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Visualising the effects of traumatic brain injury in living brains

Posted on 19th November 2016 at 17:41pm

It is important to consider the long-term effects of mild to severe traumatic brain injury on persons in disaster and combat situations, as they can be life altering, yet diagnosis can be difficult. New imaging techniques might be changing this.

Chronic traumatic encephalopathy (CTE) is common among athletes, soldiers, and civilians with multiple head traumas, and has been associated with a number of neurodegenerative diseases including Alzheimer’s, Parkinson’s and Lou Gehrig’s. The Centers for Disease Control (CDC) reports 1.7 million US civilian brain injuries annually, and the Brain Trauma Foundation estimates that 10 to 20 per cent of Iraqi veterans suffer from some level of traumatic brain injury (TBI).

A study at the US Department of Veterans Affairs found CTE to be related to degeneration of limbic structures such as the hippocampus, a brain region necessary for emotional regulation and spatial navigation. The immediate and long-term neurological effects of TBIs, as well as their impact on a diverse array of people, make diagnosing and tracking CTE in living subjects a priority. A novel positron emission tomography (PET) method may be the key to helping CTE patients.

To date, CTE can only be diagnosed postmortem. Neuropsychological exams and neuropathologies that are currently used to diagnose living subjects present human bias and are not entirely reliable. This limitation has led to the investigation of alternative methods for detecting CTE in vivo through molecular imaging.

Researchers at the University of Cambridge have successfully revealed CTE pathology in vivo via amyloid imaging. Their findings revealed increased ligand binding in areas of the brain affected by TBI just hours after the injury. Sam Gandy, MD and Director of the Center for Cognitive Health and NFL Neurological Care Program at the Icahn School of Medicine wrote: "When fully validated, this new ligand has the potential to be used as a diagnostic biomarker and represents an exciting development in the detection and tracking of CTE."

The imaging system works by using a specific ligand designed to latch onto the tau protein, an abnormal protein that accumulates and kills brain cells as a result of repetitive TBI. The ligand serves as an imaging agent by lighting up under a PET scan, providing an in vivo visualisation of TBI. These scans can be done quickly and read by healthcare professionals in the field to bring better care to patients in the midst of combat or man-made or natural disasters.

The National Institute on Neurological Diseases and Stroke (NINDS) determined that tau proteins in deep cerebral cortical sulci are indicative of CTE.

A recent study at the Icahn School of Medicine found tau deposition in deep cerebral cortical sulci via molecular imaging in subjects with symptoms of TBI. Imaging results from the same study found that a retired NFL player with suspected CTE displayed patterns of tau deposition almost identical to that of a postmortem subject diagnosed with CTE.

A biomarker diagnostic test like this is quite promising, but there are challenges to widespread use. These include perfecting the selectivity of tau tracers, because the tau protein coexists with so many others. Another obstacle is the low availability and high cost of PET scan machines in rural and war torn areas. Radiation from repeated PET scans is a concern among patients. A possible alternative to the classical PET scan machine could be the AMPET portable prototype, which has the ability to measure brain activity on the go and delivers less radiation than traditional scans.

A current clinical trial conducted by the US Army Medical Research and Materiel command at Boston University is investigating an alternative method to PET tau imaging. This study proposes a noninvasive technique that would eliminate the use of PET radiation and spinal taps currently used for tau detection by making MRI viewable tau biomarkers. Dr Robert Stern, Director of Clinical Research for the CTE center at BU, and partnering PI for this clinical trial, proposes the use of MRI technology to determine tau protein deposition. The study includes retired NFL players with clinical CTE symptoms, and retired athletes without clinical symptoms, as well as AD patients. If the new tau ligand proves successful this study expects that NFL players thought to have CTE will show elevated levels of tau protein in their spinal fluid and athletes without CTE will show no elevation.

A current in vivo technique for diagnosing CTE is structural imaging. This method allows for visualization of enlarged ventricles and cortical thinning associated with TBI via MRI. The Foundation for the Advancement of Military Medicine found similar MRI imaging results among military veterans. However, to date, no longitudinal studies have examined these structural changes in relation to repetitive TBI. This structural MRI data, in addition to longitudinal neuropsychological study and tau imaging, may provide the information needed to develop sustainable diagnostic, tracking, and treatment measures for the future.

EEG monitoring could be another alternative to PET imaging entirely. To date, non-invasive, portable EEG monitoring with cognitive testing has proved as a useful diagnostic tool for TBI. Neurovigil, a 2009 startup company, is one of the leaders in portable EEG technology. They developed a wireless EEG monitoring solution, iBrain, which can be used to assist with diagnosis and treatment of a variety of medical conditions, from sleep disorders to TBI. While this method cannot show specific brain location or amount of TBI in different areas of the brain like PET can.

TBIs owing to disaster or explosive events usually go undiagnosed in the presence of visible, life threatening trauma, or they can be misdiagnosed as post-traumatic stress disorder (PTSD) instead of post-concussion disorder (PCS). It is important to consider the long-term effects of mild to severe TBI on persons in disaster and combat situations, as they can be life altering. As an early, in vivo, diagnostic tool, molecular imaging appears promising and could change the future lives of soldiers and civilians who have suffered from TBI.

Anna Roselle, Carly Davis & Ian Portelli

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