White Matter Parcellation Research Articles

Penalized functional regression analysis of white-matter tract profiles in multiple sclerosis.

Diffusion tensor imaging (DTI) enables noninvasive parcellation of cerebral white matter into its component fiber bundles or tracts. These tracts often subserve specific functions, and damage to the tracts can therefore result in characteristic forms of disability. Attempts to quantify the extent of tract-specific damage have been limited in part by substantial spatial variation of imaging properties from one end of a tract to the other, variation that can be compounded by the effects of disease. Here, we develop a "penalized functional regression" procedure to analyze spatially normalized tract profiles, which powerfully characterize such spatial variation. The central idea is to identify and emphasize portions of a tract that are more relevant to a clinical outcome score, such as case status or degree of disability. The procedure also yields a "tract abnormality score" for each tract and MRI index studied. Importantly, the weighting function used in this procedure is constrained to be smooth, and the statistical associations are estimated using generalized linear models. We test the method on data from a cross-sectional MRI and functional study of 115 multiple-sclerosis cases and 42 healthy volunteers, considering a range of quantitative MRI indices, white-matter tracts, and clinical outcome scores, and using training and testing sets to validate the results. We show that attention to spatial variation yields up to 15% (mean across all tracts and MRI indices: 6.4%) improvement in the ability to discriminate multiple sclerosis cases from healthy volunteers. Our results confirm that comprehensive analysis of white-matter tract-specific imaging data improves with knowledge and characterization of the normal spatial variation.

Mobility decline in the elderly relates to lesion accrual in the splenium of the corpus callosum

In a previous cross-sectional study on baseline data, we demonstrated that the volume of brain white matter hyperintensities (WMH) in the splenium of corpus callosum (SCC) predicted the current mobility function of older persons. The primary aim of this follow-up study was to determine the relation of WMH volume change in SCC (SCC-∆WMH) with change in mobility measures. A secondary aim was to characterize the global and regional progression of WMH. Mobility function and WMH burden were evaluated at baseline and at 2 years in 77 community-dwelling individuals (baseline age, 82 ± 4). Regional WMH in SCC, as well as genu and body of corpus callosum, subregions of corona radiata, and superior longitudinal fasciculus were determined using a white matter parcellation atlas. The total WMH volume increased 3.3 ± 3.5 ml/year, mainly through enlargement. Significant WMH increases were observed in all selected regions, particularly within the corona radiata. While at baseline and follow-up we observed correlations between WMH burden and several measures of mobility, longitudinal change correlated only with change in chair rise (CR). SCC-∆WMH showed the highest correlation (r = -0.413, p = 0.0002) and was the best regional predictor of CR decline (OR = 1.5, r(2) = 0.3). The SCC-∆WMH was more than five times larger in the CR-decline group compared to the no-decline group (p = 0.0003). The SCC-∆WMH (top quartile) showed a higher sensitivity/specificity for CR decline compared to change in total WMH, 63/88% versus 52/84%, respectively. The findings suggest that accrual of WMHs in posterior areas of the brain supporting inter-hemispheric integration and processing of visual-spatial information is a mechanism contributing to age-related mobility deterioration.

Abnormal cell patterning at the cortical gray–white matter boundary in autism spectrum disorders

Abstract Previous research on neuronal spacing and columnar organization indicates the presence of cell patterning alterations within the cerebral cortex of individuals with autism spectrum disorders (ASD). These patterning abnormalities include irregularities at the gray–white matter boundary and may implicate early neurodevelopmental events such as migration in altering cortical organization in ASD. The present study utilized a novel method to quantify the gray–white matter boundary in eight ASD and eight typically developing control subjects. Digital photomicrographs of the gray–white matter boundary were acquired from multiple positions within the superior temporal gyrus (BA21), dorsolateral frontal lobe (BA9), and dorsal parietal lobe (BA7) of each case. A sigmoid curve was fitted to the transition zone between layer VI and underlying white matter (subplate), and the slope of the resulting curve was used as a measure of the spatial extent of the transition zone. For all three cortical regions examined, ASD subjects showed “shallower” sigmoid curves compared to neurotypicals, indicating the presence of an indistinct boundary between cortical layer VI and the underlying white matter. These results may reflect the presence of supernumerary neurons beneath the cortical plate that could be the result of migration deficits or failed apoptosis in the subplate region. Furthermore, these findings raise questions regarding the validity of cortical measures that rely on gray–white matter parcellation, since an indistinct transition zone could lead to a misplaced cortical boundary and errors in both thickness and volume measures.

White Matter Hyperintensities Predict Functional Decline in Voiding, Mobility, and Cognition in Older Adults

To compare magnetic resonance imaging data with functional assessments of mobility, urinary control, and cognition to determine common or distinctive features in the distribution of brain white matter hyperintensities (WMHs) associated with functional decline and impairment. Baseline data from subjects aged 75 to 89 enrolled in a longitudinal study. Assessors and subjects were blinded to group assignment. Healthy community-dwelling volunteers. Ninety-nine subjects were enrolled using a balanced 3 x 3 matrix stratified according to age and mobility performance. Exclusion criteria were medication, systemic conditions, and neurological diseases that can compromise mobility. WMHs were identified using a semi-automated segmentation method, and regional burdens were assessed using a white matter parcellation atlas. Quantitative measures of mobility, urinary incontinence (UI) severity, and executive function and processing speed were obtained. WMHs occur predictably in predominantly periventricular areas. There were powerful correlations between total (tWMH) and regional (rWMH) WMH, with correlation coefficients of 0.5 to 0.9 for eight of 10 structures analyzed. tWMH predicted functional measures of UI, mobility, executive function, and processing speed nearly as well as the best regional measures. The total volume of WMHs independently explains 5% to 11% of the variability for mobility, UI severity, executive function, and processing speed and is a sensitive (0.7-0.8) predictor of functional decline. The odds of decline in each of the three functional domains was 1.5 to 2.4 times greater with each 1% increase in tWMH. This work establishes the importance of brain WMH burden in three major geriatric syndromes. The findings support the inclusion of total WMH burden as a risk factor in the predictive and diagnostic criteria.

Defining Meyer's loop-temporal lobe resections, visual field deficits and diffusion tensor tractography

Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyer's loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyer's loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T1-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyer's loop to the temporal pole was 24–43 mm (mean 34 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was −15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyer's loop to the temporal pole was 24–47 mm (mean 35 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was −11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyer's loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyer's loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patient's risk of postoperative VFDs following anterior temporal lobe resection.

Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template

Brain registration to a stereotaxic atlas is an effective way to report anatomic locations of interest and to perform anatomic quantification. However, existing stereotaxic atlases lack comprehensive coordinate information about white matter structures. In this paper, white matter-specific atlases in stereotaxic coordinates are introduced. As a reference template, the widely used ICBM-152 was used. The atlas contains fiber orientation maps and hand-segmented white matter parcellation maps based on diffusion tensor imaging (DTI). Registration accuracy by linear and non-linear transformation was measured, and automated template-based white matter parcellation was tested. The results showed a high correlation between the manual ROI-based and the automated approaches for normal adult populations. The atlases are freely available and believed to be a useful resource as a target template and for automated parcellation methods.

Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification

Diffusion tensor imaging (DTI) is an exciting new MRI modality that can reveal detailed anatomy of the white matter. DTI also allows us to approximate the 3D trajectories of major white matter bundles. By combining the identified tract coordinates with various types of MR parameter maps, such as T 2 and diffusion properties, we can perform tract-specific analysis of these parameters. Unfortunately, 3D tract reconstruction is marred by noise, partial volume effects, and complicated axonal structures. Furthermore, changes in diffusion anisotropy under pathological conditions could alter the results of 3D tract reconstruction. In this study, we created a white matter parcellation atlas based on probabilistic maps of 11 major white matter tracts derived from the DTI data from 28 normal subjects. Using these probabilistic maps, automated tract-specific quantification of fractional anisotropy and mean diffusivity were performed. Excellent correlation was found between the automated and the individual tractography-based results. This tool allows efficient initial screening of the status of multiple white matter tracts.

DTI tractography based parcellation of white matter: Application to the mid-sagittal morphology of corpus callosum

Morphology of the corpus callosum (CC) at the mid-sagittal level has been a target of extensive studies. However, the lack of internal structures and its polymorphism make it a challenging task to quantitatively analyze shape differences among subjects. In this paper, diffusion tensor Imaging (DTI) and tract tracing technique were applied to incorporate cortical connectivity information to the morphological study. The CC was parcellated into six major subdivisions based on trajectories to different cortical areas. This subdivision was performed for eight normal subjects and one stroke patient. The parcellated CCs of the normal subjects were normalized for morphological analysis. When comparing the stroke patient to the normal population, we detected significant atrophy in the motor and sensory areas of the patient CC, in line with the clinical deficits. This approach provides a new tool to investigate callosal morphology and functional relationships.

MRI-Based Topographic Parcellation of Human Cerebral White Matter and Nuclei: II. Rationale and Applications with Systematics of Cerebral Connectivity

We describe a system for parcellation of the human cerebral white matter and nuclei, based upon magnetic resonance images. An algorithm for subdivision of the cerebral central white matter according to topographic criteria is developed in the companion manuscript. In the present paper we provide a rationale for this system of parcellation of the central white matter and we extend the system of cerebral parcellation to include principal subcortical gray structures such as the thalamus and the basal ganglia. The volumetric measures of the subcortical gray and white matter parcellation units in 20 young adult brains are computed and reported here as well. In addition, with the comprehensive system for cerebral gray and white matter structure parcellation as reference, we formulate a systematics of forebrain connectivity. The degree to which functionally specific brain areas correspond to topographically specific areas is an open empirical issue. The resolution of this issue requires the development of topographically specific anatomic analyses, such as presented in the current system, and the application of such systems to a comprehensive set of functional–anatomic correlation studies in order to establish the degree of structural–functional correspondence. This system is expected to be applied in both cognitive and clinical neuroscience as an MRI-based topographic systematics of human forebrain anatomy with normative volumetric reference and also as a system of reference for the anatomic organization of specific neural systems as disrupted by focal lesions in lesion–deficit correlations.