Accumulating evidence suggests that cerebral amyloid beta (Abeta) deposition, which begins rapidly following traumatic brain injury (TBI), occurs in response to axonal and oxidative damage. Our long-term goal is to validate the use of positron emission tomography (PET) imaging with a novel molecular probe, [18F]FDDNP, for visualizing Abeta plaques, in vivo, in the setting of acute TBI. We hypothesize that the amount of [18F]FDDNP binding will correlate with both the concentration of diffusible Abeta in the cerebrospinal fluid and patient outcome.
The Specific Aims are to 1) confirm the specificity of [18F]FDDNP for cerebral Abeta deposition [18F]FDDNP uptake following TBI using autoradiography and immunohistochemistry of brain specimens and, 2) determine the relationship between cerebral Abeta plaque deposition, assessed by [18F]FDDNP-PET imaging, and CSF Abeta concentration acutely following TBI. [18F]FDDNP-PET has been used successfully in imaging amyloid pathology in Alzheimer's disease patients, allowing early diagnosis and improved understanding of the disease. We believe that the ability to visualize amyloid deposition in vivo with PET, in a broad range of TBI injury severity, will allow us for the first time to assess the incidence, time course, and regional distribution. More importantly, it may also offer a noninvasive tool to monitor the efficacy of treatments aimed at decreasing amyloid deposition (including neuro-inflammation modulators). In brief, the research design entails studying a range of mild to severely head-injured patients acutely after injury (3-10 days) with FDDNP-PET. The results may have important public health implications in that improved understanding of the pathological consequences of cerebral amyloid deposition may lead to medical treatments that will improve outcome following TBI. ? ? ?
| Wong, Koon-Pong; Bergsneider, Marvin; Glenn, Thomas C et al. (2016) A semi-automated workflow solution for multimodal neuroimaging: application to patients with traumatic brain injury. Brain Inform 3:1-15 |
| Wardak, Mirwais; Wong, Koon-Pong; Shao, Weber et al. (2010) Movement correction method for human brain PET images: application to quantitative analysis of dynamic 18F-FDDNP scans. J Nucl Med 51:210-8 |
| Huang, Sung-Cheng (2008) Role of Kinetic Modeling in Biomedical Imaging. J Med Sci 28:57-63 |
