| 摘要 | 脊髓压迫症是较为常见的脊髓病变，通常伴有疼痛或其他感觉异常，以及 运动功能障碍乃至残疾等症状。脊髓压迫症按照病程可以分为急性脊髓压迫和 慢性脊髓压迫，在症状和表现上这两种不同的脊髓压迫症有很大区别，可能预 示着中枢神经机制改变上的差异。但在目前，脊髓压迫症对脊髓中枢可塑性的 影响却很少探究，特别是急性脊髓压迫症。一方面是脊髓神经影像技术的采集 和分析上的困难，特别是脊髓功能磁共振成像及分析技术。另一方面是急性脊 髓病变的症状往往比较严重，且急性期的病程很短（通常损伤几天内），因此难 以获得较为全面的行为评估。为了解急性脊髓压迫和慢性脊髓压迫对脊髓中枢 可塑性的影响，本研究采用先进的多模态脊髓磁共振成像（Magnetic Resonance Imaging, MRI）技术，从宏观结构，微观结构，脊髓功能状态等不同维度评估 脊髓压迫给脊髓中枢可塑性带来的改变，试图解释其脊髓神经机制。同时对患 者的临床行为及疼痛特征进行综合评估，探究 MRI 指标对行为评估的预测效 果。为此，本论文开展了三个研究。
研究一是脊髓静息态功能磁共振成像（functional Magnetic Resonance Imaging, fMRI）预处理流程的优化。本研究总结了以往研究中所用处理方法， 优化出合理的脊髓静息态 fMRI 预处理流程。此外，采集健康被试的脊髓静息 态 fMRI 图像。针对去噪方式不统一的问题，集中考察了不同去噪方式对时域 信噪比，静息态功能连接强度及可重复性的影响。结果发现，生理噪声模型或 者生理噪声模型加独立成分分析的方法具有较高的时域信噪比，且计算的脊髓 静息态功能连接具有较高的可重复性。
研究二考察急性颈髓压迫对脊髓可塑性的影响。以颈椎过伸伤为代表性病 症，本研究在患者急性期治疗前和治疗后，分别进行了临床行为评估，以及多 模态磁共振图像采集，包括 T2 结构像，弥散张量成像（Diffusion Tensor Imaging, DTI），静息态功能磁共振成像。同时招募年龄、性别高度匹配的健康 对照组。本研究分别在行为指标及 MRI 指标上对患者和健康对照的差异进行了 对比，同时考察了患者治疗前后脊髓 MRI 指标的改变。进一步，本研究对脊髓MRI 指标的行为预测效果进行了考察。结果发现，在宏观结构上，急性脊髓压 迫会带来白质和灰质的整体萎缩，其中白质萎缩集中在损伤节段，灰质萎缩则 弥漫至整个颈脊髓。治疗仅能改善损伤节段的灰质萎缩，对白质萎缩则无能为 力。患者的总体灰质截面积能有效预测治疗带来的疼痛改善及治疗后疼痛评 分。在微观结构上，患者的各向异性分数（Fractional Anisotropy, FA）显著高于 健康人，平均扩散系数（Mean Diffusivity, MD）和径向扩散系数（Radial Diffusivity, RD）则显著低于健康对照，并且差异集中在损伤之上的节段。治疗 不能带来微观结构可塑性的显著改变。损伤节段之下 FA 值能有效正向预测运 动相关生活功能在治疗后的改善及功能状态。在脊髓功能状态上，患者在损伤 之下节段的感觉功能连接显著低于健康人，同时整体的低频振幅（Amplitude of Low Frequency Fluctuation, ALFF）有增加趋势。治疗不能带来脊髓功能状态的 显著提升。此外，损伤节段 ALFF 能有效负向预测治疗后的基础感觉和基础运 动功能。
研究三考察慢性腰髓压迫对脊髓可塑性的影响。以腰椎间盘突出症 （Lumbar Disc Herniation, LDH）为代表病症，本研究使用多模态脊髓 MRI （T2，静息态 fMRI）及疼痛特征评估，综合探讨慢性腰髓压迫对颈脊髓可塑性 及疼痛特征的影响。在宏观结构上，可见 LDH 患者颈髓横截面积显著减少，并 且颈脊髓截面积与疼痛显著负相关。在脊髓功能状态上，与健康受试者相比， 患者颈脊髓的感觉功能连接显著增加。特别地，脊髓感觉功能连接与疼痛敏感 性显著负相关，而健康对照组的相关性则正相反。此外，患者 C3 节段的 ALFF 显著降低，并且与病程存在显著负相关。
综上所述，本研究提供了优化的脊髓静息态 fMRI 预处理流程，并且检验 了生理噪声去除的有效方法，并验证了脊髓静息态功能连接的可重复性。在此 基础上，本研究综合探究了急性脊髓压迫和慢性脊髓压迫两种病症对脊髓可塑 性的影响。本研究发现罹患脊髓压迫症后，脊髓在宏观结构，微观结构及功能 状态上都会发生改变，并且不同模态的脊髓 MRI 指标能显著预测行为评估的结 果。本研究从神经影像的角度探索了脊髓压迫症的脊髓神经机制，对脊髓压迫 症患者的临床诊断，治疗和预后评估都具有积极的指导意义。 |
| 其他摘要 | Compressive myelopathy (CM) is a common spinal cord disease, which is usually accompanied by severe symptoms such as pain or sensory abnormalities, motor dysfunction and even disability. Compressive myelopathy can be divided into acute compressive myelopathy and chronic compressive myelopathy according to the course of disease. These two subtypes have great differences in symptoms and manifestations, which indicates the different changes in central nervous system. However, by far the influences of compressive myelopathy on spinal cord plasticity are rarely explored, especially for the acute compressive myelopathy. On the one hand, it is difficult to collect and analyze the spinal MRI, especially for the spinal fMRI. On the other hand, the symptoms of acute myelopathy are usually very serious, besides the acute phase is quite short (usually within a few days after injury). Thus it is difficult to obtain comprehensive behavioral evaluation. This research utilizes advanced multimodal spinal MRI technology to evaluate the changes of spinal cord plasticity, such as macrostructure, microstructure and functional state, induced by compressive myelopathy. At the same time, the clinical behavior evaluation and pain characteristics were evaluated to test the prediction of MRI indicators on behavior evaluation. Thus carried out three studies.
Study one optimized the preprocessing pipeline for spinal fMRI. This study summarized the methods used in previous studies and optimized a reasonable pipeline. In addition, this study collected spinal resting state fMRI in healthy subjects. To solve the problem of inconsistent denoising methods in previous studies, this study focused on the influences of different denoising methods on temporal signal-to-noise ratio (tSNR), the intensity and repeatability of resting state functional connectivity. Results showed that the physiological noise model (PNM) or PNM combined with independent component analysis (ICA) method have higher tSNR and higher repeatability in functional connectivity.
Study two investigated the effects of acute compressive myelopathy on spinal cord plasticity. Taking cervical hyperextension injury as a representative disease, this study conducted clinical behavior evaluation and multimodal (T2, DTI, resting fMRI) spinal MRI before and after treatment. At the same time, an age and gender well matched healthy control group was recruited. This study compared the differences of behavioral and MRI indicators in patients and healthy controls. Besides, the changes of MRI indicators before and after treatment were explored. Further more, This study investigated the prediction of spinal MRI indicators on behavioral evaluation. Results showed that in macrostructure, acute compressive myelopathy will lead to the overall atrophy of white matter and gray matter, in which white matter atrophy is concentrated in the injured segments, and gray matter atrophy diffuses to the whole cervical spinal cord. Treatment can only improve the gray matter atrophy of the injured segments, but can't do anything about white matter atrophy. The overall gray matter cross-sectional area of patients can effectively predict the pain reduction and pain scores after treatment. In microstructure, the FA of patients was significantly higher than that of healthy people, while MD and RD of patients were significantly lower. And the differences were concentrated above the injured segments. Treatment does not bring about significant changes in microstructural plasticity. FA value under the injured segments can positively predict the improvement and functional status of exercise-related life function after treatment. In terms of spinal function, the sensory connectivity of segments below the injured was significantly lower than that of healthy controls, and the overall Amplitude of Low Frequency Fluctuation (ALFF) tended to be increased. But treatment can not bring significant improvement to spinal function. Besides, the ALFF of injured segments can effectively predict the basic sensory and basic motor function after treatment.
Study three investigated the effects of chronic compressive myelopathy on spinal plasticity. Taking lumbar disc herniation (LDH) as a representative disease, this study to comprehensively explore the effects of chronic lumbar compressive myelopathy on cervical spinal cord plasticity. In macrostructure, it can be seen that the cross-sectional area of cervical spinal cord in patients with LDH is significantly reduced, and the cross-sectional area of cervical spinal cord is significantly negatively correlated with pain. In terms of spinal functional status, compared with healthy subjects, the functional connectivity between the dorsal horns (sensory connectivity) of cervical spinal cord in patients increased significantly. In particular, the sensory connectivity was significantly negatively correlated with pain sensitivity, while the correlation in healthy control group was the opposite. In addition, the ALFF of C3 segment was significantly reduced, which was significantly negatively correlated with the course of disease.
In summary, this research provides an optimized preprocessing pipeline for spinal resting state fMRI, acquires the effective methods for physiological noise removal, and verifies the repeatability of resting state functional connectivity in spinal cord. In this context, this research comprehensively explored the effects of acute compressive myelopathy and chronic compressive myelopathy on spinal cord plasticity. This research found that after compressive myelopathy, the macrostructure, microstructure and functional state of spinal cord will change. And the results of behavior evaluation can be significantly predicted by different MRI indicators. This research explores the neural mechanism of compressive myelopathy from the perspective of neuroimaging, and showed instructive guiding for clinical diagnosis, treatment and prognosis evaluation of patients with compressive myelopathy. |
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