Analysis of Murine Vascular Function In Vivo by Optical Coherence Tomography in Response to High-fat Diet

Abstract

In this study, we demonstrate the application of optical coherence tomography (OCT) as a contactless imaging technique to analyze vasodynamics in small blood vessels in vivo. The transluminal OCT imaging of vessels avoids micro traumata in the endothelium and circumvents surgical intervention. It can be performed in the intact perfused vessel and provides a new method to measure vascular function and dynamics in vivo. The resolution of 10 μm and the velocity of image acquisition are adequate to detect differences in the inner diameter, the maximal velocity, or the time to half-maximal diameter change of small vessels. We applied this new technology to study the vascular dynamics in small vessels of 6- and 20-week-old C57BL/6 mice in vivo. In addition, we determined by this technique the impact of a high-fat diet for 14 weeks on vascular function in 20-week-old animals. The diameter of the saphenous artery was increased under resting conditions, after vasoconstriction and after vasodilatation in 20-week-old animals on normal chow and high-fat diet, compared to 6-week-old animals. High-fat diet caused a significantly impaired vasoconstriction in the saphenous artery. The maximal velocity of diameter changes of the saphenous artery was determined by time-resolved OCT imaging. A significant reduction of this parameter was found during vasoconstriction in 20-week-old mice on high-fat diet, compared to 6-week-old animals. In conclusion, transluminal optical coherence tomography imaging is a novel and useful technique to analyze the impaired vasodynamics of small arteries in response to high-fat diet in vivo.

Key words

vasodynamics - vessel diameter - velocity of diameter change - time to half-maximal diameter change

References

• 1 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension . Guidelines Subcommittee.  J Hypertens. 1999;  17 151-183
• 2 Yudkin JS. Inflammation, obesity, and the metabolic syndrome.  Horm Metab Res. 2007;  39 707-709
• 3 Schram MT, Stehouwer CD. Endothelial dysfunction, cellular adhesion molecules and the metabolic syndrome.  Horm Metab Res. 2005;  37 ((Suppl 1)) 49-55
• 4 Chatzizisis YS, Coskun AU, Jonas M, Edelman ER, Feldman CL, Stone PH. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior.  J Am Coll Cardiol. 2007;  49 2379-2393
• 5 Drexler W, Sattmann H, Hermann B, Ko TH, Stur M, Unterhuber A, Scholda C, Findl O, Wirtitsch M, Fujimoto JG, Fercher AF. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography.  Arch Ophthalmol. 2003;  121 695-706
• 6 Fercher AF, Drexler H, Hitzenberger CK, Lasser T. Optical coherence tomography- principles and applications.  Rep Prog Phys. 2003;  66 239-303
• 7 Angus JA, Wright CE. Techniques to study the pharmacodynamics of isolated large and small blood vessels.  J Pharmacol Toxicol Methods. 2000;  44 395-407
• 8 Wright CE, Angus JA. Techniques to measure pharmacodynamics in the intact vasculature.  J Pharmacol Toxicol Methods. 2000;  44 385-394
• 9 Schaar JA, Mastik F, Regar E, den Uil CA, Gijsen FJ, Wentzel JJ, Serruys PW, van der Stehen AF. Current diagnostic modalities for vulnerable plaque detection.  Curr Pharm Des. 2007;  13 995-1001
• 10 Cilingiroglu M, Oh JH, Sugunan B, Kemp NJ, Kim J, Lee S, Zaatari HN, Escobedo D, Thomsen S, Milner TE, Feldman MD. Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography.  Catheter Cardiovasc Interv. 2006;  67 915-923
• 11 Bhattacharya I, Mundy AL, Widmer CC, Kretz M, Barton M. Regional heterogeneity of functional changes in conduit arteries after high-fat diet.  Obesity (Silver Spring). 2008;  16 743-748
• 12 Torrens C, Hanson MA, Gluckman PD, Vickers MH. Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet.  Br J Nutr. 2009;  101 27-33
• 13 Holemans K, Gerber R, Meurrens K, De Clerck F, Poston L, Van Assche FA. Maternal food restriction in the second half of pregnancy affects vascular function but not blood pressure of rat female offspring.  Br J Nutr. 1999;  81 73-79
• 14 White B, Pierce M, Nassif N, Cense B, Park B, Tearney G, Bouma B, Chen T, de Boer J. In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography.  Opt Express. 2003;  11 3490-3497
• 15 Leitgeb R, Schmetterer L, Drexler W, Fercher A, Zawadzki R, Bajraszewski T. Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography.  Opt Express. 2003;  11 3116-3121
• 16 Wehbe H, Ruggeri M, Jiao S, Gregori G, Puliafito CA, Zhao W. Automatic retinal blood flow calculation using spectral domain optical coherence tomography.  Opt Express. 2007;  15 15193-15206
• 17 Vakoc B, Yun S, de Boer J, Tearney G, Bouma B. Phase-resolved optical frequency domain imaging.  Opt Express. 2005;  13 5483-5493
• 18 Saia F, Schaar J, Regar E, Rodriguez G, De Feyter PJ, Mastik F, Marzocchi A, Marrozzini C, Ortolani P, Palmerini T, Branzi A, van der Steen AF, Serruys PW. Clinical imaging of the vulnerable plaque in the coronary arteries: new intracoronary diagnostic methods.  J Cardiovasc Med (Hagerstown). 2006;  7 21-28
• 19 Schaar JA, Mastik F, Regar E, den Uil CA, Gijsen FJ, Wentzel JJ, Serruys PW, van der Stehen AF. Current diagnostic modalities for vulnerable plaque detection.  Curr Pharm Des. 2007;  13 995-1001

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