{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:17:48Z","timestamp":1789107468621,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>In this study, three problems associated with diagnosing diffuse axonal injury (DAI) in patients with traumatic brain injury are reviewed: the shortage of scientific evidence supporting the 6-hour loss of consciousness (LOC) diagnostic criterion to discriminate concussion and DAI, the low sensitivity of conventional brain MRI in the detection of DAI lesions, and the inappropriateness of the term diffuse in DAI. Pathological study by brain biopsy is required to confirm DAI; however, performing a brain biopsy for the diagnosis of DAI in a living patient is impossible. Therefore, the diagnosis of DAI in a living patient is clinically determined based on the duration of LOC, clinical manifestations, and the results of conventional brain MRI. There is a shortage of scientific evidence supporting the use of the 6-hour LOC criterion to distinguish DAI from concussion, and axonal injuries have been detected in many concussion cases with a less than 6-hour LOC. Moreover, due to the low sensitivity of conventional brain MRI, which can only detect DAI lesions in approximately half of DAI patients, diagnostic MRI criteria for DAI are not well established. In contrast, diffusion tensor imaging (DTI) has been shown to have high sensitivity for the detection of DAI lesions. As DTI is a relatively new method, further studies aimed at the establishment of diagnostic criteria for DAI detection using DTI are needed. On the other hand, because DAI distribution is not diffuse but multifocal, and because axonal injury lesions have been detected in concussion patients, steps to standardize the use of terms related to axonal injury in both concussion and DAI are necessary.<\/jats:p>","DOI":"10.3390\/diagnostics10020117","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T08:59:47Z","timestamp":1582275587000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Diagnostic Problems in Diffuse Axonal Injury"],"prefix":"10.3390","volume":"10","author":[{"given":"Sung Ho","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University 317-1, Daemyungdong, Namku, Taegu 705-717, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/ana.410120610","article-title":"Diffuse axonal injury due to nonmissile head injury in humans: An analysis of 45 cases","volume":"12","author":"Adams","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1365-2559.1989.tb03040.x","article-title":"Diffuse axonal injury in head injury: Definition, diagnosis and grading","volume":"15","author":"Adams","year":"1989","journal-title":"Histopathology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3340\/jkns.2012.52.4.377","article-title":"Locations and clinical significance of nonhemorrhagic brain lesions in diffuse axonal injuries","volume":"52","author":"Chung","year":"2012","journal-title":"J. Korean Neurosurg Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/00001199-200307000-00003","article-title":"Diffuse axonal injury in head trauma","volume":"18","author":"Smith","year":"2003","journal-title":"J. Head Trauma. Rehabil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1089\/neu.1995.12.555","article-title":"The pathobiology of traumatically induced axonal injury in animals and humans: A review of current thoughts","volume":"12","author":"Povlishock","year":"1995","journal-title":"J. Neurotrauma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00701-005-0674-4","article-title":"All roads lead to disconnection?--traumatic axonal injury revisited","volume":"148","author":"Buki","year":"2006","journal-title":"Acta. Neurochir (Wien)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1089\/neu.1997.14.419","article-title":"A mechanistic analysis of nondisruptive axonal injury: A review","volume":"14","author":"Maxwell","year":"1997","journal-title":"J. Neurotrauma"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1053\/apmr.2001.25137","article-title":"Current concepts: Diffuse axonal injury-associated traumatic brain injury","volume":"82","author":"Meythaler","year":"2001","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1590\/0004-282x20180007","article-title":"Current contribution of diffusion tensor imaging in the evaluation of diffuse axonal injury","volume":"76","author":"Grassi","year":"2018","journal-title":"Arq. Neuropsiquiatr"},{"key":"ref_10","first-page":"204","article-title":"Clinical features of diffuse axonal injury","volume":"4","author":"Jing","year":"2001","journal-title":"Chin. J. Traumatol."},{"key":"ref_11","unstructured":"Gennarelli, T.A. (1987). Cerebral concussion and diffuse brain injuries, Williams & Wilkins. [3rd ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/TA.0000000000001852","article-title":"Prognosis of diffuse axonal injury with traumatic brain injury","volume":"85","author":"Humble","year":"2018","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1136\/jnnp.31.4.299","article-title":"Microscopic lesions in the brain following head injury","volume":"31","author":"Oppenheimer","year":"1968","journal-title":"J. Neurol. Neurosurg Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0140-6736(94)91712-4","article-title":"Staining of amyloid precursor protein to study axonal damage in mild head injury","volume":"344","author":"Blumbergs","year":"1994","journal-title":"Lancet"},{"key":"ref_15","first-page":"1583","article-title":"Prevalence of MR evidence of diffuse axonal injury in patients with mild head injury and normal head CT findings","volume":"15","author":"Mittl","year":"1994","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1179\/016164108X323799","article-title":"MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury","volume":"30","author":"Topal","year":"2008","journal-title":"Neurol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.expneurol.2012.01.013","article-title":"Axonal pathology in traumatic brain injury","volume":"246","author":"Johnson","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/ana.410120611","article-title":"Diffuse axonal injury and traumatic coma in the primate","volume":"12","author":"Gennarelli","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11682-012-9156-5","article-title":"A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury","volume":"6","author":"Shenton","year":"2012","journal-title":"Brain Imaging Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4103\/0971-3026.169445","article-title":"Traumatic brain injury and the post-concussion syndrome: A diffusion tensor tractography study","volume":"25","author":"Trivedi","year":"2015","journal-title":"Indian J. Radiol Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Bae, C.H., Seo, J.P., and Jang, S.H. (2019). Diagnosis of Tinnitus Due to Auditory Radiation Injury Following Whiplash Injury: A Case Study. Diagnostics (Basel), 30.","DOI":"10.3390\/diagnostics10010019"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jang, S.H., and Lee, H.D. (2019). Diagnostic Approach to Traumatic Axonal Injury of the Spinothalamic Tract in Individual Patients with Mild Traumatic Brain Injury. Diagnostics (Basel), 21.","DOI":"10.5772\/intechopen.70988"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12786\/bn.2016.9.e1","article-title":"Diagnostic history of traumatic axonal injury in patients with cerebral concussion and mild traumatic brain injury","volume":"9","author":"Jang","year":"2016","journal-title":"Brain NeuroRehabil."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1017\/S1355617704105146","article-title":"Neuropsychological results and neuropathological findings at autopsy in a case of mild traumatic brain injury","volume":"10","author":"Bigler","year":"2004","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_25","unstructured":"Gorbunoy, N. (2018). Traumatic axonal injury in mild traumatic brain injury. Traumatic Brain Injury, In Tech. [1st ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tins.2016.03.002","article-title":"Traumatic axonal injury: Mechanisms and translational opportunities","volume":"39","author":"Hill","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2214\/ajr.150.3.663","article-title":"MR imaging of head trauma: Review of the distribution and radiopathologic features of traumatic lesions","volume":"150","author":"Gentry","year":"1988","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_28","unstructured":"Osborn, A.G., Salzman, K.L., and Barkovich, A.J. (2010). Trauma; Diffuse axonal injury. Diagnostic Imaging: Brain, Amirsys. [2nd ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00234-014-1419-y","article-title":"Injury of the lower ascending reticular activating system in patients with hypoxic-ischemic brain injury: Diffusion tensor imaging study","volume":"56","author":"Jang","year":"2014","journal-title":"Neuroradiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00234-018-2137-7","article-title":"Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging","volume":"61","author":"Yu","year":"2019","journal-title":"Neuroradiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/jmrb.1994.1037","article-title":"Estimation of the effective self-diffusion tensor from the NMR spin echo","volume":"103","author":"Basser","year":"1994","journal-title":"J. Magn. Reson."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/1531-8249(199902)45:2<265::AID-ANA21>3.0.CO;2-3","article-title":"Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging","volume":"45","author":"Mori","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_33","first-page":"370","article-title":"Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury","volume":"25","author":"Huisman","year":"2004","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1148\/radiol.12112570","article-title":"Quantitative diffusion-tensor tractography of long association tracts in patients with traumatic brain injury without associated findings at routine MR imaging","volume":"267","author":"Brandstack","year":"2013","journal-title":"Radiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/00001199-200605000-00007","article-title":"Usefulness of diffusion tensor imaging for evaluation of motor function in patients with traumatic brain injury: Three case studies","volume":"21","author":"Lee","year":"2006","journal-title":"J. Head Trauma Rehabil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1001\/archneur.65.5.619","article-title":"Diffusion tensor tractography of traumatic diffuse axonal injury","volume":"65","author":"Wang","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1080\/00207454.2019.1667779","article-title":"Difference between injuries of the corticospinal tract and corticoreticulospinal tract in patients with diffuse axonal injury: A diffusion tensor tractography study","volume":"130","author":"Jang","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1001\/archneurol.2011.1930","article-title":"Classification of cause of motor weakness in traumatic brain injury using diffusion tensor imaging","volume":"69","author":"Choi","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1089\/neu.2008.0586","article-title":"Classification of traumatic brain injury for targeted therapies","volume":"25","author":"Saatman","year":"2008","journal-title":"J. Neurotrauma"},{"key":"ref_40","first-page":"S189","article-title":"Axonal response to traumatic brain injury: Reactive axonal change, deafferentation, and neuroplasticity","volume":"9","author":"Povlishock","year":"1992","journal-title":"J. Neurotrauma"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1007\/s11682-018-9823-2","article-title":"Diffusion tensor imaging changes following mild, moderate and severe adult traumatic brain injury: A meta-analysis","volume":"12","author":"Wallace","year":"2018","journal-title":"Brain Imaging Behav."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/2\/117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:59:38Z","timestamp":1760173178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/2\/117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,21]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["diagnostics10020117"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10020117","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,21]]}}}