An imaging technique may enable earlier detection of chronic traumatic encephalopathy (CTE), researchers reported.
In a case-control study, a specific type of PET imaging picked up a pattern of tau deposition in brain areas responsible for mood, fear, stress, and cognition -- one that was distinct from neuropathological patterns seen in Alzheimer's disease, according to , of North Shore University Health System, and colleagues.
Action Points
- Note that this small study suggests that a novel use of PET CT may help to diagnose chronic traumatic encephalopathy.
- Be aware that validation in other groups of individuals at risk of CTE is necessary before this scan can be adopted clinically.
"These promising results provide the basis for a larger trial to determine the scope of this imaging procedure for CTE and for the use of the PET imaging technique to monitor disease progression in follow-up studies," they wrote .
Currently there is no way to diagnose CTE in vivo. The condition is known to be the result of an accumulation predominantly of tau proteins that manifests in a variety of cognitive, behavioral, and motor symptoms. It arises from cumulative brain damage sustained in repeated traumatic brain injury, particularly from concussions sustained in sports.
Research has shown that it appears to have an ordered and predictable progression -- opening the door to the possibility of early treatment if screening modalities could be developed.
CTE has been in the spotlight in recent years as the National Football League settled a lawsuit brought by 4,500 former players for concussion-related injuries. There have also been a number of suicides among high-profile athletes who were found to have CTE on autopsy.
For their study, Bailes and colleagues used the tracer [F-18]FDDNP in PET scanning to detect tau buildup in 14 retired American football players who'd had concussions.
They compared those scans with those from 28 healthy controls and 24 patients with Alzheimer's, a condition that could potentially be misdiagnosed as CTE.
Ultimately, the researchers saw in the retired players neuropathological patterns consistent with models of concussion in which there is early axonal damage to white matter tracts, and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior.
Specifically, they saw greater tau accumulation in the dorsal midbrain and the amygdala, regions involved in pain and negative emotions, they reported.
Bailes and colleagues noted that this deposition pattern is distinct from the progressive pattern of neuropathology in Alzheimer's, which typically begins in the medial temporal lobe and progresses along the cortical default mode network, with minimal involvement of subcortical structures.
The pattern seen in the CTE patients was also consistent with tau distribution seen in autopsies of patients with a history of mild traumatic brain injury and autopsy-confirmed diagnosis of CTE, they added.
Bailes and colleagues concluded that the imaging technique offered a "sensitive method to visualize and quantify the regional presence of neuroaggregates in living brains of patients with mild traumatic brain injury and suspected CTE, and generates useful information about mechanisms of underlying disease staging and mood disorders."
It may also provide a baseline to develop methods to monitor disease progression and measure the effectiveness of experimental treatments, they said.
, of Columbia University Medical Center in New York City, who was not involved in the research, said there's been a "longstanding need for a neuroimaging modality that can capture the extent of brain damage after sports concussion or mild traumatic brain injury."
Shams added that studies have demonstrated that PET scanning, as well as the diffusion tensor imaging (DTI) MRI, hold promise, but the use of imaging modalities in this setting, including the present study, is still in the early stages.
"It is always challenging to make generalization based on a small sample size of this study," Shams said in an email to 麻豆传媒. "In addition, each retired football player selected may have had tremendous variability in total number of concussions and biomechanics of their injury. We need to be cautious before concluding that chronic traumatic encephalopathy has a direct imaging correlate on PET scans."
The authors acknowledged that their results require confirmation in a larger patient population and one that includes people who suffer from brain concussions that are "biomechanically different from those found in American football players (e.g., war veterans, boxers)."
Disclosures
Co-authors are co-inventors of the [F-18]FDDNP PET technology that is covered under UCLA patents and licensed to TauMark. Several of the papers authors have financial interests in TauMark.
Primary Source
Proceedings of the National Academy of Sciences
Barrio JR, et al "In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging" PNAS 2015; DOI: 10.1073/pnas.1409952112.