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Human arousal is essential to survival and mediated by the ascending arousal network (AAN) and its connections. It spans from the brainstem to the diencephalon, basal forebrain, and cerebral cortex. Despite advances in mapping the AAN in adults, it is unexplored in fetal and early infant life, especially with high‐resolution magnetic resonance imaging techniques. In this study, we conducted—for the first time—high‐resolution ex vivo diffusion MRI‐based analysis of the AAN in seven fetal, infant, and adult brains, incorporating probabilistic tractography and quantifying connectivity using graph theory. We observed that AAN structural connectivity becomes increasingly integrated during development, progressively reaching rostrally during the first postconceptional year. We quantitatively identified the dorsal raphe (DR) nucleus and ventral tegmental area (VTA) as AAN connectivity hubs already in the fetus persisting into adulthood. The DR appears to form a local hub of short‐range connectivities, while the VTA evolves as a long‐range global hub. The identified connectivity maps advance our understanding of AAN architecture changes due to normative human brain development, as well as disorders of arousal, such as coma and sudden infant death syndrome. We used high‐resolution ex vivo diffusion MRI and graph theory to analyze ascending arousal network development in fetal to adult brains, revealing increasing rostral integration postnatally and identifying the dorsal raphe nucleus and ventral tegmental area as persistent connectivity hubs from fetal stages through adulthood.

Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) distinguishes different diffusion processes based on varying molecular velocities. While IVIM is used in-vivo, postmortem studies are lacking, although they could provide valuable insights and validate in-vivo results. In this study, postmortem in-situ brain MRI scans of 13 deceased subjects were performed by applying a diffusion-weighted single-shot-echo-planar imaging sequence with 16 b-values (0–2500 s/mm2). The IVIM parameters perfusion fraction (f), diffusion (D), pseudo-diffusion (D*) and kurtosis (K) were determined in segmented white matter, cerebral cortex and deep gray matter. D was additionally corrected for temperature. All parameters were correlated with forehead and core temperature, postmortem interval (PMI), age at death and brain edema presence. Furthermore, differences of IVIM parameters between cases of fatal intoxication and other causes of deaths were analyzed. Postmortem f, D and D* were lower than in-vivo, while f in deep gray matter and K in all regions were higher. f did not level to 0 %. Forehead and core temperatures and PMI revealed statistically significant correlations with D. K correlated significantly with forehead temperature in deep gray matter, core temperature in cerebral cortex and PMI in white and deep gray matter. A significant difference was found in D* when comparing fatal intoxication cases with those with other causes of death. In conclusion, postmortem IVIM parameters differ from in-vivo values and are influenced by temperature and PMI. In the future, D* might enable noninvasive detection of intoxication as the cause of death. [Display omitted] •Perfusion fraction does not level to 0 % postmortem.•Temperature and postmortem interval strongly influence diffusion.•Pseudo-diffusion may identify intoxication as cause of death.

The image contrast of postmortem magnetic resonance imaging (MRI) may differ from that of antemortem MRI because of circulator arrest, changes in postmortem tissue, and low-body-temperature scanning conditions. In fact, we have found that the signal intensity of white matter (WM) on T1-weighted spin-echo (T1WSE) images of the postmortem brain was lower than that of gray matter (GM), which resulted in image contrast reversal between GM and WM relative to the living brain. However, the reason for this phenomenon is unclear. Therefore, the aim of this study is to clarify the reason why image contrast reversal occurs between GM and WM of the postmortem brain. Twenty-three corpses were included in the study (mean age, 60.6 years; range: 19–60 years; mean rectal temperature at scan, 6.9℃; range: 4–11℃). On a 1.5 T MRI system, postmortem T1W-SE MRI of the brain was conducted in the 23 corpses prior to medico-legal autopsy. Next, T1 and T2 of the GM and WM at the level of the basal ganglia were determined in the same participants using inversion recovery and multiple SE sequences, respectively. The proton density (PD) was also calculated from the T1 and T2 images (in the same slice). T1W-SE image contrast between the GM and WM of all postmortem brains was inverted relative to the living brain. T1 (579 ms in GM and 307 ms in WM) and PD (64 in GM and 44 in WM) of the postmortem brain decreased compared with the living brain. While T1 of WM/GM remained below 1 even postmortem, the PD of WM/GM decreased. T2 (110 ms in GM and 98 ms in WM) of the postmortem brain did not differ from the living brain. The decrease in PD of WM/GM in the postmortem brain may be the major driver of contrast reversal between the GM and WM relative to the living brain. •WM/GM is preserved in postmortem brain T1W-SE images.•Postmortem brain T1 and PD are decreased.•Rates of postmortem water reduction differ between WM and GM.•Lower PD of postmortem brain WM drives contrast inversion between the GM and WM.

The purpose of this study is to create a white matter atlas of the human brain using diffusion tensor imaging (DTI) tractography and to describe the constant and variable features of the major pathways. DTI was acquired from 40 healthy right-handed adults and reconstructed tracts mapped within a common reference space (MNI). Group effect maps of each tract defined constant anatomical features while overlap maps were generated to study inter-subject variability and to compare DTI derived anatomy with a histological atlas. Two patients were studied to assess the localizing validity of the atlas. The DTI-derived maps are overall consistent with a previously published histological atlas. A statistically significant leftward asymmetry was found for the volume and number of streamlines of the cortico-spinal tract and the direct connections between Broca's and Wernicke's territories (long segment). A statistically significant rightward asymmetry was found for the inferior fronto-occipital fasciculus and the fronto-parietal connections (anterior segment) of the arcuate fasciculus. Furthermore, males showed a left lateralization of the fronto-temporal segment of the arcuate fasciculus (long segment), while females had a more bilateral distribution. In two patients with brain lesions, DTI was acquired and tractography used to show that the tracts affected by the lesions were correctly identified by the atlas. This study suggests that DTI-derived maps can be used together with a previous histological atlas to establish the relationship of focal lesions with nearby tracts and improve clinico-anatomical correlation. ►The anterior segment of the arcuate fasciculus and the inferior fronto-occipital fasciculus (IFOF) are asymmetric; with the right side larger than the left. ►Variability maps of the white matter produced with DTI tractography are consistent with the variability maps generated by prior postmortem histological studies. ►Our DTI-derived atlas is a valuable tool for learning the neuroanatomy of white matter, and establishing the relationship of focal lesions with nearby tracts.

Brain iron levels in patients of Parkinson’s disease (PD) are usually measured in postmortem samples or by MRI imaging including R2* and SWI. In this study we performed a meta-analysis to understand PD-associated iron changes in various brain regions, and to evaluate the accuracy of MRI detections comparing with postmortem results. Databases including Medline, Web of Science, CENTRAL and Embase were searched up to 19 th November 2015. Ten brain regions were identified for analysis based on data extracted from thirty-three-articles. An increase in iron levels in substantia nigra of PD patients by postmortem, R2* or SWI measurements was observed. The postmortem and SWI measurements also suggested significant iron accumulation in putamen. Increased iron deposition was found in red nucleus as determined by both R2* and SWI, whereas no data were available in postmortem samples. Based on SWI, iron levels were increased significantly in the nucleus caudatus and globus pallidus. Of note, the analysis might be biased towards advanced disease and that the precise stage at which regions become involved could not be ascertained. Our analysis provides an overview of iron deposition in multiple brain regions of PD patients, and a comparison of outcomes from different methods detecting levels of iron.

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in non-neurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.

Background Postmortem fetal magnetic resonance imaging (MRI) has been on the rise since it was proven to be a good alternative to conventional autopsy. Since the fetal brain is sensitive to postmortem changes, extensive tissue fixation is required for macroscopic and microscopic assessment. Estimation of brain maceration on MRI, before autopsy, may optimize histopathological resources. Objective The aim of the study is to develop an MRI-based postmortem fetal brain maceration score and to correlate it with brain maceration as assessed by autopsy. Materials and methods This retrospective single-center study includes 79 fetuses who had postmortem MRI followed by autopsy. Maceration was scored on MRI on a numerical severity scale, based on our brain-specific maceration score and the whole-body score of Montaldo. Additionally, maceration was scored on histopathology with a semiquantitative severity scale. Both the brain-specific and the whole-body maceration imaging scores were correlated with the histopathological maceration score. Intra- and interobserver agreements were tested for the brain-specific maceration score. Results The proposed brain-specific maceration score correlates well with fetal brain maceration assessed by autopsy (τ = 0.690), compared to a poorer correlation of the whole-body method (τ = 0.452). The intra- and interobserver agreement was excellent (correlation coefficients of 0.943 and 0.864, respectively). Conclusion We present a brain-specific postmortem MRI maceration score that correlates well with the degree of fetal brain maceration seen at histopathological exam. The score is reliably reproduced by different observers with different experience.

Synaptic dysfunction and loss are central to neurodegenerative diseases and correlate with cognitive decline. Synaptic Vesicle Protein 2A (SV2A) is a promising PET-imaging target for assessing synaptic density in vivo, but comprehensive mapping in the human brain is needed to validate its biomarker potential. This study used quantitative immunohistochemistry and Western blotting to map SV2A and synaptophysin (SYP) densities across six cortical regions in healthy controls and patients with early-onset Alzheimer’s disease (EOAD), late-onset Alzheimer’s disease (LOAD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-GRN). We identified region in SV2A density among controls and observed disease- and region-specific reductions, with the most severe in FTLD-GRN (up to 59.5%) and EOAD. EOAD showed a 49% reduction in the middle frontal gyrus (MFG), while LOAD had over 30% declines in the inferior frontal gyrus (IFG) and hippocampus (CA1). In PSP, smaller but significant reductions were noted in the hippocampal formation, with the inferior temporal gyrus (ITG) relatively unaffected. A strong positive correlation between SV2A and SYP densities confirmed SV2A’s reliability as a synaptic integrity marker. This study supports the use of SV2A PET imaging for early diagnosis and monitoring of neurodegenerative diseases, providing essential data for interpreting in vivo PET results. Further research should explore SV2A as a therapeutic target and validate these findings in larger, longitudinal studies.

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes’ monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form.