In vivo functional and myeloarchitectonic mapping of human primary auditory areas

In contrast to vision, where retinotopic mapping alone can define areal borders, primary auditory areas such as A1 are best delineated by combining in vivo tonotopic mapping with postmortem cyto- or myeloarchitectonics from the same individual. We combined high-resolution (800 μm) quantitative T(1) mapping with phase-encoded tonotopic methods to map primary auditory areas (A1 and R) within the "auditory core" of human volunteers. We first quantitatively characterize the highly myelinated auditory core in terms of shape, area, cortical depth profile, and position, with our data showing considerable correspondence to postmortem myeloarchitectonic studies, both in cross-participant averages and in individuals. The core region contains two "mirror-image" tonotopic maps oriented along the same axis as observed in macaque and owl monkey. We suggest that these two maps within the core are the human analogs of primate auditory areas A1 and R. The core occupies a much smaller portion of tonotopically organized cortex on the superior temporal plane and gyrus than is generally supposed. The multimodal approach to defining the auditory core will facilitate investigations of structure-function relationships, comparative neuroanatomical studies, and promises new biomarkers for diagnosis and clinical studies

Magnetic Resonance Spectroscopy Investigations of Alzheimer Disease

Alzheimer disease is a progressively devastating neurodegenerative disease of the brain that impairs cognition and is ultimately fatal. Cholinesterase inhibitors are the current standard treatment for Alzheimer disease and they can alleviate some of the symptoms and thus improve quality of life. Cognitive measures aid in the diagnosis and monitoring of individuals with Alzheimer disease, but they do not directly measure disease pathophysiology. The purpose of this thesis is to investigate metabolic changes measured with proton magnetic resonance spectroscopy within the hippocampus and posterior cingulate, two brain regions known to be effected in Alzheimer disease, following cholinesterase inhibitor treatment. Such treatment is aimed at increasing the deficit of acetylcholine in Alzheimer disease. Secondly, to develop a 7 Tesla proton magnetic resonance spectroscopy data acquisition and metabolite quantification protocol to be used for future studies. In one study, proton magnetic resonance spectroscopy at 4 Tesla was used to measure the effects of four months of galantamine treatment (a cholinesterase inhibitor). An increase in the excitatory neurotransmitter glutamate was detected in the right hippocampus, and was associated with increased cognitive performance. In a second study, proton magnetic resonance spectroscopy at 3 Tesla was used to measure the effects of rivastigmine (a second cholinesterase inhibitor). The ratio of the neuronal marker N-acetylaspartate to creatine was decreased in the bilateral posterior cingulate cortex, which was associated with cognition. Finally, a quantitative proton magnetic resonance spectroscopy protocol at 7 Tesla was developed that incorporates subject-specific macromolecule removal. Absolute in vivo metabolite concentrations measured were in agreement with previous studies, and this protocol is ideal for applications in diseased conditions where macromolecule contributions may deviate from the norm

Investigating Cortical Changes in Cervical Spondylotic Myelopathy Using Functional Magnetic Resonance Imaging, Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in older adults. CSM can present abruptly with severe symptoms of neurological impairment or insidiously with a slow stepwise deterioration. There is no current imaging modality or biomarker that can help predict which patient will successfully respond to conservative versus surgical treatment. The goal of this thesis was to follow CSM patients longitudinally to assess how brain function, metabolism, and structure correlate to clinical outcomes in the context of recovering neurological function following surgery. Chapter 1 of this thesis will provide a detailed literature review of the current controversies in treating CSM. Novel imaging techniques that can elucidate cortical adaptations in CSM patients will be discussed. Chapter 2 characterizes the metabolite profile of CSM patients and whether metabolites such as N-Acetylaspartate, a marker of neuronal health, can distinguish CSM patients from healthy controls. Chapter 3 will investigate whether metabolite changes in the primary motor cortex of CSM patients recover following successful surgical intervention and able to predict neurological recovery. The structural integrity of the white matter adjacent to the primary motor and sensory cortices will also be assessed. Chapter 4 will investigate the cortical adaptation and reorganization in mild and moderate CSM severities, prior to and following decompressive surgery. This thesis utilizes novel methods to explore how the cortex attempts to adapt and compensate for neurological deficit, distal to the site of injury, and identify new imaging biomarkers for characterization of CSM severity and predicting functional recovery

Intersubject Regularity in the Intrinsic Shape of Human V1

Previous studies have reported considerable intersubject variability in the three-dimensional geometry of the human primary visual cortex (V1). Here we demonstrate that much of this variability is due to extrinsic geometric features of the cortical folds, and that the intrinsic shape of V1 is similar across individuals. V1 was imaged in ten ex vivo human hemispheres using high-resolution (200 μm) structural magnetic resonance imaging at high field strength (7 T). Manual tracings of the stria of Gennari were used to construct a surface representation, which was computationally flattened into the plane with minimal metric distortion. The instrinsic shape of V1 was determined from the boundary of the planar representation of the stria. An ellipse provided a simple parametric shape model that was a good approximation to the boundary of flattened V1. The aspect ration of the best-fitting ellipse was found to be consistent across subject, with a mean of 1.85 and standard deviation of 0.12. Optimal rigid alignment of size-normalized V1 produced greater overlap than that achieved by previous studies using different registration methods. A shape analysis of published macaque data indicated that the intrinsic shape of macaque V1 is also stereotyped, and similar to the human V1 shape. Previoud measurements of the functional boundary of V1 in human and macaque are in close agreement with these results

Studying Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis with 7-T magnetic resonance

Ultra-high-field (UHF) magnetic resonance (MR) scanners, that is, equipment operating at static magnetic field of 7 tesla (7 T) and above, enable the acquisition of data with greatly improved signal-to-noise ratio with respect to conventional MR systems (e.g., scanners operating at 1.5 T and 3 T). The change in tissue relaxation times at UHF offers the opportunity to improve tissue contrast and depict features that were previously inaccessible. These potential advantages come, however, at a cost: in the majority of UHF-MR clinical protocols, potential drawbacks may include signal inhomogeneity, geometrical distortions, artifacts introduced by patient respiration, cardiac cycle, and motion. This article reviews the 7 T MR literature reporting the recent studies on the most widespread neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy

High-resolution magnetic resonance imaging (MRI) may improve the preoperative diagnosis of focal cortical dysplasia (FCD) in epilepsy. Quantitative 9.4T MRI was carried out (T1, T2, T2* and magnetization transfer ratio) on 13 cortical resections, representing pathologically confirmed FCD (five cases) and normal cortex. Quantitative immunohistochemistry for myelination (myelin basic protein/SMI94), neuronal populations [microtubule-associated protein 2 (MAP2), neurofilament (SMI31, SMI32), synaptophysin, NeuN, calbindin], reactive glia (GFAP), microglia (CD68) and blood–brain barrier permeability (albumin) was carried out in 43 regions of interest (ROI) from normal and abnormal white matter and cortex. MRI was spatially aligned and quantitative analysis carried out on corresponding ROI. Line profile analysis (LPA) of intensity gradients through the cortex was carried out on MRI and immunostained sections. An inverse correlation was noted between myelin/SMI94 and T1, T2 (P < 0.005) and T2* (P < 0.05; Spearman's correlation) and a positive correlation between neuronal MAP2 and T1 (P < 0.005) and T2* (P < 0.05) over all ROI. Similar pathology–MRI correlations were observed for histologically unremarkable white matter ROI only. LPA showed altered gradient contours in regions of FCD, reflecting abnormal cortical lamination and myelo-architecture, including a preoperatively undetected FCD case. This study demonstrates the ability of quantitative 9.4T MRI to detect subtle differences in neuronal numbers and myelination in histologically normal appearing white matter and LPA in the evaluation of cortical dyslamination. These methods may be translatable to the in vivo detection of mild cortical malformations