Lee M A, Smith S, Palace J, Matthews P M
Centre for Functional Magnetic Resonance Imaging of the Brain, John Radcliffe Hospital, Headington, UK.
Brain. 1998 Nov;121 ( Pt 11):2095-102. doi: 10.1093/brain/121.11.2095.
Serial brain MRI scanning is widely used for assessing multiple sclerosis disease activity in the evaluation of new therapies. Traditionally, the net change in T2-weighted lesion volume between paired scans has been used as a measure of disease progression and as a secondary endpoint in definitive clinical trials. However, as the net change in T2-weighted lesion volume reflects only the difference between new and resolved T2-weighted lesions, this measure significantly under-represents the total T2-weighted lesion activity. Difference images produced by subtracting labelled T2-weighted lesion volumes from serial registered T2-weighted scans allows separate measurements of individual volumes of new and resolving T2-weighted lesions, which may reflect underlying disease activity more sensitively. We generated T2-weighted differences images to define T2-weighted lesion changes over 1 year for 19 patients with relapsing multiple sclerosis. The mean new T2-weighted lesion volume change was three times greater than the mean net T2-weighted lesion volume change over the study period. New T2-weighted lesion volumes were more strongly correlated with T1-weighted gadolinium-enhancing lesion volumes (r = 0.72, P = 0.001) than were the net T2-weighted lesion volume changes (r = 0.45, P = 0.01). Baseline T2-weighted lesion volume was more highly correlated with new T2-weighted lesion volumes (r = 0.89, P < 0.0001) than with net T2-weighted lesion change (r = 0.47, P < 0.001). There was a trend for patients who showed sustained clinical progression over the year to have a greater new T2-weighted lesion volume than those who did not. This difference was not seen with net T2-weighted lesion volume change. T2-weighted lesion difference images should provide an additional and sensitive tool for monitoring disease activity in multiple sclerosis. Independent definition of new and resolving T2-weighted lesion volumes also offers the potential for discrimination of the relative effects of experimental therapies on new inflammatory activity from the effects on oedema resolution and lesion repair.
连续脑部磁共振成像扫描在评估新疗法时被广泛用于评估多发性硬化症的疾病活动。传统上，配对扫描之间T2加权病变体积的净变化被用作疾病进展的衡量指标，并作为确定性临床试验的次要终点。然而，由于T2加权病变体积的净变化仅反映新出现和消退的T2加权病变之间的差异，该指标显著低估了总的T2加权病变活动。通过从连续配准的T2加权扫描中减去标记的T2加权病变体积生成的差异图像，可以分别测量新出现和正在消退的T2加权病变的个体体积，这可能更敏感地反映潜在的疾病活动。我们生成了T2加权差异图像，以确定19例复发型多发性硬化症患者在1年期间的T2加权病变变化。在研究期间，新的T2加权病变体积的平均变化比T2加权病变体积的平均净变化大三倍。新的T2加权病变体积与T1加权钆增强病变体积的相关性更强（r = 0.72，P = 0.001），而T2加权病变体积的净变化与之相关性较弱（r = 0.45，P = 0.01）。基线T2加权病变体积与新的T2加权病变体积的相关性更高（r = 0.89，P < 0.0001），而与T2加权病变净变化的相关性较低（r = 0.47，P < 0.001）。在这一年中表现出持续临床进展的患者，其新的T2加权病变体积有比未表现出持续临床进展的患者更大的趋势。T2加权病变体积净变化未显示出这种差异。T2加权病变差异图像应为监测多发性硬化症的疾病活动提供一种额外且敏感的工具。新出现和正在消退的T2加权病变体积的独立定义也为区分实验性疗法对新炎症活动的相对影响与对水肿消退和病变修复的影响提供了可能性。
