Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aggoun Y, Szezepanski I, Bonnet D (2005) Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children. Pediatr Res 58:173–178. doi:10.1203/01.PDR.0000170900.35571.CB

    Article  PubMed  Google Scholar 

  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

    Article  PubMed Central  PubMed  Google Scholar 

  3. Babar GS, Zidan H, Widlansky ME, Das E, Hoffmann RG, Daoud M, Alemzadeh R (2011) Impaired endothelial function in preadolescent children with type 1 diabetes. Diabetes Care 34:681–685. doi:10.2337/dc10-2134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340:1111–1115

    Article  CAS  PubMed  Google 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

    Article  PubMed Central  PubMed  Google Scholar 

  6. Dyson KS, Shoemaker JK, Hughson RL (2006) Effect of acute sympathetic nervous system activation on flow-mediated dilation of brachial artery. Am J Physiol Heart Circ Physiol 290:H1446–H1453

    Article  CAS  PubMed  Google Scholar 

  7. Figueroa CA, Vignon-Clementel IE, Jansen KE, Hughes TJR, Taylor CA (2006) A coupled momentum method for modeling blood flow in three-dimensional deformable arteries. Comput Methods Appl Mech Eng 195:5685–5706. doi:10.1016/j.cma.2005.11.011

    Article  Google Scholar 

  8. Forbat SM, Mohiaddin RH, Yang GZ, Firmin DN, Underwood SR (1995) Measurement of regional aortic compliance by MR imaging: a study of reproducibility. J Magn Reson Imaging 5:635–639. doi:10.1002/jmri.1880050604

    Article  CAS  PubMed  Google Scholar 

  9. Francois CJ, Tuite D, Deshpande V, Jerecic R, Weale P, Carr J (2008) Unenhanced MR angiography of the thoracic aorta: initial clinical evaluation. Am J Roentgenol 190(4):902–906. doi:10.2214/AJR.07.2997

    Article  Google Scholar 

  10. Ghiadoni L, Huang Y, Magagna A, Buralli S, Taddei S, Salvetti A (2001) Effect of acute blood pressure reduction on endothelial function in the brachial artery of patients with essential hypertension. J Hypertens 19(3 Pt 2):547–551

    Article  CAS  PubMed  Google 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

    Article  PubMed  Google 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

    Article  CAS  PubMed  Google Scholar 

  13. Grzelak P, Czupryniak L, Olszycki M, Majos A, Stefańczyk L (2011) Age effect on vascular reactivity in type 1 diabetes. Diabet Med 28(7):833–837. doi:10.1111/j.1464-5491.2011.03277.x

    Article  CAS  PubMed  Google 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

    Article  PubMed  Google 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

    Article  CAS  PubMed  Google 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

    Article  CAS  PubMed  Google Scholar 

  17. Järvisalo MJ, Rönnemaa T, Volanen I, Kaitosaari T, Kallio K, Hartiala JJ, Irjala K, Viikari JS, Simell O, Raitakari OT (2002) Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol 282:H87–H92

    PubMed  Google Scholar 

  18. Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA (1993) Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 88(6):2510–2516. doi:10.1161/01.cir.88.6.2510

    Article  CAS  PubMed  Google Scholar 

  19. Kaiser T, Kellenberger CJ, Albisetti M, Bergstrasser E, Valsangiacomo Buechel ER (2008) Normal values for aortic diameters in children and adolescents-assessment in vivo by contrast enhanced CMR-angiography. J Cardiovas Magn Reson 10:56. doi:10.1186/1532-429X-10-56

    Article  Google Scholar 

  20. Kizhakekuttu TJ, Gutterman DD, Phillips SA, Jurva JW, Arthur EI, Das E, Widlansky ME (2010) Measuring FMD in the brachial artery: how important is QRS gating? J Appl Physiol 109:959–965. doi:10.1152/japplphysiol.00532.2010

    Article  PubMed Central  PubMed  Google 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

    Article  PubMed  Google Scholar 

  22. LaDisa JFJ, Figueroa CA, Vignon-Clementel I, Kim HJ, Xiao N, Ellwein LM, Chan FP, Feinstein JA, Taylor CA (2011) Computational simulations for aortic coarctation: representative results from a sampling of patients. J Biomech Eng 133:091008. doi:10.1115/1.4004996

    Article  PubMed  Google 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

    Article  PubMed Central  PubMed  Google Scholar 

  24. Laskey WKP (1990) Estimation of total systemic arterial compliance in humans. J Appl Physiol 69:112–119

    CAS  PubMed  Google 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

    Article  PubMed  Google 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

    Article  PubMed Central  PubMed  Google Scholar 

  27. Mohiaddin RHF (1993) Age-related changes of human aortic flow wave velocity measured noninvasively by magnetic resonance imaging. J Appl Physiol 74:492–497

    CAS  PubMed  Google Scholar 

  28. Müller J, Sahni O, Li X, Jansen KE, Shephard MS, Taylor CA (2005) Anisotropic adaptive finite element method for modelling blood flow. Comput Methods Biomech Biomed Eng 8:295–305. doi:10.1080/10255840500264742

    Article  Google 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 89:495

    Google Scholar 

  30. Pasterkamp G, Galis ZS, de Kleijn DPV (2004) Expansive arterial remodeling: location, location, location. Arterioscler Thromb Vasc Biol 24:650–657. doi:10.1161/01.ATV.0000120376.09047.fe

    Article  CAS  PubMed  Google 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

    Article  CAS  PubMed  Google 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Rosengård-Bärlund M, Bernardi L, Fagerudd J, Mäntysaari M, Af-Björkesten CG, Lindholm H, Forsblom C, Wadé NJ, Groop P-H (2009) Early autonomic dysfunction in type 1 diabetes: a reversible disorder? Diabetologia 52:1164–1172. doi:10.1007/s00125-009-1340-9

    Article  PubMed  Google Scholar 

  34. Sahni O, Müller J, Jansen KE, Shephard MS, Taylor CA (2006) Efficient anisotropic adaptive discretization of the cardiovascular system. Comput Methods Appl Mech Eng 195:5634–5655. doi:10.1016/j.cma.2005.10.018

    Article  Google Scholar 

  35. Soljanlahti S, Autti T, Hyttinen L, Vuorio AF, Keto P, Lauerma K (2008) Compliance of the aorta in two diseases affecting vascular elasticity, familial hypercholesterolemia and diabetes: a MRI study. Vasc Health Risk Manag 4:1103–1109. doi:10.2147/VHRM.S3198

    PubMed Central  PubMed  Google 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–H428

    CAS  Google Scholar 

  37. Stergiopulos N, Young DF, Rogge TR (1992) Computer simulation of arterial flow with applications to arterial and aortic stenoses. J Biomech 25:1477–1488. doi:10.1016/0021-9290(92)90060-E

    Article  CAS  PubMed  Google 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

    Article  PubMed  Google Scholar 

  39. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA (1997) Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 95:1119–1121. doi:10.1161/01.CIR.95.5.1119

    Article  CAS  PubMed  Google 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

    Article  Google 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

    Article  CAS  PubMed  Google Scholar 

  42. Vignon-Clementel IE, Figueroa CA, Jansen KE, Taylor CA (2006) Outflow boundary conditions for three-dimensional finite element modeling of blood flow and pressure in arteries. Comput Methods Appl Mech Eng 195:3776–3796. doi:10.1016/j.cma.2005.04.014

    Article  Google 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

    Article  PubMed Central  PubMed  Google Scholar 

  44. Ward MR, Pasterkamp G, Yeung AC, Borst C (2000) Arterial remodeling: mechanisms and clinical implications. Circulation 102:1186–1191. doi:10.1161/01.CIR.102.10.1186

    Article  CAS  PubMed  Google 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

    Article  PubMed  Google 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

    Article  PubMed  Google 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

    Article  CAS  PubMed  Google Scholar 

  48. Yasmin CMM, Wallace S, Mackenzie IS, Cockcroft JR, Wilkinson IB (2004) C-reactive protein is associated with arterial stiffness in apparently healthy individuals. Arterioscler Thromb Vasc Biol 24:969–974. doi:10.1161/01.ATV.zhq0504.0173

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Ethical Standards

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.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Margaret M. Samyn, Ke Yan & Pippa Simpson

  2. Stony Brook University Medical Center, Stony Brook, NY, USA

    Ronak Dholakia

  3. Department of Biomedical Engineering, Marquette University, Milwaukee, WI, USA

    Margaret M. Samyn, Hongfeng Wang & John F. LaDisa

  4. Congenital Heart Center and Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA

    Jennifer Co-Vu

  5. Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Michael E. Widlansky & John F. LaDisa

  6. Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA

    John F. LaDisa

  7. Division of Pediatric Endocrinology, University of Illinois at Chicago, Chicago, IL, USA

    Ramin Alemzadeh

Authors
  1. Margaret M. Samyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronak Dholakia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hongfeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jennifer Co-Vu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ke Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael E. Widlansky
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John F. LaDisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pippa Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ramin Alemzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margaret M. Samyn.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Samyn, M.M., Dholakia, R., Wang, H. et al. 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. Pediatr Cardiol 36, 851–861 (2015). https://doi.org/10.1007/s00246-014-1071-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-014-1071-7

Keywords

Search

Navigation