Abstract
Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States and is a contributing factor to one third of all injury related deaths annually. According to the CDC, approximately 75% of all reported TBIs are concussions or considered mild in form, although the number of unreported mild TBIs (mTBI) and patients not seeking medical attention is unknown. Currently, classification of mTBI or concussion is a clinical assessment since diagnostic imaging is typically inconclusive due to subtle, obscure, or absent changes in anatomical or physiological parameters measured using standard magnetic resonance (MR) or computed tomography (CT) imaging protocols. Molecular imaging techniques that examine functional processes within the brain, such as measurement of glucose uptake and metabolism using [18F]fluorodeoxyglucose and positron emission tomography (FDG-PET), have the ability to detect changes after mTBI. Recent technological improvements in the resolution of PET systems, the integration of PET with magnetic resonance imaging (MRI), and the availability of normal healthy human databases and commercial image analysis software contribute to the growing use of molecular imaging in basic science research and advances in clinical imaging. This review will discuss the technological considerations and limitations of FDG-PET, including differentiation between glucose uptake and glucose metabolism and the significance of these measurements. In addition, the current state of FDG-PET imaging in assessing mTBI in clinical and preclinical research will be considered. Finally, this review will provide insight into potential critical data elements and recommended standardization to improve the application of FDG-PET to mTBI research and clinical practice.
Highlights
Traumatic brain injury (TBI) is a growing public health concern worldwide and the Centers for Disease Control and Prevention (CDC) indicate about 1.7 million new cases are reported in the United States (US) each year
Injury severity is currently based on several diagnostic criteria including loss of consciousness (LOC), amnesia and altered mental state (Ruff et al, 2009). mild TBI (mTBI) is characterized by the presence of at least one of those criteria, and further restricted to LOC not to exceed 30 min, post-injury antero-or-retrograde amnesia not exceeding 24 h, or altered mental state not exceeding 24 h (Ruff et al, 2009)
Future work should: (1) consider the role of the lumped constant (LC) in evaluating the metabolic rate for glucose consumption (MRGlc), (2) further standardize the TBI imaging protocol to include subject status during FDG uptake and Positron emission tomography (PET) scan, (3) stratify data based on the stage of injury at the time of the PET scan and type of injury or mechanism, and (4) identify a robust image processing and analysis technique (e.g., Statistical Parametric Mapping (SPM)) and a FDG parameter to serve as a reproducible biomarker of injury (SUV, relative uptake value (RUV), MRGlc, MRFDG, etc.)
Summary
Traumatic brain injury (TBI) is a growing public health concern worldwide and the Centers for Disease Control and Prevention (CDC) indicate about 1.7 million new cases are reported in the United States (US) each year. Many of the clinical studies provide sparse information regarding the quantification method utilized to analyze FDG-PET images, which can affect replication efforts Despite these limitations and concerns, patterns of FDG uptake and, in some cases, metabolism can be observed after mTBI and are discussed below. CLINICAL mTBI STUDIES FDG-PET has been used clinically to study TBI in various patient populations with 10 published reports evaluating FDGPET after mTBI, excluding cases of complicated mTBI where damage was observed on the CT or MRI scan after an apparent mild injury These published results demonstrate varying degrees of sensitivity to detection at acute, subacute, and chronic phases of injury. Abu-Judeh et al report normal FDG uptake in a 28-years old female at 2 days
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