Current Cardiovascular Imaging Reports

, Volume 6, Issue 2, pp 150–157 | Cite as

Oxygenation and Flow in the Limbs: Novel Methods to Characterize Peripheral Artery Disease

Cardiac Magnetic Resonance (E Nagel, Section Editor)
  • 138 Downloads

Abstract

Peripheral artery disease (PAD) affects approximately 8 million Americans and is associated with high morbidity and increased mortality. Current therapies for PAD are limited and development of new therapeutic agents is needed. Present diagnostic methods for PAD are insensitive to the subtle microvascular and metabolic changes that occur beyond macrovacular stenosis and therefore may be less useful endpoints for clinical trials. Phosphorus-31 magnetic resonance (MR) spectroscopy, MR muscle perfusion, and MR oximetry are novel methods capable of evaluating both the macrovascular and microvascular changes that occur in PAD patients.

Keywords

Peripheral artery disease Magnetic resonance imaging Spectroscopy Perfusion Skeletal muscle 

Notes

Acknowledgments

Supported by NIH R01 HL075792 (CMK) and 5T32EB003841 (DL).

Disclosure

Dr. Kramer receives research support from Siemens Healthcare.

References

Papers of particular interest, published recently, have been highlighted as: •Of importance •• Of major importance

  1. 1.
    Roger VL, Go AS, Lloyd-Jones DM, et al. Executive summary: heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125:188–97.PubMedCrossRefGoogle Scholar
  2. 2.
    Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation. 2004;110:738–43.PubMedCrossRefGoogle Scholar
  3. 3.
    Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006;113:e463–654.PubMedCrossRefGoogle Scholar
  5. 5.
    Heald CL, Fowkes FG, Murray GD, Price JF, Ankle Brachial Index Collaboration. Risk of mortality and cardiovascular disease associated with the ankle-brachial index: systematic review. Atherosclerosis. 2006;189:61–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Criqui MH, Ninomiya JK, Wingard DL, Ji M, Fronek A. Progression of peripheral arterial disease predicts cardiovascular disease morbidity and mortality. J Am Coll Cardiol. 2008;52:1736–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Faxon DP, Fuster V, Libby P, et al. Atherosclerotic vascular disease conference: writing group III: pathophysiology. Circulation. 2004;109:2617–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Rose GA, Blackburn H. Cardiovascular survey methods. Monogr Ser World Health Organ. 1968;56:1–188.PubMedGoogle Scholar
  9. 9.
    Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, Grobbee DE. Peripheral arterial disease in the elderly: the Rotterdam study. Arterioscler Thromb Vasc Biol. 1998;18:185–92.PubMedCrossRefGoogle Scholar
  10. 10.
    Criqui MH, Fronek A, Barrett-Connor E, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985;71:510–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation. 1995;91:1472–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Regensteiner JG, Hiatt WR, Coll JR, et al. The impact of peripheral arterial disease on health-related quality of life in the peripheral arterial disease awareness, risk, and treatment: new resources for survival (PARTNERS) program. Vasc Med. 2008;13:15–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Pipinos II, Shepard AD, Anagnostopoulos PV, Katsamouris A, Boska MD. Phosphorus 31 nuclear magnetic resonance spectroscopy suggests a mitochondrial defect in claudicating skeletal muscle. J Vasc Surg. 2000;31:944–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Chance B. Applications of 31P NMR to clinical biochemistry. Ann N Y Acad Sci. 1984;428:318–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Bessman SP, Geiger PJ. Transport of energy in muscle: the phosphorylcreatine shuttle. Science. 1981;211:448–52.PubMedCrossRefGoogle Scholar
  16. 16.
    Roussel M, Bendahan D, Mattei JP, Le Fur Y, Cozzone PJ. 31P magnetic resonance spectroscopy study of phosphocreatine recovery kinetics in skeletal muscle: the issue of intersubject variability. Biochim Biophys Acta. 2000;1457:18–26.PubMedCrossRefGoogle Scholar
  17. 17.
    van der Grond J, Crolla RM, Ten Hove W, van Vroonhoven TJ, Mali WP. Phosphorus magnetic resonance spectroscopy of the calf muscle in patients with peripheral arterial occlusive disease. Invest Radiol. 1993;28:104–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Isbell DC, Berr SS, Toledano AY, et al. Delayed calf muscle phosphocreatine recovery after exercise identifies peripheral arterial disease. J Am Coll Cardiol. 2006;47:2289–95.PubMedCrossRefGoogle Scholar
  19. 19.
    Greiner A, Esterhammer R, Messner H, et al. High-energy phosphate metabolism during incremental calf exercise in patients with unilaterally symptomatic peripheral arterial disease measured by phosphor 31 magnetic resonance spectroscopy. J Vasc Surg. 2006;43:978–86.PubMedCrossRefGoogle Scholar
  20. 20.
    Schocke MF, Esterhammer R, Ostermann S, et al. High-energy phosphate metabolism during calf ergometry in patients with isolated aorto-iliac artery stenoses. Invest Radiol. 2006;41:874–82.PubMedCrossRefGoogle Scholar
  21. 21.
    Esterhammer R, Schocke M, Gorny O, et al. Phosphocreatine kinetics in the calf muscle of patients with bilateral symptomatic peripheral arterial disease during exhaustive incremental exercise. Mol Imaging Biol. 2008;10:30–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Raynaud JS, Duteil S, Vaughan JT, et al. Determination of skeletal muscle perfusion using arterial spin labeling NMRI: validation by comparison with venous occlusion plethysmography. Magn Reson Med. 2001;46:305–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Epstein FH, London JF, Peters DC, et al. Multislice first-pass cardiac perfusion MRI: validation in a model of myocardial infarction. Magn Reson Med. 2002;47:482–91.PubMedCrossRefGoogle Scholar
  24. 24.
    Wilke N, Simm C, Zhang J, et al. Contrast-enhanced first pass myocardial perfusion imaging: correlation between myocardial blood flow in dogs at rest and during hyperemia. Magn Reson Med. 1993;29:485–97.PubMedCrossRefGoogle Scholar
  25. 25.
    Thompson RB, Aviles RJ, Faranesh AZ, et al. Measurement of skeletal muscle perfusion during postischemic reactive hyperemia using contrast-enhanced MRI with a step-input function. Magn Reson Med. 2005;54:289–98.PubMedCrossRefGoogle Scholar
  26. 26.
    Isbell DC, Epstein FH, Zhong X, et al. Calf muscle perfusion at peak exercise in peripheral arterial disease: measurement by first-pass contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging. 2007;25:1013–20.PubMedCrossRefGoogle Scholar
  27. 27.
    Jiji RS, Pollak AW, Epstein FH, et al. Reproducibility of rest and exercise stress contrast-enhanced calf perfusion magnetic resonance imaging in peripheral arterial disease. J Cardiovasc Magn Reson. 2013;15:14.Google Scholar
  28. 28.
    •• Wu WC, Mohler 3rd E, Ratcliffe SJ, Wehrli FW, Detre JA, Floyd TF. Skeletal muscle microvascular flow in progressive peripheral artery disease: assessment with continuous arterial spin-labeling perfusion magnetic resonance imaging. J Am Coll Cardiol. 2009;53:2372–7. This study demonstrated the utility of continuous ASL for the assessment of PAD.PubMedCrossRefGoogle Scholar
  29. 29.
    •• Pollak A, Meyer C, Epstein F, et al. Arterial spin labeling MRI reproducibly measures peak-exercise calf muscle perfusion in healthy volunteers and patients with peripheral arterial disease. J Am Coll Cardiol. 2012;5(12):1224–30. doi: 10.1016/j.jcmg.2012.03.022. This study demonstrates the utility of pulsed ASL for the assessment of PAD.Google Scholar
  30. 30.
    • Jacobi B, Bongartz G, Partovi S, et al. Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions. J Magn Reson Imaging. 2012;35:1253–65. Good review of BOLD MRI.PubMedCrossRefGoogle Scholar
  31. 31.
    Lebon V, Carlier PG, Brillault-Salvat C, Leroy-Willig A. Simultaneous measurement of perfusion and oxygenation changes using a multiple gradient-echo sequence: application to human muscle study. Magn Reson Imaging. 1998;16:721–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Duteil S, Wary C, Raynaud JS, et al. Influence of vascular filling and perfusion on BOLD contrast during reactive hyperemia in human skeletal muscle. Magn Reson Med. 2006;55:450–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Ledermann HP, Schulte AC, Heidecker HG, et al. Blood oxygenation level-dependent magnetic resonance imaging of the skeletal muscle in patients with peripheral arterial occlusive disease. Circulation. 2006;113:2929–35.PubMedCrossRefGoogle Scholar
  34. 34.
    Logothetis NK, Wandell BA. Interpreting the BOLD signal. Annu Rev Physiol. 2004;66:735–69.PubMedCrossRefGoogle Scholar
  35. 35.
    Robbins JL, Jones WS, Duscha BD, et al. Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease. J Appl Physiol. 2011;111:81–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Versluis B, Backes WH, van Eupen MG, et al. Magnetic resonance imaging in peripheral arterial disease: reproducibility of the assessment of morphological and functional vascular status. Invest Radiol. 2011;46:11–24.PubMedCrossRefGoogle Scholar
  37. 37.
    Wright GA, Hu BS, Macovski A. I.I. Rabi Award. Estimating oxygen saturation of blood in vivo with MR imaging at 1.5 T. J Magn Reson Imaging. 1991;1:275–83.PubMedCrossRefGoogle Scholar
  38. 38.
    Chien D, Levin DL, Anderson CM. MR gradient echo imaging of intravascular blood oxygenation: T2* determination in the presence of flow. Magn Reson Med. 1994;32:540–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Haacke EM, Lai S, Reichenbach JR, et al. In vivo measurement of blood oxygen saturation using magnetic resonance imaging: a direct validation of the blood oxygen level-dependent concept in functional brain imaging. Hum Brain Mapp. 1997;5:341–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Abramson DI, Tuck Jr S, Bell Y, Mitchell RE, Zayas AM. Effect of short periods of arterial occlusion on blood flow and oxygen uptake. J Appl Physiol. 1961;16:851–7.PubMedGoogle Scholar
  41. 41.
    •• Langham MC, Floyd TF, Mohler 3rd ER, Magland JF, Wehrli FW. Evaluation of cuff-induced ischemia in the lower extremity by magnetic resonance oximetry. J Am Coll Cardiol. 2010;55:598–606. This study demonstrated the feasibility of SWI oximetry for the assessment of PAD.PubMedCrossRefGoogle Scholar
  42. 42.
    Langham MC, Magland JF, Epstein CL, Floyd TF, Wehrli FW. Accuracy and precision of MR blood oximetry based on the long paramagnetic cylinder approximation of large vessels. Magn Reson Med. 2009;62:333–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Yang L, Krefting I, Gorovets A, et al. Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration. Radiology. 2012;265:248–53.PubMedCrossRefGoogle Scholar
  44. 44.
    • Anderson JD, Epstein FH, Meyer CH, et al. Multifactorial determinants of functional capacity in peripheral arterial disease: uncoupling of calf muscle perfusion and metabolism. J Am Coll Cardiol. 2009;54:628–35. This study established the lack of association between muscle metabolism and perfusion.PubMedCrossRefGoogle Scholar
  45. 45.
    • West AM, Anderson JD, Epstein FH, et al. Percutaneous intervention in peripheral artery disease improves calf muscle phosphocreatine recovery kinetics: a pilot study. Vasc Med. 2012;17:3–9. This study showed that PCr recovery can detect therapeutic changes after PTI in a small cohort of patients.PubMedCrossRefGoogle Scholar
  46. 46.
    West AM, Anderson JD, Epstein FH, et al. Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. J Am Coll Cardiol. 2011;58:1068–76.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Cardiovascular Division, Department of MedicineUniversity of Virginia Health SystemCharlottesvilleUSA
  2. 2.Department of Medicine and Radiology, and the Cardiovascular Imaging CenterUniversity of Virginia Health SystemCharlottesvilleUSA
  3. 3.Departments of Medicine and RadiologyUniversity of Virginia Health SystemCharlottesvilleUSA

Personalised recommendations