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In Vivo MRI Assessment of Blood Flow in Arteries and Veins from Head-to-Toe Across Age and Sex in C57BL/6 Mice

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Abstract

Although widely used as a preclinical model for studying cardiovascular diseases, there is a scarcity of in vivo hemodynamic measurements of the naïve murine system in multiple arterial and venous locations, from head-to-toe, and across sex and age. The purpose of this study is to quantify cardiovascular hemodynamics in mice at different locations along the vascular tree while evaluating the effects of sex and age. Male and female, adult and aged mice were anesthetized and underwent magnetic resonance imaging. Data were acquired from four co-localized vessel pairs (carotid/jugular, suprarenal and infrarenal aorta/inferior vena cava (IVC), femoral artery/vein) at normothermia (core temperature 37 ± 0.2 °C). Influences of age and sex on average velocity differ by location in arteries. Average arterial velocities, when plotted as a function of distance from the heart, decrease nearly linearly from the suprarenal aorta to the femoral artery (adult and aged males: − 0.33 ± 0.13, R2 = 0.87; − 0.43 ± 0.10, R2 = 0.95; adult and aged females: − 0.23 ± 0.07, R2 = 0.91; − 0.23 ± 0.02, R2 = 0.99). Average velocity of aged males and average volumetric flow of aged males and females tended to be larger compared to adult comparators. With cardiovascular disease as the leading cause of death and with the implications of cardiovascular hemodynamics as important biomarkers for health and disease, this work provides a foundation for sex and age comparisons in pathophysiology by collecting and analyzing hemodynamic data for the healthy murine arterial and venous system from head-to-toe, across sex and age.

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References

  1. Amirbekian, S., R. C. Long, M. A. Consolini, J. Suo, N. J. Willett, S. W. Fielden, et al. In vivo assessment of blood flow patterns in abdominal aorta of mice with MRI: implications for AAA localization. Am. J. Physiol. Circ. Physiol. 297(4):H1290–H1295, 2009.

    CAS  Google Scholar 

  2. Arshad, A., A. J. Moss, E. Foster, L. Padeletti, A. Barsheshet, I. Goldenberg, et al. Cardiac resynchronization therapy is more effective in women than in men. J. Am. Coll. Cardiol. 57(7):813–820, 2011.

    PubMed  Google Scholar 

  3. Aslanidou, L., B. Trachet, P. Reymond, R. A. Fraga-Silva, P. Segers, and N. Stergiopulos. A 1D model of the arterial circulation in mice. ALTEX 33(1):13–28, 2016.

    PubMed  Google Scholar 

  4. Bauersachs, R. M., H. Riess, V. Hach-Wunderle, H. Gerlach, H. Carnarius, S. Eberle, et al. Impact of gender on the clinical presentation and diagnosis of deep-vein thrombosis. Thromb. Haemost. 103(4):710–717, 2010.

    CAS  PubMed  Google Scholar 

  5. Berg, J., L. Bjorck, K. Dudas, G. Lappas, and A. Rosengren. Symptoms of a first acute myocardial infarction in women and men. Gend. Med. 6(3):454–462, 2009.

    PubMed  Google Scholar 

  6. Bradley, S. E. The estimation of hepatic blood flow in man. J. Clin. Investig. 24(6):890, 1945.

    PubMed  Google Scholar 

  7. Castle, P. E., U. M. Scheven, A. C. Crouch, A. A. Cao, C. J. Goergen, and J. M. Greve. Anatomical location, sex, and age influence murine arterial circumferential cyclic strain before and during dobutamine infusion. J. Magn. Reson. Imaging 49(1):69–80, 2019.

    PubMed  Google Scholar 

  8. CDC. Aortic Aneurysm Fact Sheet Abdominal Aortic Aneurysms Other Types of Aneurysms Risk Factors for Aortic Aneurysm. Atlanta: CDC, 2016.

    Google Scholar 

  9. Cecchi, E., C. Giglioli, S. Valente, C. Lazzeri, G. F. Gensini, R. Abbate, et al. Role of hemodynamic shear stress in cardiovascular disease. Atherosclerosis 214(2):249–256, 2011.

    CAS  PubMed  Google Scholar 

  10. Cecchi, E., C. Giglioli, S. Valente, C. Lazzeri, G. F. Gensini, R. Abbate, et al. Role of hemodynamic shear stress in cardiovascular disease. Atherosclerosis 214(2):249–256, 2011.

    CAS  PubMed  Google Scholar 

  11. Clayton, J. A., and F. S. Collins. Policy: NIH to balance sex in cell and animal studies. Nature 509(7500):282–283, 2014.

    PubMed  PubMed Central  Google Scholar 

  12. Constantinides, C., R. Mean, and B. J. Janssen. Effects of isoflurane anesthesia on the cardiovascular function of the C57BL/6 mouse. ILAR J. 52(3):e21–e31, 2011.

    PubMed  PubMed Central  Google Scholar 

  13. Crouch, A. C., A. B. Manders, A. A. Cao, U. M. Scheven, and J. M. Greve. Cross-sectional area of the murine aorta linearly increases with increasing core body temperature. Int. J. Hyperth. 34(7):1121–1133, 2018.

    CAS  Google Scholar 

  14. Crouch, A. C., U. M. Scheven, and J. M. Greve. Cross-sectional areas of deep/core veins are smaller at lower core body temperatures. Physiol. Rep. 6(16):e13839, 2018.

    PubMed  PubMed Central  Google Scholar 

  15. Dart, A., X.-J. Du, and B. A. Kingwell. Gender, sex hormones and autonomic nervous control of the cardiovascular system. Cardiovasc. Res. 53(3):678–687, 2002.

    CAS  PubMed  Google Scholar 

  16. Demontis, F., R. Piccirillo, A. L. Goldberg, and N. Perrimon. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models. Dis. Model Mech. 6(6):1339–1352, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Flurkey, K., J. Mcurrer, and D. Harrison. Mouse models in aging research. In: The Mouse in Biomedical Research, edited by K. Flurkey, J. Mcurrer, and D. Harrison. New York: Elsevier, 2007, pp. 637–672.

    Google Scholar 

  18. Frayn, K. N., P. Arner, and H. Yki-Järvinen. Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem. 42:89–103, 2006.

    CAS  PubMed  Google Scholar 

  19. Greve, J. M., A. S. Les, B. T. Tang, M. T. Draney Blomme, N. M. Wilson, R. L. Dalman, et al. Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics. Am. J. Physiol. Circ. Physiol. 291(4):H1700–H1708, 2006.

    CAS  Google Scholar 

  20. Hamlin, R. L., and R. A. Altschuld. Extrapolation from mouse to man. Circ. Cardiovasc. Imaging 4(1):2–4, 2011.

    PubMed  Google Scholar 

  21. Hayward, C., W. V. Kalnins, and R. P. Kelly. Gender-related differences in left ventricular chamber function. Cardiovasc. Res. 49(2):340–350, 2001.

    CAS  PubMed  Google Scholar 

  22. Houghton, D., T. W. Jones, S. Cassidy, M. Siervo, G. A. MacGowan, M. I. Trenell, et al. The effect of age on the relationship between cardiac and vascular function. Mech. Ageing Dev. 153:1–6, 2016.

    PubMed  PubMed Central  Google Scholar 

  23. Huo, Y., X. Guo, and G. S. Kassab. The flow field along the entire length of mouse aorta and primary branches. Ann. Biomed. Eng. 36(5):685–699, 2008.

    PubMed  Google Scholar 

  24. Huxley, V. H. Sex and the cardiovascular system: the intriguing tale of how women and men regulate cardiovascular function differently. Adv. Physiol. Educ. 31(1):17–22, 2007.

    PubMed  PubMed Central  Google Scholar 

  25. Katz, M. L., and E. N. Bergman. Simultaneous measurements of hepatic and portal venous blood flow in the sheep and dog. Am. J. Physiol. 216(4):946–952, 1969.

    CAS  PubMed  Google Scholar 

  26. Kenney, W. L., and T. A. Munce. Physiology of aging invited review: aging and human temperature regulation. Pandolf KB Exp. Aging Res. Ageing Res. Rev. Exp. Aging Res. 17(17):41–76, 1997.

    Google Scholar 

  27. Lakatta, E. G., and D. Levy. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: A “set up” for vascular disease. Circulation 107(1):139–146, 2003.

    PubMed  Google Scholar 

  28. Lemieux, S., J. P. Despr, S. Moorjani, A. Nadeau, G. Th, D. Prud, et al. Are gender differences in cardiovascular disease risk factors explained by the level of visceral adipose tissue? Diabetologia 37(8):757–764, 1994.

    CAS  PubMed  Google Scholar 

  29. Lotz, J., C. Meier, A. Leppert, and M. Galanski. Cardiovascular flow measurement with phase-contrast MR imaging: basic facts and implementation. RadioGraphics 22(3):651–671, 2002.

    PubMed  Google Scholar 

  30. Maas, A. H. E. M., and Y. E. A. Appelman. Gender differences in coronary heart disease. Neth. Heart J. 18(12):598–602, 2010.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Markl, M. Velocity Encoding and Flow Imaging, 2005. http://ee-classes.usc.edu/ee591/library/Markl-FlowImaging.pdf.

  32. Mattson, J. M., and Y. Zhang. Structural and functional differences between porcine aorta and vena cava. J. Biomech. Eng. 139(7):071007, 2017.

    Google Scholar 

  33. Mensah, G. A., and D. W. Brown. An overview of cardiovascular disease burden in the United States. Health Aff. 26(1):38–48, 2007.

    Google Scholar 

  34. Mozaffarian, D., E. J. Benjamin, A. S. Go, D. K. Arnett, M. J. Blaha, M. Cushman, et al. Heart Disease and Stroke Statistics—2016 Update. Circulation 133(4):e38, 2016.

    PubMed  Google Scholar 

  35. Nerem, R. M. Vascular fluid mechanics, the arterial wall, and atherosclerosis. J. Biomech. Eng. 114(3):274, 1992.

    CAS  PubMed  Google Scholar 

  36. Palmer, O. R., C. B. Chiu, A. Cao, U. M. Scheven, J. A. Diaz, and J. M. Greve. In vivo characterization of the murine venous system before and during dobutamine stimulation: implications for preclinical models of venous disease. Ann. Anat. Anat. Anz. 214:43–52, 2017.

    Google Scholar 

  37. Rodriguez, G., S. Warkentin, J. Risberg, and G. Rosadini. Sex differences in regional cerebral blood flow. J. Cereb. Blood Flow Metab. 8(6):783–789, 1988.

    CAS  PubMed  Google Scholar 

  38. Rossouw, J. Hormones, genetic factors, and gender differences in cardiovascular disease. Cardiovasc. Res. 53(3):550–557, 2002.

    CAS  PubMed  Google Scholar 

  39. Song, W., L. Zhou, K. L. Kot, H. Fan, J. Han, and J. Yi. Measurement of flow-mediated dilation of mouse femoral artery in vivo by optical coherence tomography. J. Biophoton. 11(11):e201800053, 2018.

    Google Scholar 

  40. Suo, J., D. E. Ferrara, D. Sorescu, R. E. Guldberg, W. R. Taylor, and D. P. Giddens. Hemodynamic shear stresses in mouse aortas. Arterioscler. Thromb. Vasc. Biol. 27(2):346–351, 2007.

    CAS  PubMed  Google Scholar 

  41. WHO. WHO | Cardiovascular Diseases (CVDs). Geneva: WHO, 2017.

    Google Scholar 

  42. Williams, R., A. Needles, E. Cherin, Y.-Q. Zhou, R. M. Henkelman, S. L. Adamson, et al. Noninvasive ultrasonic measurement of regional and local pulse-wave velocity in mice. Ultrasound Med. Biol. 33(9):1368–1375, 2007.

    PubMed  Google Scholar 

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Acknowledgments

Thank you to Dr. Olivia Palmer for her assistance with venous data acquisition.

Funding

This project is supported by Grant Number T32-HL125242 from the NIH (A. Colleen Crouch).

Author Contributions

A Colleen Crouch (ACC), Amos A. Cao (AAC), Ulrich M Scheven (UMS), and Joan M Greve (JMG). ACC conceived and designed the study; AAC wrote the PCMRI pulse sequence; ACC, AAC, UMS developed the in-house image analysis method; ACC collected and analyzed data, performed statistical analysis and interpreted the data; ACC and JMG wrote the paper; ACC and JMG critically revised the paper; all authors gave final approval of the paper.

Disclosure

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Mechanical Engineering, University of Michigan, 1049 Bonisteel Interdisciplinary Research Building, 2360 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA

    A. Colleen Crouch & Ulrich M. Scheven

  2. Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

    Amos A. Cao & Joan M. Greve

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  1. A. Colleen Crouch
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Correspondence to A. Colleen Crouch.

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Associate Editor Ender A Finol oversaw the review of this article.

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10439_2019_2350_MOESM1_ESM.docx

Supplementary material 1 (DOCX 20 kb) Table S1. A summary of arterial wall shear stress (average, systolic, and diastolic) data for all groups.

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Crouch, A.C., Cao, A.A., Scheven, U.M. et al. In Vivo MRI Assessment of Blood Flow in Arteries and Veins from Head-to-Toe Across Age and Sex in C57BL/6 Mice. Ann Biomed Eng 48, 329–341 (2020). https://doi.org/10.1007/s10439-019-02350-w

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