Revolutionizing TBI Through Connectograms
Think about the last time you were sick with the flu. You probably went to the doctor. What’s really interesting is that your doctor was looking for biomarkers.
Biomarkers? Well, in medicine, biomarkers are essentially indicators of the severity of different types of diseases, infections, and environmental exposures. There’s a bunch of biomarkers we currently know of and they’re all divided into three types of categories: biomarkers of exposure, effect, and susceptibility.
When you have the flu doctors might look for the gene KLRD1. The gene is a blood-based biomarker expressed by antiviral cells and can predict who’s susceptible to the flu.
Except, we don’t have biomarkers for everything. There’s a lot of conditions and illnesses that we’re still trying to develop biomarkers for. One of the most common being traumatic brain injury, affecting 69 million people worldwide annually.
What is Traumatic Brain Injury?
You’re probably wondering why traumatic brain injury (TBI) so common. TBI results when people experience a sudden jolt to the head causing brain damage. When someone gets violently hit in the head, objects can pierce the skin and enter brain tissue, resulting in lesions (abnormal tissue in the brain causing cell death).
Injuries are dependant on the case of TBI. No two people will experience the same effects of TBI. Injuries usually range from mild concussions to severe permanent damage. These effects are classified based on severity, mechanism (closed or penetrating head injury), and other features (occurring in a specific location or widespread area, etc.).
Brain trauma occurs as a consequence of the sudden acceleration or deceleration within the cranium through a complex combiniation of movement and sudden impact. These processes result in the alteration in cerebral blood flow (blood supply in the brain) and pressure within the skull causing cerebral edema (fluid builds up around the brain causing intracranial pressure).
Most TBI can result in result in physical, cognitive, social, emotional, and behavioural symptoms. However, depending on the injury, treatment may be minimal or may include medications, emergency surgery, or surgery years later.
What’re the Biomarkers for TBI?
Due to the complexity of TBI, biomarker discovery in preclinical models have a lot of limitations. That’s because no animal model can recapitulate the full complexity of TBI. However, models all have distinct characteristics that can aid researchers in the discovery of biomarkers associated with different aspects of TBI.
Researchers are looking into elevated S100B and elevated GFAP, which can be detected in both CSF and peripheral blood as biomarkers for acute astroglial injury, but has not yet been approved. Currently, there are no approved TBI biomarkers for clinical treatment or diagnostic purposes.
Imaging and Diagnosing TBI
Confirming a diagnosis for TBI is complicated. Doctors have to assess the history of the injury, the patients symptoms, the physical examination and additional tests including neuroradiology.
We have a few methods of detecting TBI. In the period immediately after the injury, CT scans are most commonly used to diagnose acute problems that are life threatening and require emergent treatment such as surgery.
CT scans combine a series of X-ray images taken from different angles around the body and use computer processing to create slices of the brain, blood vessels, and tissues. CT scans are effective because they provide more-detailed images than plain X-rays.
CT scans are also fast and widely available. They’re highly effective in detecting bleeding and brain swelling within and surrounding the brain. Even if urgent surgery isn’t required, repeat CT scans are used to the follow the resolution of injuries.
However, CT scans are typically normal within patients with milder TBI including concussions. They’re unable to detect microhemorrhages, contusions, and scarring.
We need to make imaging techniques much more effective for microscopic lesions which aren’t currently being picked up through CT scans.
Diffusion Tensor Imaging for TBI
This can all be done through diffusion tensor imaging. DTI is a variation of standard MRI which creates images of internal organs through magnetic images. The use of specific DTI sequences along with software that generates from resulting data uses the diffusion water molecules to generate contrast in MR images.
DTI’s really effective because it allows the mapping of the diffusion process of water molecules in biological tissues, in-vivo and non-invasiely. Molecular diffusion can show the interactions in macromolecules, fibres, and membranes.
Water molecule diffusion patterns can reveal microscopic details about tissues. Allowing clinicians to see microscopic lesions, bleeding, and scarring in the brain. More extended DTI scans derive neural tract information from the data using 3D algorithms to compute the diffusion tensor.
Combining Connectograms and DTI
Now how can we combine DTI with connectomics? It’s all through connectograms. Connectograms are essentially graphical representations of connectomics through mapping and interpreting all of the white matter fiber connections in the human brain.
The white matter in our brain contains all of the myelinated axons in the brain, while grey mater contains cell bodies. The WM in the brain is essential for connecting various grey areas to each other and conducting nerve impulses through neurons.
The circular graphs based on DTI use graph theory to represent white matter connections and cortical characteristics for single structures, single subjects, and populations. Connectograms are split into the left and right hemisphere broken down into lobes.
Within each lobe, each cortical area is labeled with an assigned colour. Readers can find the corresponding cortical area on the graph and see exactly how disparate the connected regions are. In the outermost layer, the metric rings represent the grey matter volume, surface area, cortical thickness, curvature, and degree of connectivity. Inside the circles, lines connection the regions that seem to be structurally connected.
Studies have been using DTI and MRI techniques along with connectograms between various patients suffering from TBI to search for biomarkers.
The Future of TBI Biomarkers
Rapidly visualizing structural white matter connectivity may allow clinicians to compare changes in the cortical regions and connectivity with metrics of patient case evolution. The approach can also be applied to individual patients as well as be used to visualize brain morphometric connections on various populations of people.
The technique of combing DTI and connectograms for graphical representation of atrophy profiles can be useful for personalized rehabilitation. Information and data collected through imaging can inform clinicians of prospects in recovery, guidance, and the need for long-term care for individuals. Personalized rehabilitation is necessary for those experience TBI since all injuries are very distinct.
Key Takeaways
- Biomarkers are indicators of the severity of different types of diseases, infections, and environmental exposures
- TBI results when people experience a sudden jolt to the head causing brain damage
- Currently, there are no approved TBI biomarkers for clinical treatment or diagnostic purposes
- CT scans are most commonly used to diagnose acute problems that are life threatening and require emergent treatment such as surgery
- DTI is a variation of standard MRI which creates images of internal organs through magnetic images — molecular diffusion can show the interactions in macromolecules, fibres, and membranes
- Connectograms use graph theory to represent white matter connections and cortical characteristics for single structures, single subjects, and populations
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