Automatic Correction of the 3D Orientation of the Brain Imagery

Classification of human brain pathologies can be guided by the estimation of the departure of 3D internal structures from the normal bilateral symmetry. However symmetry based analysis can 't be precisely carried out when the 3D brain orientation is misaligned, a common occurrence in clinical practice. In this paper, a technique to automatically identify the symmetry plane and correct the 3D orientation of volumetric brain images in a cost effective way is developed. The algorithm seeks the best sampling strategies to realign 3D volumetric representation of the brain within scanner coordinate system. The inertia matrix is computed on the sampled brain, and the principle axes are derived from the eigen vectors of the inertia matrix. The technique is demonstrated on MR and CT brain images and the detected symmetry plane that is orthogonal to the principle vectors is provided. A spatial affine transform is applied to rotate the 3D brain images and align them within the coordinate system of the scanner. The corrected brain volume is re-sliced such that each planar image represents the brain at the same axial level

Enhanced Techniques for Asymmetry Quantification in Brain Imagery

We present an automated generic methodology for symmetry identification and asymmetry quantification, novel method of identifying and delineation of brain pathology by analyzing the opposing sides of the brain utilizing of inherent leftright symmetry in the brain. After symmetry axis has been detected, we apply non-parametric statistical tests operating on the pairs of samples to identify initial seeds points which is defined defined as the pixels where the most statistically significant difference appears. Local region growing is performed on the difference map, from where the seeds are aggregating until it captures all 8-way connected high signals from the difference map. We illustrate the capability of our method with examples ranging from tumors in patient MR data to animal stroke data. The validation results on Rat stroke data have shown that this approach has promise to achieve high precision and full automation in segmenting lesions in reflectional symmetrical objects

Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage

High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology

Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.

This is the published version. Copyright 1996 American Society for Clinical Research.Acute neutrophil (PMN) recruitment to postischemic cardiac or pulmonary tissue has deleterious effects in the early reperfusion period, but the mechanisms and effects of neutrophil influx in the pathogenesis of evolving stroke remain controversial. To investigate whether PMNs contribute to adverse neurologic sequelae and mortality after stroke, and to study the potential role of the leukocyte adhesion molecule intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of stroke, we used a murine model of transient focal cerebral ischemia consisting of intraluminal middle cerebral artery occlusion for 45 min followed by 22 h of reperfusion. PMN accumulation, monitored by deposition of 111In-labeled PMNs in postischemic cerebral tissue, was increased 2.5-fold in the ipsilateral (infarcted) hemisphere compared with the contralateral (noninfarcted) hemisphere (P < 0.01). Mice immunodepleted of neutrophils before surgery demonstrated a 3.0-fold reduction in infarct volumes (P < 0.001), based on triphenyltetrazolium chloride staining of serial cerebral sections, improved ipsilateral cortical cerebral blood flow (measured by laser Doppler), and reduced neurological deficit compared with controls. In wild-type mice subjected to 45 min of ischemia followed by 22 h of reperfusion, ICAM-1 mRNA was increased in the ipsilateral hemisphere, with immunohistochemistry localizing increased ICAM-1 expression on cerebral microvascular endothelium. The role of ICAM-1 expression in stroke was investigated in homozygous null ICAM-1 mice (ICAM-1 -/-) in comparison with wild-type controls (ICAM-1 +/+). ICAM-1 -/- mice demonstrated a 3.7-fold reduction in infarct volume (P < 0.005), a 35% increase in survival (P < 0.05), and reduced neurologic deficit compared with ICAM-1 +/+ controls. Cerebral blood flow to the infarcted hemisphere was 3.1-fold greater in ICAM-1 -/- mice compared with ICAM-1 +/+ controls (P < 0.01), suggesting an important role for ICAM-1 in the genesis of postischemic cerebral no-reflow. Because PMN-depleted and ICAM-1-deficient mice are relatively resistant to cerebral ischemia-reperfusion injury, these studies suggest an important role for ICAM-1-mediated PMN adhesion in the pathophysiology of evolving stroke

Objective Quantification of Perfusion-Weighted Computed Tomography in the Setting of Acute Aneurysmal Subarachnoid Hemorrhage

Perfusion-Weighted Computed Tomography (CTP) is a relatively recent innovation that estimates a value for cerebral blood flow (CBF) using a series of axial head CT images which tracks the time course of signal from an administered bolus of intravenous contrast. We introduce a novel computer-based method for objective quantification of CBF values calculated from CTP images. Our method corrects for the inherent variability of the CTP methodology seen in the subarachnoid hemorrhage (SAH) patient population to potentially aid in the diagnosis of cerebral vasospasm (CVS). This method analyzes and quantifies side-to-side asymmetry of CBF and represents relative differences in a construct termed a Relative Difference Map (RDM). Herein, we present our preliminary results that show that analysis of histograms of the RDM in left and right hemispheres, as well as different vascular territories of the brain, can be used for detection and diagnosis of cerebral vasospasm in patients with SAH. While this method has been designed specifically to analyze post-processed CTP images, it could be potentially applied to quantification and analysis of MR perfusion data, as well

An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques

Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB₄), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr⁻/⁻ mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB₄ ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability

A Novel Quantification Method for Determining Previously Undetected Silent Infarcts on MR-perfusion in Patients Following Carotid Endarterectomy

The purpose of this paper is to evaluate the post-operative Magnetic Resonance Perfusion (MRP) scans of patients undergoing carotid endarterectomy (CEA), using a novel image-analysis algorithm, to determine if post-operative neurocognitive decline is associated with cerebral blood flow changes. CEA procedure reduces the risk of stroke in appropriately selected patients with significant carotid artery stenosis. However, 25% of patients experience subtle cognitive deficits after CEA compared to a control group. It was hypothesized that abnormalities in cerebral blood flow (CBF) are responsible for these cognitive deficits. A novel algorithm for analyzing MRperfusion (MRP) scans to identify and quantify the amount of CBF asymmetry in each hemisphere was developed and to quantify the degree of relative difference between three corresponding vascular regions in the ipsilateral and contralateral hemispheres, the Relative Difference Map (RDM). Patients undergoing CEA and spine surgery (controls) were examined preoperatively, and one day postoperatively with a battery of neuropsychometric (NPM) tests, and labeled “injured” patients with significant cognitive deficits, and “normal” if they demonstrated no decline in neurocognitive function. There are apparently significant RDM differences with MRP scans between the two hemispheres in patients with cognitive deficits which can be used to guide expert reviews of the imagery. The proposed methodology aids in the analysis of MRP parameters in patients with cognitive impairment

Evaluation of Ischemic Stroke Hybrid Segmentation in a Rat Model of Temporary Middle Cerebral Artery Occlusion using Ground Truth from Histologic and MR data

A segmentation method that quantifies cerebral infarct using rat data with ischemic stroke is evaluated using ground truth from histologic and MR data. To demonstrate alternative approach to rapid quantification of cerebral infarct volumes using histologic stained slices that requires scarifying animal life, a study with MR acquire volumetric rat data is proposed where ground truth is obtained by manual delineations by experts and automated segmentation is assessed for accuracy. A framework for evaluation of segmentation is used that provides more detailed accuracy measurements than mere cerebral infarct volume. Our preliminary experiment shows that ground truth derived from MRI data is at least as good as the one obtained from the histologic slices for evaluating segmentation algorithms for accuracy. Therefore we can develop and evaluate automated segmentation methods for rapid quantification of stroke without the necessitating animal sacrifice

Ground Truth for Evaluation of Ischemic Stroke Hybrid Segmentation in a Rat Model of Temporary Middle Cerebral Artery Occlusion

In vivo rodent models of focal cerebral ischemia have been developed to investigate stroke therapy. Typically these models require rapid quantification of cerebral infarct volumes using vital stains with tetrazolium salts to delineate the extent of neuronal death. To avoid animal sacrifice, we sought a study with MR acquired volumetric rata data where surrogate of ground truth is obtained by repeated manual delineation by experts, and an automated hybrid segmentation is evaluated for accuracy. We propose a rating system for the expert delineations that captures intra- and inter-expert discrepancy. Our preliminary results show that surrogate ground truth derived from MR data is at least as good as the one derived from histologic stained slices. Hence animal sacrifice is not necessary to evaluate ischemic stroke automated segmentation in a rat model of temporary middle cerebral artery occlusion

Intranasal Delivery of Caspase-9 Inhibitor Reduces Caspase-6-Dependent Axon/Neuron Loss and Improves Neurological Function after Stroke

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.C.M.T.wassupported bythe American Heart Association and National Institutes of Health (NIH)GrantsNS035933 and NS43089. G.S.S. and S.J.S. were supported by NIH Grant CA69381. E.S.C. was supported by NIH Grant NS40409.Peer reviewe