Cardiovascular Magnetic Resonance Imaging-Based Computational Fluid Dynamics/Fluid–Structure Interaction Pilot Study to Detect Early Vascular Changes in Pediatric Patients with Type 1 Diabetes
- 367 Downloads
We hypothesized that pediatric patients with type 1 diabetes have cardiac magnetic resonance (CMR) detectable differences in thoracic aortic wall properties and hemodynamics leading to significant local differences in indices of wall shear stress, when compared with age-matched control subjects without diabetes. Pediatric patients with type 1 diabetes were recruited from Children’s Hospital of Wisconsin and compared with controls. All underwent morning CMR scanning, 4-limb blood pressure, brachial artery reactivity testing, and venipuncture. Patient-specific computational fluid dynamics modeling with fluid–structure interaction, based on CMR data, determined regional time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI). Twenty type 1 diabetic subjects, median age 15.8 years (11.6–18.4) and 8 controls 15.4 years (10.3–18.2) were similar except for higher glucose, hemoglobin A1c, and triglycerides for type 1 diabetic subjects. Lower flow-mediated dilation was seen for those with type 1 diabetes (6.5) versus controls (7.8), p = 0.036. For type 1 diabetic subjects, the aorta had more regions with high TAWSS when compared to controls. OSI maps appeared similar. Flow-mediated dilation positively correlated with age at diabetes diagnosis (r = 0.468, p = 0.038) and hemoglobin A1c (r = 0.472, p = 0.036), but did not correlate with aortic distensibility, TAWSS, or OSI. TAWSS did not correlate with any clinical parameter for either group. CMR shows regional differences in aortic wall properties for young diabetic patients. Some local differences in wall shear stress indices were also observed, but a longitudinal study is now warranted.
KeywordsDiabetes Magnetic resonance imaging Pediatrics
The authors would like to acknowledge Stacy Leibham (Children’s Hospital of Wisconsin) for her assistance with CMR scanning, David J. Quam, MS (Marquette University) for writing scripts for CFD quantification, and Mara Koffarnus, MA (Medical College of Wisconsin) for help in preparing this manuscript for submission. This research was supported by a Children’s Research Institute Pilot Innovative Research grant.
Conflict of interest
The authors declare they have no conflict of interest.
This study has been approved by the Children’s Hospital of Wisconsin Institutional Review Board and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All study subjects and/or their parents, gave their informed consent prior to their inclusion in the study. If the child was between the ages of 14 and 17, assent was also obtained.
- 2.Aquaro GD, Cagnolo A, Tiwari KK, Todiere G, Bevilacqua S, Di Bella G, Ait-Ali L, Festa P, Glauber M, Lombardi M (2013) Age-dependent changes in elastic properties of thoracic aorta evaluated by magnetic resonance in normal subjects. Interact CardioVasc Thorac Surg 17:674–679. doi: 10.1093/icvts/ivt261 CrossRefPubMedCentralPubMedGoogle Scholar
- 5.De Michele M, Iannuzzi A, Salvato A, Pauciullo P, Gentile M, Iannuzzo G, Panico S, Pujia A, Bond GM, Rubba P (2007) Impaired endothelium-dependent vascular reactivity in patients with familial combined hyperlipidaemia. Heart 93(1):78–81. doi: 10.1136/hrt.2006.093278 CrossRefPubMedCentralPubMedGoogle Scholar
- 11.Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2014) Heart Disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129:e28–e292. doi: 10.1161/01.cir.0000441139.02102.80 CrossRefPubMedGoogle Scholar
- 12.Goldberg RB, Mellies MJ, Sacks FM, Moyé LA, Howard BV, Howard WJ, Davis BR, Cole TG, Pfeffer MA, Braunwald E, for the CARE Investigators (1998) Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. Circulation 98:2513–2519. doi: 10.1161/01.CIR.98.23.2513 CrossRefPubMedGoogle Scholar
- 14.Haller MJ, Samyn M, Nichols WW, Brusko T, Wasserfall C, Schwartz RF, Atkinson M, Shuster JJ, Pierce GL, Silverstein JH (2004) Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes. Diabetes Care 27:2911–2917. doi: 10.2337/diacare.27.12.2911 CrossRefPubMedGoogle Scholar
- 15.Herman WH, Alexander CM, Cook JR, Boccuzzi SJ, Musliner TA, Pedersen TR, Kjekshus J, Pyörälä K (1999) Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Findings from the Scandinavian Simvastatin Survival Study. Diabetes Care 22:1771–1778. doi: 10.2337/diacare.22.11.1771 CrossRefPubMedGoogle Scholar
- 16.Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJC, Jakobs C, Bouter LM, Heine RJ, Stehouwer CDA (1998) Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol 18:133–138. doi: 10.1161/01.ATV.18.1.133 CrossRefPubMedGoogle Scholar
- 21.Kwon S, Feinstein JA, Dholakia RJ, LaDisa JF Jr (2014) Quantification of local hemodynamic alterations cuased by virtual implantation of three commercially available stents for treatment of aortic coarctation. Pediatr Cardiol 35(4):732–740. doi: 10.1007/s00246-013-0845-7 CrossRefPubMedGoogle Scholar
- 23.LaDisa JFJ, Dholakia RJ, Figueroa CA, Vignon-Clementel IE, Chan FP, Samyn MM, Cava JR, Taylor CA, Feinstein JA (2011) Computational simulations demonstrate altered wall shear stress in aortic coarctation patients treated by resection with end-to-end anastomosis. Congenit Heart Dis 6:432–443. doi: 10.1111/j.1747-0803.2011.00553.x CrossRefPubMedCentralPubMedGoogle Scholar
- 25.Les A, Shadden S, Figueroa CA, Park J, Tedesco M, Herfkens R, Dalman R, Taylor C (2010) Quantification of hemodynamics in abdominal aortic aneurysms during rest and exercise using magnetic resonance imaging and computational fluid dynamics. Ann Biomed Eng 38:1288–1313. doi: 10.1007/s10439-010-9949-x CrossRefPubMedGoogle Scholar
- 26.Mark P, Doyle A, Blyth K, Patel R, Weir R, Steedman T, Foster J, Dargie H, Jardine A (2008) Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease. J Cardiovasc Magn Reson 10:39. doi: 10.1186/1532-429X-10-39 CrossRefPubMedCentralPubMedGoogle Scholar
- 29.National Cholesterol Education Program (NCEP) (1992) Highlights of the report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 89:495Google Scholar
- 31.Raitakari OT, Pitkänen O, Lehtimäki T, Lahdenperä S, Iida H, Ylä-Herttuala S, Luoma J, Mattila K, Nikkari T, Taskinen M, Viikari JSA, Knuuti J (1997) In vivo low density lipoprotein oxidation relates to coronary reactivity in young men. J Am Coll Cardiol 30:97–102. doi: 10.1016/S0735-1097(97)00103-4 CrossRefPubMedGoogle Scholar
- 32.Redheuil A, Yu W, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura N, Bluemke D, Lima JAC (2010) Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension 55:319–326. doi: 10.1161/HYPERTENSIONAHA.109.141275 CrossRefPubMedCentralPubMedGoogle Scholar
- 36.Stergiopulos NS (1999) Use of pulse pressure method for estimating total arterial compliance in vivo. Am J Physiol Heart Circ Physiol 276:H424–H428Google Scholar
- 38.Taniguchi H, Momiyama Y, Fayad ZA, Ohmori R, Ashida K, Kihara T, Hara A, Arakawa K, Kameyama A, Noya K, Nagata M, Nakamura H, Ohsuzu F (2004) In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography. Am Heart J 148:137–143. doi: 10.1016/j.ahj.2004.03.008 CrossRefPubMedGoogle Scholar
- 40.The Diabetes Atorvastatin Lipid Intervention (DALI) Study Group (2001) The effect of aggressive versus standard lipid lowering by atorvastatin on diabetic dyslipidemia: the DALI study: a double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes and diabetic dyslipidemia. Diabetes Care 24:1335–1341. doi: 10.2337/diacare.24.8.1335 CrossRefGoogle Scholar
- 41.Toikka JO, Niemi P, Ahotupa M, Niinikoski H, Viikari JSA, Rönnemaa T, Hartiala JJ, Raitakari OT (1999) Large-artery elastic properties in young men: relationships to serum lipoproteins and oxidized low-density lipoproteins. Arterioscler Thromb Vasc Biol 19:436–441. doi: 10.1161/01.ATV.19.2.436 CrossRefPubMedGoogle Scholar
- 43.Voges I, Jerosch-Herold M, Hedderich J, Pardun E, Hart C, Gabbert D, Hansen J, Petko C, Kramer H, Rickers C (2012) Normal values of aortic dimensions, distensibility, and pulse wave velocity in children and young adults: a cross-sectional study. J Cardiovasc Magn Reson 14:77. doi: 10.1186/1532-429X-14-77 CrossRefPubMedCentralPubMedGoogle Scholar
- 45.Wendell DC, Samyn MM, Cava JR, Ellwein LM, Krolikowski MM, Gandy KL, Pelech AN, Shadden SC, LaDisa JF Jr (2013) Including aortic valve morphology in computational fluid dynamics simulations: initial findings and application to aortic coarctation. Med Eng Phys 35:723–735. doi: 10.1016/j.medengphy.2012.07.015 CrossRefPubMedGoogle Scholar
- 46.Wentzel JJ, Corti R, Fayad ZA, Wisdom P, Macaluso F, Winkelman MO, Fuster V, Badimon JJ (2005) Does shear stress modulate both plaque progression and regression in the thoracic aorta? Human study using serial magnetic resonance imaging. J Am Coll Cardiol 45:846–854. doi: 10.1016/j.jacc.2004.12.026 CrossRefPubMedGoogle Scholar
- 47.Wotherspoon F, Laight DW, Browne DL, Turner C, Meeking DR, Allard SE, Munday LJ, Shaw KM, Cummings MH (2006) Plasma homocysteine, oxidative stress and endothelial function in patients with type 1 diabetes mellitus and microalbuminuria. Diabet Med 23:1350–1356. doi: 10.1111/j.1464-5491.2006.01980.x CrossRefPubMedGoogle Scholar