PI David O. Okonkwo, MD, PhD
Co-PI Walter Schneider, PhD
Title High Definition Fiber Tracking Biological Diagnosis of TBI Providing Actionable Clinical Report of Quantified Damage
Summary: Background: There is an urgent, yet unmet demand for a definitive biological diagnosis of traumatic brain injury (TBI) that applies non-invasive methods to pinpoint the location and extent of damage. This project develops and utilizes cutting-edge High Definition Fiber Tracking (HDFT), a technology to quantify TBI induced axonal injury in military and civilian brain injury patients. Current medical imaging (i.e., CT, MRI, DTI, fMRI) rarely visualizes or detects the white matter damage presumed to underlie much of the functional, cognitive, and/or psychological deficits seen following military blast TBI or civilian mild TBI. The goal of the current application is to deliver HDFT, a MRI-based diffusion technology that can provide a definitive biological diagnosis of TBI to aid prognosis and rehabilitation of individual patients.
High Definition Fiber Tracking is a DARPA-supported technology, invented by this group in the last two years, which has been used in the pilot clinical assessment of 53 cases of TBI at the University of Pittsburgh. HDFT overcomes the central challenges that limit the clinical applicability of currently available imaging methods for TBI diagnosis. Preliminary studies have validated the ability of this cutting-edge HDFT to detect white matter damage in the human brain following injury. HDFT quantifies TBI-induced axonal injury in individual patients, without the need for a reference pre-injury scan.
Objectives: This proposal has four objectives that will be completed through the recruitment of 240 acute TBI cases and 60 healthy volunteers. An intake examination and clinical assessment followed by 3T structural MRI and HDFT imaging will be performed on all subjects.
Objective #1: For subjects with HDFT quantitatively similar to healthy controls, determine whether HDFT of 19 major tracts within normal range will be associated with a normal neurologic examination, normal neuropsychological testing, and absence of post-concussion syndrome at 3 and 6 months post-injury.
Objective #2: For TBI subjects with abnormal HDFT, contrast differences in quantitative analysis of HDFT among blast-induced combat TBI, non-blast combat TBI, and civilian TBI. This aim will also determine whether HDFT has sufficient resolution and accuracy to detect white matter damage that DTI has not been able to document.
Objective #3: For subjects with neurologic deficits or post-concussion syndrome, determine whether quantitative analysis of HDFT in the acute phase of 19 major white matter tracts implicated in TBI can document and predict neurologic and neuropsychological deficits at 3 and 6 months post-injury. Statistical analysis of correlation between HDFT assessment and quality of life/neuropsychological outcomes will be performed. This will confirm that neuroimaging of white matter pathways in the acute phase has clinical relevance. The deliverable is an actionable clinical report of quantified damage that will empower treatment teams to employ this technology in the acute phase, aiding in the diagnosis and treatment of TBI patients.
Objective #4: For subjects with edema/hemorrhage on structural imaging in the acute phase, perform a repeat structural MRI and HDFT at 6 months to confirm that HDFT is resilient to the effects of edema/hemorrhage on the analysis. These will be compared against the susceptibility of standard DTI fractional anisotropy-based measurements to edema/hemorrhage.
Study Design: This project is a multi-site clinical trial to assert the clinical utility of a novel, advanced MR imaging technology (High Definition Fiber Tracking) for the clinical detection of white matter injury following TBI. Subjects with an acute history of military or civilian TBI will be recruited at Walter Reed (WRNMMC), Washington Hospital Center, and the University of Pittsburgh Medical Center to undergo HDFT and formal neuropsychological outcomes testing.
Relevance: This technology has been piloted in 53 TBI patients and has been well received in fifteen publications, by clinical treatment teams, and the scientific media. The project team includes leaders in fiber tracking imaging and military and civilian TBI clinical care and research. Military Benefit – with the availability of a definitive biological diagnosis in individual patients using HDFT, many of the thousands of warriors and 1.7 million U.S. civilians who sustain a TBI each year would gain assurance if HDFT confirms that their brain white matter tracts are normal. For those in whom damage is found, the family and the clinical professionals will “see the damage” and be provided with detailed prognoses based on damage to specific tracts, thus facilitating improved diagnosis, prognosis, and treatment of TBI-related damage.
Source: Department of the Army — USMRAA
Term 09/30/12 – 09/29/16