Assessing Brain Tissue Viability after TBI: A Susceptibility Mapping Approach

 描述（由申请人提供）：创伤性脑损伤（TBI）是美国死亡和残疾的主要原因。原发性脑损伤后，脑缺血/缺氧是主要的破坏性并发症。早期发现脑组织缺血缺氧风险是预防继发性损伤的关键。核医学还表明，脑代谢异常，测量为脑氧代谢率（CMRO 2），与TBI患者的慢性萎缩和预后不良有关。然而，脑血流动力学是区域特异性的;颅内和脑灌注压正常的患者仍然可能存在局部缺氧。到目前为止，还没有非侵入性工具来评估重症监护中局部脑组织的不可逆缺血/缺氧损伤。 为了描绘大脑血液动力学的完整图像，需要测量动脉灌注和静脉氧合以计算局部脑血流量（CBF）（用于缺血的测量）、脑组织氧合（用于缺氧的测量）和CMRO 2。最近，我们的小组已经开发了一系列的灌注加权成像（PWI）技术，以确定动脉输入功能，并进一步量化绝对CBF比以前更准确。我们进一步开发了一种定量磁敏感成像技术，称为磁敏感加权成像和映射（SWIM），以估计主要静脉中的血氧作为引流组织氧合的标记。与基于导管的临床氧合监测器不同，其是侵入性的并且仅限于一个区域，SWIM使用大脑的主要静脉，如嵌入式导管来检测引流组织氧合。更重要的是，它是非侵入性的，内在的，并且在整个大脑中丰富。局部缺氧的风险将使其引流静脉在SWIM图上具有增强的敏感性，指示低氧合。利用动脉CBF和静脉氧合之间的关系，我们可以确定CMRO 2，这是脑组织活力的关键指标。 使用SWIM和PWI，我们建议评估脑组织活力和其预后价值在一个队列中的30名中度至重度TBI患者与30名人口统计学匹配的对照组相比。我们将首先使用血气分析仪来验证和校准所有对照中手臂静脉中血氧的SWIM估计。然后，我们将确定TBI患者急性期的局部CBF，静脉氧合和整个大脑的CMRO 2水平。我们将进一步确定急性期局部血流动力学对脑萎缩介导的TBI患者损伤后6个月神经和神经心理学结局的预测价值。该项目的成果将是一套用于评估TBI后脑组织活力的非侵入性成像技术。脑血流动力学的阐明将使医生能够识别有风险的脑组织， 局部缺血/缺氧进行适当治疗。该项目首次将SWIM用于TBI和脑血流动力学的无创评估。

 DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. After primary injury, cerebral ischemia/hypoxia are major devastating complications. Early detection of brain tissue at risk for cerebral ischemia and hypoxia is the key to preventing secondary injury. Nuclear medicine also suggests that abnormal brain metabolism, measured as cerebral metabolic rate of oxygen (CMRO2), is associated with TBI patients' chronic atrophy and poor outcome. However, cerebral hemodynamics is region-specific; patients with normal intracranial and cerebral perfusion pressures can still have regional hypoxia. To date, there are no non- invasive tools to assess regional brain tissue for irreversible ischemic/hypoxia damage in critical care. In order to painta complete picture of the brain's hemodynamics, one needs to measure both arterial perfusion and venous oxygenation to calculate local cerebral blood flow (CBF), a measure for ischemia; brain tissue oxygenation, a measure for hypoxia; and CMRO2,. Recently, our group has developed an array of perfusion-weighted imaging (PWI) techniques to determine the arterial input function and further quantify absolute CBF more accurately than before. We further developed a quantitative susceptibility mapping technique, known as susceptibility weighted imaging and mapping (SWIM), to estimate blood oxygenation in major veins as a marker of draining tissue oxygenation. Unlike clinical catheter-based oxygenation monitor, which is invasive and restricted to one region, SWIM uses the major veins of the brain like embedded catheters to detect draining tissue oxygenation. More importantly, it is non-invasive, intrinsic, and abundant throughout the brain. A risk of regional hypoxia will render its draining veins with enhanced susceptibility on the SWIM map, indicative of low oxygenation. Using the relationship between arterial CBF and venous oxygenation, we can determine CMRO2, a key measure of brain tissue viability. Using both SWIM and PWI, we propose assessing brain tissue viability and its prognostic value in a cohort of 30 moderate to severe TBI patients in comparison with 30 demographically matched controls. We will first use a blood gas analyzer to validate and calibrate the SWIM estimation of blood oxygenation in an arm vein in all controls. Then, we will determine regional CBF, venous oxygenation, and CMRO2 levels throughout the brain at the acute stage in TBI patients. We will further determine the predictive value of regional hemodynamics at the acute stage for TBI patients' neurological and neuropsychological outcome at 6 months after injury, mediated by brain atrophy. The deliverable of this project will be a set of non-invasive imaging techniques for assessing brain tissue viability after TBI. The elucidation of cerebral hemodynamics will allow physicians to identify the brain tissue at risk for regional ischemia/hypoxia for proper treatment. This project is novel for its first time use of SWIM in TBI and non-invasive assessment of brain hemodynamics.