Atlas-Based Quantification of DTI Measures in a Typically Developing Pediatric Spinal Cord.

BACKGROUND AND PURPOSE: Multi-parametric MRI, provides a variety of biomarkers sensitive to white matter integrity, However, spinal cord MRI data in pediatrics is rare compared to adults. The purpose of this work was 3-fold: 1) to develop a processing pipeline for atlas-based generation of the typically developing pediatric spinal cord WM tracts, 2) to derive atlas-based normative values of the DTI indices for various WM pathways, and 3) to investigate age-related changes in the obtained normative DTI indices along the extracted tracts. MATERIALS AND METHODS: DTI scans of 30 typically developing subjects (age range, 6-16 years) were acquired on a 3T MR imaging scanner. The data were registered to the PAM50 template in the Spinal Cord Toolbox. Next, the DTI indices for various WM regions were extracted at a single section centered at the C3 vertebral body in all the 30 subjects. Finally, an ANOVA test was performed to examine the effects of the following: 1) laterality, 2) functionality, and 3) age, with DTI-derived indices in 34 extracted WM regions. RESULTS: A postprocessing pipeline was developed and validated to delineate pediatric spinal cord WM tracts. The results of ANOVA on fractional anisotropy values showed no effect for laterality (P = .72) but an effect for functionality (P < .001) when comparing the 30 primary WM labels. There was a significant (P < .05) effect of age and maturity of the left spinothalamic tract on mean diffusivity, radial diffusivity, and axial diffusivity values. CONCLUSIONS: The proposed automated pipeline in this study incorporates unique postprocessing steps followed by template registration and quantification of DTI metrics using atlas-based regions. This method eliminates the need for manual ROI analysis of WM tracts and, therefore, increases the accuracy and speed of the measurements.

Validation of the National Institute of Neurological Disorders and Stroke Spinal Cord Injury MRI Common Data Elements Instrument.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke common data elements initiative was created to provide a consistent method for recording and reporting observations related to neurologic diseases in clinical trials. The purpose of this study is to validate the subset of common data elements related to MR imaging evaluation of acute spinal cord injury. MATERIALS AND METHODS: Thirty-five cervical and thoracic MR imaging studies of patients with acute spinal cord injury were evaluated independently in 2 rounds by 5 expert reviewers. Intra- and interrater agreement were calculated for 17 distinct MR imaging observations related to spinal cord injury. These included ordinal, categoric, and continuous measures related to the length and location of spinal cord hemorrhage and edema as well as spinal canal and cord measurements. Level of agreement was calculated using the interclass correlation coefficient and kappa. RESULTS: The ordinal common data elements spinal cord injury elements for lesion center and rostral or caudal extent of edema or hemorrhage demonstrated agreement ranging from interclass correlation coefficient 0.68 to 0.99. Reproducibility ranged from 0.95 to 1.00. Moderate agreement was observed for absolute length of hemorrhage and edema (0.54 to 0.60) with good reproducibility (0.78 to 0.83). Agreement for the Brain and Spinal Injury Center score showed the lowest interrater agreement with an overall kappa of 0.27 (0.20, 0.34). For 7 of the 8 variables related to spinal cord injury, agreement improved between the first and second evaluation. Continuous diameter measures of the spinal cord and spinal canal using interclass correlation coefficient varied substantially (0.23 to 0.83). CONCLUSIONS: Agreement was more consistent for the ordinal measures of spinal cord injury than continuous measures. Good to excellent agreement on length and location of spinal cord hemorrhage and edema can be achieved with ordinal measures alone.

American Society of Functional Neuroradiology-Recommended fMRI Paradigm Algorithms for Presurgical Language Assessment.

INTRODUCTION: Functional MR imaging is increasingly being used for presurgical language assessment in the treatment of patients with brain tumors, epilepsy, vascular malformations, and other conditions. The inherent complexity of fMRI, which includes numerous processing steps and selective analyses, is compounded by institution-unique approaches to patient training, paradigm choice, and an eclectic array of postprocessing options from various vendors. Consequently, institutions perform fMRI in such markedly different manners that data sharing, comparison, and generalization of results are difficult. The American Society of Functional Neuroradiology proposes widespread adoption of common fMRI language paradigms as the first step in countering this lost opportunity to advance our knowledge and improve patient care. LANGUAGE PARADIGM REVIEW PROCESS: A taskforce of American Society of Functional Neuroradiology members from multiple institutions used a broad literature review, member polls, and expert opinion to converge on 2 sets of standard language paradigms that strike a balance between ease of application and clinical usefulness. ASFNR RECOMMENDATIONS: The taskforce generated an adult language paradigm algorithm for presurgical language assessment including the following tasks: Sentence Completion, Silent Word Generation, Rhyming, Object Naming, and/or Passive Story Listening. The pediatric algorithm includes the following tasks: Sentence Completion, Rhyming, Antonym Generation, or Passive Story Listening. DISCUSSION: Convergence of fMRI language paradigms across institutions offers the first step in providing a "Rosetta Stone" that provides a common reference point with which to compare and contrast the usefulness and reliability of fMRI data. From this common language task battery, future refinements and improvements are anticipated, particularly as objective measures of reliability become available. Some commonality of practice is a necessary first step to develop a foundation on which to improve the clinical utility of this field.

Reduced FOV diffusion tensor MR imaging and fiber tractography of pediatric cervical spinal cord injury.

STUDY DESIGN: Quantitative study. OBJECTIVES: To evaluate the effectiveness of pediatric spinal cord diffusion tensor tractography (DTT) generated from reduced field of view diffusion tensor imaging (DTI) data and investigate whether there are differences in these values between typically developing (TD) subjects and patients with spinal cord injury (SCI). SETTING: Temple University Hospital and Shriners Hospitals for Children-Philadelphia, USA. METHODS: A total of 20 pediatric subjects including 10 healthy subjects (age 15.13±3.51 years (mean±s.d.) and age range 11-21 years) and 10 subjects with SCI in the cervical area (age 13.8±3.26 years and age range 8-20 years) were recruited, and scanned using a 3.0T MR scanner. Quantitative parameters of DTI and fiber tracking, such as mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), mean length of fiber tracts and tract density, were calculated for each subject. RESULTS: Subjects with SCI showed reduced FA and tract density, and increased ADC values and length of fiber tracts, compared with controls. Statistically significant differences were seen in FA (P=0.0238) and tract density (P=0.0005) between controls and subjects with SCI, whereas there were no significant differences in ADC values and length of fiber tracts. The tractography visually showed that the white matter tracts (blue color) of the SCI patients were overall less abundant and less organized compared with control cases. CONCLUSION: The results show that DTI and DTT could be used as surrogate markers for quantification and visualization of the injured spinal cord.

Diffusion Tensor Imaging of the Normal Cervical and Thoracic Pediatric Spinal Cord.

BACKGROUND AND PURPOSE: DTI data of the normal healthy spinal cord in children are limited compared with adults and are typically focused on the cervical spinal cord. The purpose of this study was the following: to investigate the feasibility of obtaining repeatable DTI parameters along the entire cervical and thoracic spinal cord as a function of age in typically developing pediatric subjects; to analyze the DTI parameters among different transverse levels of the cervical and thoracic spinal cord; and to examine the sex differences in DTI parameters along the cervical and thoracic spinal cord. MATERIALS AND METHODS: Twenty-two subjects underwent 2 identical scans by using a 3T MR imaging scanner. Axial diffusion tensor images were acquired by using 2 overlapping slabs to cover the cervical and thoracic spinal cord. After postprocessing, DTI parameters were calculated by using ROIs drawn on the whole cord along the entire spinal cord for both scans. RESULTS: An increase in fractional anisotropy and a decrease in mean diffusivity, axial diffusivity, and radial diffusivity were observed with age along the entire spinal cord. Significantly lower fractional anisotropy and higher mean diffusivity values were observed in the lower cervical cord compared with the upper cervical cord. Axial diffusivity values in the cervical cord were higher compared with the thoracic cord. No statistically significant sex differences were observed for all DTI parameters. There was a moderate-to-strong repeatability for all DTI parameters. CONCLUSIONS: This study provides an initial understanding of DTI values of the spinal cord relevant to age and sex and shows that obtaining repeatable DTI values of the entire cord in children is feasible.

Hot topics in functional neuroradiology.

Functional neuroradiology represents a relatively new and ever-growing subspecialty in the field of neuroradiology. Neuroradiology has evolved beyond anatomy and basic tissue signal characteristics and strives to understand the underlying physiologic processes of central nervous system disease. The American Society of Functional Neuroradiology sponsors a yearly educational and scientific meeting, and the educational committee was asked to suggest a few cutting-edge functional neuroradiology techniques (hot topics). The following is a review of several of these topics and includes "Diffusion Tensor Imaging of the Pediatric Spinal Cord"; "Diffusional Kurtosis Imaging"; "From Standardization to Quantification: Beyond Biomarkers toward Bioscales as Neuro MR Imaging Surrogates of Clinical End Points"; Resting-State Functional MR Imaging"; and "Current Use of Cerebrovascular Reserve Imaging."

Diagnostic accuracy of diffusion tensor imaging for pediatric cervical spinal cord injury.

STUDY DESIGN: Cross-sectional non-experimental study. OBJECTIVES: To examine diagnostic accuracy of diffusion tensor imaging (DTI) for pediatric spinal cord injury (SCI). SETTING: Pediatric Orthopedic Hospital. METHODS: Thirty-five subjects, 10 SCI and 25 controls, mean age 13.38 years underwent two scans with 3.0 T MR scanner. Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) values were calculated. Subjects with SCI underwent examination of muscle strength, sensation and sacral sparing. Mean and s.d. values for FA, AD and RD were compared by group (controls, SCI with sacral sparing, SCI without sacral sparing) using analysis of variance for repeated measures. Comparisons were also made of DTI values at the injury site to values from cervical regions outside of the injury site. Specificity, sensitivity, receiver operating characteristics area under the curve (ROC AUC) and corresponding 95% confidence intervals were calculated. Resampling methods were used to validate the estimates from the final models. RESULTS: FA values differed among SCI subjects with intact sacral sparing, absent sacral sparing and controls, P<0.003 (adjusted). DTI values in combination showed the strongest diagnostic accuracy for predicting the presence of anal contraction (AD, RD; ROC AUC=0.90), deep anal pressure (FA; ROC AUC=0.88), S4-5 sensation (FA, RD; ROC AUC=0.93), motor level (FA, AD, RD; ROC AUC=0.92) and MRI level (FA, AD, RD; ROC AUC=0.92). Bootstrap and Jackknife median values indicated consistency of the parameter estimates. CONCLUSION: The predictive accuracy of DTI for sacral sparing end points and motor and MRI level of injury was good to strong.

Diffusion tensor imaging of the normal pediatric spinal cord using an inner field of view echo-planar imaging sequence.

BACKGROUND AND PURPOSE: DTI in the brain has been well established, but its application in the spinal cord, especially in pediatrics, poses several challenges. The small cord size has inherent low SNR of the diffusion signal intensity, respiratory and cardiac movements induce artifacts, and EPI sequences used for obtaining diffusion indices cause eddy-current distortions. The purpose of this study was to 1) evaluate the accuracy of cervical spinal cord DTI in children using a newly developed iFOV sequence with spatially selective 2D-RF excitations, and 2) examine reproducibility of the DTI measures. MATERIALS AND METHODS: Twenty-five typically developing subjects were imaged twice using a 3T scanner. Axial DTI images of the cervical spinal cord were acquired with this sequence. After motion correction, DTI indices were calculated using regions of interest manually drawn at every axial section location along the cervical spinal cord for both acquisitions. Various DTI indices were calculated: FA, AD, RD, MD, RA, and VR. Geometric diffusion measures were also calculated: Cp, Cl, and Cs. RESULTS: The following average values for each index were obtained: FA = 0.50 ± 0.11; AD = 0.97 ± 0.20 × 10(-3)mm(2)/s; RD = 0.41 ± 0.13 × 10(-3)mm(2)/s; MD = 0.59 ± 0.15 × 10(-3)mm(2)/s; RA = 0.35 ± 0.08; VR = 0.03 ± 0.00; Cp = 0.13 ± 0.07; Cl = 0.29 ± 0.09; and Cs = 0.58 ± 0.11. The reproducibility tests showed moderate to strong ICC in all subjects for all DTI parameters (ICC>0.72). CONCLUSIONS: This study showed that accurate and reproducible DTI parameters can be estimated in the pediatric cervical spinal cord using an iFOV EPI sequence.

Diffusion tensor imaging of the pediatric spinal cord at 1.5T: preliminary results.

BACKGROUND AND PURPOSE: Recent studies suggest that pediatric subjects as old as 8-years-of-age may have difficulty with the ISNCSCI examinations. Our aim was to investigate DTI parameters of healthy spinal cord in children with noncervical IS for comparison with children with SCI and to prospectively evaluate reliability measures of DTI and to correlate the measures obtained in children with SCI with the ISNCSCI. MATERIALS AND METHODS: Five controls with thoracic and lumbar IS and 5 children with cervical SCI were imaged twice by using a single-shot echo-planar diffusion-weighted sequence. Axial imaging was performed to cover the entire cervical spinal cord in controls. For the SCI subjects, 2 vertebral bodies above and below the injury were imaged. FA and D values were obtained at different levels of the cervical spinal cord. All subjects with SCI had undergone ISNCSCI clinical examinations. Statistical analysis was performed to access differences of the DTI indices between the controls and SCI subjects, reproducibility measurements, and correlations between DTI and ISNCSCI. RESULTS: Subjects with SCI showed reduced FA and increased D values compared with controls. Test-retest reproducibility showed good ICC coefficients in all the DTI index values among controls (≥0.9), while the SCI group showed moderate ICC (≥0.77). There were statistically significant correlations between the various DTI indices and ISNCSCI scores. CONCLUSIONS: Preliminary DTI indices in children were determined and showed good reproducibility. Reduced FA and increased D values were seen in children with SCI in comparison with controls and showed good clinical correlation with ISNCSCI examinations.

NATURAL ANTIMICROBIALS AND THEIR ROLE IN VAGINAL HEALTH: A SHORT REVIEW.

Lactobacillus species maintain the vaginal ecosystem in a healthy condition by production of antimicrobial substances. Depletion of lactobacilli in the vagina results in bacterial vaginosis (BV), where the normal flora is replaced by several bacterial pathogens, usually Gardnerella vaginalis and obligate anaerobes. BV may cause complications such as premature labor, low birth weight and increased risk of HIV acquisition. The currently recommended antibiotic treatments for BV are not always effective and often lead to reoccurrence of the infection. In many cases, this is due to the antibiotic-resistant forms of the pathogens. Therefore, there is an interest in the development of treatments using antimicrobials derived primarily from Lactobacillus spp., such as ribosomally produced antimicrobial peptides (bacteriocins) and lactic acid. These substances effectively inhibit pathogenic bacteria, are safe and do not pose any threat to healthy vaginal Lactobacillus spp. It may be possible to find an effective treatment against BV while reducing the infection's reoccurrence and the treatment-related complications through hurdle technology. This would be achieved by combining antimicrobials produced by Lactobacillus spp. with different natural antimicrobials obtained from plants or other non-pathogenic organisms.

Safety study of an antimicrobial peptide lactocin 160, produced by the vaginal Lactobacillus rhamnosus.

OBJECTIVE: To evaluate the safety of the antimicrobial peptide, lactocin 160. METHODS: Lactocin 160, a product of vaginal probiotic Lactobacillus rhamnosus 160 was evaluated for toxicity and irritation. An in vitro human organotypic vaginal-ectocervical tissue model (EpiVaginal) was employed for the safety testing by determining the exposure time to reduce tissue viability to 50% (ET-50). Hemolytic activity of lactocin160 was tested using 8% of human erythrocyte suspension. Susceptibility of lactobacilli to lactocin160 was also studied. Rabbit vaginal irritation (RVI) model was used for an in vivo safety evaluation. RESULTS: The ET-50 value was 17.5 hours for lactocin 160 (4.9 hours for nonoxynol 9, N9). Hemolytic activity of lactocin 160 was 8.2% (N9 caused total hemolysis). Lactobacilli resisted to high concentrations of peptide preparation. The RVI model revealed slight vaginal irritation. An average irritation index grade was evaluated as "none." CONCLUSIONS: Lactocin 160 showed minimal irritation and has a good potential for intravaginal application.

Differential brain responses when applying criterion attribute versus family resemblance rule learning.

Subsystems of category learning have been identified on the basis of general domains of content (e.g., tools, faces). The present study examined categories from the standpoint of internal structure and determined brain topography associated with expressing two fundamentally different category rule structures (criterion attribute, CA, and family resemblance, FR). CA category learning involves processing stimuli by isolated features and classifying by properties held by all members. FR learning involves processing stimuli by integral wholes and classifying on overall similarity among members without sharing identical features. fMRI BOLD response to CA and FR categorization was measured with pseudowords as stimuli. Category knowledge for both tasks was mastered prior to brain imaging. Areas of activation emerged unique to the structure of each category and followed from the nature of the rule abstraction procedure. CA categorization was implemented by strong target monitoring and expectation (medial parietal), rule maintenance in working memory, feature selection processes (inferior frontal), and a sensitivity to high frequency components of the stimulus such as isolated features (anterior temporal). FR categorization, consistent with its multi-featural nature, involved word-level processing (left extrastriate) that evoked articulatory rehearsal (medial cerebellar). The data suggest category structure is an important determinant of brain response during categorization. For instance, anterior temporal structures may help attune visual processing systems to high frequency components to support the learning of criterial, highly predictive rules.

Cerebellar mediation of the complexity of bimanual compared to unimanual movements.

OBJECTIVE: To study rapidly alternating movements under fMRI in order to identify the brain regions that mediate increased complexity in bimanual vs unimanual movements and to verify the localization of a clinical test of limb ataxia (diadochokinesis). METHODS: Unimanual and bimanual movements, that is, palm(s) pronated then supinated, served as stimulation in a block design fMRI investigation at 1.5 T. Analyses compared bimanual movements and rest for each hand separately and the unimanual conditions combined. A pronation/supination task was chosen as it provides the same objective motor output during unimanual and bimanual formats. The increased coordination demand of the bimanual format (phase/antiphase movements) was expected to result in distinct activation in supplementary motor, primary motor, prefrontal, and cerebellar regions. RESULTS: The bimanual task uniquely elicited responses in specific anterior medial and posterior (vermal) cerebellar regions. CONCLUSIONS: The study corroborated clinical use of diadochokinesis tasks to test for aspects of cerebellar integrity. The data do not support the literature emphasizing basal ganglia mediation of this type of coordinated movement. Cerebellar medial and vermal regions (in connection with central nuclei) are proposed as the locus within the cerebellum for mediating complexity, that is, the effective integration of separate limb movements that proceed in an asynchronous but systematic fashion.

Bacteriocin susceptibility of Gardnerella vaginalis and its relationship to biotype, genotype, and metronidazole susceptibility.

OBJECTIVE: Our purpose was to investigate the bacteriocin susceptibility of Gardnerella vaginalis and its relationship to biotype, genotype, and resistance to metronidazole. STUDY DESIGN: Bacteriocin susceptibility of 36 G vaginalis clinical isolates was tested against a vaginal strain of Lactobacillus acidophilus by a growth-inhibition method. The relationship to biotype, genotype, and resistance to metronidazole were analyzed by the chi2 test and Fisher exact test. RESULTS: Eight G vaginalis strains (22%) were bacteriocin-resistant. Biotypes 5 and 7 were found to be the most frequent among these resistant strains. Eight (42%) of the 19 isolates classified as biotype 5, 6, or 7 were bacteriocin-resistant compared with none of the isolates that were classified as other biotypes (P <.01). Biotype 5 was found in higher prevalence among the isolates resistant to bacteriocin (62%) than among the susceptible isolates (14%) (P =.01). Genotype B was found more frequently among the bacteriocin-resistant strains, but this finding was not statistically significant (P =.71). Seven (88%) bacteriocin-resistant strains were also resistant to metronidazole. CONCLUSION: An association between biotype and an increased resistance to bacteriocin was found. The ability of G vaginalis to resist the antibacterial activity of Lactobacillus bacteriocin may be a pivotal factor in understanding bacterial vaginosis.

Gardnerella vaginalis isolated from patients with bacterial vaginosis and from patients with healthy vaginal ecosystems.

The differences in the phenotype and genotype of Gardnerella vaginalis isolates from patients with bacterial vaginosis (BV) and from patients without BV are unknown. In our study, 43 isolates of G. vaginalis were examined for biotype (hippurate hydrolysis, lipase, and beta-galactosidase activity), sensitivity to metronidazole, and genotype. Of the 117 women visiting the gynecology clinic at Rush-Presbyterian-St. Luke's Medical Center who were included in the study, 27.4% were found to have BV. G. vaginalis was found in samples from 87.5% of women with BV, from 34.0% of women with intermediate BV, and from 26.4% of women with healthy vaginal ecosystems. Among patients with G. vaginalis, biotypes 7 and 8 were isolated from 32% and 20% of patients, respectively. Biotype 5 was predominantly associated with a healthy vaginal ecosystem (P=.0004). Biotypes 5 and 7 were the most resistant to metronidazole. No specific phenotype or genotype of G. vaginalis causes BV.

Defense factors of vaginal lactobacilli.

OBJECTIVE: To determine the antagonistic relationship between vaginal lactobacilli and endogenous vaginal microflora. STUDY DESIGN: Twenty-two Lactobacillus strains were studied for the production of lactic acid, hydrogen peroxide, and bacteriocin. RESULTS: Under standardized growth conditions, most strains increased their biomass by more than 4 times. Lactobacillus species grew best at a pH > or = 4.5, and growth was retarded at a pH < 4.5. Lactic acid levels were 0.68 to 2.518 mg/mL and were not related to the number of cells or the pH of media. The pH of the media was caused by the secretion of lactic and other organic acids. Approximately 80% of the strains produced H(2)O(2) and were graded as 2+ in one third of the strains and 1+ in others. No statistical correlation was found between H(2)O(2) lactic acid and bacteriocin production. Bacteriocin activity was tested on 4 strains of Gardnerella vaginalis. Approximately 80% of the lactobacilli tested produced bacteriocin that inhibited growth of G vaginalis. Six of the strains did not produce bacteriocin. Thirteen strains produced all 3 defense factors, whereas the others lacked 1 or 2 properties. CONCLUSIONS: Lactobacillus species grow best at a pH > 4.5. The pH of the media is dependent on the cell mass and on all organic acids produced by Lactobacillus species. Although all species produce organic acids, not all produce H(2)O(2) and bacteriocin. Not all strains of G vaginalis can be inhibited by lactobacilli-producing bacteriocin.

Human immunodeficiency virus type 1 stimulatory activity by Gardnerella vaginalis: relationship to biotypes and other pathogenic characteristics.

Stimulation of human immunodeficiency virus (HIV) type 1 expression by Gardnerella vaginalis is one possible cause for an increase in the amount of virus in the genital tract. The ability of G. vaginalis to induce HIV expression in chronically infected U1 cells was investigated, along with its possible relationship to biotype, genotype, and resistance to metronidazole and bacteriocin. Significant HIV stimulatory activity was found in 5 (50%) lysates of G. vaginalis. The ability to induce HIV expression in U1 cells was statistically associated with G. vaginalis biotype (P=.048) but not with genotype or resistance to metronidazole and bacteriocin. Further studies to explore the in vivo relevance of HIV activation by G. vaginalis in the female genital tract are warranted, since prevention strategies of bacterial vaginosis and colonization by certain biotypes of G. vaginalis may be valuable in reducing the risk of sexual transmission of HIV.

Increased differentiation of intracranial white matter lesions by multispectral 3D-tissue segmentation: preliminary results.

MRI is a very sensitive imaging modality, however with relatively low specificity. The aim of this work was to determine the potential of image post-processing using 3D-tissue segmentation technique for identification and quantitative characterization of intracranial lesions primarily in the white matter. Forty subjects participated in this study: 28 patients with brain multiple sclerosis (MS), 6 patients with subcortical ischemic vascular dementia (SIVD), and 6 patients with lacunar white matter infarcts (LI). In routine MR imaging these pathologies may be almost indistinguishable. The 3D-tissue segmentation technique used in this study was based on three input MR images (T(1), T(2)-weighted, and proton density). A modified k-Nearest-Neighbor (k-NN) algorithm optimized for maximum computation speed and high quality segmentation was utilized. In MS lesions, two very distinct subsets were classified using this procedure. Based on the results of segmentation one subset probably represent gliosis, and the other edema and demyelination. In SIVD, the segmented images demonstrated homogeneity, which differentiates SIVD from the heterogeneity observed in MS. This homogeneity was in agreement with the general histological findings. The LI changes pathophysiologically from subacute to chronic. The segmented images closely correlated with these changes, showing a central area of necrosis with cyst formation surrounded by an area that appears like reactive gliosis. In the chronic state, the cyst intensity was similar to that of CSF, while in the subacute stage, the peripheral rim was more prominent. Regional brain lesion load were also obtained on one MS patient to demonstrate the potential use of this technique for lesion load measurements. The majority of lesions were identified in the parietal and occipital lobes. The follow-up study showed qualitatively and quantitatively that the calculated MS load increase was associated with brain atrophy represented by an increase in CSF volume as well as decrease in "normal" brain tissue volumes. Importantly, these results were consistent with the patient's clinical evolution of the disease after a six-month period. In conclusion, these results show there is a potential application for a 3D tissue segmentation technique to characterize white matter lesions with similar intensities on T(2)-weighted MR images. The proposed methodology warrants further clinical investigation and evaluation in a large patient population.