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Cardiac and respiratory-gated volumetric murine ultrasound

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Abstract

Current cardiovascular ultrasound mainly employs planar imaging techniques to assess function and physiology. These techniques rely on geometric assumptions, which are dependent on the imaging plane, susceptible to inter-observer variability, and may be inaccurate when studying complex diseases. Here, we developed a gated volumetric murine ultrasound technique to visualize cardiovascular motion with high spatiotemporal resolution and directly evaluate cardiovascular health. Cardiac and respiratory-gated cine loops, acquired at 1000 frames-per-second from sequential positions, were temporally registered to generate a four-dimensional (4D) dataset. We applied this technique to (1) evaluate left ventricular (LV) function from both healthy mice and mice with myocardial infarction and (2) characterize aortic wall strain of angiotensin II-induced dissecting abdominal aortic aneurysms in apolipoprotein E-deficient mice. Combined imaging and processing times for the 4D technique was approximately 2–4 times longer than conventional 2D approaches, but substantially more data is collected with 4D ultrasound and further optimization can be implemented to reduce imaging times. Direct volumetric measurements of 4D cardiac data aligned closely with those obtained from MRI, contrary to conventional methods, which were sensitive to transducer alignment, leading to overestimation or underestimation of estimated LV parameters in infarcted hearts. Green–Lagrange circumferential strain analysis revealed higher strain values proximal and distal to the aneurysm than within the aneurysmal region, consistent with published reports. By eliminating the need for geometrical assumptions, the presented 4D technique can be used to more accurately evaluate cardiac function and aortic pulsatility. Furthermore, this technique allows for the visualization of regional differences that may be overlooked with conventional 2D approaches.

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References

  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER, 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee, Stroke Statistics Subcommittee (2016) Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133 (4):e38–e60. https://doi.org/10.1161/CIR.0000000000000350

    Article  PubMed  Google Scholar 

  2. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ, American Heart Association Advocacy Coordinating Committee, Stroke Council, Council on Cardiovascular Radiology and Intervention, Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Cardiovascular Nursing, Council on the Kidney in Cardiovascular Disease, Council on Cardiovascular Surgery and Anesthesia, Interdisciplinary Council on Quality of Care and Outcomes Research (2011) Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation 123 (8):933–944. https://doi.org/10.1161/CIR.0b013e31820a55f5

    Article  PubMed  Google Scholar 

  3. Li G, Citrin D, Camphausen K, Mueller B, Burman C, Mychalczak B, Miller RW, Song Y (2008) Advances in 4D medical imaging and 4D radiation therapy. Technol Cancer Res Treat 7(1):67–81

    Article  CAS  PubMed  Google Scholar 

  4. Mihalef V, Ionasec RI, Sharma P, Georgescu B, Voigt I, Suehling M, Comaniciu D (2011) Patient-specific modelling of whole heart anatomy, dynamics and haemodynamics from four-dimensional cardiac CT images. Interface Focus 1(3):286–296. https://doi.org/10.1098/rsfs.2010.0036

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gao M, Huang J, Zhang S, Qian Z, Voros S, Metaxas D, Axel L (2011) 4D cardiac reconstruction using high resolution CT images. In: Functional imaging and modeling of the heart. Springer, Berlin, pp 153–160

  6. Allen BD, Barker AJ, Parekh K, Sommerville LC, Schnell S, Jarvis KB, Carr M, Carr J, Collins J, Markl M (2013) Incorporating time-resolved three-dimensional phase contrast (4D flow) MRI in clinical workflow: initial experiences at a large tertiary care medical center. Resonance 15(1):P32

    Google Scholar 

  7. Stankovic Z, Allen BD, Garcia J, Jarvis KB, Markl M (2014) 4D flow imaging with MRI. Cardiovasc Diagn Ther 4(2):173–192. https://doi.org/10.3978/j.issn.2223-3652.2014.01.02

    PubMed  PubMed Central  Google Scholar 

  8. Corsi C, Saracino G, Sarti A, Lamberti C (2002) Left ventricular volume estimation for real-time three-dimensional echocardiography. IEEE Trans Med Imaging 21(9):1202–1208. https://doi.org/10.1109/TMI.2002.804418

    Article  PubMed  Google Scholar 

  9. Qin Y, Zhang Y, Zhou X, Wang Y, Sun W, Chen L, Zhao D, Zhan Y, Cai A (2014) Four-dimensional echocardiography with spatiotemporal image correlation and inversion mode for detection of congenital heart disease. Ultrasound Med Biol 40(7):1434–1441. https://doi.org/10.1016/j.ultrasmedbio.2014.02.008

    Article  PubMed  Google Scholar 

  10. Schoechlin S, Ruile P, Neumann FJ, Pache G (2015) Early hypoattenuated leaflet thickening and restricted leaflet motion of a Lotus transcatheter heart valve detected by 4D computed tomography angiography. EuroIntervention 11(5):e1. https://doi.org/10.4244/EIJV11I5A118

    Article  PubMed  Google Scholar 

  11. Po MJ, Lorsakul A, Duan Q, Yeroushalmi KJ, Hyodo E, Oe Y, Homma S, Laine AF (2010) In-vivo clinical validation of cardiac deformation and strain measurements from 4D ultrasound. Conf Proc IEEE Eng Med Biol Soc 2010:41–44. https://doi.org/10.1109/IEMBS.2010.5626332

    PubMed  PubMed Central  Google Scholar 

  12. Derwich W, Wittek A, Pfister K, Nelson K, Bereiter-Hahn J, Fritzen CP, Blase C, Schmitz-Rixen T (2016) High resolution strain analysis comparing aorta and abdominal aortic aneurysm with real time three dimensional speckle tracking ultrasound. Eur J Vasc Endovasc Surg 51(2):187–193. https://doi.org/10.1016/j.ejvs.2015.07.042

    Article  CAS  PubMed  Google Scholar 

  13. Kaplan HM, Brewer NR, Blair WH (2007) Physiology. In: Fox JG, Barthold SW, Davisson MT et al (eds) The mouse in biomedical research, vol 3, 2nd edn. Academic Press, San Diego, pp 247–292

    Google Scholar 

  14. Badea CT, Hedlund LW, Mackel JF, Mao L, Rockman HA, Johnson GA (2007) Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice. Mol Imaging 6(4):261–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Polte CL, Lagerstrand KM, Gao SA, Lamm CR, Bech-Hanssen O (2015) Quantification of left ventricular linear, areal and volumetric dimensions: a phantom and in vivo comparison of 2-D and real-time 3-D echocardiography with cardiovascular magnetic resonance. Ultrasound Med Biol. https://doi.org/10.1016/j.ultrasmedbio.2015.03.001

    PubMed  Google Scholar 

  16. Hoit BD (2001) New approaches to phenotypic analysis in adult mice. J Mol Cell Cardiol 33(1):27–35. https://doi.org/10.1006/jmcc.2000.1294

    Article  CAS  PubMed  Google Scholar 

  17. Keall PJ, Vedam SS, George R, Williamson JF (2007) Respiratory regularity gated 4D CT acquisition: concepts and proof of principle. Australas Phys Eng Sci Med 30(3):211–220

    Article  CAS  PubMed  Google Scholar 

  18. Coatney RW (2001) Ultrasound imaging: principles and applications in rodent research. ILAR J 42(3):233–247

    Article  CAS  PubMed  Google Scholar 

  19. Hoole SP, Boyd J, Ninios V, Parameshwar J, Rusk RA (2008) Measurement of cardiac output by real-time 3D echocardiography in patients undergoing assessment for cardiac transplantation. Eur J Echocardiogr 9(3):334–337. https://doi.org/10.1016/j.euje.2007.03.033

    PubMed  Google Scholar 

  20. Damen FW, Adelsperger AR, Wilson KE, Goergen CJ (2015) Comparison of traditional and integrated digital anesthetic vaporizers. J Am Assoc Lab Anim Sci 54(6):756–762

    PubMed  PubMed Central  Google Scholar 

  21. Kolk MV, Meyberg D, Deuse T, Tang-Quan KR, Robbins RC, Reichenspurner H, Schrepfer S (2009) LAD-ligation: a murine model of myocardial infarction. J Vis Exp. https://doi.org/10.3791/1438

    PubMed  PubMed Central  Google Scholar 

  22. Muthuramu I, Lox M, Jacobs F, De Geest B (2014) Permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure. J Vis Exp. https://doi.org/10.3791/52206

    PubMed  PubMed Central  Google Scholar 

  23. Daugherty A, Cassis L (1999) Chronic angiotensin II infusion promotes atherogenesis in low density lipoprotein receptor -/- mice. Ann N Y Acad Sci 892:108–118

    Article  CAS  PubMed  Google Scholar 

  24. Daugherty A, Manning MW, Cassis LA (2000) Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest 105(11):1605–1612. https://doi.org/10.1172/JCI7818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Folland ED, Parisi AF, Moynihan PF, Jones DR, Feldman CL, Tow DE (1979) Assessment of left ventricular ejection fraction and volumes by real-time, two-dimensional echocardiography. A comparison of cineangiographic and radionuclide techniques. Circulation 60(4):760–766

    Article  CAS  PubMed  Google Scholar 

  26. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ, Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18(12):1440–1463. https://doi.org/10.1016/j.echo.2005.10.005

    Article  PubMed  Google Scholar 

  27. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28(1):1–39.e14. https://doi.org/10.1016/j.echo.2014.10.003

    Article  PubMed  Google Scholar 

  28. Dele-Michael AO, Fujikura K, Devereux RB, Islam F, Hriljac I, Wilson SR, Lin F, Weinsaft JW (2013) Left ventricular stroke volume quantification by contrast echocardiography—comparison of linear and flow-based methods to cardiac magnetic resonance. Echocardiography 30(8):880–888. https://doi.org/10.1111/echo.12155

    Article  PubMed  PubMed Central  Google Scholar 

  29. Holzapfel GA (2000) Nonlinear solid mechanics: a continuum approach for engineering. West Sussex: Wiley

    Google Scholar 

  30. Sonesson B, Hansen F, Lanne T (1997) Abdominal aortic aneurysm: a general defect in the vasculature with focal manifestations in the abdominal aorta? J Vasc Surg 26(2):247–254

    Article  CAS  PubMed  Google Scholar 

  31. Ailawadi G, Eliason JL, Upchurch GR Jr (2003) Current concepts in the pathogenesis of abdominal aortic aneurysm. J Vasc Surg 38(3):584–588

    Article  PubMed  Google Scholar 

  32. Phillips EH, Yrineo AA, Schroeder HD, Wilson KE, Cheng JX, Goergen CJ (2015) Morphological and biomechanical differences in the elastase & AngII apoE–/– rodent models of abdominal aortic aneurysms. BioMed Res Int 2015:1–12, Article ID 413189. https://doi.org/10.1155/2015/413189

  33. Otterstad JE (2002) Measuring left ventricular volume and ejection fraction with the biplane Simpson’s method. Heart 88(6):559–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kasai T, Depuey EG, Shah AA (2004) Compared with 3-dimensional analysis, 2-dimensional gated SPECT analysis overestimates left ventricular ejection fraction in patients with regional dyssynchrony. J Nucl Cardiol 11(2):159–164. https://doi.org/10.1016/j.nuclcard.2003.11.005

    Article  PubMed  Google Scholar 

  35. Michael LH, Entman ML, Hartley CJ, Youker KA, Zhu J, Hall SR, Hawkins HK, Berens K, Ballantyne CM (1995) Myocardial ischemia and reperfusion: a murine model. Am J Physiol 269(6 Pt 2):H2147–H2154

    CAS  PubMed  Google Scholar 

  36. Brekken R, Bang J, Odegard A, Aasland J, Hernes TA, Myhre HO (2006) Strain estimation in abdominal aortic aneurysms from 2-D ultrasound. Ultrasound Med Biol 32(1):33–42. https://doi.org/10.1016/j.ultrasmedbio.2005.09.007

    Article  PubMed  Google Scholar 

  37. Taniguchi R, Hoshina K, Hosaka A, Miyahara T, Okamoto H, Shigematsu K, Miyata T, Watanabe T (2014) Strain analysis of wall motion in abdominal aortic aneurysms. Ann Vasc Dis 7(4):393–398. https://doi.org/10.3400/avd.oa.14-00067

    Article  PubMed  PubMed Central  Google Scholar 

  38. Trachet B, Fraga-Silva RA, Londono FJ, Swillens A, Stergiopulos N, Segers P (2015) Performance comparison of ultrasound-based methods to assess aortic diameter and stiffness in normal and aneurysmal mice. PLoS ONE 10(5):e0129007. https://doi.org/10.1371/journal.pone.0129007

    Article  PubMed  PubMed Central  Google Scholar 

  39. Goergen CJ, Azuma J, Barr KN, Magdefessel L, Kallop DY, Gogineni A, Grewall A, Weimer RM, Connolly AJ, Dalman RL, Taylor CA, Tsao PS, Greve JM (2011) Influences of aortic motion and curvature on vessel expansion in murine experimental aneurysms. Arterioscler Thromb Vasc Biol 31(2):270–279. https://doi.org/10.1161/ATVBAHA.110.216481

    Article  CAS  PubMed  Google Scholar 

  40. Luo J, Fujikura K, Tyrie LS, Tilson MD, Konofagou EE (2009) Pulse wave imaging of normal and aneurysmal abdominal aortas in vivo. IEEE Trans Med Imaging 28(4):477–486. https://doi.org/10.1109/TMI.2008.928179

    Article  PubMed  Google Scholar 

  41. Nandlall SD, Goldklang MP, Kalashian A, Dangra NA, D’Armiento JM, Konofagou EE (2014) Monitoring and staging abdominal aortic aneurysm disease with pulse wave imaging. Ultrasound Med Biol 40(10):2404–2414. https://doi.org/10.1016/j.ultrasmedbio.2014.04.013

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nandlall SD, Konofagou EE (2016) Assessing the stability of aortic aneurysms with pulse wave imaging. Radiology 281(3):772–781. https://doi.org/10.1148/radiol.2016151407

    Article  PubMed  PubMed Central  Google Scholar 

  43. Goergen CJ, Barr KN, Huynh DT, Eastham-Anderson JR, Choi G, Hedehus M, Dalman RL, Connolly AJ, Taylor CA, Tsao PS, Greve JM (2010) In vivo quantification of murine aortic cyclic strain, motion, and curvature: implications for abdominal aortic aneurysm growth. J Magn Reson Imaging 32(4):847–858. https://doi.org/10.1002/jmri.22331

    Article  PubMed  PubMed Central  Google Scholar 

  44. FUJIFILM VisualSonics Inc (2017) Vevo3100: the ultimate preclinical imaging experience [online]. https://www.visualsonics.com/product/imaging-systems/vevo-3100

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Acknowledgements

The authors acknowledge technical assistance from Kristiina Aasa, Stephen Buttars, and Andrew Needles at FUJIFILM VisualSonics. The work of P. P. Vlachos was supported by the National Institutes of Health through Grant HL106276-01A1. The work of C. J. Goergen was supported by the American Heart Association through Grant SDG18220010 and the Indiana Clinical and Translational Sciences Institute, funded in part by Grant Number (UL1TR001108) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.

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  1. Arvin H. Soepriatna and Frederick W. Damen have contributed equally.

Authors and Affiliations

  1. Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette, IN, 47907, USA

    Arvin H. Soepriatna, Frederick W. Damen, Pavlos P. Vlachos & Craig J. Goergen

  2. School of Mechanical Engineering, Purdue University, 585 Purdue Mall, West Lafayette, IN, 47907, USA

    Pavlos P. Vlachos

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  1. Arvin H. Soepriatna
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Correspondence to Craig J. Goergen.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Purdue Animal Care and Use Committee.

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Soepriatna, A.H., Damen, F.W., Vlachos, P.P. et al. Cardiac and respiratory-gated volumetric murine ultrasound. Int J Cardiovasc Imaging 34, 713–724 (2018). https://doi.org/10.1007/s10554-017-1283-z

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