Innovative Non-Invasive Imaging of Traumatic Brain Injury

创伤性脑损伤的创新非侵入性成像

• 批准号: 10527640
• 负责人: Carlos M Rinaldi-Ramos
• 金额: $ 40.07万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527640
• 关键词: Acute; Affect; Aging; Anatomy; Animal Model; Attenuated; Axon; Biodistribution; Biological Markers; Biomechanics; Blood - brain barrier anatomy; Blood Circulation; Blood Circulation Time; Blood Vessels; Brain; Brain Edema; Brain Injuries; Cellular Membrane; Cerebrovascular Circulation; Cerebrovascular system; Cessation of life; Chronic; Clinical; Computers and Advanced Instrumentation; Contusions; Detection; Diagnosis; Diffuse; Diffusion Magnetic Resonance Imaging; Dose; Emergency Situation; Ferritin; Florida; Functional disorder; Half-Life; Hemoglobin; Hemorrhage; Histologic; Hospitalization; Human; Image; Imaging Device; Imaging technology; Individual; Injury; Ionizing radiation; Iron; Ischemia; Life; Link; Liquid substance; Magnetic Resonance Imaging; Magnetism; Measures; Methods; Microscopic; Monitor; Morbidity - disease rate; Noise; Operative Surgical Procedures; Oxygen; Pathology; Patients; Penetration; Performance; Persons; Physiological; Pre-Clinical Model; Principal Investigator; Prognosis; Property; Quantitative Evaluations; Recording of previous events; Recovery; Reporting; Research; Research Personnel; Resolution; Rodent Model; Secondary to; Severities; Signal Transduction; Site; Skull Fractures; Survivors; Swelling; T2 weighted imaging; Testing; Time; Tissues; Tracer; Traumatic Brain Injury; Universities; Work; X-Ray Computed Tomography; biomaterial compatibility; blood-brain barrier disruption; clinical imaging; cohort; controlled cortical impact; density; disability; imager; imaging capabilities; imaging detection; imaging modality; improved; in vivo; innovation; instrumentation; iron oxide; magnetic field; mechanical force; mild traumatic brain injury; molecular imaging; mouse model; nanoparticle; neurophysiology; non-invasive imaging; optical imaging; particle; pre-clinical; quantitative imaging; routine imaging; spectroscopic imaging; superparamagnetism; tool; white matter; white matter damage

Project Summary Traumatic brain injury (TBI) occurs due to the transient application of mechanical force to the brain, which causes damage to cellular membranes, axons, and brain vasculature. TBI affects millions of people in the US each year, resulting in hundreds of thousands of hospitalizations, thousands of deaths, and significant disability in survivors. In addition to acute injury, TBI leads to progressive pathophysiology, including focal bleeding and transient opening of the blood brain barrier (BBB). Accurate and fast diagnosis of severity of TBI is necessary to better prescribe treatments and reduce associated death, morbidity, and disability. However, diagnosis of TBI often relies on patient history, subjective complaints, and neurophysiological status, and classifying severity remains challenging. Computed tomography and magnetic resonance imaging are fast and accurate for injuries requiring emergency surgery but are limited to chronic issues such as excessive brain bleeding and swelling. Magnetic resonance imaging (MRI) can evaluate white matter micropathology of TBI in cohorts but fail to evaluate TBI in individuals. Therefore, innovative non-invasive imaging technologies are necessary to improve TBI diagnosis and accelerate research at the clinical and pre-clinical stage. This proposal will apply an innovative imaging modality called magnetic particle imaging (MPI) to monitor vascular pathophysiology of TBI. MPI enables non-invasive, unambiguous, and quantitative imaging of the biodistribution of biocompatible superparamagnetic iron oxide (SPION) tracers. Application of MPI to monitor TBI consists of systemic administration of SPIONs that accumulate at sites of local BBB disruption, resulting in a signal that is proportional to SPION MPI performance, rate of accumulation, and accumulation time. The PI developed a new synthesis method resulting in SPIONs with enhanced MPI performance and preliminary results demonstrate these SPIONs are superior to commercially available nanoparticles and possess long blood circulation half-life. The PI hypothesizes that MPI using SPIONs optimized for sensitivity and blood circulation time will be a powerful non-invasive complementary imaging tool to study TBI in pre-clinical rodent models. This hypothesis will be tested through two specific aims. Studies in Aim 1 will determine SPION accumulation in a controlled cortical impact (CCI) injury mouse model of TBI as a function of dose and time of administration and will establish histological factors linked to MPI measures of SPION accumulation. Studies in Aim 2 will compare MPI measures of SPION accumulation in the CCI injury mouse model against MRI measures of SPION accumulation and other changes associated with TBI. Together, the proposed studies will test the potential of MPI for non-invasive, sensitive, and quantitative evaluation of TBI in pre-clinical models by comparison to ground truth and established non-invasive imaging modalities. The proposed work is supported by a diverse team of investigators with complementary expertise and access to state-of-the-art MPI and MRI instrumentation.

项目摘要 创伤性脑损伤（TBI）是由于机械力在大脑中的短暂应用而发生的， 会损害细胞膜，轴突和脑脉管系统。 TBI影响美国数百万的人 每年，导致成千上万的住院，数千人死亡和严重的残疾 在幸存者中。除急性损伤外，TBI还导致进行性病理生理学，包括局灶性出血和 血脑屏障（BBB）的短暂开放。必须准确，快速诊断TBI的严重程度 更好地开处方治疗，并减少相关的死亡，发病率和残疾。但是，诊断为TBI 通常依靠患者病史，主观投诉和神经生理状况以及对严重程度的分类 仍然具有挑战性。计算机断层扫描和磁共振成像对于伤害快速准确 需要紧急手术，但仅限于慢性问题，例如脑出血过多和肿胀。 磁共振成像（MRI）可以评估同类中TBI的白质微病理学，但无法评估 评估个体的TBI。因此，创新的非侵入性成像技术对于 在临床和临床前阶段改善TBI诊断并加速研究。 该建议将应用一种创新的成像方式，称为磁性粒子成像（MPI）来监视 TBI的血管病理生理。 MPI实现了无创，明确和定量成像的非侵入性成像 生物相容性超磁铁氧化铁（SPION）示踪剂的生物分布。 MPI的应用监视 TBI包括在本地BBB破坏部位积累的系统给药，导致 一个与SPION MPI性能，积累速率和积累时间成正比的信号。 pi 开发了一种新的合成方法，导致SPION具有增强的MPI性能和初步结果 证明这些Spions优于市售的纳米颗粒，并拥有长血 循环半衰期。 PI假设使用SPI优化的MPI用于敏感性和血液循环 时间将是一个强大的非侵入性互补成像工具，用于研究临床前啮齿动物模型中的TBI。这 假设将通过两个具体目标进行检验。 AIM 1中的研究将确定在A中的积累 TBI的受控皮质冲击（CCI）损伤小鼠模型是剂量和给药时间的函数 将建立与MPI积累量度有关的组织学因素。 AIM 2的研究将比较 MPI在CCI损伤小鼠模型中针对SPION的MRI测量的MPI测量 与TBI相关的积累和其他变化。拟议的研究将共同​​测试 与地面相比 真理并确定了非侵入性成像方式。拟议的工作得到了一个多元化团队的支持 具有互补专业知识并获得最先进的MPI和MRI仪器的调查人员。