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September 2009 Current Trends in the Imaging of Diffuse Axonal Injury Edwin Chu, MS IV University of Texas Medical School in San Antonio Gillian Lieberman, MD Harvard Medical School Beth Israel Deaconess Medical Center Edwin Chu, MS IV Gillian Lieberman, MD Outline Introduction to Traumatic Brain Injury Our Patient: MC Diffuse Axonal Injury (DAI) Imaging Modalities for Diffuse Axonal Injury Summary Acknowledgements References Edwin Chu, MS IV Gillian Lieberman, MD Introduction to Traumatic Brain Injury (TBI) Defined as damage to the brain from an external mechanical force. Examples of such forces include rapid acceleration or deceleration motions, impact injuries, or penetration by a projectile Incidence: 200-225/100,000 12% of all U.S. hospital admissions are TBIrelated Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation 82(10): 1461-71. Edwin Chu, MS IV Gillian Lieberman, MD Our Patient: MC CC: Traumatic Brain Injury HPI: 23 y/o M with unknown medical history transferred from an outside hospital s/p high speed (~100mph) motorcycle vs. bus accident. Pt was helmeted. In the field, GCS 3. Negative tox screen. GCS- Glasgow Coma Score Edwin Chu, MS IV Gillian Lieberman, MD On Admission- Patient MC: CT Imaging Axial non contrast CT imaging showing hyperdensity (green box) in left frontal lobe consistent with a hemorrhagic contusion. No other signs of hemorrhage were seen acutely. Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD 3 Days Later- Patient MC : MRI T2 Flair Areas of Hemorrhage Axial T2 weighted Flair MR imaging showing hyperintense signal in the right and left grey-white matter interface and splenium of the corpus callosum Axial T2 weighted Flair MR Imaging showing hyperintense signal in the right posterior limb of the internal capsule and a left frontal lobe contusion Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD 3 Days Later- Patient MC : MRI T2 Flair Axial T2 weighted Flair MR imaging showing hyperintense signal in the corpus callosum Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD 3 Days Later- Patient MC : MR Susceptibility Weighted Imaging Areas of Hemorrhage Axial SW MR imaging showing hypo-intense signal in the right and left grey-white matter interface and a left frontal lobe contusion Axial SW MR imaging showing hypointense lesions in the right grey-white matter interface and splenium; left frontal lobe contusion Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD 3 Days Later- Patient MC : MR Susceptibility Weighted Imaging Axial T2 weighted SW MR imaging showing hypo-intense signal in the corpus callosum Axial T2 weighted SW MR imaging showing hypo-intense signal in the corpus callosum Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD Diffuse Axonal Injury Biomechanics, Pathogenesis, Stages of Damage, and Long-term Consequences Diffuse Axonal Injury (DAI) Severe head trauma can produce diffuse axonal injury characterized by punctate hemorrhagic or non-hemorrhagic lesions primarily in white matter tracts Common sites: Parasagittal white matter, grey-white matter junctions of the cerebral cortex, corpus callosum, and brainstem Occurs in 40-50% of patients hospitalized for TBI Affects more than 2 million people every year Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation 82(10): 1461-71. Edwin Chu, MS IV Gillian Lieberman, MD DAI and its Long-Term Consequences 26,000 deaths/yr are due to DAI 20,000- 45,000 surviving patients/yr suffer neurobehavioral or physical impairments Average hospital cost per patient: $117,000 Direct health care costs: $25 billion/year Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation 82(10): 1461-71. Edwin Chu, MS IV Gillian Lieberman, MD Biomechanics of DAI Commonly referred to as a shear force injury Rapid head motions produce inertial forces which cause rotational acceleration of the brain leading to shearing and strain of axons Rapid stretch of an axon leads to damage to the neuron’s cytoskeleton. Axonal transport continues until local inflammation causes further cytoskeleton breakdown Edwin Chu, MS IV Gillian Lieberman, MD Pathogenesis of Microscopic Axonal Changes Brain Injury Influx of Na+ and Ca2+ through respective channels Axonal Swelling Axonal cytoskeleton damage Accumulation of axonal transport proteins within swellings Increased cytoskeleton damage + protein accumulation = axon disconnection Axon disconnection leads to irreversible damage Pathologic Feature: Bulb formation Edwin Chu, MS IV Gillian Lieberman, MD Histopathology of DAI Below: Silver stain of the same area indicating the axonal terminal bulbs. Top: Low power view of hematoxylineosin stain demonstrating DAI and petechial hemorrhages Images from: Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation 82(10): 1461-71. Edwin Chu, MS IV Gillian Lieberman, MD Stages of DAI Stage Areas Affected parasagittal regions of the frontal lobes - periventricular temporal lobes - internal and external capsules - cerebellum I - II Stage I areas + corpus callosum III Stage I + Stage II areas + dorsolateral quadrants of the rostral brain stem Adams, J. H. (1989). "Diffuse axonal injury in head injury: definition, diagnosis and grading." Histopathology 15(1): 49-59. Edwin Chu, MS IV Gillian Lieberman, MD Imaging Modalities for Diffuse Axonal Injury Edwin Chu, MS IV Gillian Lieberman, MD Imaging of DAI: CT CT imaging is first line for any neurotrauma Benefits Widely available in most hospitals in the US Comparatively inexpensive Good, quick test for injuries that require immediate surgical attention Drawbacks Initially 50-80% of pts with DAI will have normal CT scans Less sensitivity for detecting DAI Edwin Chu, MS IV Toyama, Y. (2005). "CT for acute stage of closed head injury." Radiation medicine 23(5): 309-16. Gillian Lieberman, MD Examples of DAI on CT Imaging: Companion Patient TC HPI: 22 y/o F being found down in the road, entangled with her bicycle, unresponsive, unhelmeted, pupils unequal. Initial CGS was 4 upon arrival to ED. Edwin Chu, MS IV Gillian Lieberman, MD Companion Patient TC: Axial Non-Contrast CT Imaging Areas of Hemorrhage Soft Tissue Edema Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD Companion Patient TC: Axial Non-Contrast CT Imaging Areas of Hemorrhage Soft Tissue Edema Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD Companion Patient TC: Axial Non-Contrast CT Imaging Areas of Hemorrhage Edwin Chu, MS IV Images from PACS, BIDMC Gillian Lieberman, MD More Examples: Non-Contrast CT Imaging showing Hemorrhagic DAI Lesions Black arrows: areas of hemorrhagic foci Left Image from: Provenzale, J. (2007). "CT and MR imaging of acute cranial trauma." Emergency radiology 14(1): 1-12. Right Image from: Toyama, Y. (2005). "CT for acute stage of closed head injury." Radiation medicine 23(5): 309-16. Edwin Chu, MS IV Gillian Lieberman, MD Imaging of DAI: MRI MRI has greater sensitivity in detecting DAI Commonly used techniques include Flair, DWI, and GRE, and SWI* Kinoshita et al.- DWI sensitivity in detecting DAI is comparable to Flair Tong et al.- Number of hemorrhagic DAI lesions seen on SWI was 6 times greater than that on conventional T2* weighted 2D GRE imaging and the volume of hemorrhage was approx 2 fold greater * Flair- Fluid Attenuated Inversion Recovery DWI- Diffusion weighted Imaging GRE- Gradient Recalled Echo SWI- Susceptibility Weighted Imaging Edwin Chu, MS IV Gillian Lieberman, MD T2 MR Imaging of DAI Sagittal T2-weighted MR image showing hyper-intense signal within the corpus callosum (white arrows) Image from: Provenzale, J. (2007). "CT and MR imaging of acute cranial trauma." Emergency radiology 14(1): 1-12. Edwin Chu, MS IV Gillian Lieberman, MD MR Flair: Conspicuity of DAI Lesions MR FLAIR image showing hyper-intense lesion in the left splenium MR FLAIR image showing hyper-intense lesion in the left frontal grey-white matter interface Images from: Kinoshita, T. (2005). "Conspicuity of diffuse axonal injury lesions on diffusionweighted MR imaging." European journal of radiology 56(1): 5-11. Edwin Chu, MS IV Gillian Lieberman, MD MR DWI: Conspicuity of DAI Lesions MR DWI–Gx image showing high-intensity lesion in the splenium MR DWI–Gz image showing highintensity lesion in the left frontal grey-white matter interface Images from: Kinoshita, T. (2005). "Conspicuity of diffuse axonal injury lesions on diffusionweighted MR imaging." European journal of radiology 56(1): 5-11. Edwin Chu, MS IV Gillian Lieberman, MD More Lesions are seen on Susceptibility Imaging: Comparing T2 and SWI A) Axial T2 MRI B) Axial Susceptibility-weighted MRI Small hemorrhagic shearing injuries in the left frontal subcortical white matter (Black arrows) Image from: Tong, K. A., S. Ashwal, et al. (2008). "Susceptibility-weighted MR imaging: a review of clinical applications in children." AJNR. American journal of neuroradiology 29(1): 9-17. Edwin Chu, MS IV Gillian Lieberman, MD More Lesions are seen on Susceptibility Imaging: Comparing T2 and SWI C) Axial T2 MRI D) Axial Susceptibility-weighted MRI Hemorrhagic shearing foci (open arrows) in the left frontal white matter, right subinsular region, and left splenium Image from: Tong, K. A., S. Ashwal, et al. (2008). "Susceptibility-weighted MR imaging: a review of clinical applications in children." AJNR. American journal of neuroradiology 29(1): 9-17. Edwin Chu, MS IV Gillian Lieberman, MD The Emergence of MRI Diffusion Tensor Tractography (DTT) DTT is rapidly becoming another modality to look for DAI in the acute phase Modality can characterize white matter integrity by measuring fractional anisotropy (FA) Fractional anisotropy is the degree of alignment of the underlying nerve fibers (ratio: 0 to 1) Wang, J. Y., B. Khamid, et al. (2008). "Diffusion tensor tractography of traumatic diffuse axonal injury." Archives of neurology 65(5): 619-26. Edwin Chu, MS IV Gillian Lieberman, MD Using DTT for Long-Term DAI Follow-up Skoglund et al. 22 y/o F with closed head injury. Comparison images of Axial T2 and DTT at 6 days post-injury and 18 months post-injury Results: In follow-up imaging, conventional MRI showed no pathology. However, in DTT imaging, FA values had improved but did not normalize. Conclusion: MR-DTT may be more sensitive to DAI than conventional MR imaging. Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta radiologica (Stockholm, Sweden : 1987) 49(1): 98-100. Edwin Chu, MS IV Gillian Lieberman, MD Results: Long-Term DAI Follow-up with DTT a) 6 days post injury- Axial T2 MR image showing hyper-intense lesion in left pons b) 18 months post injuryAxial T2 MR image showing no lesion c) 6 days post injury- Axial DTT image showing decreased blue intensity d) 18 months post injuryAxial DTT image showing moderately improved blue intensity Images from: Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta radiologica (Stockholm, Sweden : 1987) 49(1): 98-100. Edwin Chu, MS IV Gillian Lieberman, MD Fractional Anisotropy in Long-Term DAI Follow-up FA values on left side improve 18 months postinjury but do not normalize to right-sided values Key: dx – Patient’s right side sin – Patient’s left side Graph from: Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta radiologica (Stockholm, Sweden : 1987) 49(1): 98-100. Edwin Chu, MS IV Gillian Lieberman, MD Summary Diffuse Axonal Injury is caused by traumatic brain injury and can be characterized by punctate hemorrhagic or non-hemorrhagic lesions primarily in white matter tracts MRI is now the imaging of choice for detecting DAI. SWI and DWI are the best techniques DTT holds promising results as an imaging modality for the acute and long-term follow-up of DAI patients Edwin Chu, MS IV Gillian Lieberman, MD Acknowledgements Special thanks to Dr. Rafeeque Bhadelia for help with this index case and presentation Dr. Rivka Colen Dr. Gillian Lierberman Edwin Chu, MS IV Gillian Lieberman, MD References Adams, J. H. (1989). "Diffuse axonal injury in head injury: definition, diagnosis and grading." Histopathology 15(1): 49-59. Kinoshita, T. (2005). "Conspicuity of diffuse axonal injury lesions on diffusion-weighted MR imaging." European journal of radiology 56(1): 5-11. Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation 82(10): 1461-71. Provenzale, J. (2007). "CT and MR imaging of acute cranial trauma." Emergency radiology 14(1): 1-12. Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta radiologica (Stockholm, Sweden : 1987) 49(1): 98-100. Smith, D. H. (2003). "Diffuse axonal injury in head trauma." The Journal of head trauma rehabilitation 18(4): 307-16. Tong, K. A., S. Ashwal, et al. (2008). "Susceptibility-weighted MR imaging: a review of clinical applications in children." AJNR. American journal of neuroradiology 29(1): 9-17. Toyama, Y. (2005). "CT for acute stage of closed head injury." Radiation medicine 23(5): 309-16. Wang, J. Y., B. Khamid, et al. (2008). "Diffusion tensor tractography of traumatic diffuse axonal injury." Archives of neurology 65(5): 619-26. Edwin Chu, MS IV Gillian Lieberman, MD