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To apply a texture analysis of apparent diffusion coefficient (ADC) maps to evaluate glioma heterogeneity, which was correlated with tumor grade. Forty patients with glioma (WHO grade II (n = 8), grade III (n = 10) and grade IV (n = 22)) underwent diffusion-weighted imaging (DWI), and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student's t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade. Entropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P  = 0.006). The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037). Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P<0.001). The diagnostic accuracy of ADC entropy was significantly higher than that of the fifth percentile of the ADC histogram (P = 0.0034) in distinguishing high- from low-grade glioma. A texture analysis of the ADC map based on the entire tumor volume can be useful for evaluating glioma grade, which provides tumor heterogeneity.

ObjectivesPrediction of progression-free survival (PFS) and overall survival (OS) and early identification of molecular biomarkers with prognostic information are clinically important in glioblastoma (GBM) patients. We aimed to explore the utility of arterial spin labeling perfusion-weighted imaging (ASL-PWI) in the prediction of molecular biomarkers and survival in GBM patients.MethodsWe retrospectively analyzed 149 consecutive GBM patients, who had undergone maximal surgical resection or biopsy followed by concurrent chemoradiotherapy and adjuvant chemotherapy using temozolomide between November 2010 and June 2016. On preoperative ASL-PWI, cerebral blood flow (CBF) within contrast-enhancing (CE) and nonenhancing (NE) portions were evaluated both qualitatively (perfusion pattern[CE] and perfusion pattern[NE]) and quantitatively (nCBFCE and nCBFNE). ASL-PWI findings were correlated with molecular biomarkers, including isocitrate dehydrogenase (IDH) and O6-methylguanine-DNA methyltransferase (MGMT) methylation statuses, and survival, using the Mann-Whitney U-test, Spearman rank correlation, Kaplan-Meier analysis, and receiver operating characteristics analysis.ResultsnCBFCE was significantly higher in the IDH wild-type group than in the IDH mutant group (p = .013) and in the MGMT unmethylated group than in the methylated group (p = .047). Areas under the receiver operating characteristic curve were 0.678 for IDH mutation (p = .022) and 0.601 for MGMT promoter methylation (p = .043). Hyperperfusion was associated with the shortest median PFS for both perfusion pattern[CE] (7.6 months) and perfusion pattern[NE] (4.0 months). The perfusion pattern[NE] remained an independent predictor for PFS and OS even after adjusting for clinical and molecular predictors, unlike perfusion pattern[CE].ConclusionsASL-PWI can aid to predict survival and molecular biomarkers including IDH mutation and MGMT promoter methylation statuses in GBM patients.Key Points• ASL-PWI can aid to predict survival in GBM patients.• ASL-PWI can aid to predict IDH and MGMT promoter methylation statuses in GBM.

Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903–1.000) for local recurrence; 0.864 (0.726–0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or “radiomic risk score”, increased risk of recurrence/progression (hazard ratio, 1.61; p  = 0.03) in multivariate Cox regression on progression-free survival.

An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain. The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history. In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury.

INTRODUCTION Appropriate Use Recommendations (AURs) guide real‐world use of lecanemab and donanemab in early symptomatic Alzheimer's disease (AD), but their applicability to Asian populations with diverse education backgrounds remains unclear. METHODS Among 2726 participants who visited a Korean memory clinic, 1005 amyloid‐positive participants with magnetic resonance imaging (MRI) and Clinical Dementia Rating data were included. Eligibility for lecanemab and donanemab was assessed using AUR criteria, including age, Mini‐Mental State Examination (MMSE), brain MRI, apolipoprotein E genotype (for donanemab), and anticoagulant use, applying both raw and z‐score‐based MMSE thresholds. RESULTS Among 1005 amyloid‐positive participants, 24.6% were eligible for lecanemab and 28.0% for donanemab (9.1% and 10.3% of the initial sample). Applying MMSE z‐scores increased eligibility to 38.4% and 33.7%, respectively. Over a third of participants were excluded due to MRI findings, mainly vascular lesions associated with increased amyloid‐related imaging‐abnormality risks. DISCUSSION Incorporating demographically adjusted MMSE z‐score threshold improves real‐world eligibility and promotes equitable access to anti‐amyloid therapies. Highlights About a fourth of A+ patients in Korea met AUR criteria for anti‐amyloid therapy. Donanemab eligibility slightly exceeded lecanemab despite narrower age criteria. MMSE z‐score adjustment increased eligibility in older, less‐educated individuals. Over 30% of eligible patients were excluded due to ARIA‐related MRI findings. Culturally adapted cognitive thresholds are essential for equitable treatment access.

In acute ischemic stroke (AIS), the hemodynamics around the lesion are important because they determine the recurrence or prognosis of the disease. This study evaluated the effects of perfusion deficits in multiphase arterial spin labeling (ASL) and related radiological parameters on the occurrence of early recurrent ischemic lesions (ERILs) in AIS. We assessed AIS patients who underwent multiphase ASL within 24 h of symptom onset and follow-up diffusion-weighted imaging within 7 days. ASL perfusion deficit, arterial transit artifact (ATA), and intra-arterial high-intensity signal (IAS) were manually rated as ASL parameters. A total of 134 patients were evaluated. In the multivariable analyses, ASL perfusion deficit [adjusted odds ratio (aOR) = 2.82, 95% confidence interval = 1.27–6.27] was positively associated with ERIL. Furthermore, when ATA was accompanied, the ASL perfusion deficit was not associated with ERIL occurrence. Meanwhile, IAS showed a synergistic effect with ASL perfusion deficit on the occurrence of ERIL. In conclusion, we demonstrated the association between perfusion deficits in multiphase ASL with ERIL in patients with AIS. This close association was attenuated by ATA and was enhanced by IAS. ASL parameters may help identify high-risk patients of ERIL occurrence during the acute period.

Abstract Study Objectives The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). Methods We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. Results RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and −0.466, respectively). Conclusions Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network. Graphical abstract Graphical Abstract

INTRODUCTION We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition. METHODS One hundred and seventy well‐characterized participants from an ongoing cohort were included. High‐resolution T1, tau positron emission tomography (PET), and amyloid PET were obtained. RESULTS LC tau burden was significantly linked to global tau in neocortical regions, as was tau in both early Braak stage (stage I/II) and later Braak stage areas. This relationship was significant only in Aβ‐positive individuals. While LC tau did not directly impact memory, it was indirectly associated with delayed memory through mediation or moderation pathways. DISCUSSION The findings from living human brains support the idea that LC tau closely relates to subsequent cortical tau accumulation, particularly among individuals with pathological Aβ accumulation, and identify LC tau burden as a promising indicator of cognitive trajectories of AD. Highlights Tau burden in the LC was significantly associated with cortical tau accumulation. Tau burden in SN or PPN showed no association with cortical tau accumulation. LC tau burden was serially associated with Braak stages. The tau‐LC and cortical tau relationship was significant only in the Aβ‐positive group. Cortical amyloid's impact on memory worsens with higher tau accumulation in the LC.

This study utilized arterial spin labeling-magnetic resonance imaging (ASL-MRI) to explore the developmental trajectory of brain activity associated with attention deficit hyperactivity disorder (ADHD). Pulsed arterial spin labeling (ASL) data were acquired from 157 children with ADHD and 109 children in a control group, all aged 6–12 years old. Participants were categorized into the age groups of 6–7, 8–9, and 10–12, after which comparisons were performed between each age group for ASL analysis of cerebral blood flow (CBF). In total, the ADHD group exhibited significantly lower CBF in the left superior temporal gyrus and right middle frontal gyrus regions than the control group. Further analysis revealed: (1) The comparison between the ADHD group (N = 70) aged 6–7 and the age-matched control group (N = 33) showed no statistically significant difference between. (2) However, compared with the control group aged 8–9 (N = 39), the ADHD group of the same age (N = 53) showed significantly lower CBF in the left postcentral gyrus and left middle frontal gyrus regions. (3) Further, the ADHD group aged 10–12 (N = 34) demonstrated significantly lower CBF in the left superior occipital region than the age-matched control group (N = 37). These age-specific differences suggest variations in ADHD-related domains during brain development post age 6–7.