Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
Magn Reson Imaging. 2010 Oct;28(8):1234-43. doi: 10.1016/j.mri.2010.01.005. Epub 2010 Mar 29.
Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory.
尽管近年来功能磁共振成像（fMRI）的应用越来越广泛，但信号变化的生理基础仍未完全了解。血氧水平依赖（BOLD）对比——归因于局部血流和氧合变化，因此磁敏感性——已成为功能神经影像学最常用的手段。然而，在短回波时间下，自旋回波序列显示出与 BOLD 模型相当大的偏差，暗示存在信号变化的第二个非 BOLD 成分。这被称为“血管外质子的信号增强”（SEEP），并被认为是与细胞肿胀相关的质子密度变化的结果。鉴于这种变化与磁敏感性无关，SEEP 可能为在靠近气-组织和/或骨-组织界面（例如前额叶皮层和脊髓）的区域以及靠近大血管的区域进行 fMRI 提供新的和改进的机会，这些区域可能不太适合 BOLD 成像。然而，由于文献的跨学科性质，尚未对 SEEP 理论的各个方面进行全面综合，将它们联系在一起。因此，我们旨在提供一个简洁而全面的 SEEP 概述，包括最近对其有效性的令人信服的证据、其当前应用以及对功能神经影像学快速发展领域的未来相关性。在提出内源性功能对比的非 BOLD 成分的证据之前，并为非专业读者提供更具批判性的审查，我们首先回顾 BOLD 理论的基本原理。
