: Stacked deep learning models automated the rule-based workflow in radiology and achieved highly accurate age estimation in infants and children up to 2 years of age.

Investigation of time-dependent diffusion in extra-axial brain tumors using oscillating-gradient spin-echo.

Oscillating gradient spin-echo (OGSE) sequences provide access to short diffusion times and may provide insight into micro-scale internal structures of pathologic lesions based on an analysis of changes in diffusivity with differing diffusion times. We hypothesized that changes in diffusivity acquired with a shorter diffusion time may permit elucidation of properties related to the internal structure of extra-axial brain tumors. This study aimed to investigate the utility of changes in diffusivity between short and long diffusion times for characterizing extra-axial brain tumors. In total, 12 patients with meningothelial meningiomas, 13 patients with acoustic neuromas, and 11 patients with pituitary adenomas were scanned with a 3 T magnetic resonance imaging (MRI) scanner with diffusion-weighted imaging (DWI) using OGSE and pulsed gradient spin-echo (PGSE) (effective diffusion times [Δeff]: 6.5 ms and 35.2 ms) with b-values of 0 and 1000 s/mm2. Relative percentage changes between shorter and longer diffusion times were calculated using region-of-interest (ROI) analysis of brain tumors on λ1, λ2, λ3, and mean diffusivity (MD) maps. The diffusivities of PGSE, OGSE, and relative percentage changes were compared among each tumor type using a multiple comparisons Steel-Dwass test. The mean (standard deviation) MD at Δeff of 6.5 ms was 1.07 ± 0.23 10-3 mm2/s, 1.19 ± 0.18 10-3 mm2/s, 1.19 ± 0.21 10-3 mm2/s for meningothelial meningiomas, acoustic neuromas, and pituitary adenomas, respectively. The mean (standard deviation) MD at Δeff of 35.2 ms was 0.93 ± 0.22 10-3 mm2/s, 1.07 ± 0.19 10-3 mm2/s, 0.82 ± 0.21 10-3 mm2/s for meningothelial meningiomas, acoustic neuromas, and pituitary adenomas, respectively. The mean (standard deviation) of the relative percentage change was 15.7 ± 4.4%, 12.4 ± 8.2%, 46.8 ± 11.3% for meningothelial meningiomas, acoustic neuromas, and pituitary adenomas, respectively. Compared to meningiomas and acoustic neuromas, pituitary adenoma exhibited stronger diffusion time-dependence with diffusion times between 6.5 ms and 35.2 ms (P < 0.05). In conclusion, differences in diffusion time-dependence may be attributed to differences in the internal structures of brain tumors. DWI with a short diffusion time may provide additional information on the microstructure of each tumor and contribute to tumor diagnosis.

[A Case of Liver Metastasis of Gastric Cancer Successfully Treated with SOX plus Nivolumab].

An 82-year-old, male. He visited his local doctor with a chief complaint of dyspnea on exertion. Anemia was noted, and upper gastrointestinal endoscopy was performed, which revealed an ulcerative lesion in the gastric antrum. A biopsy revealed Group 5, tub2, and HER2 negative, with PD-L1≥5%. cT3N1H1(M1 HEP), cStage ⅣB was diagnosed based on CT scan showing enlarged #8 lymph node and a single liver metastasis in the 2 cm range in S6 of the liver. The patient was deemed unresectable and was started on SOX plus nivolumab therapy. On day 11 after initiation, the patient had Grade 3 diarrhea by CTCAE v5.0, and S-1 was withdrawn for 3 days, but was administered for 2 courses. CT and MRI after chemotherapy showed shrinkage of both the primary tumor and liver metastases; R0 resection was deemed possible, and pyloric gastrectomy, D2 lymph node dissection, and partial hepatic S6 resection were performed. The histological evaluation of response to treatment was Grade 1b, and the patient was in ypStage ⅠA. The patient has been alive without recurrence for 6 months postoperatively while receiving S-1 monotherapy on an outpatient basis.

Association of MRI Indices of Glymphatic System With Amyloid Deposition and Cognition in Mild Cognitive Impairment and Alzheimer Disease.

BACKGROUND AND OBJECTIVES: The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this system may play a pivotal role in amyloid ß (Aß) accumulation. However, its involvement in Alzheimer's disease (AD) pathogenesis is not fully understood. Here, we investigated the changes in noninvasive MRI measurements related to the perivascular network in patients with mild cognitive impairment (MCI) and AD. Additionally, we explored the associations of MRI measures with neuropsychological score, PET standardized uptake value ratio (SUVR), and Aß deposition. METHODS: MRI measures, including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer's Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD. Statistical analyses were performed with age, sex, years of education, and APOE status as confounding factors. RESULTS: In total, 36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia PVSVF (Cohen's d = 1.15-1.48; p < 0.001), and FW-WM (Cohen's d = 0.73; p < 0.05) and a lower ALPS index (Cohen's d = 0.63; p < 0.05) than healthy controls. Meanwhile, the MCI group only showed significantly higher total (Cohen's d = 0.99; p < 0.05) and WM (Cohen's d = 0.91; p < 0.05) PVSVF. Low ALPS index was associated with lower CSF Aß42 (r s = 0.41, p fdr = 0.026), FDG-PET uptake (r s = 0.54, p fdr < 0.001), and worse multiple cognitive domain deficits. High FW-WM was also associated with lower CSF Aß42 (r s = -0.47, p fdr = 0.021) and worse cognitive performances. CONCLUSION: Our study indicates that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. We also report the associations between MRI parameters and Aß deposition, neuronal change, and cognitive impairment in AD.

White matter fiber-specific degeneration in older adults with metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MetS) is defined as a complex of interrelated risk factors for type 2 diabetes and cardiovascular disease, including glucose intolerance, abdominal obesity, hypertension, and dyslipidemia. Studies using diffusion tensor imaging (DTI) have reported white matter (WM) microstructural abnormalities in MetS. However, interpretation of DTI metrics is limited primarily due to the challenges of modeling complex WM structures. The present study used fixel-based analysis (FBA) to assess the effect of MetS on the fiber tract-specific WM microstructure in older adults and its relationship with MetS-related measurements and cognitive and locomotor functions to better understand the pathophysiology of MetS. METHODS: Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross-section (FC), and a combination of FD and FC (FDC), were evaluated in 16 healthy controls (no components of MetS; four men; mean age, 71.31 ± 5.06 years), 57 individuals with premetabolic syndrome (preMetS; one or two components of MetS; 29 men; mean age, 72.44 ± 5.82 years), and 46 individuals with MetS (three to five components of MetS; 27 men; mean age, 72.15 ± 4.97 years) using whole-brain exploratory FBA. Tract of interest (TOI) analysis was then performed using TractSeg across 14 selected WM tracts previously associated with MetS. The associations between fixel-based metrics and MetS-related measurements, neuropsychological, and locomotor function tests were also analyzed in individuals with preMetS and MetS combined. In addition, tensor-based metrics (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) were compared among the groups using tract-based spatial statistics (TBSS) analysis. RESULTS: In whole-brain FBA, individuals with MetS showed significantly lower FD, FC, and FDC compared with healthy controls in WM areas, such as the splenium of the corpus callosum (CC), corticospinal tract (CST), middle cerebellar peduncle (MCP), and superior cerebellar peduncle (SCP). Meanwhile, in fixel-based TOI, significantly reduced FD was observed in individuals with preMetS and MetS in the anterior thalamic radiation, CST, SCP, and splenium of the CC compared with healthy controls, with relatively greater effect sizes observed in individuals with MetS. Compared with healthy controls, significantly reduced FC and FDC were only demonstrated in individuals with MetS, including regions with loss of FD, inferior cerebellar peduncle, inferior fronto-occipital fasciculus, MCP, and superior longitudinal fasciculus part I. Furthermore, negative correlations were observed between FD and Brinkman index of cigarette consumption cumulative amount and between FC or FDC and the Trail Making Test (parts B-A), which is a measure of executive function, waist circumference, or low-density lipoprotein cholesterol. Finally, TBSS analysis revealed that FA and MD were not significantly different among all groups. CONCLUSIONS: The FBA results demonstrate that substantial axonal loss and atrophy in individuals with MetS and early axonal loss without fiber-bundle morphological changes in those with preMetS within the WM tracts are crucial to cognitive and motor function. FBA also clarified the association between executive dysfunction, abdominal obesity, hyper-low-density lipoprotein cholesterolemia, smoking habit, and compromised WM neural tissue microstructure in MetS.

Multimodal magnetic resonance imaging quantification of gray matter alterations in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder.

Herein, we combined neurite orientation dispersion and density imaging (NODDI) and synthetic magnetic resonance imaging (SyMRI) to evaluate the spatial distribution and extent of gray matter (GM) microstructural alterations in patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD). The NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) and SyMRI (myelin volume fraction [MVF]) measures were compared between age- and sex-matched groups of 30 patients with RRMS (6 males and 24 females; mean age, 51.43 ± 8.02 years), 18 patients with anti-aquaporin-4 antibody-positive NMOSD (2 males and 16 females; mean age, 52.67 ± 16.07 years), and 19 healthy controls (6 males and 13 females; mean age, 51.47 ± 9.25 years) using GM-based spatial statistical analysis. Patients with RRMS showed reduced NDI and MVF and increased ODI and ISOVF, predominantly in the limbic and paralimbic regions, when compared with healthy controls, while only increases in ODI and ISOVF were observed when compared with NMOSD. Compared to NDI and MVF, the changes in ODI and ISOVF were observed more widely, including in the cerebellar cortex. These abnormalities were associated with disease progression and disability. In contrast, patients with NMOSD only showed reduced NDI mainly in the cerebellar, limbic, and paralimbic cortices when compared with healthy controls and patients with RRMS. Taken together, our study supports the notion that GM pathologies in RRMS are distinct from those of NMOSD. However, owing to the limitations of the study, the results should be cautiously interpreted.