Tract-specific Analysis Research Articles

White matter changes in cognitively intact older adults with informant ratings of cognitive decline

Previously we found that white matter measure is more sensitive than gray matter measure to changes in cognitive function in a group of early mild cognitive impairment. In the present study, we aimed to investigate the putative changes in diffusivity in cognitively intact older adults with or without informant endorsing decline. Twenty-nine cognitively intact older adults with informant ratings of memory decline and 22 cognitively intact older adults without informant ratings of memory decline were included in this study. The groups were matched in age, education, sex distribution, frequency of apolipoprotein E (APOE) ε4 carriers, scores on the Geriatric Depression Scale, and scores on a self-rating memory questionnaire. All participants were tested with a comprehensive cognitive battery and underwent MRI to investigate their integrity of regional gray matter and segments of the cingulum bundle with Diffusion Spectrum Imaging tract-specific analysis. The results revealed that the two groups did not show significant difference in measures of memory function and medial temporal gray matter. However, the informant ratings of memory decline group showed significantly lower generalized fractional anisotropy values in right posterior cingulum and bilateral inferior cingulum bundles relative to their counterparts. Informants’ perceptions of participants’ everyday functioning and memory changes were related to the participants’ cingulate white matter changes, and the information may provide a useful and empirical method for identifying individuals at higher risk of future dementia.

The papez circuit in first-episode, treatment-naive adults with major depressive disorder: combined atlas-based tract-specific quantification analysis and voxel-based analysis.

Previous findings suggest that the Papez Circuit may have a role in major depressive disorders. We used atlas-based tract-specific quantification analysis and voxel-based analysis to examine the integrity of white matter tracts involved in mood regulation (including tracts in the Papez Circuit). Diffusion tensor imaging acquired from 35 first-episode, treatment-naive adults with major depressive disorders and 34 healthy adult controls were compared. Our statistical approach compared structural integrity of 11 major white matter tracts between the major depressive disorder and adult controls, as well as illness duration influence in patients. Fractional anisotropy was decreased in the hippocampal cingulum and in the anterior thalamic radiation according to both analytical approaches, all of which were important tracts included in the Papez Circuit. Our results support the role of the Papez Circuit in major depressive disorders with the minimal probability of false positive due to similar findings in both analyses that have complementary advantages. Dysfunction of the Papez Circuit may be a potential marker for studying the pathogenesis of major depressive disorders.

White matter fiber tractography and quantitative analysis of diffusion tensor imaging

Magnetic resonance diffusion tensor imaging (DTI) is a noninvasive technique that can identify and quantify white matter tracts by evaluating the diffusion of water in biological tissues. While association fibers are bundles of axons within the brain that unite different parts of the same cerebral hemisphere, projection fibers are bundles of axons that unite the cortex with lower parts of the brain and the spinal cord. The commissural fibers are axon bundles that connect the two hemispheres of the brain. Quantitative analysis of DTI can be roughly classified into three types: region of interest analysis, tract-specific analysis, and fully automated hypothesis free whole brain analysis.

Decoding diffusivity in multiple sclerosis: analysis of optic radiation lesional and non-lesional white matter.

ObjectivesDiffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage.MethodSeveral compartments were segmented in optic radiation (OR) of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR.ResultsAsymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD), which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD) in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local) T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI.ConclusionThis study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at least within the OR, parallel and perpendicular diffusivities are affected by tissue restructuring related to distinct pathological processes.

Intersite Reliability of Diffusion Tensor Imaging on Two 3T Scanners.

We report the intersite scan reliability of diffusion tensor imaging (DTI) parameters using identical 3T scanners and acquisition protocols at 2 sites. Voxel-based analysis revealed several regions with significant intersite differences. The intersite reliability of DTI measures showed coefficients of variation below 4% in tract-specific analysis (TSA) and below 6% in atlas-based analysis. Given the excellent reliability of TSA, our results suggest it as a promising and useful tool for multicenter DTI studies.

Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: A tract-specific analysis study

BackgroundThe corpus callosum modulates interhemispheric communication and cognitive processes. It has been suggested that white matter abnormalities in the corpus callosum are related to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to examine microstructural abnormalities in callosal fibers separated by their connection to functional brain regions and determine the relationship of these abnormalities with cognitive function in MDD and BD. MethodsThe subjects were 18 patients with MDD, 20 patients with BD, and 21 healthy controls. The callosal fibers were divided into 6 segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. We examined differences in the fractional anisotropy (FA) of callosal fibers in six segments among the three subject groups and examined the correlation between the FA in each segment and cognitive performance in the 3 groups. ResultsThe FA of anterior callosal fibers were reduced significantly in the MDD and BD groups compared to those in the HC group, and the FA of anterior callosal fibers correlated significantly with the raw scores of the digit sequencing task and symbol coding in the MDD group. LimitationsThe patients were medicated at the time of scanning, and the MDD and BD groups were not matched for symptom severity. ConclusionsOur results suggest that MDD and BD have similar microstructural abnormalities in anterior callosal fibers connecting bilateral frontal cortices, and these abnormalities may be related to impairment of working memory and attention in MDD.

Forceps minor damage and co-occurrence of depression and fatigue in multiple sclerosis

Objective: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue. Methods: Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates. Results: Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue. Conclusions: This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.

Postconcussional disorder and PTSD symptoms of military‐related traumatic brain injury associated with compromised neurocircuitry

Traumatic brain injury (TBI) is a common combat injury, often through explosive blast, and produces heterogeneous brain changes due to various mechanisms of injury. It is unclear whether the vulnerability of white matter differs between blast and impact injury, and the consequences of microstructural changes on neuropsychological function are poorly understood in military TBI patients. Diffusion tensor imaging (DTI) techniques were used to assess the neurocircuitry in 37 U.S. service members (29 mild, 7 moderate, 1 severe; 17 blast and 20 nonblast), who sustained a TBI while deployed, compared to 14 nondeployed, military controls. High-dimensional deformable registration of MRI diffusion tensor data was followed by fiber tracking and tract-specific analysis along with region-of-interest analysis. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. The most prominent white matter microstructural injury for both blast and nonblast patients was in the frontal fibers within the fronto-striatal (corona radiata, internal capsule) and fronto-limbic circuits (fornix, cingulum), the fronto-parieto-occipital association fibers, in brainstem fibers, and in callosal fibers. Subcortical superior-inferiorly oriented tracts were more vulnerable to blast injury than nonblast injury, while direct impact force had more detrimental effects on anterior-posteriorly oriented tracts, which tended to cause heterogeneous left and right hemispheric asymmetries of white matter connectivity. The tractography using diffusion anisotropy deficits revealed the cortico-striatal-thalamic-cerebellar-cortical (CSTCC) networks, where increased post-concussion and PTSD symptoms were associated with low fractional anisotropy in the major nodes of compromised CSTCC neurocircuitry, and the consequences on cognitive function were explored as well.

A reply to the letter to the editor regarding “microstructural changes of the corticospinal tract in idiopathic normal pressure hydrocephalus: a comparison of diffusion tensor and diffusional kurtosis imaging”

Dear Sir, We read with interest the letter concerning our article “Microstructural changes of the corticospinal tract in idiopathic normal pressure hydrocephalus: a comparison of diffusion tensor and diffusional kurtosis imaging.” The correspondents noted that diffusion metrics such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) depend on the combination of data (i.e., different b values) and theory (Gaussian or non-Gaussian). We quite agree with their opinion that FA of diffusion tensor imaging (DTI) should be calculated from tensor model usually from b = 0 and 1,000. Our description might lead the readers to misunderstanding. We think that our description of the section “Tractography and tract-specific analysis of CST” was unclear because we indeed calculated ADC and FA from a portion of the diffusional kurtosis imaging (DKI) data based on b values of 0 and 1,000 s/mm2 using the conventional model. These calculated values were then used as the estimates for ADC and FA. We also recognize that the conventional DTI metrics for clinical studies should be estimated by using the same b values of 0 and 1,000 s/mm2, as in the many reports in the clinical DTI literatures. In other studies concerning DKI, we explicitly stated that the DTI metrics used for comparison with DKI are calculated using the data obtained from b values of 0 and 1,000 s/mm2 and a mono-exponential fit [1–3]. Moreover, although we did not provide the details in this paper, our software for DTI and DKI calculation (dTV.II.FZRx; Image Computing and Analysis Laboratory, Department of Radiology, The University of Tokyo Hospital, Japan) [4] has the ability to calculate DTI metrics such as FA and ADC on the basis of the mono-exponential model by using user-specified b value data when performing DKI calculations. The letter, which suggests that differences between the diffusion metrics derive from differences in parameters or analysis theories, is still of great value. We agree that in DKI or other diffusion-related studies that employ non-conventional signal-fitting procedures, the authors should clarify the type of method and data used for calculating the diffusion metrics.

S12-4. Simultaneous fMRI-EEG-DTI recording of MMN in schizophrenia

Objectives: Here we investigated cognitive impairments reflected by omission mismatch negativity (MMN) aberration in schizophrenia. Methods: We recorded EEG during event-related functional MRI (fMRI) followed by diffusion tensor imaging (DTI) in 14 healthy volunteers and 12 schizophrenic patients. The fMRI data was analyzed on SPM08 and blood oxygenation level-dependent signals (BOLD) signal changes were calculated in region of interest analysis using MarsBaR software. In DTI analysis, the areas significantly deteriorated in patients compared to controls were detected with tract-based spatial statistics. Fractional anisotropy (FA) in white matter fibers related to each area was compared between groups using tract-specific analysis. The clinical manifestation in the patients was evaluated using the Positive and Negative Syndrome Scale (PANSS). Results: The correlation analysis on SPM revealed significant correlation between FA of the right uncinate fasciculus and BOLD activity in the left Insula. BOLD activity of the right anterior cingulate, the right corpus callosum and right insula significantly correlated with PANSS scores. Conclusion: The dysfunction of Insula, the uncinate fasciculus and the corpus callosum, as well as the temporal lobe and the anterior cingulate gyrus, may specifically contribute to MMN aberration of schizophrenic patients and clinical manifestations reflecting their impaired MMN generation.

Microstructural changes of the corticospinal tract in idiopathic normal pressure hydrocephalus: a comparison of diffusion tensor and diffusional kurtosis imaging

The goals of this study were to examine the usefulness of diffusional kurtosis imaging (DKI) for assessing microstructural changes in the compressed corticospinal tract (CST) among patients with idiopathic normal pressure hydrocephalus (iNPH). Eleven patients with iNPH (mean age: 73.6 years, range: 65-84), who underwent 3-T magnetic resonance imaging, including DKI before surgery, were recruited. Six age-matched, healthy subjects (mean age: 69.8 years, range: 60-75) served as the control group. DKI and diffusion tensor imaging parameters were calculated and compared between the iNPH and the control groups using tract-specific analysis of the CST at the level of the lateral ventricle. Mean diffusional kurtosis (DK) and axial diffusion kurtosis were significantly lower in iNPH patients. However, apparent diffusion coefficient, fractional anisotropy, and axial eigenvalue (λ₁) were significantly higher in the iNPH group than in the control group. The mechanical pressure caused by ventricular enlargement in iNPH patients might induce formation of well-aligned fiber tracts and increased fiber density in the CST, resulting in decreased DK. DKI is able to depict both the altered microstructure and water molecule movement within neural axons and intra- or extracellular space. In addition, the investigated DKI parameters provide different information about white matter relative to conventional diffusional metrics for iNPH.

Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with progressive supranuclear palsy

The uncinate fasciculus (UF), a major white-matter tract connecting the frontal and temporal lobes, is related to cognitive/behavioral function. Recently, the UF has been suggested to constitute an indirect pathway of the "semantic ventral pathway" in association with the inferior longitudinal fasciculus (ILF). This retrospective study aimed to evaluate damage to the UF and ILF in patients with progressive supranuclear palsy (PSP) using diffusion tensor tract-specific analysis. Diffusion tensor imaging (DTI) of 16 PSP patients with Richardson's syndrome (PSP-RS) and 21 age-matched volunteers were obtained. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values for the bilateral UF and ILF were calculated by tract-specific analysis. Student's t test was used to evaluate the differences between the patients and controls. Also, voxel-based morphometry (VBM) was performed using 3D T1-weighted images to explore the regional atrophy of gray matter in the patients. In patients with PSP-RS, FA of the left UF was significantly decreased compared with the controls, while significant increases in ADC were found in the UF and ILF bilaterally. VBM analysis showed significant clusters of reduced gray matter in the frontal cortex (predominantly in the lateral orbitofrontal cortex, pars opercularis and mesial frontal cortex) and subcortical nuclei (midbrain, caudate and thalamic). This study has shown that patients with PSP-RS had impairment of the UF and ILF. Damage to the UF is thought to be related to atrophy of the orbitofrontal cortex and may possibly be correlated with the cognitive/behavioral impairment seen in PSP.

Relationship between cognitive impairment and white-matter alteration in Parkinson’s disease with dementia: tract-based spatial statistics and tract-specific analysis

ObjectivesWe investigated the relationship between white-matter alteration and cognitive status in Parkinson’s disease (PD) with and without dementia by using diffusion tensor imaging.MethodsTwenty PD patients, 20 PDD (Parkinson’s disease with dementia) patients and 20 age-matched healthy controls underwent diffusion tensor imaging. The mean diffusivity and fractional anisotropy (FA) map of each patient group were compared with those of the control group by using tract-based spatial statistics. Tractography images of the genu of the corpus callosum fibre tracts were generated, and mean diffusivity and FA were measured.ResultsFA values in many major tracts were significantly lower in PDD patients than in control subjects; in the prefrontal white matter and the genu of the corpus callosum they were significantly lower in PDD patients than in PD patients. There was a significant correlation between the Mini-Mental State Examination (MMSE) scores and the FA values of the prefrontal white matter and the genu of the corpus callosum in patients with PD.ConclusionsOur study shows a relationship between cognitive impairment and alteration of the prefrontal white matter and genu of the corpus callosum. These changes may be useful in assessing the onset of dementia in PD patients.Key Points• Dementia is a common and important non-motor sign of Parkinson’s disease (PD).• The neuropathological basis of dementia in PD is not clear.• DTI shows abnormalities in the prefrontal white matter in PD with dementia.• Prefrontal white matter alteration may be useful biomarker of dementia in PD.

White Matter Alteration in Metabolic Syndrome

OBJECTIVEWe explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI.RESEARCH DESIGN AND METHODSSeven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF.RESULTSIn the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = −0.56, P < 0.04).CONCLUSIONSOur results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.

Automatic Extraction of the Cingulum Bundle in Diffusion Tensor Tract-specific Analysis: Feasibility Study in Parkinson's Disease with and without Dementia

Tract-specific analysis (TSA) measures diffusion parameters along a specific fiber that has been extracted by fiber tracking using manual regions of interest (ROIs), but TSA is limited by its requirement for manual operation, poor reproducibility, and high time consumption. We aimed to develop a fully automated extraction method for the cingulum bundle (CB) and to apply the method to TSA in neurobehavioral disorders such as Parkinson's disease (PD). We introduce the voxel classification (VC) and auto diffusion tensor fiber-tracking (AFT) methods of extraction. The VC method directly extracts the CB, skipping the fiber-tracking step, whereas the AFT method uses fiber tracking from automatically selected ROIs. We compared the results of VC and AFT to those obtained by manual diffusion tensor fiber tracking (MFT) performed by 3 operators. We quantified the Jaccard similarity index among the 3 methods in data from 20 subjects (10 normal controls [NC] and 10 patients with Parkinson's disease dementia [PDD]). We used all 3 extraction methods (VC, AFT, and MFT) to calculate the fractional anisotropy (FA) values of the anterior and posterior CB for 15 NC subjects, 15 with PD, and 15 with PDD. The Jaccard index between results of AFT and MFT, 0.72, was similar to the inter-operator Jaccard index of MFT. However, the Jaccard indices between VC and MFT and between VC and AFT were lower. Consequently, the VC method classified among 3 different groups (NC, PD, and PDD), whereas the others classified only 2 different groups (NC, PD or PDD). For TSA in Parkinson's disease, the VC method can be more useful than the AFT and MFT methods for extracting the CB. In addition, the results of patient data analysis suggest that a reduction of FA in the posterior CB may represent a useful biological index for monitoring PD and PDD.

White Matter Disease Correlates with Lexical Retrieval Deficits in Primary Progressive Aphasia

Objective: To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval.Methods: We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients.Results: We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA.Conclusion: SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.

Microstructural Integrity of Cerebral Fiber Tracts in Hereditary Spastic Paraparesis withSPG11Mutation

ARHSP-TCC is characterized by progressive leg spasticity, ataxia, and cognitive dysfunction. Although mutations in the human SPG11 gene were identified as responsible for ARHSP-TCC, the cerebral fiber integrity has not been assessed systemically. The objective of this study was to assess cerebral fiber integrity and its clinical significance in patients with ARHSP-TCC. Five patients from 2 families who were clinically and genetically confirmed to have ARHSP-TCC were examined by neuropsychological evaluation and DSI of the brain. We performed voxel-based GFA analysis for global white matter evaluation, tractography-based analysis for tract-to-tract comparisons, and tract-specific analysis of the CST to evaluate microstructural integrity along the axonal direction. The neuropsychological evaluation revealed widespread cognitive decline across all domains. Voxel-based analysis showed global reduction of GFA in the cerebral white matter. Tractography-based analysis revealed a significant reduction of the microstructural integrity in all neural fiber types, while commissure and association fibers had more GFA reduction than projection fibers (P < .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P < .00001, P = .018). Tract-specific analysis of the CST validated a "dying-back" phenomenon (R(2) = 0.68, P < .00001). There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation. The dying-back process in CST might explain the pathogenic mechanisms for ARHSP-TCC.

Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging

BackgroundBrain structural changes accompany major depressive disorder, but whether subclinical depression is accompanied by similar changes in brain volume and white matter integrity is unknown. By using voxel-based morphometry (VBM) of the gray matter and tract-specific analysis based on diffusion tensor imaging (DTI) of the white matter, we explored the extent to which abnormalities could be identified in specific brain structures of healthy adults with subclinical depression. MethodsThe subjects were 21 community-dwelling adults with subclinical depression, as measured by their Center for Epidemiologic Studies Depression Scale (CES-D) scores. They were not demented and had no neurological or psychiatric history. We collected brain magnetic resonance images of the patients and of 21 matched control subjects, and we used VBM to analyze the differences in regional gray matter volume between the two groups. Moreover, we examined the white matter integrity by using tract-specific analysis based on the gray matter volume changes revealed by VBM. ResultsVBM revealed that the volumes of both anterior cingulate gyri and the right rectal gyrus were smaller in subclinically depressed women than in control women. Calculation of DTI measures in the anterior cingulum bundle revealed a positive correlation between CES-D scale score and radial diffusivity in the right anterior cingulum in subclinically depressed women. LimitationsThe small sample size limits the stability of the reported findings. ConclusionsGray matter volume reduction and white matter integrity change in specific frontal brain regions may be associated with depressive symptoms in women, even at a subclinical level.

Assessment of corticospinal tract (CST) damage in acute stroke patients: Comparison of tract‐specific analysis versus segmentation of a CST template

To compare two techniques to assess corticospinal tract (CST) damage in stroke patients: tract-specific analysis by probabilistic tractography and segmentation using a CST template. We extracted fractional anisotropy (FA) values, the FA ratio, and mean diffusivity (MD) in 18 stroke patients and 21 healthy volunteers matched for age and sex. We compared the two methods in order to determine their ability to detect 1) differences between diffusion tensor imaging (DTI) parameters of healthy volunteers and stroke patients, 2) the correlation between DTI parameters and clinical scores, and 3) the correlation between DTI parameters and blood oxygen level-dependent (BOLD) signals in a fist-closure task. FA values were higher with the tractography approach than with the segmentation method, but differences between the ipsilesional CST and the homologous region in healthy subjects were detected using both methods. In patients, clinical scores were significantly correlated with FA values and FA ratios with both methods. The BOLD signal was positively correlated with FA values for CST with the segmentation but not with the tractography approach. CST damage in stroke patients can be assessed by either probabilistic tractography or segmentation of a CST template. Although each method has advantages and limitations, both are sensitive enough to detect differences among stroke patients and identify specific correlations with clinical scores.

A Diffusion Tensor Imaging Analysis of White Matter Disease in Corticobasal Syndrome (P05.041)

Objective: To determine the regions of white matter (WM) atrophy in corticobasal syndrome (CBS) using different methods of diffusion tensor imaging (DTI) analysis. Background CBS is a clinical syndrome mostly associated with frontotemporal lobar degeneration (FTLD), where gray matter atrophy predominantly encompasses frontal and parietal lobes. Although little is known about the pattern of WM disease in CBS, it is known that tau, the histopathological basis of corticobasal degeneration (CBD), has substantial WM burden. For neurodegenerative diseases, there is no gold standard for MRI-based WM analysis. Here, we compared two user-independent approaches in analyzing WM: tract-specific analysis (TSA) and whole-brain analysis. Both used fractional anisotropy (FA), which is sensitive to the integrity of white matter fiber tracts. Design/Methods: In 11 CBS patients and 35 demographically-matched healthy seniors, we analyzed 30-direction diffusion-weighted images. We extracted FA for each individual subject, and registered the image to a common stereotactic space. For TSA, 11 tracts were segmented from a DTI template, converted to 3D binary structures, and modeled as medial meshes to reflect maximum FA locally. For the whole-brain analysis, images were analyzed in local space, localized to a publicly available probabilistic template (ICDM-DTI-81), and then compared statistically with seniors in SPM8. Results: TSA revealed reduced FA in CBS relative to seniors in right uncinate, arcuate fasciculus, and inferior frontal-occipital fasiculus; and bilateral corpus callosum, corticospinal tract and superior longitudinal fasiculus. Whole-brain analysis also revealed reduced FA relative to seniors in the corpus callosum, corticospinal tract, fornix, inferior longitudinal fasiculus, superior longitudinal fasciculus, inferior frontal-occipital fasiculus, and external capsule. Conclusions: In addition to grey matter atrophy, CBS patients have considerable WM disease. TSA and whole-brain analyses display largely overlapping findings, validating user-independent approaches to DTI analyses of WM disease. Supported by: HD060406, NS44266, NS53488, AG15116, AG17586, AG32953, the Wyncote Foundation, NS065347, DA022807, EB006266, NS045839, EB009321, K25 AG027785. Disclosure: Dr. Chandrasekaren has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Brun has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Yushkevich has nothing to disclose. Dr. Gee has received research support from Pfizer Inc. Dr. Grossman has nothing to disclose.