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An Image-Based Framework for the Analysis of the Murine Microvasculature: From Tissue Clarification to Computational Hemodynamics

Author

Listed:
  • Santiago Mañosas

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain)

  • Aritz Sanz

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain)

  • Cristina Ederra

    (Imaging Platform, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain)

  • Ainhoa Urbiola

    (Imaging Platform, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain)

  • Elvira Rojas-de-Miguel

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
    Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain
    Oncohematology Research Group, Navarrabiomed, Hospital Universitario de Navarra (HUN), Irunlarrea 3, 31008 Pamplona, Spain)

  • Ainhoa Ostiz

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
    Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain
    Oncohematology Research Group, Navarrabiomed, Hospital Universitario de Navarra (HUN), Irunlarrea 3, 31008 Pamplona, Spain)

  • Iván Cortés-Domínguez

    (Imaging Platform, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain
    Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain)

  • Natalia Ramírez

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
    Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain
    Oncohematology Research Group, Navarrabiomed, Hospital Universitario de Navarra (HUN), Irunlarrea 3, 31008 Pamplona, Spain)

  • Carlos Ortíz-de-Solórzano

    (Imaging Platform, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain
    Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain
    CIBERONC, Centro de Investigación Biomédica en Red-Cáncer, Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain)

  • Arantxa Villanueva

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
    Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain)

  • Mauro Malvè

    (Department of Engineering, Campus Arrosadía s/n, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
    CIBER-BBN, Centro de Investigación Biomédica en Red-Bioingeniería, Biomateriales y Nanomedicina, C/Poeta Mariano Esquillor s/n, 50018 Zaragoza, Spain)

Abstract

The blood–brain barrier is a unique physiological structure acting as a filter for every molecule reaching the brain through the blood. For this reason, an effective pharmacologic treatment supplied to a patient by systemic circulation should first be capable of crossing the barrier. Standard cell cultures (or those based on microfluidic devices) and animal models have been used to study the human blood–brain barrier. Unfortunately, these tools have not yet reached a state of maturity because of the complexity of this physiological process aggravated by a high heterogeneity that is not easily recapitulated experimentally. In fact, the extensive research that has been performed and the preclinical trials carried out provided sometimes contradictory results, and the functionality of the barrier function is still not fully understood. In this study, we have combined tissue clarification, advanced microscopy and image analysis to develop a one-dimensional computational model of the microvasculature hemodynamics inside the mouse brain. This model can provide information about the flow regime, the pressure field and the wall shear stress among other fluid dynamics variables inside the barrier. Although it is a simplified model of the cerebral microvasculature, it allows a first insight on into the blood–brain barrier hemodynamics and offers several additional possibilities to systematically study the barrier microcirculatory processes.

Suggested Citation

  • Santiago Mañosas & Aritz Sanz & Cristina Ederra & Ainhoa Urbiola & Elvira Rojas-de-Miguel & Ainhoa Ostiz & Iván Cortés-Domínguez & Natalia Ramírez & Carlos Ortíz-de-Solórzano & Arantxa Villanueva & Ma, 2022. "An Image-Based Framework for the Analysis of the Murine Microvasculature: From Tissue Clarification to Computational Hemodynamics," Mathematics, MDPI, vol. 10(23), pages 1-20, December.
    • Handle: RePEc:gam:jmathe:v:10:y:2022:i:23:p:4593-:d:992992
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    References listed on IDEAS

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    1. Kwanghun Chung & Jenelle Wallace & Sung-Yon Kim & Sandhiya Kalyanasundaram & Aaron S. Andalman & Thomas J. Davidson & Julie J. Mirzabekov & Kelly A. Zalocusky & Joanna Mattis & Aleksandra K. Denisin &, 2013. "Structural and molecular interrogation of intact biological systems," Nature, Nature, vol. 497(7449), pages 332-337, May.
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