Increased extracellular free water is related to white matter hyperintensity burden.

BACKGROUND: Extracellular free water (FW) has important roles in the occurrence and development of white matter hyperintensity (WMH). PURPOSE: To explore the correlations between FW and WMH burden. MATERIAL AND METHODS: A prospective analysis was conducted using magnetic resonance imaging (MRI) data from 126 individuals. WMH burden was determined based on WMH volumes and Fazekas scores from deep and periventricular white matter hyperintensity (DWMH and PWMH, respectively) in fluid-attenuated inversion recovery (FLAIR) images. FW values were taken from diffusion tensor imaging (DTI). RESULTS: Univariate analysis showed that FW values were correlated with WMH burden, including WMH volumes and DWMH and PWMH Fazekas scores (P < 0.05). After multivariate analysis, FW values were correlated with WMH volumes and DWMH and PWMH Fazekas scores when adjusted for age and hypertension (P < 0.05). CONCLUSION: Using MRI, increasing extracellular FW was related to WMH burden.

Can white matter hyperintensities based Fazekas visual assessment scales inform about Alzheimer's disease pathology in the population?

BACKGROUND: White matter hyperintensities (WMH) are considered hallmark features of cerebral small vessel disease and have recently been linked to Alzheimer's disease (AD) pathology. Their distinct spatial distributions, namely periventricular versus deep WMH, may differ by underlying age-related and pathobiological processes contributing to cognitive decline. We aimed to identify the spatial patterns of WMH using the 4-scale Fazekas visual assessment and explore their differential association with age, vascular health, AD imaging markers, namely amyloid and tau burden, and cognition. Because our study consisted of scans from GE and Siemens scanners with different resolutions, we also investigated inter-scanner reproducibility and combinability of WMH measurements on imaging. METHODS: We identified 1144 participants from the Mayo Clinic Study of Aging consisting of a population-based sample from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET, and tau-PET standardized uptake value ratio, automated WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). RESULTS: Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). Both periventricular WMH and deep WMH showed weak associations with amyloidosis (R = 0.07, p = < 0.001), and none with tau burden. We found substantial agreement between data from the two scanners for Fazekas measurements (ICC = 0.82 and 0.74). The automated WMH volume had high discriminating power for identifying participants with Fazekas ≥ 2 (area under curve = 0.97) and showed poor correlation with amyloid and tau PET markers similar to the visual grading. CONCLUSION: Our study investigated risk factors underlying WMH spatial patterns and their impact on global cognition, with no discernible differences between periventricular and deep WMH. We observed minimal impact of amyloidosis on WMH severity. These findings, coupled with enhanced inter-scanner reproducibility of WMH data, suggest the combinability of inter-scanner data assessed by harmonized protocols in the context of vascular contributions to cognitive impairment and dementia biomarker research.

Can white matter hyperintensities based Fazekas visual assessment scales inform about Alzheimer's disease pathology in the population?

Background: White matter hyperintensities (WMH) are considered hallmark features of cerebral small vessel disease and have recently been linked to Alzheimer's disease pathology. Their distinct spatial distributions, namely periventricular versus deep WMH, may differ by underlying age-related and pathobiological processes contributing to cognitive decline. We aimed to identify the spatial patterns of WMH using the 4-scale Fazekas visual assessment and explore their differential association with age, vascular health, Alzheimer's imaging markers, namely amyloid and tau burden, and cognition. Because our study consisted of scans from GE and Siemens scanners with different resolutions, we also investigated inter-scanner reproducibility and combinability of WMH measurements on imaging. Methods: We identified 1144 participants from the Mayo Clinic Study of Aging consisting of older adults from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET and tau-PET standardized uptake value ratio, WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). Results: Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). Both periventricular WMH and deep WMH showed weak associations with amyloidosis (R = 0.07, p = < 0.001), and none with tau burden. We found substantial agreement between data from the two scanners for Fazekas measurements (ICC = 0.78). The automated WMH volume had high discriminating power for identifying participants with Fazekas ≥ 2 (area under curve = 0.97). Conclusion: Our study investigates risk factors underlying WMH spatial patterns and their impact on global cognition, with no discernible differences between periventricular and deep WMH. We observed minimal impact of amyloidosis on WMH severity. These findings, coupled with enhanced inter-scanner reproducibility of WMH data, suggest the combinability of inter-scanner data assessed by harmonized protocols in the context of vascular contributions to cognitive impairment and dementia biomarker research.

[A case of Hashimoto's encephalopathy with acute onset of psychiatric symptoms and diffuse deep white matter lesions on brain MRI].

A 51-year-old man developed acute disturbances in consciousness and psychiatric symptoms one month prior to admission. He was referred and admitted to the Department of Psychiatry of our hospital and transferred to the neurology department because diffuse white matter lesions were found on his brain during MRI. 123I-IMP-SPECT showed extensive cerebral hypoperfusion mainly in the frontal lobes. Anti-Tg, anti-TPO, and anti-NAE antibodies were positive. These findings led to a diagnosis of Hashimoto's encephalopathy. The patient responded to steroid pulse therapy, high-dose steroid therapy, and intravenous immunoglobulin therapy, showing improvement in symptoms and imaging findings. Hashimoto's encephalopathy often presents with MRI findings similar to those of limbic encephalitis, when the patient presents with acute consciousness disturbance and psychiatric symptoms. However, this case showed diffuse white matter lesions, which may be clinically important for the differential diagnosis.

In vivo mapping of the deep and superficial white matter connectivity in the chimpanzee brain.

Mapping the chimpanzee brain connectome and comparing it to that of humans is key to our understanding of similarities and differences in primate evolution that occurred after the split from their common ancestor around 6 million years ago. In contrast to studies on macaque species' brains, fewer studies have specifically addressed the structural connectivity of the chimpanzee brain and its comparison with the human brain. Most comparative studies in the literature focus on the anatomy of the cortex and deep nuclei to evaluate how their morphology and asymmetry differ from that of the human brain, and some studies have emerged concerning the study of brain connectivity among humans, monkeys, and apes. In this work, we established a new white matter atlas of the deep and superficial white matter structural connectivity in chimpanzees. In vivo anatomical and diffusion-weighted magnetic resonance imaging (MRI) data were collected on a 3-Tesla MRI system from 39 chimpanzees. These datasets were subsequently processed using a novel fiber clustering pipeline adapted to the chimpanzee brain, enabling us to create two novel deep and superficial white matter connectivity atlases representative of the chimpanzee brain. These atlases provide the scientific community with an important and novel set of reference data for understanding the commonalities and differences in structural connectivity between the human and chimpanzee brains. We believe this study to be innovative both in its novel approach and in mapping the superficial white matter bundles in the chimpanzee brain, which will contribute to a better understanding of hominin brain evolution.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Segmentation and differentiation of periventricular and deep white matter hyperintensities in 2D T2-FLAIR MRI based on a cascade U-net.

Background: White matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images. Methods: A total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted. Results: Compared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p < 0.001), pvWMHV (R2 = 0.933, p < 0.001), and dWMHV (R2 = 0.918, p < 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r > 0.510, p < 0.001). Conclusion: Cascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.

Association between white matter lesions and Parkinson's disease: an impact on Postural/Gait difficulty phenotype and cognitive performance.

BACKGROUND: White matter hyperintensities (WMHs) may be observed on Magnetic Resonance Imaging (MRI) in patients with Parkinson disease with or without vascular risk factors. Whether WMHs may influence motor and non-motor aspects of Parkinson disease is a subject of debate. The aim of this study is to evaluate the impact of WMH severity on various aspects of Parkinson disease in combination to the estimation of the impact of cerebrovascular risk factors. MATERIALS AND METHODS: We included a cohort of patients with Parkinson's disease who underwent MRI examination. The Fazekas visual rating scale was used to assess the severity and location of WMHs, and patient clinical characteristics were correlated with MRI data. RESULTS: All vascular risk factors were associated with higher Fazekas score in both periventricular and deep white matter. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were associated with lower scores in the ACE-R cognitive assessment scale (p < 0.001). Furthermore, PWMHs and DWMHs severity was associated with higher UPDRS motor score (p < 0.001), while the Postural Instability Gait Difficulty (PIGD) phenotype was correlated with higher burden of WMHs. CONCLUSIONS: Comorbid WMHs may contribute to multi-dimension dysfunction in patients with Parkinson disease and consequently the management of vascular risk factors may be crucial to maintain motor and non-motor functions in PD.

[Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) with a family history: an adult case].

We present an adult case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). A 26-year-old man with a family history of MERS presented to our hospital owing to dysarthria and dysesthesia of the right side of his body. The duration of these symptoms was approximately 4 hours. T2 and diffusion weighted MRI showed high signal intensity lesions in the bilateral deep white matter. On a 3-week follow-up MRI, the lesions had completely disappeared. We attributed this clinical course and image findings to MERS. The patient had experienced similar symptoms at the age of 8 years old. Furthermore, his younger brother showed a similar clinical history and experienced a few recurrence events during the age of 9-16 years old. The mechanism of MERS remains controversial. However, similar to our case, there are some case reports with a family history. In addition, a previous report has confirmed the existence of a heterozygous variant in the myelin regulatory factor gene in patients with MERS. Some genetic factors may induce MERS, especially with extensive white matter lesions.

Prognostic value of global deep white matter DTI metrics for 1-year outcome prediction in ICU traumatic brain injury patients: an MRI-COMA and CENTER-TBI combined study.

PURPOSE: A reliable tool for outcome prognostication in severe traumatic brain injury (TBI) would improve intensive care unit (ICU) decision-making process by providing objective information to caregivers and family. This study aimed at designing a new classification score based on magnetic resonance (MR) diffusion metrics measured in the deep white matter between day 7 and day 35 after TBI to predict 1-year clinical outcome. METHODS: Two multicenter cohorts (29 centers) were used. MRI-COMA cohort (NCT00577954) was split into MRI-COMA-Train (50 patients enrolled between 2006 and mid-2014) and MRI-COMA-Test (140 patients followed up in clinical routine from 2014) sub-cohorts. These latter patients were pooled with 56 ICU patients (enrolled from 2014 to 2020) from CENTER-TBI cohort (NCT02210221). Patients were dichotomised depending on their 1-year Glasgow outcome scale extended (GOSE) score: GOSE 1-3, unfavorable outcome (UFO); GOSE 4-8, favorable outcome (FO). A support vector classifier incorporating fractional anisotropy and mean diffusivity measured in deep white matter, and age at the time of injury was developed to predict whether the patients would be either UFO or FO. RESULTS: The model achieved an area under the ROC curve of 0.93 on MRI-COMA-Train training dataset, and 49% sensitivity for 96.8% specificity in predicting UFO and 58.5% sensitivity for 97.1% specificity in predicting FO on the pooled MRI-COMA-Test and CENTER-TBI validation datasets. CONCLUSION: The model successfully identified, with a specificity compatible with a personalized decision-making process in ICU, one in two patients who had an unfavorable outcome at 1 year after the injury, and two-thirds of the patients who experienced a favorable outcome.

Association of deep white matter hyperintensity with left ventricular hypertrophy in acute ischemic stroke.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with the presence of left ventricular hypertrophy (LVH). It is unclear if periventricular WMH (PV-WMH) and or deep WMH (D-WMH) are associated with LVH. We evaluated the association of PV-WMH and D-WMH with common transthoracic echocardiogram abnormalities, including LVH in acute ischemic stroke. METHODS: PV-WMH and D-WMH were graded on a 0-3 score based on the Fazekas scale. Patients were categorized into clinically significant PV-WMH and D-WMH (score 2-3) and controls (score 0-1). Multivariate logistic regression analysis was performed to determine abnormalities on echocardiogram associated with PV-WMH and D-WMH. RESULTS: Among 272 patients, 137 patients had PV-WMH and 93 patients had D-WMH with a score of 2-3 on Fazekas scale. Compared to controls, patients with PV-WMH (mean age±standard deviation: 60.8±14.4 vs. 73.8±11.2 years) and D-WMH (63.4±14.4 vs. 75.0±11.1 years) were older. Compared to controls, PV-WMH was associated with history of stroke (22 [16%] vs. 37 [27%], p = .03) and valvular calcification (33 [24%] vs. 61 [45%], p = .0005); D-WMH was associated with history of atrial fibrillation (25 [14%] vs. 22 [24%], p = .04), valvular calcification (50 [28%] vs. 44 [47%], p = .001), and LVH (30 [17%] vs. 25 [27%], p = .049). In multivariate analysis, PV-WMH was associated with age (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.06-1.12) and stroke history (OR = 2.1; 95% CI = 1.1-4.1), and D-WMH was associated with age (OR = 1.07; 95% CI = 1.05-1.10) and LVH (OR = 2.0; 95% CI = 1.0-4.0). CONCLUSION: LVH is associated with D-WMH but not with PV-WMH. Although valvular calcification is common, it is likely age related than due to WMH.

Risk of radiation necrosis after stereotactic radiosurgery for melanoma brain metastasis by anatomical location.

PURPOSE: In this retrospective study, we have explored the anatomical factors that lead to the development of radiation necrosis (RN) in the setting of stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM). METHODS: Between 2014 and 2018, 137 patients underwent SRS for 311 MBM. Lesions were assessed according to anatomical zones: zone 1-peripheral grey-white matter junction and cortical mantle, zone 2-deep white matter, including tumours located at base of sulci, zone 3-tumours adjacent to ependymal lining or in deep locations such as brainstem, basal ganglia and thalamus. Other anatomical factors including lobes, medial-peripheral, supra or infratentorial locations were also recorded. RESULTS: In all, 12.4% (n = 17) of patients and 6.1% (n = 20) of lesions developed RN, actuarial incidence of RN at 12 and 24 months was 10% and 14.2% respectively. Zone 2 lesions recorded the highest rate of development of RN (n = 7/19; 36%), zone 3 (N = 4/24; 16%) and zone 1 (n = 9/268; 3%). Five of 17 patients developed symptomatic RN and 7/17 patients underwent surgery for RN. CONCLUSION: This study raises awareness of the increased likelihood of deep lesions particularly in white matter structures to develop RN after SRS. Further studies including larger cohorts would be useful in identifying statistical differences in the rate of development of RN in different anatomical zones.

Association of regional white matter hyperintensity volumes with cognitive dysfunction and vascular risk factors in patients with amnestic mild cognitive impairment.

AIM: White matter hyperintensities (WMH) obtained by magnetic resonance imaging (MRI) have been reported to promote neurodegeneration and cognitive decline in patients with mild cognitive impairment (MCI). However, little is known about the association between regional WMH (rWMH) and cognitive dysfunction in MCI. We hence investigated the associations between rWMH volumes and cognitive dysfunction in MCI. METHODS: Thirty-eight subjects with amnestic MCI were analysed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on a T2-FLAIR MRI using a 3D-slicer, and regional PVH and DWMH (rPVH and rDWMH) volumes were calculated. The associations of rPVH and rDWMH volumes with cognition and blood levels of various molecules were investigated. Furthermore, rPVH and rDWMH volumes were compared between MCI with vascular risk factors, such as hypertension, diabetes mellitus (DM), and dyslipidemia, and those without these risk factors. RESULTS: rPVH volume (bilateral cornu frontale, pars parietalis, and cornu occipitale) positively correlated with Trail Making Test-A/B scores and CysC level, whereas rDWMH volume did not correlate with any of the items. rPVH volumes (right cornu frontale, bilateral pars parietalis and cornu occipitale, and right pars temporalis) and rDWMH volumes (left frontal and parietal lobes) were significantly larger in MCI patients with DM than in those without. CONCLUSIONS: PVH volumes (bilateral areas of cornu frontale, pars parietalis, and cornu occipitale) were closely associated with attention and executive dysfunction. Serum CysC level and DM were associated with WMH volume, suggesting that CysC level and DM might be important markers for determining treatment strategies for white matter abnormalities in MCI. Geriatr Gerontol Int 2021; 21: 644-650.

Association of White Matter Hyperintensity Progression with Cognitive Decline in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND: White matter hyperintensities (WMH) on MRI have been reported to increase the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, effects of the progression of WMH on the cognition of patients with MCI remains unclear to date. OBJECTIVE: To investigate the association between WMH progression and cognitive decline in amnestic MCI patients. METHODS: Thirty-eight subjects with amnestic MCI were analyzed prospectively every year for 2 years. Fourteen MCI subjects dropped out on the final visit, and therefore 24 subjects with MCI were analyzed for the entire duration. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 FLAIR using the 3D-slicer. The associations between PVH/DWMH progression and cognitive decline were investigated. RESULTS: An increase in DWMH volume significantly correlated with changes in Mini-Mental State Examination and category verbal fluency scores, whereas an increase in PVH volume did not correlate with changes in any item. CONCLUSION: DWMH progression was closely associated with a decline in frontal lobe function and semantic memory, suggesting that WMH progression might affect some AD pathophysiologies in amnestic MCI patients.

A 10-year longitudinal study of deep white matter lesions on magnetic resonance imaging.

PURPOSE: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. METHODS: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. RESULTS: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. CONCLUSION: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.

Relationship between Deep White Matter Hyperintensities on Magnetic Resonance Imaging and Postoperative Cognitive Function Following Clipping of Unruptured Intracranial Aneurysm.

To evaluate the effects on cognitive function of deep white matter hyperintensities (DWMHs) on magnetic resonance imaging (MRI) in patients treated surgically for unruptured intracranial aneurysms (UIAs). The subjects were 106 patients in whom a Wechsler adult intelligence scale-revised (WAIS-R) examination was performed 1 week before and 1 month after clipping surgery for asymptomatic UIAs. DWMH severity was evaluated on preoperative MR images by Fazekas scale, as follows: none (absence), mild (punctate foci), moderate (beginning confluence of foci), or severe (large confluent areas). A decrease of 7 or more points in intelligence quotient (IQ) postoperatively was considered deterioration. Fazekas score was none in 41 (none group), mild in 42 (mild group), moderate in 21, and severe in 2 patients (moderate/severe group). Patient characteristics, surgical factors, IQ change, and abnormal findings on postoperative MRI were compared among the groups. Although there was no statistically significant deterioration in IQ postoperatively in any group, the percentage of deteriorated patients was significantly higher in the moderate/severe group (34.8%) than in the other groups (4.9% in the none group, 7.1% in the mild group; p <0.01, p <0.05, respectively). Brain injury was observed more frequently on postoperative MR images in the moderate/severe group (17.4%) compared with the none group (2.4%; p = 0.052). The presence of moderate/severe DWMHs was an independent prognostic factor for postoperative cognitive dysfunction. In conclusion, the presence of moderate/severe DWMHs was a prognostic factor for postoperative cognitive dysfunction after surgery for UIAs.

Silent brain infarcts and white matter lesions in patients with asymptomatic carotid stenosis.

The association of carotid atherosclerosis with silent brain infarcts (SBIs) and white matter lesions (WMLs) currently remains unknown. This study aims to compare SBIs, deep white matter lesions (DWMLs), and periventricular white matter lesions (PWMLs) in ipsilateral and contralateral hemispheres to internal carotid artery (ICA) stenosis, and investigate their association with stenosis grade in patients with asymptomatic ≥ 50% unilateral extracranial ICA stenosis. Patients without previous history of stroke and/or transient ischemic attack who had ≥ 50% stenosis in unilateral ICA on carotid color Doppler ultrasound were enrolled in the study. Patient demographics, vascular risk factors and ICA stenosis grades; number, location, and size of SBIs, DWMLs, and PWMLs in ICA territory were evaluated in both hemispheres using magnetic resonance imaging of the brain. Of the 69 patients, 53 had 50-69% (76.8%) and 16 had ≥ 70% (23.2%) unilateral ICA stenosis. There was no statistically significant difference in SBIs between ipsilateral and contralateral hemispheres to ≥ 50% ICA stenosis. Comparison of ICA stenoses as 50-69% and ≥ 70% revealed a greater number of patients with SBI in ipsilateral hemisphere to ≥ 70% stenosis compared to contralateral (p = 0.025). The number of SBIs was also higher in ipsilateral hemisphere to ≥ 70% stenosis compared to contralateral (p = 0.022). While DWMLs and PWMLs did not differ between hemispheres, frequency of Fazekas grade 1 DWMLs was lower in ipsilateral hemisphere to either 50-69% or ≥ 70% ICA stenosis compared to contralateral (p = 0.035 and p = 0.025, respectively). Results of the present study indicate that stenosis grade may be relevant in the association between asymptomatic carotid stenosis and SBIs, and ≥ 70% stenosis may pose a risk of SBI development.

Changes of blood-brain barrier permeability of the deep white matter during hypoperfusion caused by asymptomatic cerebral artery stenosis / 中华神经医学杂志

Objective:To investigate the blood-brain barrier (BBB) permeability changes in the deep white matter (DWM) during hypoperfusion caused by asymptomatic cerebral artery stenosis.Methods:The CT perfusion weighted imaging (CTP) images of 36 patients with asymptomatic severe stenosis and unilateral internal carotid artery or middle cerebral artery, admitted to our hospital from January 2017 to April 2020, which revealed the prolongation of contrast medium delayed contrast medium max-time (Tmax), were analyzed. The regions of interest (ROIs) in the DWM of CTP images at the body of lateral ventricle and centrum semiovale, were drawn respectively: the anterior DWM (ROIa), middle DWM (ROIm), and posterior DWM (ROIp) in the stenotic side of maximum intensity projection maps; DWM with normal-appeared Tmax (ROI1), DWM with relatively delayed Tmax (ROI2), and DWM with obviously delayed Tmax (ROI3) in the stenotic side of Tmax maps; and their mirrored ROI on the healthy side. Statistical analysis was used to compare the value differences of Tmax, cerebral blood flow (CBF) and transfer constant (Ktrans) between/among the ROIs.Results:As compared with the mirrored ROI in the healthy side, respectively, the ROIa and ROIm in the stenotic side had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans at the body of lateral ventricle ( P<0.05). As compared with the mirrored ROI in the healthy side, respectively, the ROIa and ROIp in the stenotic side had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans at the centrum semiovale ( P<0.05). As compared with the mirrored ROI in the healthy side, respectively, the ROI2 and ROI3 in the stenotic side had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans at the body of lateral ventricle and centrum semiovale ( P<0.05). In the stenotic side at the body of lateral ventricle, as compared with the mirrored ROIp, the ROIa and ROIm had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans ( P<0.05). In the stenotic side at the body of lateral ventricle and centrum semiovale, as compared with the mirrored ROI1, the ROI2 and ROI3 had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans ( P<0.05). Conclusion:The BBB permeability of DWM in the regions with delayed contrast medium Tmax is augmented when asymptomatic cerebral artery stenosis causes cerebral hypoperfusion.

A Nonlinear Reduced-Order Model of the Corpus Callosum Under Planar Coronal Excitation.

Traumatic brain injury (TBI) is often associated with microstructural tissue damage in the brain, which results from its complex biomechanical behavior. Recent studies have shown that the deep white matter (WM) region of the human brain is susceptible to being damaged due to strain localization in that region. Motivated by these studies, in this paper, we propose a geometrically nonlinear dynamical reduced order model (ROM) to model and study the dynamics of the deep WM region of the human brain under coronal excitation. In this model, the brain hemispheres were modeled as lumped masses connected via viscoelastic links, resembling the geometry of the corpus callosum (CC). Employing system identification techniques, we determined the unknown parameters of the ROM, and ensured the accuracy of the ROM by comparing its response against the response of an advanced finite element (FE) model. Next, utilizing modal analysis techniques, we determined the energy distribution among the governing modes of vibration of the ROM and concluded that the demonstrated nonlinear behavior of the FE model might be predominantly due to the special geometry of the brain deep WM region. Furthermore, we observed that, for sufficiently high input energies, high frequency harmonics at approximately 45 Hz, were generated in the response of the CC, which, in turn, are associated with high-frequency oscillations of the CC. Such harmonics might potentially lead to strain localization in the CC. This work is a step toward understanding the brain dynamics during traumatic injury.

Two-step deep neural network for segmentation of deep white matter hyperintensities in migraineurs.

BACKGROUND AND OBJECTIVE: Patients with migraine show an increased presence of white matter hyperintensities (WMHs), especially deep WMHs. Segmentation of small, deep WMHs is a critical issue in managing migraine care. Here, we aim to develop a novel approach to segmenting deep WMHs using deep neural networks based on the U-Net. METHODS: 148 non-elderly subjects with migraine were recruited for this study. Our model consists of two networks: the first identifies potential deep WMH candidates, and the second reduces the false positives within the candidates. The first network for initial segmentation includes four down-sampling layers and four up-sampling layers to sort the candidates. The second network for false positive reduction uses a smaller field-of-view and depth than the first network to increase utilization of local information. RESULTS: Our proposed model segments deep WMHs with a high true positive rate of 0.88, a low false discovery rate of 0.13, and F1 score of 0.88 tested with ten-fold cross-validation. Our model was automatic and performed better than existing models based on conventional machine learning. CONCLUSION: We developed a novel segmentation framework tailored for deep WMHs using U-Net. Our algorithm is open-access to promote future research in quantifying deep WMHs and might contribute to the effective management of WMHs in migraineurs.