Microwave scan and brain biomarkers to rule out intracranial hemorrhage: study protocol of a planned prospective study (MBI01)

Tomas Vedin, Henrik Bergenfeldt, Emanuel Holmström, Jakob Lundager-Forberg, Marcus Edelhamre, Tomas Vedin, Henrik Bergenfeldt, Emanuel Holmström, Jakob Lundager-Forberg, Marcus Edelhamre

Abstract

Purpose: The aim of this planned study is to evaluate the ability of a cranial microwave scanner in conjunction with nine brain biomarkers (Aβ40, Aβ42, GFAP, H-FABP, S100B, NF-L, NSE, UCH-L1 and IL-10) to detect and rule out traumatic intracranial hemorrhage in an emergency department setting. Traumatic brain injury is a world-wide topic of interest for researchers and clinicians. It affects 2% of the population per annum and presents challenges for physicians as patients' initial signs and symptoms do not always correlate with the extent of brain injury. The gold standard for diagnosis of intracranial hemorrhage is head computerized tomography (CT) with the drawbacks of high cost and radiation exposure. A fast, secure way of diagnosing without these drawbacks has potential to make care more effective and reduce cost.

Methods: Study will be prospective and enroll adult, consenting patients with head trauma who seek emergency department care. Only patients where the treating physician prescribes a head-CT will be included. The microwave scan and blood sampling will be performed in close temporal proximity to the CT scan. Results will be analyzed with sensitivity, specificity and receiver operator characteristics analysis to provide the best combination of a number of biomarkers and the microwave scan.

Conclusion: This study will explore the diagnostic accuracy of a head microwave scanner in combination with biomarkers in ruling out intracranial hemorrhage in traumatic brain injury patients presenting to the emergency department. Potentially, this combined diagnostic approach could achieve both high sensitivity and high specificity, thereby reducing the need of CT-head scans when managing these patients.

Clinicaltrials: gov identifier: NCT04666766. Registered December 11, 2020.

Keywords: Biomarkers; Brain hemorrhage, traumatic; CT scan, X-ray; Microwaves; TBI traumatic brain injury.

Conflict of interest statement

Authors declare no conflicts of interest. Study is performed in collaboration with Medfield Diagnostics AB. (the company that sells the MD100) as co-sponsor but they do not contribute with financial support.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Figure is showing the origin of study biomarkers. Published with permission by creator, Henrik Zetterberg, professor of clinical chemistry, Gothenburg University
Fig. 2
Fig. 2
Flow chart of inclusion process for Group A and Group B

References

    1. Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, et al. Surgical management of traumatic parenchymal lesions. Neurosurgery. 2006;58:S25–46.
    1. Leach P, Childs C, Evans J, Johnston N, Protheroe R, King A. Transfer times for patients with extradural and subdural haematomas to neurosurgery in Greater Manchester. Br J Neurosurg. 2007;21:11–15. doi: 10.1080/02688690701210562.
    1. Nakahara S, Matsuoka T, Ueno M, Mizushima Y, Ichikawa M, Yokota J, et al. Predictive factors for undertriage among severe blunt trauma patients: what enables them to slip through an established trauma triage protocol. J Trauma. 2010;68:1044–1051.
    1. Brazinova A, Rehorcikova V, Taylor MS, Buckova V, Majdan M, Psota M, et al. Epidemiology of traumatic brain injury in Europe: a living systematic review. J Neurotrauma. 2016 doi: 10.1089/neu.2015.4126.
    1. Stocchetti N, Paternò R, Citerio G, Beretta L, Colombo A. Traumatic brain injury in an aging population. J Neurotrauma. 2012;29:1119–1125. doi: 10.1089/neu.2011.1995.
    1. Haas B, Gomez D, Zagorski B, Stukel TA, Rubenfeld GD, Nathens AB. Survival of the fittest: the hidden cost of undertriage of major trauma. J Am Coll Surg. 2010;211:804–811. doi: 10.1016/j.jamcollsurg.2010.08.014.
    1. Svensson S, Vedin T, Clausen L, Larsson PA, Edelhamre M. Application of NICE or SNC guidelines may reduce the need for computerized tomographies in patients with mild traumatic brain injury: a retrospective chart review and theoretical application of five guidelines. Scand J Trauma Resusc Emerg Med. 2019;27:99. doi: 10.1186/s13049-019-0673-8.
    1. Foks KA, van den Brand CL, Lingsma HF, van der Naalt J, Jacobs B, de Jong E, et al. External validation of computed tomography decision rules for minor head injury: prospective, multicentre cohort study in the Netherlands. BMJ. 2018;362:k3527. doi: 10.1136/bmj.k3527.
    1. Aygun N, Masaryk TJ. Diagnostic imaging for intracerebral hemorrhage. Neurosurg Clin N Am. 2002;13(3):313–334. doi: 10.1016/S1042-3680(02)00009-8.
    1. Thelin EP, Nelson DW, Bellander BM. A review of the clinical utility of serum S100B protein levels in the assessment of traumatic brain injury. Acta Neurochir. 2017;159:209–225. doi: 10.1007/s00701-016-3046-3.
    1. Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17:782–789. doi: 10.1016/S1474-4422(18)30231-X.
    1. Thelin E, Al Nimer F, Frostell A, Zetterberg H, Blennow K, Nyström H, et al. A serum protein biomarker panel improves outcome prediction in human traumatic brain injury. J Neurotrauma. 2019;36:2850–2862. doi: 10.1089/neu.2019.6375.
    1. Undén L, Calcagnile O, Undén J, Reinstrup P, Bazarian J. Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults. BMC Med. 2015;13:292. doi: 10.1186/s12916-015-0533-y.
    1. Paul AB, Oklu R, Saini S, Prabhakar AM. How much is that head CT? Price transparency and variability in radiology. J Am Coll Radiol. 2015;12:453–457. doi: 10.1016/j.jacr.2014.12.016.
    1. Smith-Bindman R, Lipson J, Marcus R, Kim KP, Mahesh M, Gould R, et al. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med. 2009;169:2078–2086. doi: 10.1001/archinternmed.2009.427.
    1. Brenner DJ. Should we be concerned about the rapid increase in CT usage? Rev Environ Health. 2010;25:63–68. doi: 10.1515/REVEH.2010.25.1.63.
    1. Persson M, Fhager A, Trefná HD, Yu Y, McKelvey T, Pegenius G, et al. Microwave-based stroke diagnosis making global prehospital thrombolytic treatment possible. IEEE Trans Biomed Eng. 2014;61:2806–2817. doi: 10.1109/TBME.2014.2330554.
    1. Fhager A, Candefjord S, Elam M, Persson M. Microwave diagnostics ahead: saving time and the lives of trauma and stroke patients. IEEE Microw Mag. 2018;19:78–90. doi: 10.1109/MMM.2018.2801646.
    1. Ljungqvist J, Candefjord S, Persson M, Jönsson L, Skoglund T, Elam M. Clinical evaluation of a microwave-based device for detection of traumatic intracranial hemorrhage. J Neurotrauma. 2017;34:2176–2182. doi: 10.1089/neu.2016.4869.
    1. Kobeissy FH. Brain neurotrauma. Boca Raton: CRC Press; 2015.
    1. Vedin T, Svensson S, Edelhamre M, Karlsson M, Bergenheim M, Larsson PA. Management of mild traumatic brain injury-trauma energy level and medical history as possible predictors for intracranial hemorrhage. Eur J Trauma Emerg Surg. 2018;45(5):901–907. doi: 10.1007/s00068-018-0941-8.
    1. Mondello S, Sorinola A, Czeiter E, Vámos Z, Amrein K, Synnot A, et al. Blood-based protein biomarkers for the management of traumatic brain injuries in adults presenting to emergency departments with mild brain injury: a living systematic review and meta-analysis. J Neurotrauma. 2018 doi: 10.1089/neu.2017.5182.
    1. Gan ZS, Stein SC, Swanson R, Guan S, Garcia L, Mehta D, et al. Blood biomarkers for traumatic brain injury: a quantitative assessment of diagnostic and prognostic accuracy. Front Neurol. 2019;10:446. doi: 10.3389/fneur.2019.00446.
    1. Posti JP, Takala RSK, Lagerstedt L, Dickens AM, Hossain I, Mohammadian M, et al. Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury. J Neurotrauma. 2019;36:2178–2189. doi: 10.1089/neu.2018.6254.
    1. Vedin T, Karlsson M, Edelhamre M, Clausen L, Svensson S, Bergenheim M, et al. A proposed amendment to the current guidelines for mild traumatic brain injury: reducing computerized tomographies while maintaining safety. Eur J Trauma Emerg Surg. 2019 doi: 10.1007/s00068-019-01145-x.
    1. Fujii T, Faul M, Sasser S. Risk factors for cervical spine injury among patients with traumatic brain injury. J Emerg Trauma Shock. 2013;6:252–258. doi: 10.4103/0974-2700.120365.
    1. Adrian H, Mårten K, Salla N, Lasse V. Biomarkers of traumatic brain injury: temporal changes in body fluids. Eneuro. 2016 doi: 10.1523/ENEURO.0294-16.2016.
    1. Chenoweth JA, Gaona SD, Faul M, Holmes JF, Nishijima DK, Sacramento CPRC. Incidence of delayed intracranial hemorrhage in older patients after blunt head trauma. JAMA Surg. 2018;153:570–575. doi: 10.1001/jamasurg.2017.6159.
    1. Kim B, Jeong H, Kim J, Kim T, Kim K, Lee H, et al. Incidence and risk factors of delayed intracranial hemorrhage in the emergency department. Am J Emerg Med. 2018;36:271–276. doi: 10.1016/j.ajem.2017.08.009.
    1. Zurek J, Bartlová L, Fedora M. Hyperphosphorylated neurofilament NF-H as a predictor of mortality after brain injury in children. Brain Inj. 2011;25:221–226. doi: 10.3109/02699052.2010.541895.
    1. Vajtr D, Benada O, Linzer P, Sámal F, Springer D, Strejc P, et al. Immunohistochemistry and serum values of S-100B, glial fibrillary acidic protein, and hyperphosphorylated neurofilaments in brain injuries. Soud Lek. 2012;57:7–12.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner