Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
PLoS One. 2013;8(2):e56375. doi: 10.1371/journal.pone.0056375. Epub 2013 Feb 18.
Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS).
METHODOLOGY/PRINCIPAL FINDINGS: Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046).
CONCLUSIONS/SIGNIFICANCE: We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS.
多发性硬化症（MS）会影响血脑屏障（BBB）的完整性。对比增强 T1 加权磁共振成像（MRI）广泛用于描述局灶性 MS 病变中 BBB 破坏的位置和程度。我们采用静脉注射顺磁对比剂前后的定量 T1 测量来评估复发缓解型 MS（RR-MS）患者正常表现的白质（NAWM）中的 BBB 通透性。
方法/主要发现：59 名接受免疫调节治疗的 RR-MS 患者（38 名女性）和 9 名健康对照者（4 名女性）在 3T 下进行定量 T1 测量，在注射顺磁对比剂（0.2mmol/kg Gd-DTPA）前后进行。RR-MS 患者和健康受试者分别为 T1 测量前后的 NAWM 和总脑白质计算 T1 值。RR-MS 患者 NAWM 的 T1 值在注射 Gd-DTPA 前的基线值（945±55 [SD] ms）比健康对照组延长（903±23 ms，p=0.028）。两组 Gd-DTPA 注射均缩短 T1 值。RR-MS 患者 NAWM 的平均 T1 值为 866±47 ms，健康对照者的白质平均 T1 值为 824±13 ms。两组 T1 值的区域变异性（以变异系数表示）在注射对比剂前后均相似。静脉注射 Gd-DTPA 后，RR-MS 患者 NAWM 的 T1 值变化较大（CV=0.198±0.046），而健康对照组的脑白质变化较小（CV=0.166±0.018，p=0.046）。
结论/意义：我们在接受免疫调节治疗的 RR-MS 患者的 NAWM 中未发现 BBB 整体破坏的证据。然而，静脉注射 Gd-DTPA 后 NAWM 中 T1 值的变化增加表明 RR-MS 中 NAWM 的 BBB 功能区域性不均匀性增加。
