Alzheimer’s disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer’s disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.

Functional connectivity (FC) disruption is a remarkable characteristic of schizophrenia. However, heterogeneous patterns reported across sites severely hindered its clinical generalization. Based on qualified nodal‐based FC of 340 schizophrenia patients (SZ) and 348 normal controls (NC) acquired from seven different scanners, this study compared four commonly used site‐effect correction methods in removing the site‐related heterogeneities, and then tried to cluster the abnormal FCs into several replicable and independent disrupted subnets across sites, related them to clinical symptoms, and evaluated their potentials in schizophrenia classification. Among the four site‐related heterogeneity correction methods, ComBat harmonization (F1 score: 0.806 ± 0.145) achieved the overall best balance between sensitivity and false discovery rate in unraveling the aberrant FCs of schizophrenia in the local and public data sets. Hierarchical clustering analysis identified three replicable FC disruption subnets across the local and public data sets: hypo‐connectivity within sensory areas (Net1), hypo‐connectivity within thalamus, striatum, and ventral attention network (Net2), and hyper‐connectivity between thalamus and sensory processing system (Net3). Notably, the derived composite FC within Net1 was negatively correlated with hostility and disorientation in the public validation set (p < .05). Finally, the three subnet‐specific composite FCs (Best area under the receiver operating characteristic curve [AUC] = 0.728) can robustly and meaningfully discriminate the SZ from NC with comparable performance with the full identified FCs features (best AUC = 0.765) in the out‐of‐sample public data set (Z = −1.583, p = .114). In conclusion, ComBat harmonization was most robust in detecting aberrant connectivity for schizophrenia. Besides, the three subnet‐specific composite FC measures might be replicable neuroimaging markers for schizophrenia.

Florbetapir 18F (AV45), a highly sensitive and specific positron emission tomographic (PET) molecular biomarker binding to the amyloid‐β of Alzheimer's disease (AD), is constrained by radiation and cost. We sought to combat it by combining multimodal magnetic resonance imaging (MRI) images and a collaborative generative adversarial networks model (CollaGAN) to develop a multimodal MRI‐derived Amyloid‐β (MRAβ) biomarker. We collected multimodal MRI and PET AV45 data of 380 qualified participants from the ADNI dataset and 64 subjects from OASIS3 dataset. A five‐fold cross‐validation CollaGAN were applied to generate MRAβ. In the ADNI dataset, we found MRAβ could characterize the subject‐level AV45 spatial variations in both AD and mild cognitive impairment (MCI). Voxel‐wise two‐sample t‐tests demonstrated amyloid‐β depositions identified by MRAβ in AD and MCI were significantly higher than healthy controls (HCs) in widespread cortices (p < .05, corrected) and were much similar to those by AV45 (r > .92, p < .001). Moreover, a 3D ResNet classifier demonstrated that MRAβ was comparable to AV45 in discriminating AD from HC in both the ADNI and OASIS3 datasets, and in discriminate MCI from HC in ADNI. Finally, we found MRAβ could mimic cortical hyper‐AV45 in HCs who later converted to MCI (r = .79, p < .001) and was comparable to AV45 in discriminating them from stable HC (p > .05). In summary, our work illustrates that MRAβ synthesized by multimodal MRI could mimic the cerebral amyloid‐β depositions like AV45 and lends credence to the feasibility of advancing MRI toward molecular‐explainable biomarkers.

The study aimed to unravel abnormal cerebral blood ow (CBF) in patients with Leber's hereditary optic neuropathy (LHON) using arterial spin labeling (ASL) and to investigate the associations among disrupted CBF, disease duration, and neuro-ophthalmological impairment. MethodsASL perfusion imaging data was collected from 20 patients with acute LHON, 29 patients with chronic LHON, and 37 healthy controls. We used a one-way analysis of covariance to test the intergroup differences in CBF. Linear and nonlinear curve t models were applied to explore the associations among CBF, disease duration, and neuroophthalmological metrics. ResultsBrain regions differed in LHON patients included the left sensorimotor and bilateral visual areas (p < 0.05, cluster-wise family-wise error correction). Acute and chronic LHON patients demonstrated lower CBF in bilateral calcarine than the healthy controls. Chronic LHON had lower CBF in the left middle frontal gyrus and sensorimotor cortex, and temporalpartial junction than the healthy controls and acute LHON. A signi cant logarithmic negative correlation was shown between CBF of left middle frontal gyrus and disease duration. There showed a signi cant logarithmic positive correlation between retinal nerve ber layer thickness and CBF in left middle frontal gyrus, and negative correlations between loss of variance and CBF in left middle frontal gyrus and sensorimotor cortex (p < 0.05, Bonferroni correction). ConclusionLHON patients exhibited reduced CBF in the visual pathway, sensorimotor and higher-tier cognitive areas. Disease duration and neuro-ophthalmological impairments can in uence the metabolism of non-visual areas.

The study aimed to investigate the neurovascular coupling abnormalities in Leber’s hereditary optic neuropathy (LHON) and their associations with clinical manifestations. Twenty qualified acute Leber’s hereditary optic neuropathy (A-LHON, disease duration ≤ 1 year), 29 chronic Leber’s hereditary optic neuropathy (C-LHON, disease duration &gt; 1 year), as well as 37 healthy controls (HCs) were recruited. The neurovascular coupling strength was quantified as the ratio between regional homogeneity (ReHo), which represents intrinsic neuronal activity and relative cerebral blood flow (CBF), representing microcirculatory blood supply. A one-way analysis of variance was used to compare intergroup differences in ReHo/CBF ratio with gender and age as co-variables. Pearson’s Correlation was used to clarify the association between ReHo, CBF, and neurovascular coupling strength. Furthermore, we applied linear and exponential non-linear regression models to explore the associations among ReHo/CBF, disease duration, and neuro-ophthalmological metrics. Compared with HCs, A_LHON, and C_LHON patients demonstrated a higher ReHo/CBF ratio than the HCs in the bilateral primary visual cortex (B_CAL), which was accompanied by reduced CBF while preserved ReHo. Besides, only C_LHON had a higher ReHo/CBF ratio and reduced CBF in the left middle temporal gyrus (L_MTG) and left sensorimotor cortex (L_SMC) than the HCs, which was accompanied by increased ReHo in L_MTG (p &lt; 1.85e–3, Bonferroni correction). A-LHON and C-LHON showed a negative Pearson correlation between ReHo/CBF ratio and CBF in B_CAL, L_SMC, and L_MTG. Only C_LHON showed a weak positive correlation between ReHo/CBF ratio and ReHo in L_SMC and L_MTG (p &lt; 0.05, uncorrected). Finally, disease duration was positively correlated with ReHo/CBF ratio of L_SMC (Exponential: Radj2 = 0.23, p = 8.66e–4, Bonferroni correction). No statistical correlation was found between ReHo/CBF ratio and neuro-ophthalmological metrics (p &gt; 0.05, Bonferroni correction). Brain neurovascular “dyscoupling” within and outside the visual system might be an important neurological mechanism of LHON.