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Toward a High-Resolution Neuroimaging Biomarker for Mild Traumatic Brain Injury: From Bench to Bedside.

Jaiswal MK - Front Neurol (2015)

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience and Regenerative Medicine , Bethesda, MD , USA ; Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.

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To fully gauge the efficacy of emerging therapeutic drug candidates for the treatment of mTBI, reliable biomarkers have to be identified for early detection of brain injury and subsequent prediction of the outcome... Such a multicenter, collaborative approach for the study of neuroimaging biomarkers for mTBI has the prospect to generate data sets large enough to judge the feasibility of MRI as an outcome measure for different treatment strategies... Optimize matching of patients to available therapies for personalized mTBI treatments... Develop effective mTBI patients outcome measures for drug treatments... In a study examining 30 war veterans with a history of mTBI, with a subgroup of 13 showing impaired neuropsychological performance, evaluated as executive function (EF) measure, DTI detected WM differences that correlated with reduced EF performance... Damage to tracts of WM causes freer movement of water molecules in these areas, resulting in a decrease in the fractional anisotropy value which can function as a measure for the extent of injury... Application of resting-state functional MRI (rs-fMRI) to patients with mTBI suggests that reduced inter-hemispheric hemorrhage and functional connectivity between motor and sensory cortices is a feature of early symptoms and might be used as a biomarker for detection of mTBI disease... Use of rs-fMRI for mTBI patients suggests that reduced inter-hemispheric hemorrhage and decreases in functional connectivity between motor and sensory cortices are a characteristic features of mTBI and can be used as an early biomarker for diagnosis... While specifics like severity or progression are important for future treatments, in my view, an accurate diagnosis of mTBI is the first most important criteria... By obtaining pre-injury exposure studies, and by more accurately identifying pre-mortem and studying disease progression, we can establish further insight into the effects of mTBI and improved therapeutic approaches for cure... A recent study demonstrated in their prospective cohort of those who sustain mTBI, a prior concussion distinctly and significantly prolonged symptoms and put forward the concept of “recovered” mTBI even in the presence of a lesion... This is a serious issue for clinicians and researchers to contemplate before they would conclude that “no injury” had occurred based on neuropsychological and behavioral findings alone, and that there were “no untoward” effects of mTBI... Nevertheless, neuroimaging provides biomarkers of underlying structural and physiological abnormalities in TBI, concussion, and blast-related injury, and these pathological changes occur in regions and within neural systems that plausibly give rise to the common types of neurobehavioral and neurocognitive sequelae associated with mTBI that need to be incorporated into neuropsychological outcome studies... The use of various MRI techniques in clinical settings and connecting structure and function by combining rsfMRI with DTI and VBM might advance sensitivity and specificity to diagnose mTBI and concussed patients as demonstrated earlier where mTBI patients in which the combination of cortical, GM/WM, and hippocampal DTI, VBM, fMRI, and MRS resulted in 75% for all four indices and 90% for first two indices... The use of neuroimaging based biomarkers for mTBI has a broad range of potential use that includes whole brain system biology, brain area specific, and connectomics study, which might lead to the discovery of multiple therapeutics and efficient clinical trials with the hope of translating findings into a better future for patients.

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Comparison of spatial and temporal resolution and penetration depth of different neuroimaging techniques used in clinical and laboratory setting to investigate mild TBI, moderate/severe TBI, and blast injury. Illustration of functional neuroimaging and neurophysiological techniques showing comparison of spatiotemporal resolution and penetration depth of neurometabolic optical techniques. The x-axis (time in seconds to day or size of object/animal/patients) and the y-axis (distance in millimeters) are scaled logarithmically. Penetration depths are color-coded from non-invasive to invasive, ranging from blue to red color [modified from Ref. (4–8)].
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Figure 1: Comparison of spatial and temporal resolution and penetration depth of different neuroimaging techniques used in clinical and laboratory setting to investigate mild TBI, moderate/severe TBI, and blast injury. Illustration of functional neuroimaging and neurophysiological techniques showing comparison of spatiotemporal resolution and penetration depth of neurometabolic optical techniques. The x-axis (time in seconds to day or size of object/animal/patients) and the y-axis (distance in millimeters) are scaled logarithmically. Penetration depths are color-coded from non-invasive to invasive, ranging from blue to red color [modified from Ref. (4–8)].

Mentions: Mild traumatic brain injury (mTBI) continues to be a major public health issue among our active military, veterans, and society at large. The Centers for Disease Control and Prevention (CDC) estimates that ~1.5 million people annually survive a TBI and ~230,000 require in-patient treatment. To fully gauge the efficacy of emerging therapeutic drug candidates for the treatment of mTBI, reliable biomarkers have to be identified for early detection of brain injury and subsequent prediction of the outcome. Guidelines about the use of high-resolution neuroimaging techniques in the treatment and management of mTBI recognized the substantial contribution of magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), and 2-photon imaging for their sensitivity in visualizing white matter (WM) tracts and sensorimotor circuits (1–3). MRI imaging, with its increased sensitivity to visualize WM tracts and sensorimotor circuits, the cerebellum, and extra-motor pathology and pathways, thus, is a favored approach in the search for biomarkers. The power of cutting edge imaging methodologies, in combination with collaboration and data sharing among numerous centers, is recognized in neurodegenerative research. Such a multicenter, collaborative approach for the study of neuroimaging biomarkers for mTBI has the prospect to generate data sets large enough to judge the feasibility of MRI as an outcome measure for different treatment strategies. A comparison of spatiotemporal resolution and penetration depth of various neuroimaging methods compared to MRI is shown in Figure 1.


Toward a High-Resolution Neuroimaging Biomarker for Mild Traumatic Brain Injury: From Bench to Bedside.

Jaiswal MK - Front Neurol (2015)

Comparison of spatial and temporal resolution and penetration depth of different neuroimaging techniques used in clinical and laboratory setting to investigate mild TBI, moderate/severe TBI, and blast injury. Illustration of functional neuroimaging and neurophysiological techniques showing comparison of spatiotemporal resolution and penetration depth of neurometabolic optical techniques. The x-axis (time in seconds to day or size of object/animal/patients) and the y-axis (distance in millimeters) are scaled logarithmically. Penetration depths are color-coded from non-invasive to invasive, ranging from blue to red color [modified from Ref. (4–8)].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492079&req=5

Figure 1: Comparison of spatial and temporal resolution and penetration depth of different neuroimaging techniques used in clinical and laboratory setting to investigate mild TBI, moderate/severe TBI, and blast injury. Illustration of functional neuroimaging and neurophysiological techniques showing comparison of spatiotemporal resolution and penetration depth of neurometabolic optical techniques. The x-axis (time in seconds to day or size of object/animal/patients) and the y-axis (distance in millimeters) are scaled logarithmically. Penetration depths are color-coded from non-invasive to invasive, ranging from blue to red color [modified from Ref. (4–8)].
Mentions: Mild traumatic brain injury (mTBI) continues to be a major public health issue among our active military, veterans, and society at large. The Centers for Disease Control and Prevention (CDC) estimates that ~1.5 million people annually survive a TBI and ~230,000 require in-patient treatment. To fully gauge the efficacy of emerging therapeutic drug candidates for the treatment of mTBI, reliable biomarkers have to be identified for early detection of brain injury and subsequent prediction of the outcome. Guidelines about the use of high-resolution neuroimaging techniques in the treatment and management of mTBI recognized the substantial contribution of magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), and 2-photon imaging for their sensitivity in visualizing white matter (WM) tracts and sensorimotor circuits (1–3). MRI imaging, with its increased sensitivity to visualize WM tracts and sensorimotor circuits, the cerebellum, and extra-motor pathology and pathways, thus, is a favored approach in the search for biomarkers. The power of cutting edge imaging methodologies, in combination with collaboration and data sharing among numerous centers, is recognized in neurodegenerative research. Such a multicenter, collaborative approach for the study of neuroimaging biomarkers for mTBI has the prospect to generate data sets large enough to judge the feasibility of MRI as an outcome measure for different treatment strategies. A comparison of spatiotemporal resolution and penetration depth of various neuroimaging methods compared to MRI is shown in Figure 1.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience and Regenerative Medicine , Bethesda, MD , USA ; Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

To fully gauge the efficacy of emerging therapeutic drug candidates for the treatment of mTBI, reliable biomarkers have to be identified for early detection of brain injury and subsequent prediction of the outcome... Such a multicenter, collaborative approach for the study of neuroimaging biomarkers for mTBI has the prospect to generate data sets large enough to judge the feasibility of MRI as an outcome measure for different treatment strategies... Optimize matching of patients to available therapies for personalized mTBI treatments... Develop effective mTBI patients outcome measures for drug treatments... In a study examining 30 war veterans with a history of mTBI, with a subgroup of 13 showing impaired neuropsychological performance, evaluated as executive function (EF) measure, DTI detected WM differences that correlated with reduced EF performance... Damage to tracts of WM causes freer movement of water molecules in these areas, resulting in a decrease in the fractional anisotropy value which can function as a measure for the extent of injury... Application of resting-state functional MRI (rs-fMRI) to patients with mTBI suggests that reduced inter-hemispheric hemorrhage and functional connectivity between motor and sensory cortices is a feature of early symptoms and might be used as a biomarker for detection of mTBI disease... Use of rs-fMRI for mTBI patients suggests that reduced inter-hemispheric hemorrhage and decreases in functional connectivity between motor and sensory cortices are a characteristic features of mTBI and can be used as an early biomarker for diagnosis... While specifics like severity or progression are important for future treatments, in my view, an accurate diagnosis of mTBI is the first most important criteria... By obtaining pre-injury exposure studies, and by more accurately identifying pre-mortem and studying disease progression, we can establish further insight into the effects of mTBI and improved therapeutic approaches for cure... A recent study demonstrated in their prospective cohort of those who sustain mTBI, a prior concussion distinctly and significantly prolonged symptoms and put forward the concept of “recovered” mTBI even in the presence of a lesion... This is a serious issue for clinicians and researchers to contemplate before they would conclude that “no injury” had occurred based on neuropsychological and behavioral findings alone, and that there were “no untoward” effects of mTBI... Nevertheless, neuroimaging provides biomarkers of underlying structural and physiological abnormalities in TBI, concussion, and blast-related injury, and these pathological changes occur in regions and within neural systems that plausibly give rise to the common types of neurobehavioral and neurocognitive sequelae associated with mTBI that need to be incorporated into neuropsychological outcome studies... The use of various MRI techniques in clinical settings and connecting structure and function by combining rsfMRI with DTI and VBM might advance sensitivity and specificity to diagnose mTBI and concussed patients as demonstrated earlier where mTBI patients in which the combination of cortical, GM/WM, and hippocampal DTI, VBM, fMRI, and MRS resulted in 75% for all four indices and 90% for first two indices... The use of neuroimaging based biomarkers for mTBI has a broad range of potential use that includes whole brain system biology, brain area specific, and connectomics study, which might lead to the discovery of multiple therapeutics and efficient clinical trials with the hope of translating findings into a better future for patients.

No MeSH data available.


Related in: MedlinePlus