Novel white matter and subependymal MRI findings in Brain Death.
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1 Novel white matter and subependymal MRI findings in Brain Death. Poster No.: C-2105 Congress: ECR 2013 Type: Educational Exhibit Authors: G. Santacana-Laffitte, D. Loubriel-Torres, D. Del Prado; San Juan, PR/US Keywords: Pathology, Medico-legal issues, MR-Diffusion/Perfusion, MR, Neuroradiology brain, MR physics DOI: /ecr2013/C-2105 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 19
2 Learning objectives Review the Clinical Diagnostic Criteria of Brain Death as established by The American Academy of Neurology. Review the most common MRI findings in Brain Death. Propose two new MRI findings not previously described which may prove to be specific for the diagnosis of brain death. Provide a theory on the possible pathophysiological mechanism of these findings. Background Brain death is defined as "absence of clinical brain function when the proximate cause is 7 known and demonstrably irreversible". Diagnostic criteria established by the American Academy of Neurology for diagnosing brain death include clinical or neuroimaging evidence of an acute CNS catastrophic insult compatible with a clinical diagnosis of brain death, excluding complicating medical conditions that may resemble brain death, absence of poisoning or drug intoxication and a core temperature equal to or greater than 32 degrees Celsius. The three most important findings for brain death to be determined are coma or unresponsiveness, absence of brainstem reflexes, and apnea. For coma or unresponsiveness to be determined there must be absence of cerebral motor response to elicited pain in all extremities. Absence of brainstem reflexes includes evaluation of pupils, ocular movements, facial sensation & motor response, and pharyngeal & tracheal reflexes. Apnea is tested for with a CO2 challenge searching for an absence of breathing drive. The use of MRI as an ancillary tool in the diagnosis of brain death, and as a conjunct to the above criteria in equivocal cases has been recently investigated. Studies have proven that the use of ancillary tests such as MRI may shorten the time of observation and provide an early diagnosis of brain death which is particularly useful in certain cases such as preserving organ viability for transplant. The two most recognized conventional diagnostic criteria for brain death on MRI are tonsillar herniation and absent intracranial vascular flow voids in both conventional MRI and MRA. Diffuse cortical high signal intensity and swelling of the cerebral sulci on T2WI; diffuse hemispheric hyperintensities on DWI; and a drop in the apparent diffusion coefficient (ADC) due to cytotoxic edema have also been described. Page 2 of 19
3 The loss of white matter signal intensity on T2 weighted images, with relative hyperintensity to the substantia nigra, and periventricular/subependymal diffusion restriction have not been previously described. We quantified the relative decrease in white matter intensity using ROI's and compared with Brain MRI's which had no white matter pathology. We propose that these findings are highly specific and when combined with the previously reported MRI findings in brain death may be used as a potential ancillary diagnostic test for the diagnosis of brain death. Imaging findings OR Procedure details Procedure Details: We compared two cases of clinically diagnosed brain death who underwent Brain MRI evaluation (Patients A and B) with findings of previous studies. The average white matter T2 signal intensity was calculated using Regions of Interest (ROI's) measured bilaterally at the frontal lobes adjacent to the roof of the lateral ventricles. Average ROI was obtained in one of our patients clinically diagnosed with brain death (Patient A) and compared with those of 10 pediatric and 10 adult patients with no evidence of white matter pathology. All studies were performed in a Philips 1.5T Intera MR scanner. Image analysis was performed in a Kodak Carestream PACS System Workstation. Imaging Findings: Findings of tonsillar herniation with sagging brainstem (Fig 1 and 2) and absence of vascular flow voids (Fig 3) are consistent with findings in previous studies. Additionally we found white matter to be significantly more hypointense (Figs 4, 5, and 6) when compared with MRI of patients with no white matter pathology. We found the ROI's of the brain dead patient to be significantly decreased (Fig 7) when compared with those of normal white matter (Fig 8) (Table 1). There is also a relative hyperintensity to the substantia nigra which has not been previously described in the literature (Fig 9 and 10). Subependymal diffusion restriction is also identified in both cases of brain death (Figs 11, 12, and 13), a finding that has not been previously described. (Table 1) Average White Matter Signal Intensity Page 3 of 19
4 Average Pediatric Average Adult Patient A (Brain Death) Images for this section: Page 4 of 19
5 Fig. 1: T2 weighted sagittal image of Patient A shows tonsillar herniation (yellow arrow), and sagging brainstem (yellow asterix). Page 5 of 19
6 Fig. 2: T2 weighted sagittal image of Patient B shows tonsillar herniation and sagging brainstem (yellow arrows). Page 6 of 19
7 Fig. 3: T2 weighted axial image of Patient A shows absence of vascular flow voids (yellow arrows). Page 7 of 19
8 Fig. 4: T2 weighted axial image of Patient A shows hypointense white matter (yellow asterixs). Large right epidural hematoma is also present. Page 8 of 19
9 Fig. 5: T2 weighted image of Patient A shows hypointense white matter (yellow asterixs). Large right epidural hematoma is also present. Page 9 of 19
10 Fig. 6: T2 weighted image of Patient B shows hypointense white matter (yellow asterixs). Page 10 of 19
11 Fig. 7: T2 weighted image shows average white matter signal intensity (ROI) in Patient A. Page 11 of 19
12 Fig. 8: T2 weighted image shows the average white matter signal intensity (ROI) for a normal brain. Page 12 of 19
13 Fig. 9: T2 weighted axial image of Patient A shows relative hyperintensity to the substantia nigra (yellow arrows). Page 13 of 19
14 Page 14 of 19
15 Fig. 10: T2 weighted axial image of Patient B shows relative hyperintensity to the substantia nigra (yellow arrows). Fig. 11: DWI of Patient A shows subependymal diffusion restriction (yellow arrows). Page 15 of 19
16 Fig. 12: DWI of Patient B shows subependymal diffusion restriction (yellow arrows). Page 16 of 19
17 Fig. 13: DWI and ADC map of Patient A shows diffusion restriction Page 17 of 19
18 Conclusion The MRI findings in brain death are numerous and likely vary according to the cause and timing of the MRI examination, however there is consistency in some findings which may render them valuable in aiding in the diagnosis of brain death. Tonsillar herniation with a sagging brain stem and absence of cerebral flow voids appear to be some of the common findings in cases of brain death. Previously, a relative gray matter hyperintensity had been described in some cases of brain death, however the relative decrease in signal intensity in the cerebral white matter has not been mentioned. Our two cases demonstrate a relative decrease in white matter signal intensity when compared with MRI's of patients with no white matter pathology. This difference is quantifiable by ROI measurements of the cerebral white matter. Our measurements show that there is a measurable decrease in average ROI in one of our cases of brain death when compared with normal white matter. We theorize that this relative decrease in white matter intensity may be due to axonal desiccation as a consequence of neuronal cell death. This however remains to be elucidated. Whether this finding is significant remains to be investigated as we could only aquire measurements from one case. We are currently working towards further investigating these findings. Our two cases also showed subependymal diffusion restriction. Histologically, the cells lining the blood brain barrier are endothelial in origin, while the cells lining the brain-csf barrier are epithelial. We theorize that restricted diffusion observed is not reflective of ischemia but rather a change in macromolecular arrangements in organic components typically seen in epithelial tissues such as cholesterol, phospholipids or keratin. Restricted diffusion is observed in lesions containing these components such as CNS epidermoids, cholesterol granulomas or xanthogranulomas. This also remains to be further investigated. The use of MRI as an adjunct to the diagnosis of brain death related to several specific findings have been described. These new observations may prove an important and specific addition in the use of MRI for diagnosing Brain Death. References Bergeron M, Evans SM, Sharp FR, Koch CJ, Lord EM, Ferriero DM. Detection of hypoxic cells with the 2-nitroimidazole, EF5, correlates with early redox changes in rat brain after perinatal hypoxia-ischemia. Neuroscience. 1999; 89: Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci July 1; 17(13): Page 18 of 19
19 Karantanas AH, Hadjigeorgiou GM, Paterakis K, Sfiras D, Komnos A. Contribution of MRI and MR angiography in early diagnosis of brain death. Eur Radiol Apr 17; 12: Lovblad KO, Bassetti C. Diffusion-weighted magnetic resonance imaging in brain death. Stroke. 2000; 31: Matsumura A, Meguro K, Tsurushima H, Komatsu Y, Kikuchi Y, Wada M, Nakata Y, Ohashi N, Nose T. Magnetic Resonance Imaging of Brain Death. Neurol Med Chir(Tokyo) March; 36: Sohn CH, Lee HP, Park JB, Chang HW, Kim E, Kim E, Park UJ, Kim HT, Ku J. Imaging findings of Brain Death on 3-Tesla MRI. Korean J Radiol Sep/Oct; 13(5): Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM. Evidence-based guideline update: Determining brain death in adults Report of the quality standards subcommittee of the American academy of neurology. Neurology. 2010; 74: Personal Information Page 19 of 19
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