Serial CT Myelography in Syringomyelia Patients

脊髓空洞症患者的系列 CT 脊髓造影

• 批准号: 7146079
• 负责人: Peter M Bungay
• 金额: --
• 依托单位: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7146079
• 关键词: bioimaging /biomedical imaging; cerebrospinal fluid; clinical research; computed axial tomography; contrast media; human subject; mathematical model; model design /development; radiography; spinal cord disorders; spinal cord imaging /visualization

Syringomyelia denotes a fluid-filled cyst, termed a syrinx, that forms in the spinal cord. Affected patients suffer from progressive paralysis. Syringomyelia is most frequently associated with Chiari I malformation in which cerebellar tonsils ectopically protrude through the foramen magnum into the spinal canal. Subarachnoid cerebrospinal fluid (CSF) outflow from the spinal canal is constricted such that, during systole, heightened pressure waves are generated in the partially enclosed spinal subarachnoid space and transmitted compressively to the spinal cord. One hypothesis for the unknown mechanism underlying the development and progression of syringomyelia is that the cyst fluid accumulates because of an imbalance of CSF movement through the spinal cord extracellular space during the cardiac-derived pressure cycles. This hypothesis might be testable by following a marker that tracks the movement of CSF. The computed tomography (CT) contrast agent, iopamidol was tested as a surrogate marker. Serial CT iopamidol myelography was performed in 15 Chiari I patients before and after corrective surgery for the Chiari malformation. The surgery consisted of craniocervical decompression and duraplasty to improve CSF flow at the foramen magnum. For the myelography, iopamidol was injected into the CSF through lumbar punctures and CT scans were obtained at the level of the C4-C7 vertebrae at nominal post-injection times of 2, 4, 6, 8, 10, 22 and, in a few cases, 30 and 48 hrs. The scan images were segmented into subarachnoid space (SAS), spinal cord (SC) and syrinx regions. The gray-scale values within each region were spatially averaged and recorded in Hounsfield units. Three scanners were used and each was individually calibrated to permit conversion from Hounsfield units to iopamidol concentrations. The half-life of iopamidol in the SAS was shorter after surgery as expected for enhanced CSF flow. The time profiles of iopamidol concentration in the SAS and syrinx were fit to simulations from an empirical two-compartment pharmacokinetic model to quantitatively characterize the kinetics of iopamidol exchange between these two regions. There were no statistically significant differences either between the rate constants for iopamidol influx to and efflux from the syrinx or between the preoperative and postoperative mean rate constants. A mechanistic mathematical model was developed to describe the exchange based on the assumption that it occurs as a result of iopamidol diffusion through the extracellular space of the intervening spinal cord tissue. The measured SAS, spinal cord and syrinx concentration profiles were compared to profiles predicted from this mathematical model to assess whether the observations could be explained without invoking other mechanisms for exchange besides extracellular diffusion. The comparison suggested that diffusion could be the predominant mechanism, provided that the intervening spinal cord is edematous with an extracellular volume fraction that is enlarged to the order of 0.4 from a value in normal tissue of about 0.2. The result suggests that a less diffusive marker would be needed for assessing whether CSF convection through the extracellular space is appreciable.

脊髓空洞症是指一个充满液体的囊肿，称为空洞，形成于脊髓。受影响的患者患有进行性瘫痪。脊髓空洞症最常与基亚里I畸形相关，其中小脑扁桃体异位突出通过枕骨大孔进入椎管。从椎管流出的蛛网膜下腔脑脊液（CSF）被收缩，使得在心脏收缩期间，在部分封闭的脊髓蛛网膜下腔中产生升高的压力波，并压缩地传输到脊髓。关于脊髓空洞症发生和进展的未知机制的一个假设是，在心脏源性压力循环期间，由于CSF通过脊髓细胞外间隙的运动不平衡，囊液积聚。这一假设可以通过追踪CSF运动的标记来检验。将计算机断层扫描（CT）造影剂碘帕醇作为替代标记物进行试验。对15例基亚里I型患者在基亚里畸形矫正手术前后进行了连续CT碘帕醇脊髓造影。手术包括颅颈减压和硬膜成形术，以改善枕骨大孔处的CSF流量。对于脊髓造影术，通过腰椎穿刺将碘帕醇注射到CSF中，并在标称注射后时间（2、4、6、8、10、22小时，以及在少数情况下，30和48小时）在C4-C7椎骨水平进行CT扫描。将扫描图像分割为蛛网膜下腔（SAS）、脊髓（SC）和空洞区。将每个区域内的灰度值进行空间平均并以Hounsfield单位记录。使用了三台扫描仪，每台扫描仪均单独校准，以允许从Hounsfield单位转换为碘帕醇浓度。手术后SAS中碘帕醇的半衰期较短，与增强CSF流量的预期一致。将SAS和空洞中碘帕醇浓度的时间曲线拟合至经验二室药代动力学模型的模拟，以定量表征这两个区域之间碘帕醇交换的动力学。碘帕醇流入和流出空洞的速率常数之间或术前和术后平均速率常数之间均无统计学显著差异。建立了一个机械数学模型来描述这种交换，该模型基于碘帕醇通过介入脊髓组织的细胞外间隙扩散的假设。将测量的SAS、脊髓和脊髓空洞浓度曲线与从该数学模型预测的曲线进行比较，以评估观察结果是否可以在不调用除细胞外扩散之外的其他交换机制的情况下得到解释。比较表明，扩散可能是主要的机制，只要介入脊髓水肿，细胞外体积分数从正常组织中的约0.2的值扩大到约0.4。结果表明，需要一种扩散性较低的标记物来评估CSF通过细胞外间隙的对流是否明显。