A mobile battery-powered brain perfusion ultrasound (BPU) device designed for prehospital stroke diagnosis: correlation to perfusion MRI in healthy volunteers

Mustafa Kilic, Fabien Scalzo, Chandler Lyle, Dobri Baldaranov, Maximilian Dirnbacher, Tristan Honda, David S Liebeskind, Felix Schlachetzki, Mustafa Kilic, Fabien Scalzo, Chandler Lyle, Dobri Baldaranov, Maximilian Dirnbacher, Tristan Honda, David S Liebeskind, Felix Schlachetzki

Abstract

Background: Early prehospital stroke identification is crucial for goal directed hospital admission especially in rural areas. However, clinical prehospital stroke scales are designed to identify any stroke but cannot sufficiently differentiate hemorrhagic from ischemic stroke, including large vessel occlusion (LVO) amenable to mechanical thrombectomy. We report on a novel small, portable and battery driven point-of-care ultrasound system (SONAS®) specifically developed for mobile non-invasive brain perfusion ultrasound (BPU) measurement after bolus injection of an echo-enhancing agent suitable for the use in prehospital stroke diagnosis filling a current, unmet and critical need for LVO identification.

Methods: In a phase I study of healthy volunteers we performed comparative perfusion-weighted magnetic resonance imaging (PWI) and BPU measurements, including safety analysis.

Results: Twelve volunteers (n = 7 females, n = 5 males, age ranging between 19 and 55 years) tolerated the measurement extremely well including analysis of blood-brain barrier integrity, and the correlation coefficient between the generated time kinetic curves after contrast agent bolus between PWI and BPU transducers ranged between 0.89 and 0.76.

Conclusions: Mobile BPU using the SONAS® device is feasible and safe with results comparable to PWI. When applied in conjunction with prehospital stroke scales this may lead to a more accurate stroke diagnosis and patients bypassing regular stroke units to comprehensive stroke centers. Further studies are needed in acute stroke patients and in the prehospital phase including assessment of immediate and long-term morbidity and mortality in stroke.

Trial registration: Clinical trials.gov, registered 28.Sep.2017, Identifier: NCT03296852.

Keywords: Brain perfusion ultrasound; Ischemic stroke; Large vessel occlusion; Point-of-care ultrasound; Prehospital diagnostics.

Conflict of interest statement

CL and MD are employees of BURL Concepts, Inc..

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Left: SONAS® headset. Right: SONAS® device, pre-commercial/trial version. Positioning of the transducers above the temporal bone window on both sides of the head with subject in supine position. 1: headset, 2: transducer, 3: power button, 4: “enter” button, 5: LCD screen, 6: USB port. Size: 19 × 19x12cm. Weight: 2,2 kg
Fig. 2
Fig. 2
Time intensity curves SONAS® (orange) versus pw-MRI (blue) for both, ipsilateral (left) and contralateral (right) data
Fig. 3
Fig. 3
Potential prehospital work flow with or without brain perfusion ultrasound (BPU), numbers are estimates based on all emergency stroke calls, including intracerebral hemorrhage (ICH), stroke mimics, stroke with large vessel occlusion (LVO). (1)—Primary transport of all suspected stroke patients admitted to the next regional stroke unit (rSU): short transport, widely available, fast symptom-to-needle time for thrombolysis, but no mechanical thrombectomy (MT) for LVO available. (2)—Secondary transport from the rSU to comprehensive stroke centers (CSC) for MT resulting in delay in symptom-to-groin time. (3)—Primary transport of all suspected stroke patients to CSCs: Longer symptom-to-needle times, short symptom-to-groin time, but congestion of CSC with non-LVO stroke patients. (4)—Prehospital identification of LVO using BPU and either direct transfer to CSC for MT or to rSU if no perfusion deficit detected

References

    1. Aronen HJ, Perkio J, Karonen JO, Vanninen RL, Ostergaard L, Liu Y, Kononen M, Vanninen EJ, Soimakallio S, Kuikka JT. Perfusion-weighted MRI in human acute ischemic stroke: A comparison with the progression of the infarct on diffusion-weighted images. Academic Radiology. 2002;9(Suppl 1):S160–164. doi: 10.1016/S1076-6332(03)80427-0.
    1. Copen WA, Lev MH, Rapalino O. Brain perfusion: Computed tomography and magnetic resonance techniques. Handbook of Clinical Neurology. 2016;135:117–135. doi: 10.1016/B978-0-444-53485-9.00006-4.
    1. Shaker H, Khan M, Mulderink T, Koehler TJ, Scurek R, Tubergen T, Packard L, Singer J, Mazaris P, Min J, et al. The Role of CT Perfusion in Defining the Clinically Relevant Core Infarction to Guide Thrombectomy Selection in Patients with Acute Stroke. Journal of Neuroimaging. 2019;29(3):331–334. doi: 10.1111/jon.12599.
    1. Smith LGF, Milliron E, Ho ML, Hu HH, Rusin J, Leonard J, Sribnick EA. Advanced neuroimaging in traumatic brain injury: An overview. Neurosurgical Focus. 2019;47(6):E17. doi: 10.3171/2019.9.FOCUS19652.
    1. Tong E, Sugrue L, Wintermark M. Understanding the Neurophysiology and Quantification of Brain Perfusion. Topics in Magnetic Resonance Imaging. 2017;26(2):57–65. doi: 10.1097/RMR.0000000000000128.
    1. Vilela P, Rowley HA. Brain ischemia: CT and MRI techniques in acute ischemic stroke. European Journal of Radiology. 2017;96:162–172. doi: 10.1016/j.ejrad.2017.08.014.
    1. Saver JL. Time is brain–quantified. Stroke. 2006;37(1):263–266. doi: 10.1161/01.STR.0000196957.55928.ab.
    1. Zhang X, Tong F, Li CX, Yan Y, Kempf D, Nair G, Wang S, Muly EC, Zola S, Howell L. Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study. PLoS ONE. 2015;10(2):e0117290. doi: 10.1371/journal.pone.0117290.
    1. Audebert H, Fassbender K, Hussain MS, Ebinger M, Turc G, Uchino K, Davis S, Alexandrov A, Grotta J, Group P. The PRE-hospital stroke treatment organization. International Journal of Stroke. 2017;12(9):932–940. doi: 10.1177/1747493017729268.
    1. Walter S, Zhao H, Easton D, Bil C, Sauer J, Liu Y, Lesmeister M, Grunwald IQ, Donnan GA, Davis SM, et al. Air-Mobile Stroke Unit for access to stroke treatment in rural regions. International Journal of Stroke. 2018;13(6):568–575. doi: 10.1177/1747493018784450.
    1. Schlachetzki F, Herzberg M, Holscher T, Ertl M, Zimmermann M, Ittner KP, Pels H, Bogdahn U, Boy S. Transcranial ultrasound from diagnosis to early stroke treatment: Part 2: prehospital neurosonography in patients with acute stroke: the Regensburg stroke mobile project. Cerebrovascular Diseases. 2012;33(3):262–271. doi: 10.1159/000334667.
    1. Herzberg M, Boy S, Holscher T, Ertl M, Zimmermann M, Ittner KP, Pemmerl J, Pels H, Bogdahn U, Schlachetzki F. Prehospital stroke diagnostics based on neurological examination and transcranial ultrasound. Critical Ultrasound Journal. 2014;6(1):3. doi: 10.1186/2036-7902-6-3.
    1. Kilic M, Pflug K, Theiss S, Webert M, Hirschmann N, Wagner A, Boy S, Ertl M, Linker RA, Schlachetzki F, et al. Prehospital identification of middle cerebral artery occlusion—A stroke education program and transcranial ultrasound for paramedics. Austin Journal of Clinical Neurology. 2020;7(2):1142.
    1. Backhaus R, Boy S, Fuchs K, Ulrich B, Schuierer G, Schlachetzki F. Hyperperfusion syndrome after MCA embolectomy - a rare complication? American Journal of Case Reports. 2013;14:513–517. doi: 10.12659/AJCR.889672.
    1. Rubiera M, Garcia-Tornel A, Olive-Gadea M, Campos D, Requena M, Vert C, Pagola J, Rodriguez-Luna D, Muchada M, Boned S, et al. Computed tomography perfusion after thrombectomy: An immediate surrogate marker of outcome after recanalization in acute stroke. Stroke. 2020;51(6):1736–1742. doi: 10.1161/STROKEAHA.120.029212.
    1. Imanishi Y, Fukui A, Niimi H, Itoh D, Nozaki K, Nakaji S, Ishizuka K, Tabata H, Furuya Y, Uzura M, et al. Radiation-induced temporary hair loss as a radiation damage only occurring in patients who had the combination of MDCT and DSA. European Radiology. 2005;15(1):41–46. doi: 10.1007/s00330-004-2459-1.
    1. Cohnen M, Wittsack HJ, Assadi S, Muskalla K, Ringelstein A, Poll LW, Saleh A, Modder U. Radiation exposure of patients in comprehensive computed tomography of the head in acute stroke. AJNR. American Journal of Neuroradiology. 2006;27(8):1741–1745.
    1. Parmentier-Decrucq E, Poissy J, Favory R, Nseir S, Onimus T, Guerry MJ, Durocher A, Mathieu D. Adverse events during intrahospital transport of critically ill patients: Incidence and risk factors. Annals of Intensive Care. 2013;3(1):10. doi: 10.1186/2110-5820-3-10.
    1. Bogdahn U, Holscher T, Rosin L, Gotz B, Schlachetzki F. Contrast-enhanced transcranial and extracranial duplex sonography: Preliminary results of a multicenter phase II/III study with SonoVuetrade mark. Echocardiography. 1999;16(7, Pt 2):761–766. doi: 10.1111/j.1540-8175.1999.tb00147.x.
    1. Scalzo F, Hao Q, Alger JR, Hu X, Liebeskind DS. Regional prediction of tissue fate in acute ischemic stroke. Annals of Biomedical Engineering. 2012;40(10):2177–2187. doi: 10.1007/s10439-012-0591-7.
    1. Schlachetzki F, Holscher T, Koch HJ, Draganski B, May A, Schuierer G, Bogdahn U. Observation on the integrity of the blood-brain barrier after microbubble destruction by diagnostic transcranial color-coded sonography. Journal of Ultrasound in Medicine. 2002;21(4):419–429. doi: 10.7863/jum.2002.21.4.419.
    1. Holodinsky JK, Patel AB, Thornton J, Kamal N, Jewett LR, Kelly PJ, Murphy S, Collins R, Walsh T, Cronin S, et al. Drip and ship versus direct to endovascular thrombectomy: The impact of treatment times on transport decision-making. European Stroke Journal. 2018;3(2):126–135. doi: 10.1177/2396987318759362.
    1. Weber R, Eyding J, Kitzrow M, Bartig D, Weimar C, Hacke W, Krogias C. Distribution and evolution of acute interventional ischemic stroke treatment in Germany from 2010 to 2016. Neurological Research and Practice. 2019;1:4. doi: 10.1186/s42466-019-0010-8.
    1. Jauch EC, Schwamm LH, Panagos PD, Barbazzeni J, Dickson R, Dunne R, Foley J, Fraser JF, Lassers G, Martin-Gill C, et al. Recommendations for Regional Stroke Destination Plans in Rural, Suburban, and Urban Communities From the Prehospital Stroke System of Care Consensus Conference: A Consensus Statement From the American Academy of Neurology, American Heart Association/American Stroke Association, American Society of Neuroradiology, National Association of EMS Physicians, National Association of State EMS Officials, Society of NeuroInterventional Surgery, and Society of Vascular and Interventional Neurology: Endorsed by the Neurocritical Care Society. Stroke. 2021;52(5):e133–e152. doi: 10.1161/STROKEAHA.120.033228.
    1. Duvekot MHC, Venema E, Rozeman AD, Moudrous W, Vermeij FH, Biekart M, Lingsma HF, Maasland L, Wijnhoud AD, Mulder L, et al. Comparison of eight prehospital stroke scales to detect intracranial large-vessel occlusion in suspected stroke (PRESTO): A prospective observational study. Lancet Neurology. 2021;20(3):213–221. doi: 10.1016/S1474-4422(20)30439-7.
    1. Duloquin G, Graber M, Garnier L, Mohr S, Giroud M, Vergely C, Bejot Y. Assessment of clinical scales for detection of large vessel occlusion in ischemic stroke patients from the Dijon stroke registry. Journal of Clinical Medicine. 2021;10(24):5893. doi: 10.3390/jcm10245893.
    1. Haight T, Tabaac B, Patrice KA, Phipps MS, Butler J, Johnson B, Aycock A, Toral L, Yarbrough KL, Schrier C, et al. The Maryland acute stroke emergency medical services routing pilot: expediting access to thrombectomy for stroke. Frontiers in Neurology. 2021;12:663472. doi: 10.3389/fneur.2021.663472.
    1. Yperzeele L, Van Hooff RJ, De Smedt A, Valenzuela Espinoza A, Van de Casseye R, Hubloue I, De Keyser J, Brouns R. Prehospital stroke care: Limitations of current interventions and focus on new developments. Cerebrovascular Diseases. 2014;38(1):1–9. doi: 10.1159/000363617.
    1. Antipova D, Eadie L, Macaden A, Wilson P. Diagnostic accuracy of clinical tools for assessment of acute stroke: A systematic review. BMC Emergency Medicine. 2019;19(1):49. doi: 10.1186/s12873-019-0262-1.
    1. Diaz-Gomez JL, Mayo PH, Koenig SJ. Point-of-Care Ultrasonography. New England Journal of Medicine. 2021;385(17):1593–1602. doi: 10.1056/NEJMra1916062.
    1. Valaikiene, J., Schlachetzki, F., Azevedo, E., Kaps, M., Lochner, P., Katsanos, A. H., Walter, U., Baracchini, C., & Skoloudik, D. (2021). Point-of-Care Ultrasound in Neurology. Statement of Report of the EAN SPN/ESNCH/ERcNsono Neuro-POCUS Working Group. Ultraschall Med, accepted.
    1. Postert T, Braun B, Meves S, Koster O, Przuntek H, Weber S, Buttner T. Contrast-enhanced transcranial color-coded sonography in acute hemispheric brain infarction. Stroke. 1999;30(9):1819–1826. doi: 10.1161/01.STR.30.9.1819.
    1. Meairs S. Contrast-enhanced ultrasound perfusion imaging in acute stroke patients. European Neurology. 2008;59(Suppl 1):17–26. doi: 10.1159/000114456.
    1. Rim SJ, Leong-Poi H, Lindner JR, Couture D, Ellegala D, Mason H, Durieux M, Kassel NF, Kaul S. Quantification of cerebral perfusion with "Real-Time" contrast-enhanced ultrasound. Circulation. 2001;104(21):2582–2587. doi: 10.1161/hc4601.099400.
    1. Antipova D, Eadie L, Makin S, Shannon H, Wilson P, Macaden A. The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas. PLoS ONE. 2020;15(10):e0239653. doi: 10.1371/journal.pone.0239653.
    1. Mort A, Eadie L, Regan L, Macaden A, Heaney D, Bouamrane MM, Rushworth G, Wilson P. Combining transcranial ultrasound with intelligent communication methods to enhance the remote assessment and management of stroke patients: Framework for a technology demonstrator. Health Informatics Journal. 2016;22(3):691–701. doi: 10.1177/1460458215580353.
    1. Emanuel AL, Meijer RI, van Poelgeest E, Spoor P, Serne EH, Eringa EC. Contrast-enhanced ultrasound for quantification of tissue perfusion in humans. Microcirculation. 2020;27(1):e12588. doi: 10.1111/micc.12588.
    1. Shen YT, Chen L, Yue WW, Xu HX. Artificial intelligence in ultrasound. European Journal of Radiology. 2021;139:109717. doi: 10.1016/j.ejrad.2021.109717.

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