BACKGROUND Brain volume loss measured from magnetic resonance imaging (MRI) is a marker of neurodegeneration and predictor of disability progression in MS, and is commonly used to assess drug efficacy at the group level in clinical trials. Whether measures of brain volume loss could be useful to help guide management of individual patients depends on the relative magnitude of the changes over a given interval to physiological and technical sources of variability. GOAL To understand the relative contributions of neurodegeneration vs. physiological and technical sources of variability to measurements of brain volume loss in individuals. MATERIAL AND METHODS Multiple T1-weighted 3D MPRAGE images were acquired from a healthy volunteer and MS patient over varying time intervals: 7 times on the first day (before breakfast at 7:30AM and then every 2 h for 12 h), each day for the next 6 working days, and 6 times over the remainder of the year, on 2 S MRI scanners: 1.5T Sonata (S1) and 3.0T TIM Trio (S2). Scan-reposition-rescan data was acquired on S2 for daily, monthly and 1-year visits. Percent brain volume change (PBVC) was measured from baseline to each follow-up scan using FSL/SIENA. We estimated the effect of physiologic fluctuations on brain volume using linear regression of the PBVC values over hourly and daily intervals. The magnitude of the physiological effect was estimated by comparing the root-mean-square error (RMSE) of the regression of all the data points relative to the regression line, for the hourly scans vs the daily scans. Variance due to technical sources was assessed as the RMSE of the regression over time using the intracranial volume as a reference. RESULTS The RMSE of PBVC over 12 h, for both scanners combined, ("Hours", 0.15%), was similar to the day-to-day variation over 1 week ("Days", 0.14%), and both were smaller than the RMS error over the year (0.21%). All of these variations, however, were smaller than the scan-reposition-rescan RMSE (0.32%). The variability of PBVC for the individual scanners followed the same trend. The standard error of the mean (SEM) for PBVC was 0.26 for S1, and 0.22 for S2. From these values, we computed the minimum detectable change (MDC) to be 0.7% on S1 and 0.6% on S2. The location of the brain along the z-axis of the magnet inversely correlated with brain volume change for hourly and daily brain volume fluctuations (p < 0.01). CONCLUSION Consistent diurnal brain volume fluctuations attributable to physiological shifts were not detectable in this small study. Technical sources of variation dominate measured changes in brain volume in individuals until the volume loss exceeds around 0.6-0.7%. Reliable interpretation of measured brain volume changes as pathological (greater than normal aging) in individuals over 1 year requires changes in excess of about 1.1% (depending on the scanner). Reliable brain atrophy detection in an individual may be feasible if the rate of brain volume loss is large, or if the measurement interval is sufficiently long.

中文翻译：

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随着时间的推移，个体的脑容量损失：方差的来源和可检测性的限制

背景从磁共振成像（MRI）测量的脑容量损失是神经变性的标志物和MS残疾进展的预测因子，并且通常用于在临床试验中在组级别评估药物功效。脑容量损失的测量是否有助于指导个体患者的管理取决于给定间隔内变化的相对幅度与生理和技术变异性来源。目标 了解神经变性与变异的生理和技术来源对个体脑容量损失测量的相对贡献。材料和方法 在不同的时间间隔内从一名健康志愿者和 MS 患者获取多张 T1 加权 3D MPRAGE 图像：第一天 7 次（早餐前 7 点：上午 30 点，然后在 12 小时内每 2 小时一次），接下来 6 个工作日的每一天，以及一年中剩余时间的 6 次，使用 2 S MRI 扫描仪：1.5T Sonata (S1) 和 3.0T TIM Trio (S2) . 在 S2 上获取每日、每月和 1 年访问的扫描-重新定位-重新扫描数据。使用 FSL/SIENA 测量从基线到每次后续扫描的脑体积变化百分比 (PBVC)。我们使用每小时和每天间隔的 PBVC 值的线性回归来估计生理波动对脑容量的影响。对于每小时扫描与每日扫描，通过比较所有数据点相对于回归线的回归的均方根误差 (RMSE) 来估计生理效应的大小。由于技术来源的差异被评估为使用颅内体积作为参考随时间回归的 RMSE。结果 PBVC 在 12 小时内的均方根误差（“小时”，0.15%）与 1 周内的日常变化（“天”，0.14%）相似，两者均小于年均方根误差 (0.21%)。然而，所有这些变化都小于扫描-重新定位-重新扫描 RMSE (0.32%)。单个扫描仪的 PBVC 变化遵循相同的趋势。PBVC 的平均值 (SEM) 的标准误差对于 S1 为 0.26，对于 S2 为 0.22。根据这些值，我们计算出 S1 上的最小可检测变化 (MDC) 为 0.7%，S2 上为 0.6%。大脑沿磁体 z 轴的位置与每小时和每日脑容量波动的脑容量变化呈负相关 (p < 0.01)。结论 在这项小型研究中，无法检测到由于生理变化导致的昼夜脑容量持续波动。变异的技术来源主导着个体大脑体积的测量变化，直到体积损失超过 0.6-0.7% 左右。将测量的脑容量变化作为病理性（大于正常老化）的个体超过 1 年的可靠解释需要超过约 1.1% 的变化（取决于扫描仪）。如果脑容量损失率很大，或者如果测量间隔足够长，则对个体进行可靠的脑萎缩检测可能是可行的。将测量的脑容量变化作为病理性（大于正常老化）的个体超过 1 年的可靠解释需要超过约 1.1% 的变化（取决于扫描仪）。如果脑容量损失率很大，或者如果测量间隔足够长，则对个体进行可靠的脑萎缩检测可能是可行的。将测量的脑容量变化作为病理性（大于正常衰老）的个体超过 1 年的可靠解释需要超过约 1.1% 的变化（取决于扫描仪）。如果脑容量损失率很大，或者如果测量间隔足够长，则对个体进行可靠的脑萎缩检测可能是可行的。