A modified protocol to improve the detection of enhancing brain and spinal cord leasions in multiple sclerosis

Abstract

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows assessment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory trials. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive techniques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T on two occasions 24-72 h apart using a conventional imaging protocol with T1-weighted MRI at single-dose (0.1 mmol/kg) Gd-DTPA and a potentially more sensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturation for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) were assessed. The total number of enhancing lesions seen was 347/75 on conventional brain/cord MRI respectively, and 754/123 on modified brain/cord MRI. The respective numbers of new enhancing lesions were 168/40 on conventional and 276/71 on modified scans. Smaller increases were seen in the proportion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study but a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either trial design. A combined modified brain and cord imaging protocol markedly improves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces sample size requirements for crossover studies but not necessarily for parallel design trials.

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society

“…The brain, encompassing the larger part of the total CNS parenchyma, should always be examined in routine MRI for diagnosis or follow‐up of MS. Examination with spinal cord MRI can provide additional information, but is generally not as informative as the brain examination in the typical case 31, 32, 33. However, in line with the recommendations of the recently published MAGNIMS consensus guidelines,21 we suggest that spinal cord MRI should be included in the diagnostic workup if the presenting symptoms indicate spinal cord involvement.…”

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

“…MRI of the spinal cord is less sensitive than brain MRI for detecting disease activity, particu larly with regard to contrast enhancing lesions. 21,22 This limitation arises from the technical challenges of spinal cord MRI acquisition-relating mostly to image arte facts associated with vascular and cerebrospinal fluid pulsation-and the difficulty of standardizing the assess ment of lesion count and lesion volume. In addition, most spinal cord lesions are clinically symptomatic, and a strong relationship exists between the development of new lesions in the brain and the development of new lesions in the spinal cord.…”

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

“…In practice, such approaches are rarely used in clinical trials and have little impact on sample size requirements for trials because variability between patients also increases. 31 In relapsing remitting MS, a parallel groups design with a placebo arm requires ϳ2 ϫ 40 patients to show a 60% reduction in new enhancing lesions over 6 months, 32 with a 1-month run in scan reducing sample sizes by ϳ30%. 33 Such a trial design has become the standard way to evaluate efficacy of new anti-inflammatory therapies in phase 2 trials.…”