Comparison of two different methods of image analysis for the assessment of microglial activation in patients with multiple sclerosis using (R)-[N-methyl-carbon-11]PK11195.
Comparison of two different methods of image analysis for the assessment of microglial activation in patients with multiple sclerosis using (R)-[N-methyl-carbon-11]PK11195.
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DOI：
10.1371/journal.pone.0201289
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Gauthier SA
中科院分区：
文献类型：
--
作者：
Kang Y;Schlyer D;Kaunzner UW;Kuceyeski A;Kothari PJ;Gauthier SA
慢性活动性多发性硬化（MS）病变具有活化的小胶质细胞/巨噬细胞（m/M）的边缘，导致持续的组织损伤，因此代表了潜在的治疗靶点。MS中这种先天性免疫应答的激活已经使用[11 C]-（R）-PK 11195（PK）的PET成像可视化和定量。慢性MS病变中m/M激活的准确识别需要在小组织体积内检测较低水平活性的灵敏度。我们评估了PK PET数据的动力学建模检测不同大小的中枢神经系统（CNS）组织区域和慢性MS病变中m/M活性的能力。10例MS患者接受了单次脑MRI和两次PK PET扫描，间隔2小时。为白色物质（WM）、皮质灰质（CGM）和丘脑（TH）生成感兴趣体积（VOI）掩模。分布容积（VT）采用Logan图解法（LGM-VT）计算，该方法使用图像导出的输入函数（IDIF）。采用参考Logan图解法（RLGM）计算结合潜力（BPND），使用监督聚类算法（SuperPK）确定非特异性结合区域。在CNS中创建不同体积的掩模，以评估区域大小对高摄取区域和低摄取区域之间的各种指标的影响。还对慢性MS病变进行了评价，并生成了个体病变掩模。如平均时间活性曲线所示，最高PK摄取发生在TH中，最低发生在WM中。在TH中，基于参考和IDIF的方法导致的估计并不显著依赖于VOI的大小。然而，在WM中，BPND的重测信度在最小VOI中显著低于LGM-VT的估计值。这些观察结果与检查的所有慢性MS病变一致。在这项研究中，我们证明了BPND和LGM-VT都是可靠的定量m/M激活的高摄取区域，但与血液输入功能LGM-VT是首选评估纵向m/M激活的区域相对较低的摄取，如慢性MS病变。
Chronic active multiple sclerosis (MS) lesions have a rim of activated microglia/macrophages (m/M) leading to ongoing tissue damage, and thus represent a potential treatment target. Activation of this innate immune response in MS has been visualized and quantified using PET imaging with [11C]-(R)-PK11195 (PK). Accurate identification of m/M activation in chronic MS lesions requires the sensitivity to detect lower levels of activity within a small tissue volume. We assessed the ability of kinetic modeling of PK PET data to detect m/M activity in different central nervous system (CNS) tissue regions of varying sizes and in chronic MS lesions. Ten patients with MS underwent a single brain MRI and two PK PET scans 2 hours apart. Volume of interest (VOI) masks were generated for the white matter (WM), cortical gray matter (CGM), and thalamus (TH). The distribution volume (VT) was calculated with the Logan graphical method (LGM-VT) utilizing an image-derived input function (IDIF). The binding potential (BPND) was calculated with the reference Logan graphical method (RLGM) utilizing a supervised clustering algorithm (SuperPK) to determine the non-specific binding region. Masks of varying volume were created in the CNS to assess the impact of region size on the various metrics among high and low uptake regions. Chronic MS lesions were also evaluated and individual lesion masks were generated. The highest PK uptake occurred the TH and lowest within the WM, as demonstrated by the mean time activity curves. In the TH, both reference and IDIF based methods resulted in estimates that did not significantly depend on VOI size. However, in the WM, the test-retest reliability of BPND was significantly lower in the smallest VOI, compared to the estimates of LGM-VT. These observations were consistent for all chronic MS lesions examined. In this study, we demonstrate that BPND and LGM-VT are both reliable for quantifying m/M activation in regions of high uptake, however with blood input function LGM-VT is preferred to assess longitudinal m/M activation in regions of relatively low uptake, such as chronic MS lesions.
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