Neuroimaging in Intracerebral Hemorrhage

Hemorrhagic stroke accounts for 15% of all strokes but results in nearly a third of the mortality. Neuroimaging forms the mainstay in diagnosis, which has resulted in improved treatment outcomes. The mandate of neuroimaging includes management, risk assessment, prognostication, and research. This involves rapid identification not only to direct treatment but also to discover the underlying etiology such as vascular malformations or tumors, monitor the evolving course of the hemorrhage and rapidly identify complications. While computed tomography (CT) remains the imaging of choice to rapidly detect acute hemorrhage, growing evidence shows that magnetic resonance imaging (MRI) is comparable to CT for detecting blood in the immediate setting and superior in this regard at subacute and chronic time points. Several advances have been made in the image sequencing protocols to detect bleeds at varying time points and to distinguish possible etiology. Initial and serial imaging is used to identify patients who may benefit from intervention. Advances in this field such as diffusion tensor imaging and functional MRI are being studied for their impact in understanding the extent of injury and possible recovery mechanisms, possibly allowing prognostication for patients

Pathophysiology of Meniere\u27s Disease

Meniere’s disease, with its characteristic symptom triad of vertigo, balance and hearing disorders has yet to have its pathophysiology outlined conclusively. Any theory must elucidate all aspects of the natural progression, including vestibular and auditory symptoms. While the central dogma revolves around endolymphatic hydrops, this theory is not without flaws, such as its inability to explain all the physiological changes seen in patients, or the often absence of symptoms. While several degenerative changes are observed in temporal bone histopathology, they do not necessarily explain the sequence of events in the development and progress of the disease. This chapter explores the pathophysiology of the disease, focusing on the hydrops theory, while presenting evidence for and against it. Various changes in the inner ear physiology such as pressure changes, ionic disequilibrium, endocochlear potentials; in human and animal models are described. Alternative explanations for symptoms are discussed. This chapter touches briefly upon etiology associated with Meniere’s (and hydrops), and aims to assist a deeper understanding of the relationship of the process to clinical and experimental findings. A clear understanding of the process guides not only the clinical management to improve quality of life but also the direction of future research endeavors

Visualization and Quantification of Post-Stroke Neural Connectivity and Neuroinflammation Using Serial Two-Photon Tomography in the Whole Mouse Brain

Whole-brain volumetric microscopy techniques such as serial two-photon tomography (STPT) can provide detailed information on the roles of neuroinflammation and neuroplasticity throughout the whole brain post-stroke. STPT automatically generates high-resolution images of coronal sections of the entire mouse brain that can be readily visualized in three dimensions. We developed a pipeline for whole brain image analysis that includes supervised machine learning (pixel-wise random forest models via the “ilastik” software package) followed by registration to a standardized 3-D atlas of the adult mouse brain (Common Coordinate Framework v3.0; Allen Institute for Brain Science). These procedures allow the detection of cellular fluorescent signals throughout the brain in an unbiased manner. To illustrate our imaging techniques and automated image quantification, we examined long-term post-stroke motor circuit connectivity in mice that received a motor cortex photothrombotic stroke. Two weeks post-stroke, mice received intramuscular injections of pseudorabies virus (PRV-152), a trans-synaptic retrograde herpes virus driving expression of green fluorescent protein (GFP), into the affected contralesional forelimb to label neurons in descending tracts to the forelimb musculature. Mice were sacrificed 3 weeks post-stroke. We also quantified sub-acute neuroinflammation in the post-stroke brain in a separate cohort of mice following a 60 min transient middle cerebral artery occlusion (tMCAo). Naive e450+-labeled splenic CD8+ cytotoxic T cells were intravenously injected at 7, 24, 48, and 72 h post-tMCAo. Mice were sacrificed 4 days after stroke. Detailed quantification of post-stroke neural connectivity and neuroinflammation indicates a role for remote brain regions in stroke pathology and recovery. The workflow described herein, incorporating STPT and automated quantification of fluorescently labeled features of interest, provides a framework by which one can objectively evaluate labeled neuronal or lymphocyte populations in healthy and injured brains. The results provide region-specific quantification of neural connectivity and neuroinflammation, which could be a critical tool for investigating mechanisms of not only stroke recovery, but also a wide variety of brain injuries or diseases