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Modeling selective therapeutic hypothermia in case of acute ischemic stroke using a 1D hemodynamics model and a simplified brain geometry

1 Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany
2 Adceris GmbH & Co KG, Pforzheim, Germany (now at University of Stuttgart, Stuttgart, Germany)
3 Department of Neuroradiology, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany

Special Issues: Computational Techniques for Bio-Hemodynamics and Heat Transfer

Therapeutic hypothermia (TH) is an approved neuroproctetive treatment to reduce neurological morbidity and mortality after hypoxic-ischemic damage related to cardiac arrest and neonatal asphyxia. Also in the treatment of acute ischemic stroke (AIS), which in Western countries still shows a very high mortality rate of about 25 %, selective mild TH by means of Targeted Temperature Management (TTM) could potentially decrease final infarct volume. In this respect, a novel intracarotid blood cooling catheter system has recently been developed, which allows for combined carotid blood cooling and mechanical thrombectomy (MT) and aims at selective mild TH in the affected ischemic brain (core and penumbra). Unfortunately, so far direct measurement and control of cooled cerebral temperature requires invasive or elaborate MRI-assisted measurements. Computational modeling provides unique opportunities to predict the resulting cerebral temperatures on the other hand. In this work, a simplified 3D brain model was generated and coupled with a 1D hemodynamics model to predict spatio-temporal cerebral temperature profiles using finite element modeling. Cerebral blood and tissue temperatures as well as the systemic temperature were analyzed for physiological conditions as well as for a middle cerebral artery (MCA) M1 occlusion. Furthermore, vessel recanalization and its effect on cerebral temperature was analyzed. The results show a significant influence of collateral flow on the cooling effect and are in accordance with experimental data in animals. Our model predicted a possible neuroprotective temperature decrease of 2.5 ℃ for the territory of MCA perfusion after 60 min of blood cooling, which underlines the potential of the new device and the use of TTM in case of AIS.
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1. V. D. Worp, H. Bart, E. S. Sena, et al., Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis, Brain, 12 (2007), 3063-3074.

2. H. Chen, M. Chopp, Z. G. Zhang, et al., The Effect of Hypothermia on Transient Middle Cerebral Artery Occlusion in the Rat, J. Cereb. Blood Flow. Metab., 4 (1992), 621-628.

3. Y. H. Hwang, J. S. Jeon, Y. W. Kim, et al., Impact of immediate post-reperfusion cooling on outcome in patients with acute stroke and substantial ischemic changes, J. NeuroInt. Surg., 1 (2017), 21-25.

4. S. Schwab, D. Georgiadis, J. Berrouschot, et al., Feasibility and safety of moderate hypothermia after massive hemispheric infarction, Stroke, 32 (2001), 2033-2035.

5. H. B. van der Worp, M. R. Macleod, P. M. W. Bath, et al., EuroHYP-1 investigators, 2014. EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke, Int. J. Stroke, 9 (2014), 642-645.    

6. T. C. Wu and J. C. Grotta, Hypothermia for acute ischaemic stroke, Lancet Neurol., 3 (2013), 275-284.

7. C. Wu, W. Zhao, H. An, et al., Safety, feasibility, and potential efficacy of intraarterial selective cooling infusion for stroke patients treated with mechanical thrombectomy. J. Cereb. Blood Flow. Metab., 12 (2018), 2251-2260.

8. S. S. Song and P. D. Lyden, Overview of Therapeutic Hypothermia, Curr. Treat Options Neurol., 6 (2012), 541-548.

9. G. Cattaneo, M. Schumacher, J. Wolfertz, et al., Open access combined selective cerebral hypothermia and mechanical artery recanalization in acute ischemic stroke: In vitro study of cooling performance, Am. J. Neuroradiol. 11 (2015), 2114-2120.

10. G. Cattaneo, M. Schumacher, C. Maurer, et al., Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance, Am. J. Neuroradiol., 5 (2016), 885-891.

11. A. P. Avolio, Multi-branched model of the human arterial system, Med. Biol. Eng. Comput., 6 (1980), 709-718.

12. M. Schwarz, Modellbasierte Operationsplanung und Überwachung hypothermer Patienten, KIT Scientific Publishing, 2009.

13. M. Schwarz, M. W. Krueger, H. J. Busch, et al., Model-Based Assessment of Tissue Perfusion and Temperature in Deep Hypothermic Patients, IEEE Transact. Biomed. Eng., 7 (2010), 1577-1686.

14. F. Umansky, S. M. Juarez, M. Dujovny, et al., Microsurgical anatomy of the proximal segments of the middle cerebral artery, J. Neurosurg., 3 (1984), 458-467.

15. L. M. Parkes, W. Rashid, D. T. Chard, et al. Normal cerebral perfusion measurements using arterial spin labeling: Reproducibility, stability, and age and gender effects, Magnet. Reson. Med., 4 (2004), 736-743.

16. R. Fahrig, H. Nikolov, A. J. Fox, et al., A threedimensional cardiovascular flow phantom, Med. Phys., 8 (1999), 1589-1599.

17. J. S. Allen, H. Damasio and T. J. Grabowski, Normal neuroanatomical variation in the human brain: an MRI-volumetric study, Am. J. Phys. Anthropol., 4 (2002), 341-358.

18. Y. Ge, R. I. Grossman, J. S. Babb, et al., Age-related total gray matter and white matter changes in normal adult brain, Part II: Quantitative magnetization transfer ratio histogram analysis, Am. J. Neuroradiol., 8 (2002), 1334-1341.

19. Y. Taki, B. Thyreau, S. Kinomura, et al., Correlations among brain gray matter volumes, age, gender, and hemisphere in healthy individuals, PLOS ONE, 7 (2011), e22734.

20. F. Mut, S. Wright, G. A. Ascoli, et al., Morphometric, geographic, and territorial characterization of brain arterial trees, Int. J. Numer. Method Biomed. Eng., 7 (2014), 755-766.

21. J. Waschke and F. P. Sobotta, Atlas der Anatomie des Menschen: Kopf, Hals und Neuroanatomie. Urban und Fischer Verlag, 2010.

22. W. C. Wu, S. C. Lin, K. L. Wang, et al., Measurement of cerebral white matter perfusion using pseudocontinuous arterial spin labeling 3t magnetic resonance imaging - an experimental and theoretical investigation of feasibility, PLoS ONE, 2013.

23. K. Zilles and B. N. Tillmann, Anatomie Springer Verlag, 2010.

24. N. Tariq and R. Khatri, Leptomeningeal collaterals in acute ischemic stroke, J. Vasc. Interv. Neurol., 1 (2008), 91-95.

25. D. S. Liebeskind, Collateral circulation, Stroke, 8 (2003), 2279-2284.

26. H. M. Vander Eecken and R. D. Adams, The anatomy and functional significance of the meningeal arterial anastomoses of the human brain, J. Neuropathol. Exper. neurol., 12 (1953), 132-157.

27. A. Frydrychowski, A. Szarmach, B. Czaplewski, et al., Subarachnoid space: New tricks by an old dog. PloS one, 7 (2012), 37529.

28. A. Bashkatov, E. Genina, Y. P. Sinichkin, et al., Glucose and mannitol diffusion in human dura mater, Biophys. J., 85 (2003), 3310-3318.

29. H. Li, J. Ruan, Z. Xie, et al., Investigation of the critical geometric characteristics of living human skulls utilising medical image analysis techniques, Int. J. Veh. Saf.,2 (2007), 345-367.

30. H. Hori, G. Moretti, A. Rebora, et al., The thickness of human scalp: normal and bald, J. Invest. Dermatol., 6 (1972), 396-369.

31. M. Geerligs, Skin layer mechanics, PhD thesis, Department of Biomedical Engineering, TU Eindhoven, Eindhoven 2010.

32. H. H. Pennes, Analysis of Tissue and Arterial Blood Temperatures in the Resting Human Forearm, J. Appl. Physiol., 1 (1948), 5-34.

33. B. Pliskov, K. Mitra and M. Kaya, Simulation of scalp cooling by external devices for prevention of chemotherapy-induced alopecia, J. Therm. Biol., 56 (2016), 199-205.

34. P. Hasgall, F. Di Gennaro, C. Baumgartner, et al., IT'IS Database for thermal and electromagnetic parameters of biological tissues, vol. 4.0, May 2018. Available from: itis.swiss/database 35. A.-A. Konstas, M. A. Neimark, A. F. Laine, et al., A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain, J. Appl. Physiol., 4 (2007), 1329-1340.

36. L. Mcilvoy, Comparison of brain temperature to core temperature: a review of the literature. J. Neurosci. Nurs., 1 (2004), 23-31.

37. B. Karaszewski, J. M. Wardlaw, I. Marshall, et al., Measurement of brain temperature with magnetic resonance spectroscopy in acute ischemic stroke., Ann. Neurol., 4 (2006), 438-446.

38. T. C. Jackson and P. M. Kochanek. A New Vision for Therapeutic Hypothermia in the Era of Targeted Temperature Management: A Speculative Synthesis. Ther. Hypothermia Tem. Manag., 1 (2019), 13-47.

39. J. N. Stankowski and R. Gupta, Therapeutic targets for neuroprotection in acute ischemic stroke: lost in translation?, Antioxid. Redox Signal., 10 (2011), 1841-1851.

40. J. Wolfertz, S. Meckel, A. Guber, et al., Mathematical, numerical and in-vitro investigation of cooling performance of an intra-carotid catheter for selective brain hypothermia, Curr. Direct. Biomed. Eng., 1 (2015), 390-394.

41. J. Caroff, R. M. King, J. E. Mitchell, et al., Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept, J. NeuroInt. Surg., (2019), 1-6.

42. Y. Lutz, A. Loewe, S. Meckel, et al., Combined Local Hypothermia and Recanalization Therapy for Acute Ischemic Stroke: Estimation of Brain and Systemic Temperature Using an Energetic Numerical Model, Thermal Biol., 84 (2019), 316-322.

43. H. Lippert and R. Papst, Arterial variations in man: classification and frequency, J.F. BergmannVerlag Mnchen, 1985.

44. K. Cilliers, Anatomy of the middle cerebral artery: Cortical branches, branching pattern and anomalies, Trukish Neurosurg., 5(2017), 671-681.

45. M. A. Stefani, F. L. Schneider, A. C. H. Marrone, et al., Anatomic variations of anterior cerebral artery cortical branches, Clin. Anat., 4 (2000), 231-236.

46. K. Cilliers and B. Page, Detailed description of the anterior cerebral artery anomalies observed in a cadaver population, Ann. Anatomy-Anat. Anz., 208 (2016),1-8.

47. A. A. Zeal and A. L. Rhoton Jr., Microsurgical anatomy of the posterior cerebral artery, J. Neurosurg., 4 (1978), 534-559.

48. M. Pham and M. Bendszus, Facing time in ischemic stroke: an alternative hypothesis for collateral failure, Clin. Neuroradiol., 2 (2016), 141-151.

© 2020 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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