A longitudinal brain MRI study comparing the sensitivities of the conventional and a newer approach for detecting active lesions in multiple sclerosis

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Abstract

Monthly dual-echo spin–echo (SE) and enhanced magnetic resonance imaging (MRI) after the injection of a standard dose (SD) of gadolinium (Gd) is the conventional approach to monitor short-term disease activity in multiple sclerosis (MS). In this study, the sensitivity of this approach in detecting active lesions in MS was compared with that of monthly fast fluid attenuated inversion recovery (FLAIR) scans associated with enhanced MRI after the injection of a triple dose (TD) of Gd. Thirteen patients with relapsing–remitting MS entered the study. Monthly MRI scans were obtained on four occasions in two separate sessions (interval between 12 and 24 h). In one session, dual-echo conventional SE and SD T1-weighted scans were obtained; in the other, fast-FLAIR and TD T1-weighted scans. The order of the two sessions was randomized. Three observers counted the numbers of active lesions detected by each of the two approaches. One hundred and four active lesions were detected by the conventional approach and 199 by the newer approach (average increase per patient=75%, range=0–325%). The mean number of active lesions per month per patient was 2.0 for the conventional approach and 3.8 for the new approach (P=0.004). Scans with active lesions were 34/52 (65%) with the conventional approach and 37/52 (71%) with the new approach. Our data indicate that the combined use of monthly fast-FLAIR and TD enhanced T1-weighted scans increases the number of active lesions detected on serial MRI scans from patients with MS.

Introduction

Serial monthly magnetic resonance imaging (MRI) scans of the brain are used to monitor short-term multiple sclerosis (MS) activity, either natural or modified by treatment 5, 22. In patients with relapsing–remitting or secondary progressive MS, this technique has the unique advantage of revealing episodes of disease activity five to ten times more frequently than clinical measures [24], thus allowing the efficacy of new experimental treatments to be monitored using smaller numbers of patients and shorter follow-up periods 20, 26.

Traditionally, two MRI measures have been used to monitor MS short-term activity, namely (a) counting the number of new or enlarging lesions seen on monthly dual-echo conventional spin–echo (CSE) scans and (b) counting the number of enhancing lesions on monthly post-contrast T1-weighted scans after the injection of a standard dose (SD) of gadolinium-DTPA (Gd) 5, 22, 25. Recently, it has been demonstrated that the use of a triple dose (TD) of Gd is the best strategy to increase the sensitivity of MRI in detecting enhancing lesions 8, 29, 33and significantly increases [6]the statistical power of longitudinal MRI studies for detecting treatment effect. On the other hand, cross-sectional studies showed that fast-fluid attenuated inversion recovery (fast-FLAIR) sequences detect more MS lesions than CSE sequences 2, 7, 34. In this longitudinal study, we evaluated and compared the sensitivities of the conventional approach (i.e. dual echo CSE and SD post-contrast T1-weighted) and of a newer approach (i.e. fast-FLAIR and TD post-contrast T1-weighted) in detecting active lesions on four monthly serial MRI scans from patients with relapsing–remitting MS.

Section snippets

Patients

Patients with clinically definite MS [27]and a relapsing–remitting disease course [19]were studied. To be included, all patients must not have been subject to a clinical relapse, nor treated with steroids during the three months preceding study initiation. Other immunomodulating or immunosuppressive treatments were terminated at least one year before the start of the study. MRI scans were obtained from all patients at 28 day (±5 days) intervals on four occasions (i.e. the follow up was of 3

Clinical data

Thirteen patients (nine women and four men) were studied. Their mean age was 34.6 (±5.5) years, the median duration of the disease was 7.0 years (range=2–10 years) and the median EDSS score was 1.5 (range=0.0–4.0). No patient had changes of their EDSS score between entry and exit. One patient had one relapse during the follow-up and received steroid treatment. In this case, MRI was obtained 15 days after the steroid treatment was ended. No patient complained of discomfort or presented side

Discussion

This study indicates that enhanced MRI after the injection of a TD of Gd is the most sensitive approach to detect `active' lesions in MS, and that our fast-FLAIR sequence maximises the sensitivity of unenhanced MRI. The combination of these two techniques detected significantly more active lesions than the conventional combination of post contrast T1-weighted scans after the injection of a SD of Gd and dual-echo CSE scans.

Several previous cross-sectional studies showed that fast-FLAIR sequences

Acknowledgements

The study was generously supported by the Associazione Italiana Sclerosi Multipla (AISM) and Istituto Superiore di Sanità (Contract number: 96/J/T49).

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