Publications

2005
Alexandre Prat, Katarzyna Biernacki, Tanya Saroli, John E Orav, Charles RG Guttmann, Howard L Weiner, Samia J Khoury, and Jack P Antel. 2005. “Kinin B1 receptor expression on multiple sclerosis mononuclear cells: correlation with magnetic resonance imaging T2-weighted lesion volume and clinical disability.” Arch Neurol, 62, 5, Pp. 795-800.Abstract
BACKGROUND: We have previously shown that the inducible kinin B(1) receptor is expressed on T lymphocytes during relapses and progression in multiple sclerosis. OBJECTIVE: To evaluate the correlation between the expression of B1 receptor on peripheral blood mononuclear cells derived from patients who have multiple sclerosis with serial, clinical magnetic resonance imaging and immunological study-derived measures. DESIGN: Using frozen samples obtained from a high-frequency magnetic resonance imaging-immunological study, we analyzed B1 receptor messenger RNA (mRNA) expression in peripheral blood-derived mononuclear cells serially collected from 6 patients with multiple sclerosis and 8 healthy control subjects by semiquantitative radioactive duplex reverse transcriptase-polymerase chain reaction amplification. Time-course kinin B1-actin mRNA ratios were subsequently compared with corresponding clinical magnetic resonance imaging and immune parameters. RESULTS: The time-course kinin B1-actin mRNA ratio correlated positively with the Expanded Disability Status Scale index (P<.001), occurrence of clinical relapse (P = .02), volume of lesion on T2-weighted images (P<.003) and interleukin 2 receptor and major histocompatibility complex class II expression on CD4+ lymphocytes, but not with gadolinium-enhancing lesions. The time-course kinin B1-actin mRNA ratios were 5 to 25 times lower in samples derived from healthy controls. CONCLUSION: The correlation of kinin B1 receptor mRNA levels with dynamic clinical and magnetic resonance imaging measures suggests that expression of this receptor can serve as an index of disease activity in multiple sclerosis.
Alexandre Prat, Katarzyna Biernacki, Tanya Saroli, John E Orav, Charles RG Guttmann, Howard L Weiner, Samia J Khoury, and Jack P Antel. 2005. “Kinin B1 receptor expression on multiple sclerosis mononuclear cells: correlation with magnetic resonance imaging T2-weighted lesion volume and clinical disability.” Arch Neurol, 62, 5, Pp. 795-800.Abstract
BACKGROUND: We have previously shown that the inducible kinin B(1) receptor is expressed on T lymphocytes during relapses and progression in multiple sclerosis. OBJECTIVE: To evaluate the correlation between the expression of B1 receptor on peripheral blood mononuclear cells derived from patients who have multiple sclerosis with serial, clinical magnetic resonance imaging and immunological study-derived measures. DESIGN: Using frozen samples obtained from a high-frequency magnetic resonance imaging-immunological study, we analyzed B1 receptor messenger RNA (mRNA) expression in peripheral blood-derived mononuclear cells serially collected from 6 patients with multiple sclerosis and 8 healthy control subjects by semiquantitative radioactive duplex reverse transcriptase-polymerase chain reaction amplification. Time-course kinin B1-actin mRNA ratios were subsequently compared with corresponding clinical magnetic resonance imaging and immune parameters. RESULTS: The time-course kinin B1-actin mRNA ratio correlated positively with the Expanded Disability Status Scale index (P<.001), occurrence of clinical relapse (P = .02), volume of lesion on T2-weighted images (P<.003) and interleukin 2 receptor and major histocompatibility complex class II expression on CD4+ lymphocytes, but not with gadolinium-enhancing lesions. The time-course kinin B1-actin mRNA ratios were 5 to 25 times lower in samples derived from healthy controls. CONCLUSION: The correlation of kinin B1 receptor mRNA levels with dynamic clinical and magnetic resonance imaging measures suggests that expression of this receptor can serve as an index of disease activity in multiple sclerosis.
Seung-Schik Yoo, Xingchang Wei, Chandlee C Dickey, Charles RG Guttmann, and Lawrence P Panych. 2005. “Long-term reproducibility analysis of fMRI using hand motor task.” Int J Neurosci, 115, 1, Pp. 55-77.Abstract
This article reports test-retest reproducibility of functional MRI (fMRI) measurement on brain activation elicited by auditory-cued sequential finger tapping. Eight right-handed volunteers participated in nine fMRI sessions, approximately eight weeks apart, for the duration of more than a year. The first scan session was repeated within a day to examine the intra-session reproducibility. The frequency of activation for neural substrates relevant to the task was constructed across the subjects and sessions. The spatial reproducibility was measured as the ratio of the size of the volume as well as its overlaps with respect to the first scan session from regions-of-interest in the selected motor circuitry. Consistent activation patterns between sessions and across subjects were observed in the sensorimotor areas such as the left primary, supplementary, and premotor areas, as well as in the right cerebellar areas without evidence of session-dependent trends. Quantitative analysis showed that the reproducibility measures varied within the range obtained from studies on fMRI reproducibility covering much shorter terms. Intra-session fMRI scans yielded slightly better reproducibility measures compared to the results obtained from other scan sessions. The findings suggest that the reproducible fMRI measurement can be obtained for long-term monitoring of brain function.
Lifeng Liu, Dominik Meier, Mariann Polgar-Turcsanyi, Pawel Karkocha, Rohit Bakshi, and Charles RG Guttmann. 2005. “Multiple sclerosis medical image analysis and information management.” J Neuroimaging, 15, 4 Suppl, Pp. 103S-117S.Abstract
Magnetic resonance imaging (MRI) has become a central tool for patient management, as well as research, in multiple sclerosis (MS). Measurements of disease burden and activity derived from MRI through quantitative image analysis techniques are increasingly being used. There are many complexities and challenges in building computerized processing pipelines to ensure efficiency, reproducibility, and quality control for MRI scans from MS patients. Such paradigms require advanced image processing and analysis technologies, as well as integrated database management systems to ensure the most utility for clinical and research purposes. This article reviews pipelines available for quantitative clinical MRI research in MS, including image segmentation, registration, time-series analysis, performance validation, visualization techniques, and advanced medical imaging software packages. To address the complex demands of the sequential processes, the authors developed a workflow management system that uses a centralized database and distributed computing system for image processing and analysis. The implementation of their system includes a web-form-based Oracle database application for information management and event dispatching, and multiple modules for image processing and analysis. The seamless integration of processing pipelines with the database makes it more efficient for users to navigate complex, multistep analysis protocols, reduces the user's learning curve, reduces the time needed for combining and activating different computing modules, and allows for close monitoring for quality-control purposes. The authors' system can be extended to general applications in clinical trials and to routine processing for image-based clinical research.
2004
Daniel Goldberg-Zimring, Anat Achiron, Simon K Warfield, Charles RG Guttmann, and Haim Azhari. 2004. “Application of spherical harmonics derived space rotation invariant indices to the analysis of multiple sclerosis lesions' geometry by MRI.” Magn Reson Imaging, 22, 6, Pp. 815-25.Abstract
In the longitudinal study of multiple sclerosis (MS) lesions, varying position of the patient inside the MRI scanner is one of the major sources of assessment errors. We propose to use analytical indices that are invariant to spatial orientation to describe the lesions, rather than focus on patient repositioning or image realignment. Studies were made on simulated lesions systematically rotated, from in vitro MS lesions scanned on different days, and from in vivo MS lesions from a patient that was scanned five times the same day with short intervals of time between scans. Each of the lesions' 3D surfaces was approximated using spherical harmonics, from which indices that are invariant to space rotation were derived. From these indices, an accurate and highly reproducible volume estimate can be derived, which is superior to the common approach of 2D slice stacking. The results indicate that the suggested approach is useful in reducing part of the errors that affect the analysis of changes of MS lesions during follow-up studies. In conclusion, our proposed method circumvents the need for precise patient repositioning and can be advantageous in MRI longitudinal studies of MS patients.
Xingchang Wei, Seung-Schik Yoo, Chandlee C Dickey, Kelly H Zou, Charles RG Guttmann, and Lawrence P Panych. 2004. “Functional MRI of auditory verbal working memory: long-term reproducibility analysis.” Neuroimage, 21, 3, Pp. 1000-8.Abstract
Although functional MRI (fMRI) has shown to be a tool with great potential to study the normal and diseased human brain, the large variability in the detected hemodynamic responses across sessions and across subjects hinders a wider application. To investigate the long-term reproducibility of fMRI activation of verbal working memory (WM), eight normal subjects performed an auditory version of the 2-back verbal WM task while fMRI images were acquired. The experiment was repeated nine times with the same settings for image acquisition and fMRI task. Data were analyzed using SPM99 program. Single-session activation maps and multi-subject session-specific activation maps were generated. Regions of interest (ROIs) associated to specific components of verbal WM were defined based on the voxels' coordinates in Talairach space. Visual observation of the multi-subject activation maps showed similar activation patterns, and quantitative analysis showed small coefficients of variance of activation within ROIs over time, suggesting small longitudinal variability of activation. Visual observation of the activation maps of individual sessions demonstrated striking variation of activation across sessions and across subjects, and quantitative analysis demonstrated larger contribution from between-subject variation to overall variation than that from within-subject variation. We concluded that by multi-subject analysis of data from a relatively small number of subjects, reasonably reproducible activation for the 2-back verbal WM paradigm can be achieved. The level of reproducibility encourages the application of this fMRI paradigm to the evaluation of cognitive changes in future investigations. The quantitative estimation of the proportions of within-subject and between-subject variabilities in the overall variability may be helpful for the design of future studies.
Xingchang Wei, Seung-Schik Yoo, Chandlee C Dickey, Kelly H Zou, Charles RG Guttmann, and Lawrence P Panych. 2004. “Functional MRI of auditory verbal working memory: long-term reproducibility analysis.” Neuroimage, 21, 3, Pp. 1000-8.Abstract
Although functional MRI (fMRI) has shown to be a tool with great potential to study the normal and diseased human brain, the large variability in the detected hemodynamic responses across sessions and across subjects hinders a wider application. To investigate the long-term reproducibility of fMRI activation of verbal working memory (WM), eight normal subjects performed an auditory version of the 2-back verbal WM task while fMRI images were acquired. The experiment was repeated nine times with the same settings for image acquisition and fMRI task. Data were analyzed using SPM99 program. Single-session activation maps and multi-subject session-specific activation maps were generated. Regions of interest (ROIs) associated to specific components of verbal WM were defined based on the voxels' coordinates in Talairach space. Visual observation of the multi-subject activation maps showed similar activation patterns, and quantitative analysis showed small coefficients of variance of activation within ROIs over time, suggesting small longitudinal variability of activation. Visual observation of the activation maps of individual sessions demonstrated striking variation of activation across sessions and across subjects, and quantitative analysis demonstrated larger contribution from between-subject variation to overall variation than that from within-subject variation. We concluded that by multi-subject analysis of data from a relatively small number of subjects, reasonably reproducible activation for the 2-back verbal WM paradigm can be achieved. The level of reproducibility encourages the application of this fMRI paradigm to the evaluation of cognitive changes in future investigations. The quantitative estimation of the proportions of within-subject and between-subject variabilities in the overall variability may be helpful for the design of future studies.
Xingchang Wei, Charles RG Guttmann, Simon K Warfield, Michael Eliasziw, and Ross J Mitchell. 2004. “Has your patient's multiple sclerosis lesion burden or brain atrophy actually changed?” Mult Scler, 10, 4, Pp. 402-6.Abstract
Changes in mean magnetic resonance imaging (MRI)-derived measurements between patient groups are often used to determine outcomes in therapeutic trials and other longitudinal studies of multiple sclerosis (MS). However, in day-to-day clinical practice the changes within individual patients may also be of interest In this paper, we estimated the measurement error of an automated brain tissue quantification algorithm and determined the thresholds for statistically significant change of MRI-derived T2 lesion volume and brain atrophy in individual patients. Twenty patients with MS were scanned twice within 30 min. Brain tissue volumes were measured using the computer algorithm. Brain atrophy was estimated by calculation of brain parenchymal fraction. The threshold of change between repeated scans that represented statistically significant change beyond measurement error with 95% certainty was 0.65 mL for T2 lesion burden and 0.0056 for brain parenchymal fraction. Changes in lesion burden and brain atrophy below these thresholds can be safely (with 95% certainty) explained by measurement variability alone. These values provide clinical neurologists with a useful reference to interpret MRI-derived measures in individual patients.
Ronald J Killiany, Dominick S Meier, and Charles RG Guttmann. 2004. “Image processing: global and regional changes with age.” Top Magn Reson Imaging, 15, 6, Pp. 349-53.Abstract
Our knowledge about the process of aging has continued to evolve as the methods used to study this process become more sophisticated. As more becomes known about the diagnostic criteria for dementia, the population of subjects taking part in aging studies has become more carefully screened minimizing the role of dementia as a confounding variable. Furthermore, advances in imaging techniques now allow us to view the anatomy of the brain in vivo better than any time in the past paving the way for longitudinal studies of the brain. It should not be surprising given the changes seen in studies of aging that our conventional wisdom of the aging process is being called into question.
Dominik S Meier, Howard L Weiner, Samia J Khoury, and Charles RG Guttmann. 2004. “Magnetic resonance imaging surrogates of multiple sclerosis pathology and their relationship to central nervous system atrophy.” J Neuroimaging, 14, 3 Suppl, Pp. 46S-53S.Abstract
This article focuses on the various magnetic resonance imaging metrics currently used in multiple sclerosis and discusses how they relate to central nervous system atrophy. The authors discuss the significance of T2 lesion burden, gray matter damage, T1 hypointense lesions (black holes), contrast-enhanced lesions, magnetization transfer imaging, diffusion imaging, and magnetic resonance spectroscopy. These magnetic resonance imaging surrogates exhibit different sensitivities for each of the underlying pathogenic processes of multiple sclerosis. By exploiting the complementary nature and varying sensitivities of these magnetic resonance imaging surrogates, it is possible to create a more comprehensive picture of the degenerative process of multiple sclerosis.
Dorota Kozinska, Christopher M Holland, Karl Krissian, Carl-Fredrik Westin, and Charles RG Guttmann. 2004. “A method for the analysis of the geometrical relationship between white matter pathology and the vascular architecture of the brain.” Neuroimage, 22, 4, Pp. 1671-8.Abstract
A novel method for the visual and quantitative analysis of the geometrical relationship between the vascular architecture of the brain and white matter pathology is presented. The cerebro vascular system is implicated in the pathogenesis of many diseases of the cerebral white matter, for example, stroke, microcerebrovascular disease, and multiple sclerosis (MS). In our work, white matter lesions and vessels are depicted using magnetic resonance imaging (MRI) and extracted using image analysis techniques. We focus on measuring distance relationships between white matter lesions and vessels, and distribution of lesions with respect to vessel caliber. Vascular distance maps are generated by computing for each voxel the Euclidean distance to the closest vessel. Analogously, radius maps assign the radius of the closest vessel to each voxel in the image volume. The distance and radius maps are used to analyze the distribution of lesions with respect to the vessels' locations and their calibers. The method was applied to three MS patients to demonstrate its functionality and feasibility. Preliminary findings indicate that larger MS lesions tend to be farther from detected vessels and that the caliber of the vessels nearest to larger lesions tends to be smaller, suggesting a possible role of relative hypoperfusion or hypoxia in lesion formation.
2003
Nan-kuei Chen, Svetlana Egorova, Charles RG Guttmann, and Lawrence P Panych. 2003. “Functional MRI with variable echo time acquisition.” Neuroimage, 20, 4, Pp. 2062-70.Abstract
A new functional MRI protocol that integrates variable echo time (TE) acquisition and a block-design paradigm is proposed and evaluated with finger-tapping motor task. Simulations and experimental data show that the blood oxygenation level-dependent (BOLD) sensitivity achieved with this approach is comparable to that achieved using a conventional constant-TE protocol. The proposed variable-TE fMRI protocol provides valuable information that cannot be obtained with the constant-TE protocol. First, a field inhomogeneity map can be derived from the multi-TE data and used to correct EPI geometric distortions. Second, changes of T2* values due to the BOLD effect can be quantified. Third, for brain regions with pronounced susceptibility field gradients, the reduced BOLD sensitivity may be compensated for when the acquired multi-TE data are processed appropriately (e.g., with weighted summation). Fourth, large venules and veins may possibly be identified (depending on the vessel orientation and volume fraction) by evaluating the phase values of the multi-TE data. Finally, magnetic field drift over time can be measured from dynamic field maps available with this protocol.
Francois Cotton, Howard L Weiner, Ferenc A Jolesz, and Charles RG Guttmann. 2003. “MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals.” Neurology, 60, 4, Pp. 640-6.Abstract
BACKGROUND: One of the diagnostic imaging hallmarks of MS is the uptake of IV administered contrast material in new lesions in the brain, signaling blood-brain barrier breakdown and active inflammation. Many clinical drug trials are designed based on the assumption that lesion enhancement on MRI remains visible on average for 1 month. For practical reasons, few serial MRI studies of patients with MS have been performed at intervals shorter than 4 weeks. METHODS: The authors performed a year-long longitudinal study in 26 patients with relapsing-remitting MS (RRMS), which comprised an initial phase of MRI follow-up at weekly intervals for 8 weeks, followed by imaging every other week for another 16 weeks, and monthly thereafter. They present a quantitative analysis (using a supervised interactive thresholding procedure) of new enhancing lesions appearing during the first 6 weeks in this cohort and evaluated from the time of first detection until enhancement was no longer seen. RESULTS: The average duration of Gd-DTPA enhancement in individual new lesions was 3.07 weeks (median, 2 weeks). Significant correlations were demonstrated between the duration of contrast enhancement or initial growth rates and lesion volumes. Different lesions in the same patient appeared to develop largely independent of each other and demonstrated a large range in the duration of enhancement during the acute phase of their evolution. CONCLUSIONS: The average duration of blood-brain barrier impairment in RRMS is shorter than earlier estimates. Early lesion growth parameters may predict final lesion size. Within-patient heterogeneity of lesion evolution suggests that individual lesions develop independently.
Nan-kuei Chen, Chandlee C Dickey, Seung-Schik Yoo, Charles RG Guttmann, and Lawrence P Panych. 2003. “Selection of voxel size and slice orientation for fMRI in the presence of susceptibility field gradients: application to imaging of the amygdala.” Neuroimage, 19, 3, Pp. 817-25.Abstract
The impact of voxel geometry on the blood oxygenation level-dependent (BOLD) signal detectability in the presence of field inhomogeneity is assessed and a quantitative approach to selecting appropriate voxel geometry is developed in this report. Application of the developed technique to BOLD sensitivity improvement of the human amygdala is presented. Field inhomogeneity was measured experimentally at 1.5 T and 3 T and the dominant susceptibility field gradient in the human amygdala was observed approximately along the superior-inferior direction. Based on the field mapping studies, an optimal selection for the slice orientation would be an oblique pseudo-coronal plane with its frequency-encoding direction parallel to the field gradient measured from each subject. Experimentally this was confirmed by comparing the normalized standard deviation of time-series echo-planar imaging signals acquired with different slice orientations, in the absence of a functional stimulus. A further confirmation with a carefully designed functional magnetic resonance imaging study is needed. Although the BOLD sensitivity may generally be improved by a voxel size commensurable with the activation volume, our quantitative analysis shows that the optimal voxel size also depends on the susceptibility field gradient and is usually smaller than the activation volume. The predicted phenomenon is confirmed with a hybrid simulation, in which the functional activation was mathematically added to the experimentally acquired rest-period echo-planar imaging data.
Nan-kuei Chen, Chandlee C Dickey, Seung-Schik Yoo, Charles RG Guttmann, and Lawrence P Panych. 2003. “Selection of voxel size and slice orientation for fMRI in the presence of susceptibility field gradients: application to imaging of the amygdala.” Neuroimage, 19, 3, Pp. 817-25.Abstract
The impact of voxel geometry on the blood oxygenation level-dependent (BOLD) signal detectability in the presence of field inhomogeneity is assessed and a quantitative approach to selecting appropriate voxel geometry is developed in this report. Application of the developed technique to BOLD sensitivity improvement of the human amygdala is presented. Field inhomogeneity was measured experimentally at 1.5 T and 3 T and the dominant susceptibility field gradient in the human amygdala was observed approximately along the superior-inferior direction. Based on the field mapping studies, an optimal selection for the slice orientation would be an oblique pseudo-coronal plane with its frequency-encoding direction parallel to the field gradient measured from each subject. Experimentally this was confirmed by comparing the normalized standard deviation of time-series echo-planar imaging signals acquired with different slice orientations, in the absence of a functional stimulus. A further confirmation with a carefully designed functional magnetic resonance imaging study is needed. Although the BOLD sensitivity may generally be improved by a voxel size commensurable with the activation volume, our quantitative analysis shows that the optimal voxel size also depends on the susceptibility field gradient and is usually smaller than the activation volume. The predicted phenomenon is confirmed with a hybrid simulation, in which the functional activation was mathematically added to the experimentally acquired rest-period echo-planar imaging data.
Daniel Goldberg-Zimring, Anat Achiron, Charles RG Guttmann, and Haim Azhari. 2003. “Three-dimensional analysis of the geometry of individual multiple sclerosis lesions: detection of shape changes over time using spherical harmonics.” J Magn Reson Imaging, 18, 3, Pp. 291-301.Abstract
PURPOSE: To suggest a quantitative method for assessing the temporal changes in the geometry of individual multiple sclerosis (MS) lesions in follow-up studies of MS patients. MATERIALS AND METHODS: Computer simulated and in vivo magnetic resonance (MR) imaged MS lesions were studied. Ten in vivo MS lesions were identified from sets of axial MR images acquired from a patient scanned consecutively for 24 times during a one-year period. Each of the lesions was segmented and its three-dimensional surface approximated using spherical harmonics (SH). From the obtained SH polynomial coefficients, indices of shape were defined, and analysis of the temporal changes in each lesion's geometry throughout the year was performed by determining the mean discrete total variation of the shape indices. RESULTS: The results demonstrate that most of the studied lesions undergo notable geometrical changes with time. These changes are not necessarily associated with similar changes in size/volume. Furthermore, it was found that indices corresponding to changes in lesion shape could be 1.4 to 8.0 times higher than those corresponding to changes in the lesion size/volume. CONCLUSION: Quantitative three-dimensional shape analysis can serve as a new tool for monitoring MS lesion activity and study patterns of MS lesion evolution over time.
Dominik S Meier and Charles RG Guttmann. 2003. “Time-series analysis of MRI intensity patterns in multiple sclerosis.” Neuroimage, 20, 2, Pp. 1193-209.Abstract
In progressive neurological disorders, such as multiple sclerosis (MS), magnetic resonance imaging (MRI) follow-up is used to monitor disease activity and progression and to understand the underlying pathogenic mechanisms. This article presents image postprocessing methods and validation for integrating multiple serial MRI scans into a spatiotemporal volume for direct quantitative evaluation of the temporal intensity profiles. This temporal intensity signal and its dynamics have thus far not been exploited in the study of MS pathogenesis and the search for MRI surrogates of disease activity and progression. The integration into a four-dimensional data set comprises stages of tissue classification, followed by spatial and intensity normalization and partial volume filtering. Spatial normalization corrects for variations in head positioning and distortion artifacts via fully automated intensity-based registration algorithms, both rigid and nonrigid. Intensity normalization includes separate stages of correcting intra- and interscan variations based on the prior tissue class segmentation. Different approaches to image registration, partial volume correction, and intensity normalization were validated and compared. Validation included a scan-rescan experiment as well as a natural-history study on MS patients, imaged in weekly to monthly intervals over a 1-year follow-up. Significant error reduction was observed by applying tissue-specific intensity normalization and partial volume filtering. Example temporal profiles within evolving multiple sclerosis lesions are presented. An overall residual signal variance of 1.4% +/- 0.5% was observed across multiple subjects and time points, indicating an overall sensitivity of 3% (for axial dual echo images with 3-mm slice thickness) for longitudinal study of signal dynamics from serial brain MRI.
2002
RR Benson, CRG Guttmann, X Wei, SK Warfield, C Hall, JA Schmidt, R Kikinis, and LI Wolfson. 2002. “Older people with impaired mobility have specific loci of periventricular abnormality on MRI.” Neurology, 58, 1, Pp. 48-55.Abstract
BACKGROUND: Recent investigations using MRI suggest that older persons with mobility impairment have a greater volume of abnormal cerebral white matter compared with persons with normal mobility, thus raising the possibility that those with impairment have lesions in areas critical for the control of mobility. OBJECTIVE: To utilize automated image analysis methods to localize the specific regions of abnormal white matter that distinguish subjects with lower mobility from subjects with higher mobility. METHODS: Tissue classification was performed on subjects' dual-echo long repetition time spin-echo MRI using computer algorithms operating on intensity criteria integrated with anatomic information. Statistical analysis of group differences was obtained after spatially normalizing each brain to a standard reference brain. RESULTS: Four discrete periventricular regions, including bilaterally symmetric frontal and bilateral occipitoparietal regions, were identified as being sensitive (frontal) or specific (occipitoparietal) in discriminating the subjects with lower mobility from subjects with higher mobility. The symmetry of these lesions in individual subjects suggested pathology other than arteriolar infarction. CONCLUSIONS: These results suggest that damage to discrete frontal and occipitoparietal periventricular white matter locations may be associated with a mobility disorder of aging.
Xingchang Wei, Simon K Warfield, Kelly H Zou, Ying Wu, Xiaoming Li, Alexandre Guimond, John P Mugler, Randall R Benson, Leslie Wolfson, Howard L Weiner, and Charles RG Guttmann. 2002. “Quantitative analysis of MRI signal abnormalities of brain white matter with high reproducibility and accuracy.” J Magn Reson Imaging, 15, 2, Pp. 203-9.Abstract
PURPOSE: To assess the reproducibility and accuracy compared to radiologists of three automated segmentation pipelines for quantitative magnetic resonance imaging (MRI) measurement of brain white matter signal abnormalities (WMSA). MATERIALS AND METHODS: WMSA segmentation was performed on pairs of whole brain scans from 20 patients with multiple sclerosis (MS) and 10 older subjects who were positioned and imaged twice within 30 minutes. Radiologist outlines of WMSA on 20 sections from 16 patients were compared with the corresponding results of each segmentation method. RESULTS: The segmentation method combining expectation-maximization (EM) tissue segmentation, template-driven segmentation (TDS), and partial volume effect correction (PVEC) demonstrated the highest accuracy (the absolute value of the Z-score was 0.99 for both groups of subjects), as well as high interscan reproducibility (repeatability coefficient was 0.68 mL in MS patients and 1.49 mL in aging subjects). CONCLUSION: The addition of TDS to the EM segmentation and PVEC algorithms significantly improved the accuracy of WMSA volume measurements, while also improving measurement reproducibility.
2001
J Pelletier, L Suchet, T Witjas, M Habib, CR Guttmann, G Salamon, O Lyon-Caen, and AA Chérif. 2001. “A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis.” Arch Neurol, 58, 1, Pp. 105-11.Abstract
OBJECTIVES: To determine if callosal atrophy and interhemispheric dysfunction can be detected in the early stages of relapsing-remitting multiple sclerosis (MS) and to evaluate their progression in relation to the disability and evolution of lesions seen on magnetic resonance imaging during a 5-year period. METHODS: We compared 30 patients who had clinically definite early-onset replasing-remitting MS and mild disability with control subjects. Regional and segmental callosal size and extent of white matter abnormalities on magnetic resonance imaging, as well as performance on tasks exploring interhemispheric transfer of motor, auditory, and sensory information were assessed. Patients with MS were evaluated at baseline and after 5 years. Physical disability was determined at both times using the Expanded Disability Status Scale score. RESULTS: Patients with MS were seen with significant callosal atrophy and functional impairment of interhemispheric transfer at baseline that worsened during the 5-year study. A significant correlation was found between the magnitude of disability and the severity of morphological and functional callosal involvement at baseline. This association persisted at year 5. Baseline clinical characteristics such as age and prestudy relapse rate were unrelated to callosal size or interhemispheric performance. However, the number of baseline T2-weighted lesions was correlated with callosal involvement and this relation persisted at year 5. CONCLUSION: Patients who had relapsing-remitting MS in the early stages of the disease and mild disability had significant callosal involvement that progressed over time. The relationship between disability, T2-weighted lesions load, and degree of morphological and functional callosal impairment confirm the potential value of using callosal dysfunction as a surrogate marker of disease progression in MS.

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