Bastiaan Moraal

In vivo MR imaging of hippocampal lesions in multiple sclerosis.

To investigate whether a recently improved version of the three‐dimensional double inversion‐recovery (3D‐DIR) technique enables the in vivo detection of hippocampal lesions in multiple sclerosis (MS).

Improved detection of active multiple sclerosis lesions: 3D subtraction imaging.

PURPOSE To examine the benefits of using near-isotropic single-slab three-dimensional (3D) magnetic resonance (MR) imaging for the creation of subtraction images and to evaluate their performance in the detection of active multiple sclerosis (MS) brain lesions in comparison with two-dimensional (2D) subtraction images. MATERIALS AND METHODS The study protocol was approved by the local ethics review board and all subjects gave written informed consent before investigation. Three-dimensional MR sequences, including double inversion-recovery, fluid-attenuated inversion recovery, T2-weighted, and T1-weighted magnetization-prepared rapid acquisition gradient-echo (MP-RAGE), and corresponding 2D sequences were performed twice in 14 patients (eight women, six men; mean age, 37.6 years) with MS and nine age-matched healthy control subjects (three women, six men; mean age, 31.7 years). Active lesions were scored by two independent raters, followed by a consensus reading. Lesion counts were evaluated by using negative binomial regression; interrater agreement was evaluated by using intraclass correlation coefficient. RESULTS Three-dimensional subtraction images had less residual misregistration and flow artifacts and depicted higher numbers of active lesions with greater interobserver agreement compared with 2D subtraction images. Among the 3D sequences, MP-RAGE subtraction imaging enabled detection of a significantly higher mean number of positive active MS lesions compared with 2D subtraction imaging (2.8 versus 1.7, P = .012), particularly infratentorial lesions (0.6 vs 0.1, P < .05), and a substantially higher (nonsignificant) mean number of small (<3 mm) lesions (0.6 vs 0.1, P > .05). CONCLUSION Three-dimensional subtraction imaging, after image registration, produced better image quality, leading to increased detection of active MS lesions with greater interobserver agreement in comparison with 2D subtraction imaging; 3D MP-RAGE subtraction imaging represents a promising technique to increase sensitivity in ascertaining lesion dissemination in time and increase the power of MR imaging metrics for the evaluation of treatment effects in clinical trials.

Subtraction MR images in a multiple sclerosis multicenter clinical trial setting.

PURPOSE To explore the applicability of subtraction magnetic resonance (MR) images to (a) detect active multiple sclerosis (MS) lesions, (b) directly quantify lesion load change, and (c) detect treatment effects (distinguish treatment arms) in a placebo-controlled multicenter clinical trial by comparing the subtraction scheme with a conventional pair-wise comparison of nonregistered MR images. MATERIALS AND METHODS Forty-six pairs of MR studies in 40 patients (31 women; mean age, 31.9 years) from a multicenter clinical trial were used. The clinical trial was approved by local ethics review boards, and all subjects gave written informed consent. Active MS lesions were scored by two independent raters, and lesion load measurements were conducted by using semiautomated software. Lesion counts were evaluated by using the Wilcoxon signed rank test, interrater agreement was evaluated by using the intraclass correlation coefficient (ICC), and treatment (interferon beta-1b) effect was evaluated by using the Mann-Whitney U test. RESULTS When subtraction images were used, there was a 1.7-fold increase in the detection of positive active lesions, as compared with native image pairs, and significantly greater interobserver agreement (ICC = 0.98 vs 0.91, P < .001). Subtraction images also allowed direct quantification of positive disease activity, a measure that provided sufficient power to distinguish treatment arms (P = .012) compared with the standard measurement of total lesion load change on native images (P = .455). CONCLUSION MR image subtraction enabled detection of higher numbers of active MS lesions with greater interobserver agreement and exhibited increased power to distinguish treatment arms, as compared with a conventional pair-wise comparison of nonregistered MR images.

Magnetic resonance imaging predictors of conversion to multiple sclerosis in the BENEFIT study

BACKGROUND Several studies have confirmed the predictive value of baseline and follow-up magnetic resonance (MR) imaging variables for conversion to clinically definite multiple sclerosis (CDMS), depending on the population, follow-up duration, and treatment intervention. However, the timing of follow-up imaging and the effect of treatment intervention on the predictive value of baseline MR imaging variables require further elucidation. OBJECTIVES To assess the prognostic value of baseline MR imaging variables for conversion to CDMS over 3 years and whether this was affected by treatment intervention and (2) to assess the increased risk for conversion posed by dissemination in time on follow-up MR imaging. DESIGN Cohort study. SETTING Multicenter randomized clinical trial. PATIENTS Four hundred sixty-eight patients with a clinically isolated syndrome who had an initial clinical demyelinating event within the past 60 days who received early treatment (3 years of interferon beta-1b) or delayed treatment (placebo first, followed by > or =1 year of interferon beta-1b). Intervention Magnetic resonance imaging. Main Outcome Measure Time to CDMS. RESULTS The overall conversion rate to CDMS was 42%. Barkhof criteria with the strongest prognostic value were the presence at baseline of at least 9 T2-weighted lesions (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.15-2.33; P = .006) and at least 3 periventricular lesions (1.66; 1.14-2.41; P = .009). No specific advantage was noted in using a fixed cutoff of at least 3 Barkhof criteria (HR, 1.31; 95% CI, 0.95-1.79; P = .10). The prognostic value of all MR imaging criteria was unaffected by treatment intervention (P > or = .20 for all). Dissemination in time resulted in increased risk for CDMS only in patients without dissemination in space at baseline and was most informative at the 9-month MR imaging (HR, 2.72; 95% CI, 1.26-5.87; P = .01). CONCLUSIONS The modified Barkhof criteria showed moderate predictive value for conversion to CDMS, although all patients had received interferon beta-1b therapy for at least 1 year. The predictive value was unaffected by treatment intervention. Follow-up MR imaging was most informative after 9 months in patients without dissemination in space at baseline.

Long-Interval T2-Weighted Subtraction Magnetic Resonance Imaging A Powerful New Outcome Measure in Multiple Sclerosis Trials

To compare long‐interval T2‐weighted subtraction (T2w‐Sub) imaging with monthly gadolinium‐enhanced T1‐weighted (Gd‐T1w) imaging for (1) detection of active lesions, (2) assessment of treatment efficacy, and (3) statistical power, in a multiple sclerosis (MS), phase 2, clinical trial setting.

Segmentation of subtraction images for the measurement of lesion change in multiple sclerosis.

BACKGROUND AND PURPOSE: Lesion volume change (LVC) assessment is essential in monitoring MS progression. LVC is usually measured by independently segmenting serial MR imaging examinations. Subtraction imaging has been proposed for improved visualization and characterization of lesion change. We compare segmentation of subtraction images (SSEG) with serial single time-point conventional segmentation (CSEG) by assessing the LVC relationship to brain atrophy and disease duration, as well as scan-rescan reproducibility and annual rates of lesion accrual. MATERIALS AND METHODS: Pairs of scans were acquired 1.5 to 4.7 years apart in 21 patients with multiple sclerosis (MS). Scan-rescan MR images were acquired within 30 minutes in 10 patients with MS. LVC was measured with CSEG and SSEG after coregistration and normalization. Coefficient of variation (COV) and Bland-Altman analyses estimated method reproducibility. Spearman rank correlations probed associations between LVC and other measures. RESULTS: Atrophy rate and net LVC were associated for SSEG (R = −0.446; P < .05) but not when using CSEG (R = −0.180; P = .421). Disease duration did not show an association with net lesion volume change per year measured by CSEG (R = −0.360; P = .11) but showed an inverse correlation with SSEG-derived measurements (R = −0.508; P < .05). Scan-rescan COV was lower for SSEG (0.98% ± 1.55%) than for CSEG (8.64% ± 9.91%). CONCLUSION: SSEG unveiled a relationship between T2 LVC and concomitant brain atrophy and demonstrated significantly higher measurement reproducibility. SSEG, a promising tool providing detailed analysis of subtle alterations in lesion size and intensity, may provide critical outcome measures for clinical trials of novel treatments, and may provide further insight into progression patterns in MS.

Multi-Contrast, Isotropic, Single-Slab 3D MR Imaging in Multiple Sclerosis

To describe signal and contrast properties of an isotropic, single-slab 3D dataset [double inversion-recovery (DIR), fluid-attenuated inversion recovery (FLAIR), T2, and T1-weighted magnetization prepared rapid acquisition gradient-echo (MPRAGE)] and to evaluate its performance in detecting multiple sclerosis (MS) brain lesions compared to 2D T2-weighted spin-echo (T2SE). All single-slab 3D sequences and 2D-T2SE were acquired in 16 MS patients and 9 age-matched healthy controls. Lesions were scored independently by two raters and characterized anatomically. Two-tailed Bonferroni-corrected Students t-tests were used to detect differences in lesion detection between the various sequences per anatomical area after log-transformation. In general, signal and contrast properties of the 3D sequences enabled improved detection of MS brain lesions compared to 2D-T2SE. Specifically, 3D-DIR showed the highest detection of intracortical and mixed WM-GM lesions, whereas 3D-FLAIR showed the highest total number of WM lesions. Both 3D-DIR and 3D-FLAIR showed the highest number of infratentorial lesions. 3D-T2 and 3D-MPRAGE did not improve lesion detection compared to 2D-T2SE. Multi-contrast, isotropic, single-slab 3D MRI allowed an improved detection of both GM and WM lesions compared to 2D-T2SE. A selection of single-slab 3D contrasts, for example, 3D-FLAIR and 3D-DIR, could replace 2D sequences in the radiological practice.

Direkte und indirekte Verfahren zur Quantifizierung der zerebralen Atrophie bei MS

DOI 10.1007/s00115-009-2769-2