Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig

McGowan, Joseph C.; McCormack, Timothy M.; Grossman, Robert I.; Mendonça, Renato Adam; Chen, Xiao‐Han; Berlin, Jesse A.; Meaney, David F.; Xu, Bainan; Cecil, Kim M.; McIntosh, Tracy K.; Smith, Douglas H.

doi:10.1002/(sici)1522-2594(199904)41:4<727::aid-mrm11>3.0.co;2-6

Cited by 49 publications

(31 citation statements)

References 19 publications

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“…So, in WM lesions in which demyelination or axonal loss is present, the MTR values decrease, even before conventional MR imaging sequences reveal visible signal-intensity change in the damaged areas. [13][14][15] Reduction of MTR values measured in WM after TBI was already demonstrated 13,16 and also at the CC in victims of mild TBI. 17 We also BFR and BCR, T2-relaxation time, ADC, MTR and NAA/Cr ratio mean value differences between the test and control groups, measured at the NAWM and CC Note:-MRI indicates MR imaging; BFR, bifrontal ventricle-to-brain ratio; BCR, bicaudate ventricle-to-brain ratio; ADC, apparent diffusion coefficient; MTR, magnetization transfer ratio; NAA/Cr, N-acetylaspartate/creatine; NAWM, normal-appearing white matter; CC, corpus callosum.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Delayed Neuronal and Axonal Damage Secondary to Moderate and Severe Traumatic Brain Injury Using Quantitative MR Imaging Techniques

Mamere¹,

Saraiva²,

Matos³

et al. 2009

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a classic model of monophasic neuronal and axonal injury, in which tissue damage mainly occurs at the moment of trauma. There is some evidence of delayed progression of the neuronal and axonal loss. Our purpose was to test the hypothesis that quantitative MR imaging techniques can estimate the biologic changes secondary to delayed neuronal and axonal loss after TBI.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Delayed Neuronal and Axonal Damage Secondary to Moderate and Severe Traumatic Brain Injury Using Quantitative MR Imaging Techniques

Mamere¹,

Saraiva²,

Matos³

et al. 2009

AJNR Am J Neuroradiol

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“…The contour-plotting approach displays the MTR values as an overlay on MR images. 5,6 In this way, it is possible to detect gradients and boundaries of abnormal MTR that are too subtle to be detected by conventional reading of the MTR maps.…”

Section: Analysis Of Mt-mr Imagesmentioning

confidence: 94%

Magnetization Transfer Magnetic Resonance Imaging of the Brain, Spinal Cord, and Optic Nerve

Filippi

Rocca

2007

Neurotherapeutics

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Summary:Magnetic resonance imaging is highly sensitive in revealing CNS abnormalities associated with several neurological conditions, but lacks specificity for their pathological substrates. In addition, MRI does not allow evaluation of the presence and extent of damage in regions that appear normal on conventional MRI sequences and that postmortem studies have shown to be affected by pathology. Quantitative MR-based techniques with increased pathological specificity to the heterogeneous substrates of CNS pathology have the potential to overcome such limitations. Among these techniques, one of the most extensively used for the assessment of CNS disorders is magnetization transfer MRI (MT-MRI). The application of this technique for the assessment of damage in macroscopic lesions, in normal-appearing white and gray matter, and in the spinal cord and optic nerve of patients with several neurological conditions is providing important in vivo information-dramatically improving our understanding of the factors associated with the appearance of clinical symptoms and the accumulation of irreversible disability. MT-MRI also has the potential to contribute to the diagnostic evaluation of several neurological conditions and to improve our ability to monitor treatment efficacy in experimental trials.

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“…For example, DTI and other advanced neuroimaging techniques can elucidate signal changes in the white matter that have been shown to correlate with axonal pathology in animal models. [106][107][108][109][110] In humans with mild TBI, DTI has also shown changes in the white matter, including both increases and decreases in fractional anisotropy and other DTI-related metrics that evolve over time. [111][112][113][114][115][116][117] In some cases, these imaging changes have been linked to varying degrees of morbidity, suggesting a causal relationship.…”

Section: Advanced Neuroimagingmentioning

confidence: 96%

Therapy Development for Diffuse Axonal Injury

Smith

Hicks

Povlishock

2013

Journal of Neurotrauma

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174

146

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Diffuse axonal injury (DAI) remains a prominent feature of human traumatic brain injury (TBI) and a major player in its subsequent morbidity. The importance of this widespread axonal damage has been confirmed by multiple approaches including routine postmortem neuropathology as well as advanced imaging, which is now capable of detecting the signatures of traumatically induced axonal injury across a spectrum of traumatically brain-injured persons. Despite the increased interest in DAI and its overall implications for brain-injured patients, many questions remain about this component of TBI and its potential therapeutic targeting. To address these deficiencies and to identify future directions needed to fill critical gaps in our understanding of this component of TBI, the National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled.

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Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig

Cited by 49 publications

References 19 publications

Evaluation of Delayed Neuronal and Axonal Damage Secondary to Moderate and Severe Traumatic Brain Injury Using Quantitative MR Imaging Techniques

Evaluation of Delayed Neuronal and Axonal Damage Secondary to Moderate and Severe Traumatic Brain Injury Using Quantitative MR Imaging Techniques

Magnetization Transfer Magnetic Resonance Imaging of the Brain, Spinal Cord, and Optic Nerve

Therapy Development for Diffuse Axonal Injury

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