Premature white matter microstructure in female children with a history of concussion

As maturation of the brain continues throughout development, there is a risk of interference from concussions which are common in childhood. A concussion can cause widespread disruption to axons and inflammation in the brain and may influence emerging cognitive abilities. Females are more likely to experience persistent problems after a concussion, yet the sex-specific impact of concussions on brain microstructure in childhood is not well understood.In children from a large population sample, this study (1) investigated differences in white matter and cortical microstructure between children with and without a history of concussion, and (2) examined relationships between altered brain microstructure and cognitive performance.Neurite density measures from diffusion weighted magnetic resonance imaging were examined in 9-to 10-year-old children in the Adolescent Brain Cognitive Development Study with (n = 336) and without (n = 7368) a history of concussion. (1) Multivariate regression models were used to investigate the relationships between concussion history, sex, and age in the deep white matter, superficial white matter, subcortical structures, and cortex. (2) Principal component analysis was performed on neurite density, and components were examined in relation to performance on the Flanker Inhibitory Control and Attention Task and the Pattern Comparison Processing Speed Task to investigate the relationship between altered neurite density and cognitive performance.Neurite density in all tissue types demonstrated robust positive relationships with age reflecting maturation of brain microstructure. (1) Comparisons between children with and without a history of concussion revealed higher neurite density in deep and superficial white matter in females with concussion. No group differences were observed in subcortical or cortical neurite density. (2) Higher neurite density in superficial white matter beneath the frontal and temporal cortices was associated with lower scores on the processing speed test in females with concussion, and higher scores on the processing speed test in males with concussion.These findings suggest that concussion in childhood leads to premature white matter maturation in females and that this may be associated with slower processing speed. These sex-specific effects on the developing brain may contribute to the enhanced vulnerability to persistent symptoms after concussion in females.

NI-2 Use of neurite orientation dispersion and density imaging(NODDI)for early distinction between infiltrating tumor and vasogenic edema in non-enhancing lesions with glioblastoma patients

Background: Glioblastoma is a highly infiltrative tumor. In the non-enhancing T2-weighted hyperintense area, differentiating between non-enhancing tumors (NETs) and vasogenic edema is challenging. Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique that reveals the inhomogeneity of the brain microstructure. The aim of this study is to differentiate between NETs and edema in glioblastomas using NODDI. Methods: Data were collected from 20 patients with glioblastoma as well as three patients with metastasis and two with meningioma (control), who underwent MRI as part of pre-surgical examination. The MRI data included T2- and T1-weighted contrast-enhanced images and NODDI images. Three neurosurgeons manually placed the volume of interest (VOI) on the NETs and edema based on the previous reports. ICVF, ODI, ISOVF, FA, and ADC were calculated for each VOI. Results: Fifteen and 13 VOIs were placed on NETs and edema, respectively. Each parameter was measured and the unpaired t-test revealed a significant difference between NETs and edema (p <0.0001). The ROC curve analysis revealed a large difference in the ADC, FA, and ISOVF between NETs and edema compared to ICVF and ODI. Principal component analysis of the five parameters showed that ADC, ISOVF, and FA contributed to the differentiation between NETs and edema. Multiple logistic regression analysis was performed with the three aforementioned parameters. A predictive formula could be created to discriminate between NETs and edema, following the use of which, the ROC curve revealed an AUC value of 0.8891. Furthermore, this formula was applied to the edematous regions of the images of the negative control group, and the prediction degree of the tumor was well below 0.5, thus enabling differentiation as edema.Conclusions: NODDI may prove to be a useful tool to discriminate between NETs and edema in the non-contrast T2 hyperintensity region of glioblastoma.

Higher-order interaction of brain microstructural and functional connectome

Despite a relatively fixed anatomical structure, the human brain can support rich cognitive functions, triggering particular interest in investigating structure-function relationships. Myelin is a vital brain microstructure marker, yet the individual microstructure-function relationship is poorly understood. Here, we explore the brain microstructure-function relationships using a higher-order framework. Global (network-level) higher-order microstructure-function relationships negatively correlate with male participants' personality scores and decline with aging. Nodal (node-level) higher-order microstructure-function relationships are not aligned uniformly throughout the brain, being stronger in association cortices and lower in sensory cortices, showing gender differences. Notably, higher-order microstructure-function relationships are maintained from the whole-brain to local circuits, which uncovers a compelling and straightforward principle of brain structure-function interactions. Additionally, targeted artificial attacks can disrupt these higher-order relationships, and the main results are robust against several factors. Together, our results increase the collective knowledge of higher-order structure- function interactions that may underlie cognition, individual differences, and aging.

CHANGES IN THE MICROSTRUCTURE AND FUNCTION OF BRAIN TISSUE IN PD BY DIFFUSION KURTOSIS IMAGING

This study proposed to detect changes in brain microstructure in patients with Parkinson’s disease (PD) using diffusion kurtosis imaging (DKI) to quantitatively diagnose early-stage PD. Conventional magnetic resonance imaging and DKI scanning were performed in 24 patients with PD and in 12 age- and sex-matched healthy participants. Hoehn and Yahr (H–Y) stage and Unified Parkinson’s Disease Rating Scale-III (UPDRS-III) scores were obtained from both groups. The mean kurtosis (MK), axial kurtosis, and radial kurtosis of the bilateral substantia nigra on DKI were measured and compared between the two groups. The correlations between MK, H–Y stage, and UPDRS-III scores were determined. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of MK for PD in the substantia nigra. The MK value in the PD group was 0.971. The area under the ROC curve of the substantia nigra was 0.905; the sensitivity and specificity were 0.917 and 0.875, respectively, and the cutoff value was 1.046. The MK of the substantia nigra in the PD group had no significant correlation with the H–Y stages but was negatively correlated with the UPDRS-III scores ([Formula: see text]; [Formula: see text]). Our research identified DKI as a novel tool for the qualitative diagnosis of PD. The optimal MK value for PD diagnosis could be determined with ROC analysis.

An open MRI dataset for multiscale neuroscience

Multimodal neuroimaging grants a powerful window into the structure and function of the human brain at multiple scales. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends (also referred to as gradients) in brain microstructure and connectivity, offering an integrative framework to study multiscale brain organization. Here, we share a multimodal MRI dataset for Microstructure-Informed Connectomics (MICA-MICs) acquired in 50 healthy adults (23 women; 29.54±5.62 years) who underwent high-resolution T1-weighted MRI, myelin-sensitive quantitative T1 relaxometry, diffusion-weighted MRI, and resting-state functional MRI at 3 Tesla. In addition to raw anonymized MRI data, this release includes brain-wide connectomes derived from i) resting-state functional imaging, ii) diffusion tractography, iii) microstructure covariance analysis, and iv) geodesic cortical distance, gathered across multiple parcellation scales. Alongside, we share large-scale gradients estimated from each modality and parcellation scale. Our dataset will facilitate future research examining the coupling between brain microstructure, connectivity, and macroscale function. MICA-MICs is available on the Canadian Open Neuroscience Platform data portal (https://portal.conp.ca).

Role of diffusion kurtosis imaging for detecting brain microstructural changes in complete remission childhood survivors undergoing chemotherapy for acute lymphoblastic leukemia

Objectives Some children with acute lymphoblastic leukemia receiving chemotherapy may sustain brain microstructural damages that impair their neurocognitive function and affect their quality of life to varying degrees. This study aims to determine whether diffusion kurtosis imaging could detect brain microstructural changes in newly diagnosed acute lymphoblastic leukemia patients before and after normalization in complete remission after chemotherapy. Methods Twenty newly diagnosed patients with acute lymphoblastic leukemia and 20 healthy controls matched by sex and were enrolled in this study in the Shenzhen Children's Hospital from August 2019 to December 2020. Head MRI scans were performed mean kurtosis, axial kurtosis and radial kurtosis values were calculated before and after complete remission. Results There were significant decreases observed in mean kurtosis and axial kurtosis in both the genu and splenium of the corpus callosum after chemotherapy among patients under 5 years old who have also achieved complete remission. The diffusion kurtosis imaging parameters were measured in the bilateral frontal lobe and corpus callosum; there were no obvious changes observed among patients older than 5 years old. Conclusion Brain microstructure damage can occur in patients with acute lymphoblastic leukemia during the early stage of chemotherapy. The location of the damage is significantly correlated with the patient’s age. Early recognition of changes in diffusion kurtosis imaging parameters of brain microstructure damage in acute lymphoblastic leukemia patients may help improve patient prognosis.

Imaging and reconstruction of the cytoarchitecture of axonal fibres: enabling biomedical engineering studies involving brain microstructure

There is an increased need and focus to understand how local brain microstructure affects the transport of drug molecules directly administered to the brain tissue, for example in convection-enhanced delivery procedures. This study reports the first systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fibers, namely: the corpus callosum, the fornix and the corona radiata. Ovine samples from three different subjects were stained with osmium tetroxide (to enhance contrast from cell organelles and the fibers), embedded in resin and then imaged using scanning electron microscope combined with focused ion beam milling to generate 3D volume reconstructions of the tissue at subcellular spatial resolution. Particular focus has been given to the characteristic cytological feature of the white matter: the axons and their alignment in the tissue. Via 2D images a homogeneous myelination has been estimated via detection of ~40% content of lipids in all the different fiber tracts. Additionally, for each tract, a 3D reconstruction of relatively large volumes (15μm x 15μm x 15μm – including a significant number of axons) has been performed. Namely, outer axonal ellipticity, outer axonal cross-sectional area and their relative perimeter have been measured. The study of well-resolved microstructural features provides useful insight into the fibrous organization of the tissue, whose micromechanical behaviour is that of a composite material presenting elliptical tortuous tubular fibers embedded in the extra-cellular matrix. Drug flow can be captured through microstructurally-based models, leading to a workflow to enable physically-accurate simulations of drug delivery to the targeted tissue.

Diffusion Tensor Imaging: A Promising New Technique for Accurate Identification of the Stria Medullaris and Habenula

The Stria Medullaris (SM) is a white-matter tract that contains afferent fibres that connect the cognitive-emotional areas in the forebrain to the Habenula (Hb). The Hb plays an important role in behavioral responses to reward, stress, anxiety, pain, and sleep through its action on neuromodulator systems. The Fasciculus Retroflexus (FR) forms the primary output of the Hb to the midbrain. The SM, Hb, and FR are part of a special pathway between the forebrain and the midbrain known as the Dorsal Diencephalic Conduction system (DDC). Hb dysfunction is accompanied by different types of neuropsychiatric disorders, such as schizophrenia, depression, and Treatment-Resistant Depression (TRD). Due to difficulties in the imaging assessment of the SM and HB in vivo, they had not been a focus of clinical studies until the invention of Diffusion Tensor Imaging (DTI), which has revolutionized the imaging and investigation of the SM and Hb. DTI has facilitated the imaging of the SM and Hb and has provided insights into their properties through the investigation of their monoamine dysregulation. DTI is a well-established technique for mapping brain microstructure and white matter tracts; it provides indirect information about the microstructural architecture and integrity of white matter in vivo, based on water diffusion properties in the intra- and extracellular space, such as Axial Diffusivity (AD), Radial Diffusivity (RD), mean diffusivity, and Fractional Anisotropy (FA). Neurosurgeons have recognized the potential value of DTI in the direct anatomical targeting of the SM and Hb prior to Deep Brain Stimulation (DBS) surgery for the treatment of certain neuropsychiatric conditions, such as TRD. DTI is the only non-invasive method that offers the possibility of visualization in vivo of the white-matter tracts and nuclei in the human brain. This review study summarizes the use of DTI as a promising new imaging method for accurate identification of the SM and Hb, with special emphasis on direct anatomical targeting of the SM and Hb prior to DBS surgery.