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Abstract：
OBJECTIVE: A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach.
METHODS: For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures.
RESULTS: We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found.
CONCLUSIONS: CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.
METHODS: For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures.
RESULTS: We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found.
CONCLUSIONS: CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.
摘要：
目的：在多发性硬化症（MS）中发现了皮质和丘脑灰质（GM）中的CSF-in梯度。我们同时探索了皮质的模式，丘脑,以及使用多参数MRI方法在距CSF的渐进距离处的尾状微结构异常。
方法：对于这项横断面研究，从3T3DT1加权扫描，我们从脑膜表面25％-50％-75％深度的皮质层以及从心室-GM界面2-3-4体素的丘脑和尾状带采样。使用线性混合模型，我们测试了磁化转移比(MTR)和R2*层特定z分数的组间比较，CSF-in跨层z分数变化，以及它们与临床(疾病持续时间和残疾)和结构(局灶性病变，大脑,和脉络丛体积）MRI测量。
结果：我们招募了52例MS患者（33例复发缓解[RRMS]，19渐进式[PMS]，平均年龄：46.4岁，中位病程：15.1年，中位数：EDSS2.0）和70名对照（平均年龄41.5±12.8）。与对照组相比，RRMS在外层和中层皮质层中显示较低的MTR值（错误发现率[FDR]-p≤0.025），在所有3个皮质层中显示较低的R2*值（FDR-p≤0.016）。PMS在皮质外层和中层（FDR-p≤0.016）和丘脑（FDR-p≤0.048）层的MTR值较低，并在外尾状层（FDR-p=0.024）。他们在皮质外层（FDR-p=0.003）和丘脑外层（FDR-p=0.046）中显示出较低的R2*值，在所有3个尾状层（FDR-p≤0.031）中显示出较高的R2*值。RRMS和PMS都有损伤梯度，较低的值更接近CSF，用于皮质（FDR-p≤0.002）和丘脑（FDR-p≤0.042）MTR。PMS显示皮质R2*（FDR-p=0.005）的损伤梯度，丘脑R2*（FDR-p=0.004），和尾状MTR（FDR-p≤0.013）。外皮质的较低MTR和R2*，丘脑,和尾状层和更陡的梯度对CSF的损伤与年龄显著相关，较高的T2-高强度白质病变体积，上丘脑病变体积，和较低的脑容量（β≥0.08，所有FDR-p≤0.040）。尾状外层的MTR较低与更严重的残疾有关（β=-0.26，FDR-p=0.040）。未发现与脉络丛体积相关。
结论：CSF-in损伤梯度在不同GM区域和整个MS过程中是异质的，可能反映了脱髓鞘和铁流失/积累的不同动力学。
方法：对于这项横断面研究，从3T3DT1加权扫描，我们从脑膜表面25％-50％-75％深度的皮质层以及从心室-GM界面2-3-4体素的丘脑和尾状带采样。使用线性混合模型，我们测试了磁化转移比(MTR)和R2*层特定z分数的组间比较，CSF-in跨层z分数变化，以及它们与临床(疾病持续时间和残疾)和结构(局灶性病变，大脑,和脉络丛体积）MRI测量。
结果：我们招募了52例MS患者（33例复发缓解[RRMS]，19渐进式[PMS]，平均年龄：46.4岁，中位病程：15.1年，中位数：EDSS2.0）和70名对照（平均年龄41.5±12.8）。与对照组相比，RRMS在外层和中层皮质层中显示较低的MTR值（错误发现率[FDR]-p≤0.025），在所有3个皮质层中显示较低的R2*值（FDR-p≤0.016）。PMS在皮质外层和中层（FDR-p≤0.016）和丘脑（FDR-p≤0.048）层的MTR值较低，并在外尾状层（FDR-p=0.024）。他们在皮质外层（FDR-p=0.003）和丘脑外层（FDR-p=0.046）中显示出较低的R2*值，在所有3个尾状层（FDR-p≤0.031）中显示出较高的R2*值。RRMS和PMS都有损伤梯度，较低的值更接近CSF，用于皮质（FDR-p≤0.002）和丘脑（FDR-p≤0.042）MTR。PMS显示皮质R2*（FDR-p=0.005）的损伤梯度，丘脑R2*（FDR-p=0.004），和尾状MTR（FDR-p≤0.013）。外皮质的较低MTR和R2*，丘脑,和尾状层和更陡的梯度对CSF的损伤与年龄显著相关，较高的T2-高强度白质病变体积，上丘脑病变体积，和较低的脑容量（β≥0.08，所有FDR-p≤0.040）。尾状外层的MTR较低与更严重的残疾有关（β=-0.26，FDR-p=0.040）。未发现与脉络丛体积相关。
结论：CSF-in损伤梯度在不同GM区域和整个MS过程中是异质的，可能反映了脱髓鞘和铁流失/积累的不同动力学。
