Depth-dependent intracortical myelin organization in the living human brain determined by in vivo ultra-high field magnetic resonance imaging

Background: Intracortical myelin is a key determinant of neuronal synchrony and plasticity that underpin optimal brain function. Magnetic resonance imaging (MRI) facilitates the examination of intracortical myelin but presents with methodological challenges. Here we describe a whole-brain approach for the in vivo investigation of intracortical myelin in the human brain using ultra-high field MRI. Methods: Twenty-five healthy adults were imaged in a 7 Tesla MRI scanner using diffusion-weighted imaging and a T 1 -weighted sequence optimized for intracortical myelin contrast. Using an automated pipeline, T 1 values were extracted at 20 depth-levels from each of 148 cortical regions. In each cortical region, T 1 values were used to infer myelin concentration and to construct a non-linearity index as a measure the spatial distribution of myelin across the cortical ribbon. The relationship of myelin concentration and the non-linearity index with other neuroanatomical properties were investigated. Five patients with multiple sclerosis were also assessed using the same protocol as positive controls. Results: Intracortical T 1 values decreased between the outer brain surface and the gray-white matter boundary following a slope that showed a slight leveling between 50% and 75% of cortical depth. Higher-order regions in the prefrontal, cingulate and insular cortices, displayed higher non-linearity indices than sensorimotor regions. Across all regions, there was a positive association between T 1 values and non-linearity indices (P < 10 125 ). Both T 1 values (P < 10 125 ) and non-linearity indices (P < 10 1215 ) were associated with cortical thickness. Higher myelin concentration but only in the deepest cortical levels was associated with increased subcortical fractional anisotropy (P = 0.05). Conclusions: We demonstrate the usefulness of an automatic, whole-brain method to perform depth-dependent examination of intracortical myelin organization. The extracted metrics, T 1 values and the non-linearity index, have characteristic patterns across cortical regions, and are associated with thickness and underlying white matter microstructure

Seven-tesla magnetic resonance imaging of the nervus terminalis, olfactory tracts, and olfactory bulbs in COVID-19 patients with anosmia and hypogeusia

Introduction: Linking olfactory epithelium to the central nervous system are cranial nerve 1, the olfactory nerve, and cranial nerve “0,” and the nervus terminalis (NT). Since there is minimal expression of angiotensin-converting enzyme-2 (ACE-2) in the olfactory nerve, it is unclear how SARS-CoV-2 causes anosmia (loss of smell) and hypogeusia (reduction of taste). In animal models, NT expresses ACE-2 receptors, suggesting a possible SARS-CoV-2 viral entry site in humans. The purpose of this study was to determine whether ultra-high-field 7 T magnetic resonance imaging (MRI) could visualize the NT, olfactory bulbs (OB), and olfactory tract (OT) in healthy controls and COVID-19 anosmia or hypogeusia and to qualitatively assess for volume loss and T2 alterations. Methods: In this study, 7 T MRI was used to evaluate the brain and olfactory regions in 45 COVID-19 patients and 29 healthy controls. Neuroimaging was qualitatively assessed by four board-certified neuroradiologists who were blinded to outcome assignments: for the presence or absence of NT; for OB, OT, and brain volume loss; and altered T2 signal, white matter T2 hyperintensities, microhemorrhages, enlarged perivascular spaces, and brainstem involvement. Results: NT was identifiable in all COVID-19 patients and controls. T2 hyperintensity in the NT, OB, and OT in COVID-19 patients with anosmia or hypogeusia was statistically significant compared to controls and COVID-19 patients without anosmia or hypogeusia. Discussion: On 7 T MRI, NT was radiographically identifiable, adjacent to OB and OT. In COVID-19 anosmia and hypogeusia, T2 hyperintensity of NT, OB, and OT was statistically significant compared to COVID-19 patients without anosmia or hypogeusia and controls. The NT may be a potential entry site for SARs-CoV-2 and may play a role in the pathophysiology of COVID-19 anosmia

Application of 7T MRS to High-Grade Gliomas

MRS, including single-voxel spectroscopy and MR spectroscopic imaging, captures metabolites in high-grade gliomas. Emerging evidence indicates that 7T MRS may be more sensitive to aberrant metabolic activity than lower-field strength MRS. However, the literature on the use of 7T MRS to visualize high-grade gliomas has not been summarized. We aimed to identify metabolic information provided by 7T MRS, optimal spectroscopic sequences, and areas for improvement in and new applications for 7T MRS. Literature was found on PubMed using "high-grade glioma," "malignant glioma," "glioblastoma," "anaplastic astrocytoma," "7T," "MR spectroscopy," and "MR spectroscopic imaging." 7T MRS offers higher SNR, modestly improved spatial resolution, and better resolution of overlapping resonances. 7T MRS also yields reduced Cramér-Rao lower bound values. These features help to quantify D-2-hydroxyglutarate in isocitrate dehydrogenase 1 and 2 gliomas and to isolate variable glutamate, increased glutamine, and increased glycine with higher sensitivity and specificity. 7T MRS may better characterize tumor infiltration and treatment effect in high-grade gliomas, though further study is necessary. 7T MRS will benefit from increased sample size; reductions in field inhomogeneity, specific absorption rate, and acquisition time; and advanced editing techniques. These findings suggest that 7T MRS may advance understanding of high-grade glioma metabolism, with reduced Cramér-Rao lower bound values and better measurement of smaller metabolite signals. Nevertheless, 7T is not widely used clinically, and technical improvements are necessary. 7T MRS isolates metabolites that may be valuable therapeutic targets in high-grade gliomas, potentially resulting in wider ranging neuro-oncologic applications

Semi-automated segmentation and quantification of perivascular spaces at 7 Tesla in COVID-19

While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes. Perivascular spaces (PVS) are small fluid-filled spaces in the brain that appear on MRI scans near blood vessels and are believed to play a role in modulation of the immune response, leukocyte trafficking, and glymphatic drainage. Some studies have suggested that increased number or presence of PVS could be considered a marker of increased blood-brain barrier permeability or dysfunction and may be involved in or precede cascades leading to neuroinflammatory processes. Due to their size, PVS are better detected on MRI at ultrahigh magnetic field strengths such as 7 Tesla, with improved sensitivity and resolution to quantify both concentration and size. As such, the objective of this prospective study was to leverage a semi-automated detection tool to identify and quantify differences in perivascular spaces between a group of 10 COVID-19 patients and a similar subset of controls to determine whether PVS might be biomarkers of COVID-19-mediated neuroinflammation. Results demonstrate a detectable difference in neuroinflammatory measures in the patient group compared to controls. PVS count and white matter volume were significantly different in the patient group compared to controls, yet there was no significant association between PVS count and symptom measures. Our findings suggest that the PVS count may be a viable marker for neuroinflammation in COVID-19, and other diseases which may be linked to neuroinflammatory processes

Multimodal Assessment of Bottlenose Dolphin Auditory Nuclei Using 7-Tesla MRI, Immunohistochemistry and Stereology

: The importance of assessing neurochemical processes in the cetacean brain as a tool for monitoring their cognitive health and to indirectly model human neurodegenerative conditions is increasingly evident, although available data are largely semiquantitative. High-resolution MRI for post-mortem brains and stereology allow for quantitative assessments of the cetacean brain. In this study, we scanned two brains of bottlenose dolphins in a 7-Tesla (7T) MR scanner and assessed the connectivity of the inferior colliculi and ventral cochlear nuclei using diffusion tensor imaging (DTI). Serial thick sections were investigated stereologically in one of the dolphins to generate rigorous quantitative estimates of identifiable cell types according to their morphology and expression of molecular markers, yielding reliable cell counts with most coefficients of error <10%. Fibronectin immunoreactivity in the dolphin resembled the pattern in a human chronic traumatic encephalopathy brain, suggesting that neurochemical compensation for insults such as hypoxia may constitute a noxious response in humans, while being physiological in dolphins. These data contribute to a growing body of knowledge on the morphological and neurochemical properties of the dolphin brain and highlight a stereological and neuroimaging workflow that may enable quantitative and translational assessment of pathological processes in the dolphin brain in the future

Imaging the patient with epilepsy

Approximately 4 % of the general population will experience a seizure during their lifetime. Imaging in these "first-ever" seizure patients is in most cases normal, and abnormalities are only present in approximately 15 % of patients as seizures can be provoked by fever, sleep deprivation, stroboscopic lights, or drugs. However, an underlying lesion will lower the seizure threshold and thus make a patient more susceptible to experience a seizure. As "first-ever seizures" are a medical emergency, the treatment modality of choice in these cases is an unenhanced CT to exclude acute medical emergencies that may go along with seizures prior to a more extensive workup depending on clinical history and presentation. Imaging abnormalities encountered in patients experiencing their first-ever seizures include (but are not restricted to) virtually all diseases affecting the brain. As such you may find vascular abnormalities (such as microangiopathy, arteriovenous malformations (AVM), sinus thrombosis, hemorrhage, cavernomas, or stroke), tumors (metastases, primary tumors), infections (encephalitis, meningitis, abscess), sequelae of previous head injury, and toxic or metabolic conditions (e.g., PRES) in these patients