Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer's continuum.

BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aß42, Aß40, Aß42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aß42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. RESULTS: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aß42 and Aß40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aß42 and Aß40 levels with MMSE scores (19.08% and 36.57%), and Aß42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aß42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aß42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05). CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

Mapping macrostructural and microstructural brain alterations in patients with neuronal intranuclear inclusion disease.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) is a rare complex neurodegenerative disorder presents with various radiological features. The study aimed to investigate the structural abnormalities in NIID using multi-shell diffusion MR. MATERIALS AND METHODS: Twenty-eight patients with adult-onset NIID and 32 healthy controls were included. Volumetric and diffusion MRI measures, including volume, fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) of six brain structures, including cortex, subcortical GM, cerebral WM, cerebellar GM and WM, and brainstem, were obtained and compared between NIID and healthy controls. Associations between MRI measures and clinical variables were investigated. RESULTS: Brain lesions of NIID included corticomedullary junction lesions on DWI, confluent leukoencephalopathy, lesions on callosum, cerebellar middle peduncle, cerebellar paravermal area and brainstem, and brain atrophy. Compared to healthy controls, NIID showed extensive volume loss of all the six brain regions (all p < 0.001); lower FA in cerebral WM (p < 0.001); higher MD in all WM regions; lower ODI in cortex (p < 0.001); higher ODI in subcortical GM (p < 0.001) and brainstem (p = 0.016); lower ICVF in brainstem (p = 0.001), and cerebral WM (p < 0.001); higher ISOVF in all the brain regions (p < 0.001). Higher MD of cerebellar WM was associated with worse cognitive level as evaluated by MoCA scores (p = 0.011). CONCLUSIONS: NIID patients demonstrated widespread brain atrophy but heterogeneous diffusion alterations. Cerebellar WM integrity impairment was correlated with the cognitive decline. The findings of the current study offer a sophisticated picture of brain structural alterations in NIID.

Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases.

Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.

Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis.

OBJECTIVE: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. METHODS: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported. RESULTS: We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. INTERPRETATION: GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276-288.

Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

Effects of the Fasting-Postprandial State on Arterial Spin Labeling MRI-Based Cerebral Perfusion Quantification in Alzheimer's Disease.

BACKGROUND: The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). PURPOSE: To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. STUDY TYPE: Prospective. SUBJECTS: Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. ASSESSMENT: Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. STATISTICAL TESTS: Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. RESULTS: Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. DATA CONCLUSION: Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Susceptibility-weighted image features in AQP4-negative-NMOSD versus MS.

OBJECTIVE: To characterize the susceptibility-weighted image (SWI) features including paramagnetic rim and nodular lesions with signal intensity changes and central vein sign (CVS) associated with aquaporin 4 (AQP4)-immunoglobulin G (IgG)-negative neuromyelitis optica spectrum disorder (NMOSD), and explore whether they can be used as potential imaging biomarkers for differentiating multiple sclerosis (MS) from this disorder. METHODS: We prospectively recruited NMOSD with AQP4-IgG-negative (AQP4- NMOSD) and IgG-positive (AQP4+ NMOSD), and MS subjects from the Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE) project (NCT0410683) between 2019 and 2021. The SWI features including paramagnetic rim and nodular lesions with signal intensity changes and CVS were analyzed and compared among groups, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for distinguishing MS from AQP4- NMOSD. RESULTS: We enrolled a total of 160 consecutive patients (22 AQP4- NMOSD, 65 AQP4+ NMOSD, and 73 MS). We observed paramagnetic rim lesion (0/120 lesions, 0 %) and nodular (1/120, 1 %) lesions with hypointense signals on SWI in the AQP4- NMOSD group. These characteristics were similar to those recorded from AQP4+ NMOSD patients (rim: 0/369 lesions, 0 %, P = 1.000; nodular: 10/369 lesions, 2.7 %, P = 1.000), but differed significantly from those observed in the MS group (rim: 162/1665 lesions, 9.7 %, P<0.001; nodular: 392/1665 lesions, 23.5 %, P < 0.001). AQP4- NMOSD patients had fewer average CVS+ rate (12 %) than MS patients (46 %, p<0.001), similar to AQP4+ NMOSD (13 %, p = 1.000). The SWI imaging features denoting lesions with paramagnetic rim or nodular hypointense SWI signals showed 90.4 % sensitivity, 95.5 % specificity, 98.5 % PPV, and 75 % NPV, and the criteria with≥3 CVS lesions showed sensitivity of 91.8 %, specificity of 90.9 %%, PPV of 97.1 %, and NPV of 76.9 % in distinguishing MS from AQP4- NMOSD. DISCUSSION: The SWI imaging features including lesions with paramagnetic rim or nodular hypointense SWI signals and 3 CVS lesions carries useful information in distinguishing MS from AQP4- NMOSD.

Independent and reproducible hippocampal radiomics biomarkers for multisite multiple sclerosis and neuromyelitis optica spectrum disorders.

OBJECTIVE: To investigate the abnormal radiomics features of the hippocampus in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and to explore the clinical implications of these features. METHODS: 752 participants were recruited in this retrospective multicenter study (7 centers), which included 236 MS, 236 NMOSD, and 280 normal controls (NC). Radiomics features of each side of the hippocampus were extracted, including intensity, shape, texture, and wavelet features (N = 431). To identify the variations in these features, two-sample t-tests were performed between the NMOSD vs. NC, MS vs. NC, and NMOSD vs. MS groups at each site. The statistical results from each site were then integrated through meta-analysis. To investigate the clinical significance of the hippocampal radiomics features, we conducted further analysis to examine the correlations between these features and clinical measures such as Expanded Disability Status Scale (EDSS), Brief Visuospatial Memory Test (BVMT), California Verbal Learning Test (CVLT), and Paced Auditory Serial Addition Task (PASAT). RESULTS: Compared with NC, patients with MS exhibited significant differences in 78 radiomics features (P < 0.05/862), with the majority of these being texture features. Patients with NMOSD showed significant differences in 137 radiomics features (P < 0.05/862), most of which were intensity features. The difference between MS and NMOSD patients was observed in 47 radiomics features (P < 0.05/862), mainly texture features. In patients with MS and NMOSD, the most significant features related to the EDSS were intensity and textural features, and the most significant features related to the PASAT were intensity features. Meanwhile, both disease groups observed a weak correlation between radiomics data and BVMT. CONCLUSION: Variations in the microstructure of the hippocampus can be detected through radiomics, offering a new approach to investigating the abnormal pattern of the hippocampus in MS and NMOSD.

A Fully Automated Deep-Learning Model for Predicting the Molecular Subtypes of Posterior Fossa Ependymomas Using T2-Weighted Images.

PURPOSE: We aimed to develop and validate a deep learning (DL) model to automatically segment posterior fossa ependymoma (PF-EPN) and predict its molecular subtypes [Group A (PFA) and Group B (PFB)] from preoperative MR images. EXPERIMENTAL DESIGN: We retrospectively identified 227 PF-EPNs (development and internal test sets) with available preoperative T2-weighted (T2w) MR images and molecular status to develop and test a 3D nnU-Net (referred to as T2-nnU-Net) for tumor segmentation and molecular subtype prediction. The network was externally tested using an external independent set [n = 40; subset-1 (n = 31) and subset-2 (n =9)] and prospectively enrolled cases [prospective validation set (n = 27)]. The Dice similarity coefficient was used to evaluate the segmentation performance. Receiver operating characteristic analysis for molecular subtype prediction was performed. RESULTS: For tumor segmentation, the T2-nnU-Net achieved a Dice score of 0.94 ± 0.02 in the internal test set. For molecular subtype prediction, the T2-nnU-Net achieved an AUC of 0.93 and accuracy of 0.89 in the internal test set, an AUC of 0.99 and accuracy of 0.93 in the external test set. In the prospective validation set, the model achieved an AUC of 0.93 and an accuracy of 0.89. The predictive performance of T2-nnU-Net was superior or comparable to that of demographic and multiple radiologic features (AUCs ranging from 0.87 to 0.95). CONCLUSIONS: A fully automated DL model was developed and validated to accurately segment PF-EPNs and predict molecular subtypes using only T2w MR images, which could help in clinical decision-making.

Automated Determination of the H3 K27-Altered Status in Spinal Cord Diffuse Midline Glioma by Radiomics Based on T2-Weighted MR Images.

BACKGROUND AND PURPOSE: Conventional MR imaging is not sufficient to discern the H3 K27-altered status of spinal cord diffuse midline glioma. This study aimed to develop a radiomics-based model based on preoperative T2WI to determine the H3 K27-altered status of spinal cord diffuse midline glioma. MATERIALS AND METHODS: Ninety-seven patients with confirmed spinal cord diffuse midline gliomas were retrospectively recruited and randomly assigned to the training (n = 67) and test (n = 30) sets. One hundred seven radiomics features were initially extracted from automatically-segmented tumors on T2WI, then 11 features selected by the Pearson correlation coefficient and the Kruskal-Wallis test were used to train and test a logistic regression model for predicting the H3 K27-altered status. Sensitivity analysis was performed using additional random splits of the training and test sets, as well as applying other classifiers for comparison. The performance of the model was evaluated through its accuracy, sensitivity, specificity, and area under the curve. Finally, a prospective set including 28 patients with spinal cord diffuse midline gliomas was used to validate the logistic regression model independently. RESULTS: The logistic regression model accurately predicted the H3 K27-altered status with accuracies of 0.833 and 0.786, sensitivities of 0.813 and 0.750, specificities of 0.857 and 0.833, and areas under the curve of 0.839 and 0.818 in the test and prospective sets, respectively. Sensitivity analysis confirmed the robustness of the model, with predictive accuracies of 0.767-0.833. CONCLUSIONS: Radiomics signatures based on preoperative T2WI could accurately predict the H3 K27-altered status of spinal cord diffuse midline glioma, providing potential benefits for clinical management.

Prediction of H3K27M Alteration Status in Brainstem Glioma Using Multi-Shell Diffusion MRI Metrics.

BACKGROUND: Multi-shell diffusion characteristics may help characterize brainstem gliomas (BSGs) and predict H3K27M status. PURPOSE: To identify the diffusion characteristics of BSG patients and investigate the predictive values of various diffusion metrics for H3K27M status in BSG. STUDY TYPE: Prospective. POPULATION: Eighty-four BSG patients (median age 10.5 years [IQR 6.8-30.0 years]) were included, of whom 56 were pediatric and 28 were adult patients. FIELD STRENGTH/SEQUENCE: 3 T, multi-shell diffusion imaging. ASSESSMENT: Diffusion kurtosis imaging and neurite orientation dispersion and density imaging analyses were performed. Age, gender, and diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis, intracellular volume fraction (ICVF), orientation dispersion index, and isotropic volume fraction (ISOVF), were compared between H3K27M-altered and wildtype BSG patients. STATISTICAL TESTS: Chi-square test, Mann-Whitney U test, multivariate analysis of variance (MANOVA), step-wise multivariable logistic regression. P-values <0.05 were considered significant. RESULTS: 82.4% pediatric and 57.1% adult patients carried H3K27M alteration. In the whole group, the H3K27M-altered BSGs demonstrated higher FA, AK and lower RD, ISOVF. The combination of age and median ISOVF showed fair performance for H3K27M prediction (AUC = 0.78). In the pediatric group, H3K27M-altered BSGs showed higher FA, AK, MK, ICVF and lower RD, MD, ISOVF. The combinations of median ISOVF, 5th percentile of FA, median MK and median MD showed excellent predictive power (AUC = 0.91). In the adult group, H3K27M-altered BSGs showed higher ICVF and lower RD, MD. The 75th percentile of RD demonstrated fair performance for H3K27M status prediction (AUC = 0.75). DATA CONCLUSION: Different alteration patterns of diffusion measures were identified between H3K27M-altered and wildtype BSGs, which collectively had fair to excellent predictive value for H3K27M alteration status, especially in pediatric patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

"Soap bubble" sign as an imaging marker for posterior fossa ependymoma Group B.

PURPOSE: To investigate the predictive value of the "soap bubble" sign on molecular subtypes (Group A [PFA] and Group B [PFB]) of posterior fossa ependymomas (PF-EPNs). METHODS: MRI scans of 227 PF-EPNs (internal retrospective discovery set) were evaluated by two independent neuroradiologists to assess the "soap bubble" sign, which was defined as clusters of cysts of various sizes that look like "soap bubbles" on T2-weighted images. Two independent cohorts (external validation set [n = 31] and prospective validation set [n = 27]) were collected to validate the "soap bubble" sign. RESULTS: Across three datasets, the "soap bubble" sign was observed in 21 PFB cases (7.4% [21/285] of PF-EPNs and 12.9% [21/163] of PFB); none in PFA. Analysis of the internal retrospective discovery set demonstrated substantial interrater agreement (1st Rating: κ = 0.71 [0.53-0.90], 2nd Rating: κ = 0.83 [0.68-0.98]) and intrarater agreement (Rater 1: κ = 0.73 [0.55-0.91], Rater 2: κ = 0.74 [0.55-0.92]) for the "soap bubble" sign; all 13 cases positive for the "soap bubble" sign were PFB (p = 0.002; positive predictive value [PPV] = 100%, negative predictive value [NPV] = 44%, sensitivity = 10%, specificity = 100%). The findings from the external validation set and the prospective validation set were similar, all cases positive for the "soap bubble" sign were PFB (p < 0.001; PPV = 100%). CONCLUSION: The "soap bubble" sign represents a highly specific imaging marker for the PFB molecular subtype of PF-EPNs.

Amide proton transfer-weighted imaging and derived radiomics in the classification of adult-type diffuse gliomas.

OBJECTIVES: To evaluate the utility of amide proton transfer-weighted (APTw) MRI imaging and its derived radiomics in classifying adult-type diffuse glioma. MATERIALS AND METHODS: In this prospective study, APTw imaging was performed on 129 patients with adult-type diffuse gliomas. The mean APTw-related metrics (chemical exchange saturation transfer ratio (CESTR), CESTR normalized with the reference value (CESTRnr), and relaxation-compensated inverse magnetization transfer ratio (MTRRex)) and radiomic features within 3D tumor masks were extracted. APTw-radiomics models were developed using a support vector machine (SVM) classifier. Sensitivity analysis with tumor area of interest, different histogram cutoff values, and other classifiers were conducted. RESULTS: CESTR, CESTRnr, and MTRRex in glioblastomas were all significantly higher (p < 0.0003) than those of oligodendrogliomas and astrocytomas, with no significant difference between oligodendrogliomas and astrocytomas. The APTw-related metrics for IDH-wildtype and high-grade gliomas were significantly higher (p < 0.001) than those for the IDH-mutant and low-grade gliomas, with area under the curve (AUCs) of 0.88 for CESTR. The CESTR-radiomics models demonstrated accuracies of 84% (AUC 0.87), 83% (AUC 0.83), 90% (AUC 0.95), and 84% (AUC 0.86) in predicting the IDH mutation status, differentiating glioblastomas from astrocytomas, distinguishing glioblastomas from oligodendrogliomas, and determining high/low grade prediction, respectively, but showed poor performance in distinguishing oligodendrogliomas from astrocytomas (accuracy 63%, AUC 0.63). The sensitivity analysis affirmed the robustness of the APTw signal and APTw-derived radiomics prediction models. CONCLUSION: APTw imaging, along with its derived radiomics, presents a promising quantitative approach for prediction IDH mutation and grading adult-type diffuse glioma. CLINICAL RELEVANCE STATEMENT: Amide proton transfer-weighted imaging, a quantitative imaging biomarker, coupled with its derived radiomics, offers a promising non-invasive approach for predicting IDH mutation status and grading adult-type diffuse gliomas, thereby informing individualized clinical diagnostics and treatment strategies. KEY POINTS: • This study evaluates the differences of different amide proton transfer-weighted metrics across three molecular subtypes and their efficacy in classifying adult-type diffuse glioma. • Chemical exchange saturation transfer ratio normalized with the reference value and relaxation-compensated inverse magnetization transfer ratio effectively predicts IDH mutation/grading, notably the first one. • Amide proton transfer-weighted imaging and its derived radiomics holds potential to be used as a diagnostic tool in routine clinical characterizing adult-type diffuse glioma.

Male and female are not the same: a multicenter study of static and dynamic functional connectivity in relapse-remitting multiple sclerosis in China.

Background: Sex-related effects have been observed in relapsing-remitting multiple sclerosis (RRMS), but their impact on functional networks remains unclear. Objective: To investigate the sex-related differences in connectivity strength and time variability within large-scale networks in RRMS. Methods: This is a multi-center retrospective study. A total of 208 RRMS patients (135 females; 37.55 ± 11.47 years old) and 228 healthy controls (123 females; 36.94 ± 12.17 years old) were included. All participants underwent clinical and MRI assessments. Independent component analysis was used to extract resting-state networks (RSNs). We assessed the connectivity strength using spatial maps (SMs) and static functional network connectivity (sFNC), evaluated temporal properties and dynamic functional network connectivity (dFNC) patterns of RSNs using dFNC, and investigated their associations with structural damage or clinical variables. Results: For static connectivity, only male RRMS patients displayed decreased SMs in the attention network and reduced sFNC between the sensorimotor network and visual or frontoparietal networks compared with healthy controls [P<0.05, false discovery rate (FDR) corrected]. For dynamic connectivity, three recurring states were identified for all participants: State 1 (sparse connected state; 42%), State 2 (middle-high connected state; 36%), and State 3 (high connected state; 16%). dFNC analyses suggested that altered temporal properties and dFNC patterns only occurred in females: female patients showed a higher fractional time (P<0.001) and more dwell time in State 1 (P<0.001) with higher transitions (P=0.004) compared with healthy females. Receiver operating characteristic curves revealed that the fraction time and mean dwell time of State 1 could significantly distinguish female patients from controls (area under the curve: 0.838-0.896). In addition, female patients with RRMS also mainly showed decreased dFNC in all states, particularly within cognitive networks such as the default mode, frontoparietal, and visual networks compared with healthy females (P < 0.05, FDR corrected). Conclusion: Our results observed alterations in connectivity strength only in male patients and time variability in female patients, suggesting that sex-related effects may play an important role in the functional impairment and reorganization of RRMS.

Amide proton transfer-weighted imaging of pediatric brainstem glioma and its predicted value for H3 K27 alteration.

BACKGROUND: Non-invasive determination of H3 K27 alteration of pediatric brainstem glioma (pedBSG) remains a clinical challenge. PURPOSE: To predict H3 K27-altered pedBSG using amide proton transfer-weighted (APTw) imaging. MATERIAL AND METHODS: This retrospective study included patients with pedBSG who underwent APTw imaging and had the H3 K27 alteration status determined by immunohistochemical staining. The presence or absence of foci of markedly increased APTw signal in the lesion was visually assessed. Quantitative APTw histogram parameters within the entire solid portion of tumors were extracted and compared between H3 K27-altered and wild-type groups using Student's t-test. The ability of APTw for differential diagnosis was evaluated using logistic regression. RESULTS: Sixty pedBSG patients included 48 patients with H3 K27-altered tumor (aged 2-48 years) and 12 patients with wild-type tumor (aged 3-53 years). Visual assessment showed that the foci of markedly increased APTw signal intensity were more common in the H3 K27-altered group than in wild-type group (60% vs. 16%, P = 0.007). Histogram parameters of APTw signal intensity in the H3 K27-altered group were significantly higher than those in the wild-type group (median, 2.74% vs. 2.22%, P = 0.02). The maximum (area under the receiver operating characteristic curve [AUC] = 0.72, P = 0.01) showed the highest diagnostic performance among histogram analysis. A combination of age, median and maximum APTw signal intensity could predict H3 K27 alteration with a sensitivity of 81%, specificity of 75% and AUC of 0.80. CONCLUSION: APTw imaging may serve as an imaging biomarker for H3 K27 alteration of pedBSGs.

[Difference in Brain Age Between Alzheimer's Disease and Mild Cognitive Impairment].

Objective To investigate the brain age differences between Alzheimer's disease(AD)and mild cognitive impairment(MCI)patients,and further explore the correlations between brain age gap(BAG)and clinical features.Methods The clinical data and radiologic findings of 132 probable AD and AD-derived MCI patients diagnosed at Beijing Tiantan Hospital,Capital Medical University from December 2018 to July 2021 were retrospectively analyzed.According to the diagnostic criteria for AD and MCI,the patients were assigned into AD and MCI groups.In addition,156 volunteers without neurological diseases and other severe diseases were recruited as the control group.The general data,Montreal cognitive assessment(MoCA)score,and mini-mental state examination(MMSE)score were compared among the three groups.The deep learning-based brain age prediction model was employed to calculate the BAGs of the three groups.Spearman correlation analysis was conducted to explore the correlations between BAG and clinical features.Results The 132 patients included 106 patients in the AD group and 26 patients in the MCI group.The MoCA and MMSE scores followed an ascending trend of AD group

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay.

Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.