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Minor Brain Trauma: Pathology, Imaging, and Clinical Aspects Donald W Chakeres MD, FACR Professor Minor Brain Trauma: Pathology, Imaging, and Clinical Aspects Donald W Chakeres MD, FACR Professor of Radiology Department of Radiology The Ohio State University Columbus, Ohio, USA XIX Symposium Neuroradiologicum, Bologna, Italy 2010

Thanks to the Collaborators Seongjin Choi, Ph. D Postdoctoral Fellow Department of Radiology John Thanks to the Collaborators Seongjin Choi, Ph. D Postdoctoral Fellow Department of Radiology John D. Corrigan, Ph. D Professor Department of Phys. Med. and Rehab. Department of Psychology Jennifer A. Bogner, Ph. D Associate Professor Department of Phys. Med. and Rehab. W Jerry Mysiw, MD Professor and Vice Chair Department of Phys. Med. and Rehab. Department of Psychology S. Sammet MD, Ph. D Assistant Professor Department of Radiology Dustin Cunningham Student Research Assistant Department of Radiology Devin F. Prior Student Research Assistant Department of Radiology Cherian R Zachariah, BS Graduate Research Associate Department of Radiology Michael V. Knopp, MD, Ph. D Professor and Vice Chair Department of Radiology Petra Schmalbrock, Ph. D Associate Professor Department of Radiology

Goals Preview of the presentation Define minor head trauma Clinical findings/ spectrum Pathology, animal Goals Preview of the presentation Define minor head trauma Clinical findings/ spectrum Pathology, animal and human Imaging findings, focusing on 7 T MRI Conclusions

Disclaimer for the Presentation If you are looking for great imaging findings that will Disclaimer for the Presentation If you are looking for great imaging findings that will impact your routine practice, you are going to be disappointed Minor head trauma by definition usually does not have routine imaging findings Still a very important topic since it is a common indication for imaging Advanced imaging does have the potential to become the biomarker measure

Significance - Incidence Head trauma is extremely common Minor head trauma is commonly followed Significance - Incidence Head trauma is extremely common Minor head trauma is commonly followed by repeated or major head trauma In America there are over 5 million with long term disability as a result of head trauma The incidence of minor head trauma is essentially everyone It is a very serious problem dwarfing many other medical issues

Treatment There is no known effective therapy Most therapy is just to wait and Treatment There is no known effective therapy Most therapy is just to wait and see if the symptoms improve, frequently they do The treatment for stress and trauma are frequently identical If you cannot measure the injury directly you cannot measure if your therapy is effective either

Definitions The classification is not well defined for imaging or clinical measures Glasgow Coma Definitions The classification is not well defined for imaging or clinical measures Glasgow Coma Scale, not good for minor head injuries, better for serious injuries

Definition: Minor Head Trauma American Academy of Neurology Grade 1: transient confusion with no Definition: Minor Head Trauma American Academy of Neurology Grade 1: transient confusion with no loss of consciousness, and symptoms resolve in less than 15 minutes Grade 2: symptoms last for more than 15 minutes Grade 3: loss of consciousness

Definition Minor Head Trauma: Imaging Normal routine CT and MRI Definition Minor Head Trauma: Imaging Normal routine CT and MRI

Clinical Symptoms Loss of consciousness Head ache Confusion Dizzy Inability to concentrate Does not Clinical Symptoms Loss of consciousness Head ache Confusion Dizzy Inability to concentrate Does not recall the event Change in personality Executive function impairment

Clinical Symptoms: Compounded because the findings overlap with many other issues Post traumatic stress Clinical Symptoms: Compounded because the findings overlap with many other issues Post traumatic stress syndrome Depression Drug dependence Workman’s compensation incentives

Major Trauma Pathology: Major brain injuries much better understood because of excellent pathologic material Major Trauma Pathology: Major brain injuries much better understood because of excellent pathologic material Minor Trauma Pathology: Disruption without physical shearing of the neurofilaments Animal studies show “ball” like swelling of axons suggesting separation, but without gross visible focal parenchymal injury, analogous to MS and normal appearing white matter Stretching and tearing of neurons occur at the instant of trauma Povlishock JT, Becker DP, et al, Axonal change in minor head Injury, Journal of Neuropathology and Experimental Neurology

Minor Trauma Pathology Wide spread damage to the white matter need not be associated Minor Trauma Pathology Wide spread damage to the white matter need not be associated with hemorrhage, contusion, or laceration This is why advanced imaging may be very important Nevin, Norman, Neuropahtological changes in white matter following head trauma, Journal of Neuropathology and Experimental Neurology 1967

Palmgren silver impregnation of swollen Purkinje cell dendrites (arrows) in cerebellar molecular layer Kors Palmgren silver impregnation of swollen Purkinje cell dendrites (arrows) in cerebellar molecular layer Kors E, et al, Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA 1 A calcium channel subunit gene and relationship with familial hemiplegic migraine, Ann Neurol 2001: 49: 753 -760

Minor Trauma Pathology Loss of consciousness may the clinical marker of the “tearing” of Minor Trauma Pathology Loss of consciousness may the clinical marker of the “tearing” of the neurons The brainstem foci may well account for loss of consciousness Location can be “anywhere”, but classic anatomic distribution Animal studies show injuries to the inferior colliculus, pons and dorsolateral medulla Axonal injury is highly under estimated Jane J, et al, Axonal degeneration induced by experimental noninvasive minor head injury Gentleman, SM, Roberts GW, et al , Axonal injury: a universal consequence of Fatal closed head injury, Acta Neuropathol 1995: 89: 537 -543

Major Trauma Pathology: Midbrain Lesion and Prognosis Midbrain lesions found in 23 of 35 Major Trauma Pathology: Midbrain Lesion and Prognosis Midbrain lesions found in 23 of 35 autopsied, head injury subjects Abnormal evoked potential before death Midbrain damage almost always associated with major hemispheric injury Rosenblum, W, et al, Midbrain lesion: frequent and significant prognostic feature in closed head injury Neurosurgery, Congress of Neurologic Surgeons

Genetic Predispositions Apo. E is a genetic marker that is associated with Alzheimer’s disease Genetic Predispositions Apo. E is a genetic marker that is associated with Alzheimer’s disease An error in “healing” the brain after injury The risk of significant post traumatic disability is increased for subjects with the same Apo. E genes as patients at risk for Alzheimer’s disease Beta-amyloid deposits are found with the apolipoprotine. E (apo. E)-ε 4 allele. β‐Amyloid (Aβ)42(43), Aβ 42, Aβ 40 and apo. E immunostaining of plaques in fatal head injury K. Horsburgh, G. M. Cole, F. Yang, M. J. Savage B. D. Greenberg, S. M. Gentleman, D. I. Grahamand J. A. R. Nicoll Association of apolipoprotein E polymophism with outcome after head injury, The Lancet volume 350, issue 9084, 1069 -1071

Blast Injuries, Minor or Major 90% improve with no therapy Can occur without any Blast Injuries, Minor or Major 90% improve with no therapy Can occur without any head motion, classic acceleration- deceleration The blast waves can go through the thinner bone skull regions such as the orbit and still lead to distortion/ injury of the brain Usually more than one blast needed before any clinical symptoms

Imaging of Major Head Trauma Subdural hematoma Epidural hematoma Subarachnoid hemorrhage Brain contusions Diffuse Imaging of Major Head Trauma Subdural hematoma Epidural hematoma Subarachnoid hemorrhage Brain contusions Diffuse axonal injuries Brain lacerations Depressed skull fracture Vessel disruption, spasm, dissection, aneurym

Susceptibility Weighted Imaging Technique developed by Haacke/ et al More commonly available now, and Susceptibility Weighted Imaging Technique developed by Haacke/ et al More commonly available now, and standard on some systems Uses a image processed combination of phase and magnitude data Very sensitive to deoxyhemoglobin since it has strong paramagnetic properties that accelerate the local phase Good for the veins and hemorrhage

Susceptibility Weighted Imaging Much better than simple gradient echo imaging for subtle blood products Susceptibility Weighted Imaging Much better than simple gradient echo imaging for subtle blood products Patients with “normal CT and MRI” may have many lesions by SWI Seen as low “signal” regions in typical locations for shear injuries and trauma

MRI Spin Echo: Brain Contusions T 2 FLAIR MRI Spin Echo: Brain Contusions T 2 FLAIR

SWI: Brain Contusions T 2 SWI SWI: Brain Contusions T 2 SWI

SWI: Brain Contusions SWI: Brain Contusions

Diffusion Imaging of Trauma Diffusion imaging should be a good technique for a subtle Diffusion Imaging of Trauma Diffusion imaging should be a good technique for a subtle injury since it is sensitive to the integrity of the axons FA and ADC values may be abnormal with brain injury Diffusion tensor/ tract imaging, DTT, should even be more sensitive

7 T Research Study of Trauma Data comparable to 3 T data, but higher 7 T Research Study of Trauma Data comparable to 3 T data, but higher resolution Fractional anisotropy, FA, values lower in corpus callosum, CC, compared to controls Healthy normal subjects showed changes of FA with age, FA decreases with increasing age Tractography of CC showed fewer and less well defined tracts in the trauma group

7 T Tractography of Normal and Post Traumatic Subjects Normal control Post Traumatic Subject 7 T Tractography of Normal and Post Traumatic Subjects Normal control Post Traumatic Subject

7 T DTI in Chronic Mild Traumatic Brain Injury: Assessment of the Superior Longitudinal 7 T DTI in Chronic Mild Traumatic Brain Injury: Assessment of the Superior Longitudinal Fasciculus and Cingulum Bundle Dustin T. Cunningham, Seongjin Choi, John D. Corrigan, Jennifer Bogner, W. Jerry Mysiw, Cherian R. Zachariah, Michael V. Knopp and Petra Schmalbrock The Ohio State University Department of Radiology Wright Center of Innovation in Biomedical Imaging

Methods Subjects § 7 chronic mild TBI with normal conventional MRI (ages 2260) § Methods Subjects § 7 chronic mild TBI with normal conventional MRI (ages 2260) § (Glasgow Coma Scale GCS 13 -15) § 10 approx. age matched healthy (22 -56) Imaging § 7 T (Philips, Achieva) § 16 -channel receive (Nova Medical) § SS-SE-EPI DTI, TR/TE = 5126/75 ms § voxel: 1. 6× 3. 2 mm 3 § b = 0, 1000 s/mm 2 § 6 b-directions, 3 high b averages § SENSE-factor = 5 § DTI scan time: 2 min, 24 sec § 3 D SWI, voxel: . 40×. 68× 1. 6 mm 3 § flip angle = 5, scan time: 5 min, 4 sec

Cingulum Bundles 7 T Identification Philips Fiber. Trak Wakana et al. Neuro. Image 2007 Cingulum Bundles 7 T Identification Philips Fiber. Trak Wakana et al. Neuro. Image 2007

CB Tractography Scoring 2 3 1 DTI Studio – H. Jiang and S. Mori, CB Tractography Scoring 2 3 1 DTI Studio – H. Jiang and S. Mori, Johns Hopkins University

CB Tractography Scoring Control TBI Mean Scores 3 3 2 2 1 1 0 CB Tractography Scoring Control TBI Mean Scores 3 3 2 2 1 1 0 0 Left Control Left TBI Right Control Observer 1 Right TBI Left Control Left TBI Right Control Observer 2 Right TBI

Summary § Visual tractography differences can be detected in chronic mild TBI compared with Summary § Visual tractography differences can be detected in chronic mild TBI compared with controls with 7 T § Quantitative FA values were lower in chronic mild TBI than controls § Despite B 0 and B 1 inhomogeneity, 7 T DTI consistent with 3 T and 1. 5 T studies of mild TBI

References Inglese M, Makani S, Johnson G, Cohen BA, Silver JA, Gonen O, and References Inglese M, Makani S, Johnson G, Cohen BA, Silver JA, Gonen O, and Grossman RI, Diffuse Axonal Injury in Mild Traumatic Brain Injury: A Diffusion Tensor Imaging Study, Journal of Neurosurgery 103: 298 -303, 2005 Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, and Little DM, White Matter Integrity and Cognition in Chronic Traumatic Brain Injury: A Diffusion Tensor Imaging Study, Brain 130: 2508 -2519, 2007 Kumar R, Husain M, Gupta RK, Hasan KM, Haris M, Agarwal AK, Pandey CM, and Narayana PA, Serial Changes in the White Matter Diffusion Tensor Imaging Metrics in Moderate Traumatic Brain Injury and Correlation with Neuro-Cognitive Function, Journal of Neurotrauma 26: 481 -495, April 2009 Li TQ, van Gelderen P, Merkle H, Talagala L, Koretsky AP, Duyn J, Extensive heterogeneity in white matter intensity in high-resolution T 2* -weighted MRI of the human brain at 7 T, Neuro. Image 32, 1032 -1040, 2006 Sugiyama K, Kondo T, Higano S, Endo M, Watanabe H, Shindo K, Izumi SI, Diffusion tensor imaging fiber tractography for evaluating diffuse axonal injury, Brain Injury, 21: 413 -419, 2007

Conclusion: “Minor” head trauma is a major medical issue Pathology has shown many important Conclusion: “Minor” head trauma is a major medical issue Pathology has shown many important findings not commonly identified otherwise Some patients are at a genetic risk MR imaging may be the future of an accurate biomarker for brain injury “Normal” imaging may not be normal Advanced techniques are much more sensitive for imaging findings of TBI

Thanks to the organizers of the meeting and have a great day in lovely Thanks to the organizers of the meeting and have a great day in lovely Italy