A modified protocol to improve the detection of enhancing brain and spinalcord lesions in multiple sclerosis

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA ) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows ass essment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory tri als. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive tech niques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T o n 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 s ensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/ kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturatio n for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) w ere assessed. The total number of enhancing lesions seen was 347/75 on conv entional, brain/cord MRI respectively, and 754/123 on modified brain/cord M RI. The respective numbers of new enhancing lesions were 168/40 on conventi onal and 276/71 on modified scans. Smaller increases were seen in the propo rtion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study bu t a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either tria l design. A combined modified brain and cord imaging protocol markedly impr oves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces samp le size requirements for crossover studies but not necessarily for parallel design trials.