Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo
Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo
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DOI：
10.1073/pnas.1002113107
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发表时间：
2010-07-13
影响因子：
11.1
通讯作者：
Stark, Craig E. L.
中科院分区：
文献类型：
--
作者：
Yassa, Michael A.;Muftuler, L. Tugan;Stark, Craig E. L.
穿通路径（PP）在衰老和痴呆过程中经历突触变化。先前的研究尝试使用扩散张量成像 (DTI) 评估人体 PP 的完整性，但由于分辨率低且无法具体识别 PP 纤维，因此受到限制。在这里，我们展示了超高亚毫米分辨率的 DTI 应用，使我们能够成功识别 PP 特有的扩散信号，并比较年轻人和老年人样本中这些信号的强度。我们报告了人类体内与年龄相关的 PP 降解的直接证据。我们没有发现控制通路（肺泡）出现这种损失的证据，这表明这些发现并不是全球衰退的证据。我们还没有发现特定的内嗅灰质萎缩的证据。 PP 退化的程度与对海马缺陷敏感的单词列表学习任务的表现相关。我们还显示了灰质扩散信号与海马和大脑皮层锥体树突方向一致的证据。超高分辨率微结构 DTI 是一种独特的生物标记物，可与传统的结构和功能神经成像方法结合使用，以增强阿尔茨海默病早期阶段的检测、测试新疗法的有效性并监测疾病进展。
The perforant path (PP) undergoes synaptic changes in the course of aging and dementia. Previous studies attempting to assess the integrity of the PP in humans using diffusion tensor imaging (DTI) were limited by low resolution and the inability to identify PP fibers specifically. Here we present an application of DTI at ultrahigh submillimeter resolution that has allowed us to successfully identify diffusion signals unique to the PP and compare the intensity of these signals in a sample of young adults and older adults. We report direct evidence of age-related PP degradation in humans in vivo. We find no evidence of such loss in a control pathway, the alveus, suggesting that these findings are not evidence for a global decline. We also find no evidence for specific entorhinal gray matter atrophy. The extent of PP degradation correlated with performance on a word-list learning task sensitive to hippocampal deficits. We also show evidence for gray matter diffusion signals consistent with pyramidal dendrite orientation in the hippocampus and cerebral cortex. Ultrahigh-resolution microstructural DTI is a unique bio-marker that can be used in combination with traditional structural and functional neuroimaging methods to enhance detection of Alzheimer disease in its earliest stages, test the effectiveness of new therapies, and monitor disease progression.