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Showing papers by "Maria A. Rocca published in 1998"


Journal ArticleDOI
TL;DR: It is suggested that changes in the NAWM of patients with MS occur before lesions becomes evident on conventional MRI scans.
Abstract: Serial monthly magnetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing-remitting MS were scanned with a T1-weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium-DTPA (Gd-DTPA). During each of the monthly sessions, MT and dual echo scans were also performed before Gd-DTPA injection. On coregistered images, the MT ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions, in NAWM areas on the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their appearance. Forty-eight new enhancing lesions with no corresponding abnormalities on previous scans were identified. Their average MTR was 33.1% (+/-8.4%). Three, 2, and 1 month before enhancement appearance, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions become evident on conventional MRI scans.

391 citations


Journal ArticleDOI
TL;DR: Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains in patients with MS.
Abstract: Objective This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques [proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall cognitive, frontal lobe, and memory impairments in patients with MS. Patients There were 30 clinically definite MS patients, with different disease courses. Exclusion criteria: psychoactivelsteroid treatments, mood disorders, acute relapse phase. Main Outcome Measures Neuropsychological test results. Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and analysis of the MTR histograms from brain tissue axial slabs on MTI scans. Results Patients with frontal lobe deficits (n = 15) or memory impairment (n = 17) had a higher TLL on PD scans ( p = 0.04 and p = 0.01, respectively). Patients with frontal lobe deficits had higher FLL on PD scans ( p = 0.01) and TLL on MTI ( p = 0.03) scans. No significant relationships between the extent of T1-weighted lesion loads and the presence of any neuropsychological impairment. Mean MTR of both MS lesions and whole brain tissue was lower in patients with frontal lobe impairment ( p = 0.04). MRI lesion loads correlated significantly with some neuropsychological test scores. Conclusions Lesion loads on PD-weighted MRI and MTI-derived measures are associated with cognitive decline in MS patients. Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains.

267 citations


Journal ArticleDOI
TL;DR: It is suggested that annual lesion load quantification provides an efficient measure of ongoing disease activity, and this supports its application as a surrogate marker of disease evolution in phase III treatment trials.
Abstract: Magnetic resonance imaging (MRI) provides a powerful tool for assessing disease activity in multiple sclerosis (MS), and its role as a surrogate marker for monitoring treatment efficacy is now becoming established. The most commonly used MRI parameters in treatment trials are (1) monthly gadolinium-enhanced MRI, with the number of active lesions serving as the outcome measure, and (2) annual lesion load quantification, in which change in MS lesion volume provides the MRI endpoint. We evaluated clinical/MRI correlations and the relationship between these two markers of disease activity in 73 patients with clinically definite MS. Quantification of T2 lesion load was performed at study entry and exit, with a median study duration of 11 months (range, 9 to 14 months). Monthly postgadolinium T1-weighted images were acquired between these time points. Lesion load at study entry was significantly correlated with the baseline Expanded Disability Status Scale (EDSS) score, but no significant longitudinal correlation was demonstrated. The number of enhancing lesions on the entry scan was predictive of subsequent relapse rate over the study duration and also correlated with the subsequent enhancing lesion activity over the study period. A significant correlation was found between change in lesion load and disease activity on the monthly scans. Our results suggest that annual lesion load quantification provides an efficient measure of ongoing disease activity, and this supports its application as a surrogate marker of disease evolution in phase III treatment trials.

161 citations


Journal ArticleDOI
TL;DR: The results indicate that the enhancing lesion population in MS is heterogeneous and that the tissue damage occurring within lesions enhancing only after TD injection is less severe than in lesions enhancing after the injection of an SD.
Abstract: We performed serial monthly magnetization transfer (MT) imaging to evaluate whether MS lesions that enhance only after the injection of a triple dose (TD) of gadolinium-DTPA (Gd) have different pathologic characteristics and evolution than those that enhance after the injection of a standard dose(SD). Every 4 weeks for 3 months and in two separate sessions, we obtained T1-weighted scans from 10 patients with relapsing-remitting MS, 5 minutes after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. During each of the first monthly sessions, we obtained MT images and dual-echo scans before Gd injection. We measured the MT ratio (MTR) of newly enhancing lesions on co-registered quantitative MTR images. During the 3-month follow-up, 81 newly enhancing lesions were seen on SD scans. An additional 46 lesions enhanced only on TD scans. The mean (± standard deviation) MTR values were 31.4% ± 8.4% for lesions enhancing after SD and 38.2% ± 6.0% for lesions enhancing only after TD injection ( p p p = 0.002) increased significantly during the follow-up. At each time point during the follow-up, the MTR values of TD lesions were significantly higher than the SD lesions. These results indicate that the enhancing lesion population in MS is heterogeneous and that the tissue damage occurring within lesions enhancing only after TD injection is less severe than in lesions enhancing after the injection of an SD.

85 citations


Journal ArticleDOI
TL;DR: It is concluded that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.

66 citations


Journal ArticleDOI
TL;DR: It is suggested that enhancing lesions in MS have heterogeneous pathological substrates, which may be associated with different durations of the enhancing phase.

52 citations


Journal ArticleDOI
30 Jun 1998
TL;DR: The pathological processes in MS are at different stages in relapsing-remitting and secondary progressive MS and the effectiveness of recovery mechanisms within lesions might be one of the major factors responsible for such a difference.
Abstract: In this study, 14 patients with either relapsing-remitting or secondary progressive multiple sclerosis (MS) were scanned monthly using gadolinium enhanced magnetic resonance imaging (MRI). At the start of the study and at 1 year follow up, T2-weighted and magnetization transfer (MT) scans were also performed. The correlation between the frequency and extent of enhancement and changes of lesion load over a 1 year period on T2-weighted and MT images were assessed. For all patients, and for the relapsing-remitting patients only, the number and volume of enhancing lesions per month showed no significant correlation with the change between baseline and 1 year follow up of lesion volumes on T2 and MT images. However, strong correlations were found between the number and volume of gadolinium enhancing lesions with changes of T2 (r = 0.93, P = 0.02) and MT (r = 0.82, P = 0.04) lesion loads in patients with secondary progressive MS. Strong correlations were also found between the lesion loads on T2-weighted scans and on MT images both at baseline and at 1 year follow up (r = 0.83, P = 0.003). In addition, the changes in lesion load over 1 year, detected using the two techniques, were moderately correlated (r = 0.51, P = 0.05). This study provides further evidence that the pathological processes in MS are at different stages in relapsing-remitting and secondary progressive MS. It also suggests that the effectiveness of recovery mechanisms within lesions might be one of the major factors responsible for such a difference.

26 citations


Journal Article
TL;DR: The best MR correlations with disability were several MTR histographic parameters, which may favor the use of these MR parameters over T2 lesion load to monitor disease progression in patients with MS, findings that should be explored further in longitudinal studies.
Abstract: BACKGROUND AND PURPOSES MR imaging is now widely used to monitor disease progression in patients with multiple sclerosis (MS). The purpose of this study was to explore the relationship between disability status and existing and new MR parameters in MS patients. METHODS Forty-one patients with clinically definitive MS were studied. MR imaging included T2- and T1-weighted imaging as well as gradient-echo imaging with and without magnetization transfer contrast. We used surface-based thresholding segmentation techniques to obtain T2 and T1 lesion load, T1/T2 ratio, and several magnetization transfer ratio (MTR) lesion load parameters. MTR histographic analysis included measurements of absolute peak height (aHp), relative peak height (rHp), MTR of the peak (MTRp), mean MTR (MTRm), and MTR25, MTR50, and MTR75, relating to the integrals of the histogram at 25%, 50%, and 75%, respectively, of the total area under the curve. All MR parameters were correlated with Expanded Disability Status Scale (EDSS) score, disease duration, and patient9s age. RESULTS Using surface-based thresholding segmentation techniques, we found relatively low correlations with EDSS. T1 lesion load and T1/T2 ratios correlated most strongly. Regarding MTR histographic parameters, EDSS correlated best with rHp but only weakly with others. Similar correlations were found with disease duration, but not with age. CONCLUSION The best MR correlations with disability were several MTR histographic parameters. Our findings may favor the use of these MR parameters over T2 lesion load to monitor disease progression in patients with MS, findings that should be explored further in longitudinal studies.

25 citations


Journal Article
TL;DR: The data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis.
Abstract: PURPOSE We evaluated the intraobserver and interobserver variability in measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick MR sections in patients with multiple sclerosis. METHODS Eighteen 18 patients were scanned on two separate occasions with a mean interval of 16.4 months between the two examinations. In each session, a scan with 24 contiguous 5-mm-thick axial sections and another with 40 contiguous 3-mm-thick axial sections was acquired consecutively without moving the patient. We assessed MR lesion load by using a semiautomated local thresholding technique. RESULTS Lesion volume was significantly higher on images with 3-mm-thick sections than on those with 5-mm-thick sections both at baseline and at follow up. Significant increases in total lesion volume were observed during the follow-up period on images obtained with both 5- and 3-mm-thick sections. The intra- and interobserver variability in measurements of changes in lesion volume was significantly higher on images with 5-mm-thick sections than on those with 3-mm-thick sections. CONCLUSION Our data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis.

19 citations


Journal ArticleDOI
TL;DR: It is indicated that the combined use of monthly fast-FLAIR and TD enhanced Tl-weighted scans increases the number of active lesions detected on serial MRI scans from patients with MS.

16 citations


Journal Article
TL;DR: In this paper, a magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS.
Abstract: PURPOSE: Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). METHODS: A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. RESULTS: The median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2-weighted lesion load. CONCLUSION: Our findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.

Journal ArticleDOI
TL;DR: The data suggest that acquisition of thinner slices does not significantly increase the sensitivity of MRI of the brain in the detection of lesion load changes in MS, and the correlation between MRI and EDSS changes was significant.
Abstract: In this longitudinal study the authors evaluated the sensitivity of 3-mm and 5-mm magnetic resonance imaging (MRI) of the brain in the detection of lesion load changes over time in multiple sclerosis (MS). The authors also correlated the changes detected with these two techniques with the changes in disability. Eighteen patients with MS underwent two MRI examinations of the brain--one at entrance into the study and one follow-up examination. At both sessions, images with 24 contiguous slices 5 mm thick and another with 40 contiguous axial slices 3 mm thick were consecutively acquired. On the same occasions, the patients' Expanded Disability Status Scale (EDSS) scores were rated. MR images with slices 3 mm thick showed higher lesion loads than those with slices 5 mm thick at both entrance and follow-up examinations (median, 13.4 vs 12.8 ml and 17.5 vs 17.0 ml, respectively; p < 0.0001). The correlation between MRI and EDSS changes was significant for both MRI acquisition schemes (3 mm, r = 0.64; 5 mm, r = 0.59). The data suggest that acquisition of thinner slices does not significantly increase the sensitivity of MRI of the brain in the detection of lesion load changes in MS.

Journal ArticleDOI
TL;DR: It is suggested that both dual-echo and postcontrast T1-weighted scans are useful to detect newly formed lesions in patients with MS.
Abstract: In this study, we evaluated the frequency of formation of new lesions on brain magnetic resonance imaging (MRI) from patients with relapsing-remitting multiple sclerosis (MS) and defined the relative

Journal ArticleDOI
TL;DR: Lesion volumes were significantly higher when scheme B was used and inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.
Abstract: We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patients and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3.1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesions volumes were significantly higher when scheme B was used (P = 0.024). This was due to higher lesion volumes on TSE images (P = 0.006), especially on even-numbered slices (P = 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.

01 Jan 1998
TL;DR: It is indicated that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.
Abstract: PURPOSE: Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). METHODS: A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. RESULTS: The median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2-weighted lesion load. CONCLUSION: Our findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.