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Journal of Cardiovascular Magnetic Resonance
Published in: Journal of Cardiovascular Magnetic Resonance 1/2013

Open Access 01-12-2013 | Research

Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg

Authors: Erin K Englund, Michael C Langham, Cheng Li, Zachary B Rodgers, Thomas F Floyd, Emile R Mohler, Felix W Wehrli

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2013

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Abstract

Background

The function of the peripheral microvascular may be interrogated by measuring perfusion, tissue oxygen concentration, or venous oxygen saturation (SvO2) recovery dynamics following induced ischemia. The purpose of this work is to develop and evaluate a magnetic resonance (MR) technique for simultaneous measurement of perfusion, SvO2, and skeletal muscle T2*.

Methods

Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT) is comprised of interleaved pulsed arterial spin labeling (PASL) and multi-echo gradient-recalled echo (GRE) sequences. During the PASL post-labeling delay, images are acquired with a multi-echo GRE to quantify SvO2 and T2* at a downstream slice location. Thus time-courses of perfusion, SvO2, and T2* are quantified simultaneously within a single scan. The new sequence was compared to separately measured PASL or multi-echo GRE data during reactive hyperemia in five young healthy subjects. To explore the impairment present in peripheral artery disease patients, five patients were evaluated with PIVOT.

Results

Comparison of PIVOT-derived data to the standard techniques shows that there was no significant bias in any of the time-course-derived metrics. Preliminary data show that PAD patients exhibited alterations in perfusion, SvO2, and T2* time-courses compared to young healthy subjects.

Conclusion

Simultaneous quantification of perfusion, SvO2, and T2* is possible with PIVOT. Kinetics of perfusion, SvO2, and T2* during reactive hyperemia may help to provide insight into the function of the peripheral microvasculature in patients with PAD.
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Literature
1.
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. 10.1161/01.CIR.71.3.510.CrossRefPubMed
2.
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. 10.1161/01.ATV.18.2.185.CrossRefPubMed
3.
Hirsch AT HCM, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME: Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA: J Am Med Assoc. 2001, 286: 1317-24. 10.1001/jama.286.11.1317.CrossRef
4.
Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WRC, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B: 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. 2005, 2006: e463-654.
5.
Faxon DP, Fuster V, Libby P, Beckman JA, Hiatt WR, Thompson RW, Topper JN, Annex BH, Rundback JH, Fabunmi RP, Robertson RM, Loscalzo J, American Heart Association: Atherosclerotic vascular disease conference: writing group III: pathophysiology. Circulation. 2004, 109: 2617-25. 10.1161/01.CIR.0000128520.37674.EF.CrossRefPubMed
6.
Bragadeesh T, Sari I, Pascotto M, Micari A, Kaul S, Lindner JR: Detection of peripheral vascular stenosis by assessing skeletal muscle flow reserve. J Am Coll Cardiol. 2005, 45: 780-5. 10.1016/j.jacc.2004.11.045.CrossRefPubMed
7.
Ledermann HP, Heidecker H-G, Schulte A-C, Thalhammer C, Aschwanden M, Jaeger KA, Scheffler K, Bilecen D: Calf muscles imaged at BOLD MR: correlation with TcPO2 and flowmetry measurements during ischemia and reactive hyperemia–initial experience. Radiology. 2006, 241: 477-84. 10.1148/radiol.2412050701.CrossRefPubMed
8.
Toussaint J-F, Kwong KK, M'Kparu F, Weisskoff RM, LaRaia PJ, Kantor HL: Perfusion changes in human skeletal muscle during reactive hyperemia measured by echo-planar imaging. Magn Reson Med. 1996, 35: 62-9. 10.1002/mrm.1910350109.CrossRefPubMed
9.
Damon BM, Hornberger JL, Wadington MC, Lansdown DA, Kent-Braun JA: Dual gradient-echo MRI of post-contraction changes in skeletal muscle blood volume and oxygenation. Magn Reson Med. 2007, 57: 670-9. 10.1002/mrm.21191.PubMedCentralCrossRefPubMed
10.
Langham MC, Floyd TF, Mohler 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. 10.1016/j.jacc.2009.08.068.PubMedCentralCrossRefPubMed
11.
Detre J, Leigh J, Williams D: Detre, MRM 1992 Perfusion imaging. Magn Reson Med. 1992, 23: 1-9. 10.1002/mrm.1910230102.CrossRef
12.
Williams DS, Detre JA, Leigh JS, Koretsky AP: Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci. 1992, 89: 212-6. 10.1073/pnas.89.1.212.PubMedCentralCrossRefPubMed
13.
Kim SG: Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med. 1995, 34: 293-301. 10.1002/mrm.1910340303.CrossRefPubMed
14.
Kim SG, Tsekos NV: Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique: application to functional brain imaging. Magn Reson Med. 1997, 37: 425-35. 10.1002/mrm.1910370321.CrossRefPubMed
15.
Wu W-C, Wang J, Detre JA, Wehrli FW, Mohler E, Ratcliffe SJ, Floyd TF: Hyperemic flow heterogeneity within the calf, foot, and forearm measured with continuous arterial spin labeling MRI. Am J Physiol Heart Circ Physiol. 2008, 294: H2129-36. 10.1152/ajpheart.01399.2007.PubMedCentralCrossRefPubMed
16.
Raynaud JS, Duteil S, Vaughan JT, Hennel F, Wary C, Leroy-Willig A, Carlier PG: Determination of skeletal muscle perfusion using arterial spin labeling NMRI: validation by comparison with venous occlusion plethysmography. Magn Reson Med. 2001, 46: 305-11. 10.1002/mrm.1192.CrossRefPubMed
17.
Wu W-C, Mohler 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. 10.1016/j.jacc.2009.03.033.CrossRefPubMed
18.
Ogawa S, Lee T, Kay A: Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci. 1990, 87: 9868-72. 10.1073/pnas.87.24.9868.PubMedCentralCrossRefPubMed
19.
Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Uğurbil K: Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J. 1993, 64: 803-12. 10.1016/S0006-3495(93)81441-3.PubMedCentralCrossRefPubMed
20.
Prasad PV, Edelman RR, Epstein FH: Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. Circulation. 1996, 94: 3271-5. 10.1161/01.CIR.94.12.3271.CrossRefPubMed
21.
Noseworthy M, Bulte DP, Alfonsi J: BOLD magnetic resonance imaging in skeletal muscle. Semin Musculoskelet Radiol. 2003, 7: 307-15.CrossRefPubMed
22.
Damon BM, Gore JC: Physiological basis of muscle functional MRI: predictions using a computer model. J Appl Physiol. 2004, 98: 264-73. 10.1152/japplphysiol.00369.2004.CrossRefPubMed
23.
Lebon V, Brillault-Salvat C, Bloch G, Leroy-Willig A, Carlier PG: Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient-echo NMRI and myoglobin NMRS during leg ischemia. Magn Reson Med. 1998, 40: 551-8. 10.1002/mrm.1910400408.CrossRefPubMed
24.
Fernández-Seara MA, Techawiboonwong A, Detre JA, Wehrli FW: MR susceptometry for measuring global brain oxygen extraction. Magn Reson Med. 2006, 55: 967-73. 10.1002/mrm.20892.CrossRefPubMed
25.
Langham MC, Englund EK, Mohler ER, Li C, Rodgers ZB, Floyd TF, Wehrli FW: Quantitative CMR markers of impaired vascular reactivity associated with age and peripheral artery disease. J Cardiov Magn Reson. 2013, 15: 17-10.1186/1532-429X-15-17.CrossRef
26.
Ledermann HP, Schulte A-C, Heidecker H-G, Aschwanden M, Jäger KA, Scheffler K, Steinbrich W, Bilecen D: Blood oxygenation level-dependent magnetic resonance imaging of the skeletal muscle in patients with peripheral arterial occlusive disease. Circulation. 2006, 113: 2929-35. 10.1161/CIRCULATIONAHA.105.605717.CrossRefPubMed
27.
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. 10.1016/S0730-725X(98)00088-5.CrossRefPubMed
28.
Duteil S, Wary C, Raynaud JS, Lebon V, Lesage D, Leroy-Willig A, Carlier PG: Influence of vascular filling and perfusion on BOLD contrast during reactive hyperemia in human skeletal muscle. Magn Reson Med. 2006, 55: 450-4. 10.1002/mrm.20760.CrossRefPubMed
29.
Wong EC, Buxton RB, Frank LR: Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling. NMR Biomed. 1997, 10: 237-49. 10.1002/(SICI)1099-1492(199706/08)10:4/5<237::AID-NBM475>3.0.CO;2-X.CrossRefPubMed
30.
Lu H, Clingman C, Golay X, van Zijl PCM: Determining the longitudinal relaxation time (T1) of blood at 3.0 Tesla. Magn Reson Med. 2004, 52: 679-82. 10.1002/mrm.20178.CrossRefPubMed
31.
Gold GE, Han E, Stainsby J, Wright G, Brittain J, Beaulieu C: Musculoskeletal MRI at 3.0 T: relaxation times and image contrast. Am J Roentgenol. 2004, 183: 343-51. 10.2214/ajr.183.2.1830343.CrossRef
32.
Carlier PG, Bertoldi D, Baligand C, Wary C, Fromes Y: Muscle blood flow and oxygenation measured by NMR imaging and spectroscopy. NMR Biomed. 2006, 19: 954-67. 10.1002/nbm.1081.CrossRefPubMed
33.
Haacke EM, Lai S, Reichenbach JR, Kuppusamy K, Hoogenraad FG, Takeichi H, Lin W: 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. 10.1002/(SICI)1097-0193(1997)5:5<341::AID-HBM2>3.0.CO;2-3.CrossRefPubMed
34.
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. 10.1002/mrm.21981.PubMedCentralCrossRefPubMed
35.
Spees WM, Yablonskiy DA, Oswood MC, Ackerman JJ: Water proton MR properties of human blood at 1.5 Tesla: magnetic susceptibility, T(1), T(2), T*(2), and non-Lorentzian signal behavior. Magn Reson Med. 2001, 45: 533-42. 10.1002/mrm.1072.CrossRefPubMed
36.
Jain V, Abdulmalik O, Propert KJ, Wehrli FW: Investigating the magnetic susceptibility properties of fresh human blood for noninvasive oxygen saturation quantification. Magn Reson Med. 2011, 68: 863-7.PubMedCentralCrossRefPubMed
37.
Li C, Langham MC, Epstein CL, Magland JF, Wu J, Gee J, Wehrli FW: Accuracy of the cylinder approximation for susceptometric measurement of intravascular oxygen saturation. Magn Reson Med. 2011, 67: 808-13.CrossRefPubMed
38.
Donahue KM, Van Kylen J, Guven S, El Bershawi A, Luh WM, Bandettini PA, Cox RW, Hyde JS, Kissebah AH: Simultaneous gradient‒echo/spin‒echo EPI of graded ischemia in human skeletal muscle. J Magn Reson Imaging. 1998, 8: 1106-13. 10.1002/jmri.1880080516.CrossRefPubMed
39.
Sanchez OA, Copenhaver EA, Elder CP, Damon BM: Absence of a significant extravascular contribution to the skeletal muscle BOLD effect at 3 T. Magn Reson Med. 2010, 64: 527-35.PubMedCentralPubMed
40.
Partovi S, Karimi S, Jacobi B, Schulte A-C, Aschwanden M, Zipp L, Lyo JK, Karmonik C, Müller-Eschner M, Huegli RW, Bongartz G, Bilecen D: Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI. Mag Reson Mater Phy. 2012, 25: 251-61. 10.1007/s10334-012-0306-y.CrossRef
41.
Slade JM, Towse TF, Gossain VV, Meyer RA: Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age. J Appl Physiol. 2011, 111: 1361-71.PubMedCentralCrossRefPubMed
42.
Towse TF, Slade JM, Ambrose JA, DeLano MC, Meyer RA: Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle. J Appl Physiol. 2011, 111: 27-39. 10.1152/japplphysiol.01054.2009.PubMedCentralCrossRefPubMed
43.
Elder CP, Cook RN, Wilkens KL, Chance MA, Sanchez OA, Damon BM: A method for detecting the temporal sequence of muscle activation during cycling using MRI. J Appl Physiol. 2011, 110: 826-33. 10.1152/japplphysiol.00185.2010.PubMedCentralCrossRefPubMed
44.
Potthast S, Schulte A, Kos S, Aschwanden M, Bilecen D: Blood oxygenation level-dependent MRI of the skeletal muscle during ischemia in patients with peripheral arterial occlusive disease. Rofo. 2009, 181: 1157-61. 10.1055/s-0028-1109786.CrossRefPubMed
45.
Van Vaals JJ, Brummer ME, Thomas Dixon W, Tuithof HH, Engels H, Nelson RC, Gerety BM, Chezmar JL, Den Boer JA: “Keyhole” method for accelerating imaging of contrast agent uptake. J Magn Reson Imaging. 2005, 3: 671-5.CrossRef
46.
Magland J, Wehrli F: Pulse sequence programming in a dynamic visual environment. Proc Int Soc Magnet Reson Med. 2006, 3032-
47.
Wu W-C, Wang J, Detre JA, Ratcliffe SJ, Floyd TF: Transit delay and flow quantification in muscle with continuous arterial spin labeling perfusion-MRI. J Magn Reson Imaging. 2008, 28: 445-52. 10.1002/jmri.21322.PubMedCentralCrossRefPubMed
48.
Langham MC, Magland JF, Floyd TF, Wehrli FW: Retrospective correction for induced magnetic field inhomogeneity in measurements of large-vessel hemoglobin oxygen saturation by MR susceptometry. Magn Reson Med. 2009, 61: 626-33. 10.1002/mrm.21499.CrossRefPubMed
49.
Versluis B, Backes WH, van Eupen MGA, Jaspers K, Nelemans PJ, Rouwet EV, Teijink JAW, Mali WPTM, Schurink G-W, Wildberger JE, Leiner T: Magnetic resonance imaging in peripheral arterial disease: reproducibility of the assessment of morphological and functional vascular status. Invest Radiol. 2011, 46: 11-24. 10.1097/RLI.0b013e3181f2bfb8.CrossRefPubMed
50.
Etsuda H, Takase B, Uehata A, Kusano H, Hamabe A, Kuhara R, Akima T, Matsushima Y, Arakawa K, Satomura K, Kurita A, Ohsuzu F: Morning attenuation of endothelium-dependent, flow-mediated dilation in healthy young men: possible connection to morning peak of cardiac events?. Clin Cardiol. 1999, 22: 417-21. 10.1002/clc.4960220610.CrossRefPubMed
51.
Nadel ER, Fortney SM, Wenger CB: Effect of hydration state of circulatory and thermal regulations. J Appl Physiol. 1980, 49: 715-21.PubMed
52.
Bungum L, Kvernebo K, Oian P, Maltau JM: Laser doppler-recorded reactive hyperaemia in the forearm skin during the menstrual cycle. Brit J Obstet Gynaec. 1996, 103: 70-5. 10.1111/j.1471-0528.1996.tb09517.x.CrossRefPubMed
53.
Parkes LM, Rashid W, Chard DT, Tofts PS: Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magn Reson Med. 2004, 51: 736-43. 10.1002/mrm.20023.CrossRefPubMed
54.
Proctor DN, Le KU, Ridout SJ: Age and regional specificity of peak limb vascular conductance in men. J Appl Physiol. 2005, 98: 193-202.CrossRefPubMed
55.
Langham MC, Englund EK, Li C, Floyd TF, Mohler ER, Wehrli FW: Balanced tissue magnetization reduces confounding BOLD effect in post-ischemic muscle perfusion quantification. Proc Int Soc Magnet Reson Med. 2012, 2027-
56.
Langham MC, Wehrli FW: mproved temporal resolution of dynamic oximetry via keyhole acquisition for quantifying reactive hyperemia. Proc Int Soc Magnet Reson Med. 2012, 1147-
57.
Brillault-Salvat C, Giacomini E, Jouvensal L, Wary C, Bloch G, Carlier PG: Simultaneous determination of muscle perfusion and oxygenation by interleaved NMR plethysmography and deoxymyoglobin spectroscopy. NMR Biomed. 1997, 10: 315-23. 10.1002/(SICI)1099-1492(199710)10:7<315::AID-NBM489>3.0.CO;2-X.CrossRefPubMed
58.
Partovi S, Schulte A-C, Jacobi B, Klarhöfer M, Lumsden AB, Loebe M, Davies MG, Noon GP, Karmonik C, Zipp L, Bongartz G, Bilecen D: Blood oxygenation level-dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T. J Magn Reson Imaging. 2012, 35: 1227-32. 10.1002/jmri.23583.CrossRefPubMed
59.
Schulte AC, Aschwanden M, Bilecen D: Calf muscles at blood oxygen level-dependent MR imaging: aging effects at postocclusive reactive hyperemia. Radiology. 2008, 247: 482-9. 10.1148/radiol.2472070828.CrossRefPubMed
60.
Mohler ER, Beebe HG, Salles-Cuhna S, Zimet R, Zhang P, Heckman J, Forbes WP: Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication. Vasc Med. 2001, 6: 151-6. 10.1177/1358836X0100600305.CrossRefPubMed
61.
Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ, Reynolds MR, Massaro JM, Lewis BA, Cerezo J, Oldenburg NC, Thum CC, Goldberg S, Jaff MR, Steffes MW, Comerota AJ, Ehrman J, Treat-Jacobson D, Walsh ME, Collins T, Badenhop DT, Bronas U, Hirsch AT, for the CLEVER Study Investigators: Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation. 2012, 125: 130-9. 10.1161/CIRCULATIONAHA.111.075770.PubMedCentralCrossRefPubMed
Metadata
Title
Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg
Authors
Erin K Englund
Michael C Langham
Cheng Li
Zachary B Rodgers
Thomas F Floyd
Emile R Mohler
Felix W Wehrli
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Cardiovascular Magnetic Resonance / Issue 1/2013
Electronic ISSN: 1532-429X
DOI
https://doi.org/10.1186/1532-429X-15-70

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