Asymmetry Analysis in Rodent Cerebral Ischemia Models

Rationale and Objectives: An automated method for identification and segmentation of acute/subacute ischemic stroke, using the inherent bi-fold symmetry in brain images, is presented. An accurate and automated method for localization of acute ischemic stroke could provide physicians with a mechanism for early detection and potentially faster delivery of effective stroke therapy. Materials and Methods: Segmentation of ischemic stroke was performed on magnetic resonance (MR) images of subacute rodent cerebral ischemia. Eight adult male Wistar rats weighing 225–300 g were anesthetized with halothane in a mix of 70% nitrous oxide/30% oxygen. Animal core temperature was maintained at 37°C during the entire surgical procedure, including occlusion of the middle cerebral artery (MCA) and the 90-minute post-reperfusion period. To confirm cerebral ischemia, transcranial measurements of cerebral blood flow were performed with laser-Doppler flowmetry, using 15-mm flexible fiberoptic Doppler probes attached to the skull over the MCA territory. Animal MR scans were performed at 1.5 T using a knee coil. Three experts performed manual tracing of the stroke regions for each rat, using the histologic-stained slices to guide delineation of stroke regions. A strict tracing protocol was followed that included multiple (three) tracings of each stroke region. The volumetric MR image data were processed for each rat by computing the axis of symmetry and extracting statistical dissimilarities. A nonparametric Wilcoxon rank sum test operating on paired windows in opposing hemispheres identified seeds in the pixels exhibiting statistically significant bi-fold mirror asymmetry. Two brain reference maps were used for analysis: an absolute difference map (ADM) and a statistical difference map (SDM). Although an ADM simply displays the absolute difference by subtracting one brain hemisphere from its reflection, SDM highlights regions by labeling pixels exhibiting statistically significant asymmetry. Results: To assess the accuracy of the proposed segmentation method, the surrogate ground truth (the stroke tracing data) was compared to the results of our proposed automated segmentation algorithm. Three accuracy segmentation metrics were utilized: true-positive volume fraction (TPVF), false-positive volume fraction (FPVF), and false-negative volume fraction (FNVF). The mean value of the TPVF for our segmentation method was 0.8877; 95% CI 0.7254 to 1.0500; the mean FPVF was 0.3370, 95% CI –0.0893 to 0.7633; the mean FNVF was 0.1122, 95% CI –0.0502 to 0.2747. Conclusions: Unlike most segmentation methods that require some degree of manual intervention, our segmentation algorithm is fully automated and highly accurate in identifying regions of brain asymmetry. This approach is attractive for numerous neurologic applications where the operator's intervention should be minimal or null

Mid-sagittal plane and mid-sagittal surface optimization in brain MRI using a local symmetry measure

This paper describes methods for automatic localization of the mid-sagittal plane (MSP) and mid-sagittal sur-face (MSS). The data used is a subset of the Leukoaraiosis And DISability (LADIS) study consisting of three-dimensional magnetic resonance brain data from 62 elderly subjects (age 66 to 84 years). Traditionally, the mid-sagittal plane is localized by global measures. However, this approach fails when the partitioning plane between the brain hemispheres does not coincide with the symmetry plane of the head. We instead propose to use a sparse set of profiles in the plane normal direction and maximize the local symmetry around these using a general-purpose optimizer. The plane is parameterized by azimuth and elevation angles along with the distance to the origin in the normal direction. This approach leads to solutions confirmed as the optimal MSP in 98 percent of the subjects. Despite the name, the mid-sagittal plane is not always planar, but a curved surface resulting in poor partitioning of the brain hemispheres. To account for this, this paper also investigates an opti-mization strategy which fits a thin-plate spline surface to the brain data using a robust least median of squares estimator. Albeit computationally more expensive, mid-sagittal surface fitting demonstrated convincingly better partitioning of curved brains into cerebral hemispheres. 1

Employing Symmetry Features for Automatic Misalignment Correction in Neuroimages

A novel method to automatically compute the symmetry plane and to correct the 3D orientation of neuro-images is presented. In acquisition of neuroimaging scans, the lack of perfect alignment of a patient's head makes it challenging to evaluate brain images. By deploying a shape-based criterion, the symmetry plane is defined as a plane that best matches external surface points on one side of the head, with their counterparts on the other side. In our method, the head volume is represented as a re-parameterized surface point cloud, where each location is parameterized by its elevation (latitude), azimuth (longitude), and radius. The search for the best matching surfaces is implemented in a multi-resolution paradigm, and the computation time is significantly decreased. The algorithm was quantitatively evaluated using in both simulated data and in real T1, T2, Flair magnetic resonance patient images. This algorithm is found to be fast (< 10s per MR volume), robust and accurate (< .6 degree of Mean Angular Error), invariant to the acquisition noise, slice thickness, bias field, and pathological asymmetries

Longitudinal Morphometric Study of Genetic Influence of APOE e4 Genotype on Hippocampal Atrophy - An N=1925 Surface-based ADNI Study

abstract: The apolipoprotein E (APOE) e4 genotype is the most prevalent known genetic risk factor for Alzheimer's disease (AD). In this paper, we examined the longitudinal effect of APOE e4 on hippocampal morphometry in Alzheimer's Disease Neuroimaging Initiative (ADNI). Generally, atrophy of hippocampus has more chance occurs in AD patients who carrying the APOE e4 allele than those who are APOE e4 noncarriers. Also, brain structure and function depend on APOE genotype not just for Alzheimer's disease patients but also in health elderly individuals, so APOE genotyping is considered critical in clinical trials of Alzheimer's disease. We used a large sample of elderly participants, with the help of a new automated surface registration system based on surface conformal parameterization with holomorphic 1-forms and surface fluid registration. In this system, we automatically segmented and constructed hippocampal surfaces from MR images at many different time points, such as 6 months, 1- and 2-year follow up. Between the two different hippocampal surfaces, we did the high-order correspondences, using a novel inverse consistent surface fluid registration method. At each time point, using Hotelling's T^2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes.Dissertation/ThesisMasters Thesis Computer Science 201

Brain tumor detection from 3D magnetic resonance images

Master'sMASTER OF SCIENC

Influence of APOE Genotype on Hippocampal Atrophy over Time - An N=1925 Surface-Based ADNI Study

abstract: The apolipoprotein E (APOE) e4 genotype is a powerful risk factor for late-onset Alzheimer’s disease (AD). In the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, we previously reported significant baseline structural differences in APOE e4 carriers relative to non-carriers, involving the left hippocampus more than the right—a difference more pronounced in e4 homozygotes than heterozygotes. We now examine the longitudinal effects of APOE genotype on hippocampal morphometry at 6-, 12- and 24-months, in the ADNI cohort. We employed a new automated surface registration system based on conformal geometry and tensor-based morphometry. Among different hippocampal surfaces, we computed high-order correspondences, using a novel inverse-consistent surface-based fluid registration method and multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance. At each time point, using Hotelling’s T[superscript 2] test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the full cohort as well as in the non-demented (pooled MCI and control) subjects at each follow-up interval. In the complete ADNI cohort, we found greater atrophy of the left hippocampus than the right, and this asymmetry was more pronounced in e4 homozygotes than heterozygotes. These findings, combined with our earlier investigations, demonstrate an e4 dose effect on accelerated hippocampal atrophy, and support the enrichment of prevention trial cohorts with e4 carriers.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.015290

Statistical shape analysis in neuroimaging : methods, challenges, validation : applications to the study of brain asymmetries in schizophrenia

The study of brain shape and its patterns of variations can provide insights into the understanding of normal and pathological brain development and brain degenerative processes. This thesis focuses on the in vivo analysis of human brain shape as extracted from three-dimensional magnetic resonance images. Major automatic methods for the analysis of brain shape are discussed particularly focusing on the computation of shape metrics, the subsequent inference procedures, and their applications to the study of brain asymmetries in schizophrenia. Methodological challenges as well as possible biological factors that complicate the analysis of brain shape, and its validation, are also discussed. The contributions of this research work are as it follows. First, a novel automatic method for the statistical shape analysis of local interhemispheric asymmetries is presented and applied to the study of cerebral structural asymmetries in schizophrenia. The method extracts and analyzes smooth surface representations approximating the gross shape of the outlines of cerebral hemispheres. Second, a novel and fully automatic image processing framework for the validation of measures of brain asymmetry is proposed. The framework is based on the synthesis of realistic three-dimensional magnetic resonance images with a known asymmetry pattern. It employs a parametric model emulating the normal interhemispheric bending of the human brain while retaining other subject-specific features of brain anatomy. The framework is applied for the quantitative validation of measures of asymmetry in brain tissues' composition as computed by voxel-based morphometry. Particularly, the framework is used to investigate the dependence of voxel-based measures of brain asymmetry on the spatial normalization scheme, template space, and amount of spatial smoothing applied. The developed automatic framework is made available as open-source software. Third, a novel Simplified Reeb Graph based descriptor of the human striatum is proposed. The effectiveness of such a descriptor is demonstrated for the purposes of automatic registration, decomposition, and comparison of striatal shapes in schizophrenia patients and matched normal controls. In conclusion, this thesis proposes novel methods for shape representation and analysis within three-dimensional magnetic resonance brain images, an original way for validating these methods, and applies the methods for the study of brain asymmetries in schizophrenia. The impact of this research lies in its potential implications for the development of biomarkers aiming to a better understanding of the brain in normal and pathological conditions, early diagnosis of a number of brain diseases, and development of novel therapeutic strategies for improving the quality of life of affected individuals. In addition, the distribution of simulated data and automatic tools for validation of morphometric measures of brain asymmetry is expected to have a great impact in enabling systematic validation of novel and existing methods for the analysis of brain asymmetries, quantitatively comparing them, and possibly clarifying contradicting findings in the neuroimaging literature of brain lateralizations

Quantitative multi-modal analysis of pediatric focal epilepsy

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (p. 101-103).For patients with medically refractive focal epilepsy, surgical intervention to remove the epileptic foci is often the last alternative for permanent cure. The success of such surgery is highly dependent on the doctor's ability to accurately locate the epileptogenic region during the pre-surgical planning and evaluation phase. Hence the goal of this project is to provide an end-to-end quantitative analysis pipeline that fuses an array of imaging modalities including magnetic resonance imaging (MRI), diffusion tensor MRI, positron emission tomography (PET), single-photon emission computerized tomography (SPECT) as well as EEG data to build patient-specific head models and to compute prior probability maps of epileptic hotspots for more accurate EEG source localization. By improving the ability to accurately locate these epileptogenic seizure sources, patients can benefit tremendously from accurate surgical resection and consequently have a better chance for complete seizure free recovery.by Andy Khai Siang Eow.S.M

The assessment of distorted facial muscles movements in facial palsy

Introduction The clinical evaluation of facial palsy remains the routine approach for the assessment of facial muscle movements. However, there is a lack of data to link the mathematical analysis of 3D dynamic facial morphology with the subjective clinical assessments. Quantifying the degree of distortion of facial expressions is a vital step in evaluating the clinical impact of facial palsy. 4D imaging is a reliable modality for recording the dynamics of facial expressions. This study aimed to assess distorted facial muscles movements in unilateral facial palsy and mathematically validate clinical grading indices. Material & Method The study recruited 50 patients who suffered from unilateral facial palsy and a control group of an equal number (50) of age- and sex-matched cases. The dynamics of facial expressions were captured using a stereophotogrammetric 4D imaging system. Six facial expressions were recorded (rest, maximum smile, cheek puff, lip purse, eyebrow-raising, eye closure), each one took 4 seconds and generated about 240 3D images for analysis. An advanced geometric morphometric approach using Dense Surface Models was applied for the mathematical quantification of the 3D facial dysmorphology over time. The asymmetries of 10 facial anatomical regions were calculated. For each participant, six mathematical values which quantify asymmetry were measured per expression (the minimal, mean, median, maximum, range, and standard deviation). The 4D image data of sixteen facial paralysis patients were assessed by 7 expert assessors using two clinical grading indices for the assessment of unilateral facial palsy, the modified Sunnybrook index, and the Glasgow Index. The reproducibility of the clinical gradings between two rating sessions was examined. The measured asymmetries of the 4D images were treated as the gold standard to evaluate the performance of the subjective grading indices. Cross-correlations between the mathematical measurements and the subjective grades were calculated. The Modified Sunnybrook index assessed 8 parameters (3 at rest and 5 at individual facial expression). The Glasgow index assessed 29 parameters for the assessment of dynamic facial abnormalities with considerations for the directionality and severity of asymmetry. The similarities and dissimilarities between the two clinical assessments and to the mathematical measurements were investigated. Results The modified Sunnybrook index was reproducible for grading the dysmorphology and dysfunction of unilateral facial paralysis. The Glasgow Index was reproducible after excluding three parameters of poor reproducibility. The modified Sunnybrook index and the Glasgow index correlated reasonably well with the mathematical measurements of facial asymmetry at rest and with facial expressions. • The minimal value of facial asymmetries of the rest expression had a stronger correlation coefficient than that of other values. • The mean and median values of facial asymmetries of the other five nonverbal expressions had a stronger correlation coefficient than that of other values. The following were the main regions affected by facial dysmorphology which showed a correlation above -0.6 between the subjective and objective assessments: • The full face at rest as well as the forehead, cheek, nose and nasolabial, upper lip, corner of the mouth, and chin regions. • The full face, cheek, nasolabial, upper lip, and lower lip of the smile. • The full face, upper and lower lips of the lip purse. • Most of the facial regions, except the cheek, showed moderate to weak correlations with cheek puff. • A strong correlation was detected between the subjective and objective assessments of the forehead and eye regions with eye closure. Based on the correlation results between the mathematical measurements and clinical evaluation of facial asymmetry in unilateral facial paralysis, the study highlighted the following points: • Smile expression: the assessors encountered difficulties to judge the direction of the asymmetry of the corner of the mouth. It is easier to observe the upper lip and the cheek instead of the corner of the mouth when assessing the smile. • Lip purse: the evaluation of the directionality of lip movement was more accurate and sensitive at the lower lip. • Cheek puff: grading the cheek may not grasp the severity of the asymmetry. We would suggest observing the corner of the mouth and lower lip in cheek puff expressions. • Eyebrow raising expression: grading the 4D movement of the upper margin of the eyebrow may be more sensitive than depending on the assessment of the wrinkles of the forehead. • Eye closure: the clinical assessment of the eyes based on 4D image data was not ideal due to the 4D imaging surface defects secondary to the reflective surface of the cornea. Conclusion The mathematical assessment of the dynamics of facial expressions in unilateral facial palsy using advanced geometric morphometrics provides a state-of-art approach for the quantification and visualization of facial dysmorphology. The Glasgow Index and the Modified Sunnybrook Index were reproducible. The clinical assessors were reasonably consistent in the grading of facial palsy. The significant correlations between the clinical grading of facial palsy and the mathematical calculation of the same facial muscle movements provided satisfactory evidence of objectivity to the clinical assessments. The Glasgow index provided more validated parameters for the assessment of facial palsy in comparison to the modified Sunnybrook index. The mathematical quantification of the 3D facial dysmorphology and the associated dynamic asymmetry provides invaluable information to complement the clinical assessments. This is particularly important for the assessment of regional asymmetries and the directionality of the asymmetry for the evaluation of facial contour (anteroposterior direction), face drooping (vertical direction), especially in cases where surgical rehabilitation is indicated

Friction Stir Welding Manufacturing Advancement by On-Line High Temperature Phased Array Ultrasonic Testing and Correlation of Process Parameters to Joint Quality

Welding, a manufacturing process for joining, is widely employed in aerospace, aeronautical, maritime, nuclear, and automotive industries. Optimizing these techniques are paramount to continue the development of technologically advanced structures and vehicles. In this work, the manufacturing technique of friction stir welding (FSW) with aluminum alloy (AA) 2219-T87 is investigated to improve understanding of the process and advance manufacturing efficiency. AAs are widely employed in aerospace applications due to their notable strength and ductility. The extension of good strength and ductility to cryogenic temperatures make AAs suitable for rocket oxidizer and fuel tankage. AA-2219, a descendent of the original duralumin used to make Zeppelin frames, is currently in wide use in the aerospace industry. FSW, a solid-state process, joins the surfaces of a seam by stirring the surfaces together with a pin while the metal is held in place by a shoulder. The strength and ductility of friction stir (FS) welds depends upon the weld parameters, chiefly spindle rotational speed, feedrate, and plunge force (pinch force for self-reacting welds). Between conditions that produce defects, it appears in this study as well as those studies of which we are aware that FS welds show little variation in strength; however, outside this process parameter “window” the weld strength drops markedly. Manufacturers operate within this process parameter window, and the parameter establishment phase of welding operations constitutes the establishment of this process parameter window. The work herein aims to improve the manufacturing process of FSW by creating a new process parameter window selection methodology, creation of a weld quality prediction model, developing an analytical defect suppression model, and constructing a high temperature on-line phased array ultrasonic testing system for quality inspection