Peripheral vascular disease (PVD) caused by smoking, diabetes mellitus, and hypertension, results in limb ischemia in approximately 10% of the population over age 65 years. PVD results in claudication, tissue ischemia, gangrene, and amputation when not treated aggressively. Ninety thousand amputations are performed each year as a result of PVD. Diagnostic methods available at present include invasive techniques such as radiographic angiography, which, because of contrast dye toxicity, can result in serious complications such as renal failure. The diagnostic armamentarium is burgeoning however. Noninvasive techniques such as duplex Doppler and MRI angiography are today allowing surgery to be completed without radiographic angiography and with a high degree of success in selected populations. Patients with Chronic Critical Limb Ischemia (CCLI) are at the highest levels of risk for limb loss and perioperative morbidity and mortality when re-vascularization or amputation is performed. Evidence indicates that current diagnostic methods, again directed primarily at identifying macro-vascular flow impediments, do not adequately assist the surgeon in assessing potential for revascularization in patients with CCLI. As a result, grafting success is much poorer in this population, leading to repeated procedures, often delayed amputation, prolonged rehabilitation, and excessive morbidity and mortality. Astoundingly, when surgeons predicted that amputation stump wounds would not heal, they were wrong 50% of the time, leading one to wonder if their estimation of appropriate level for amputation doesn't tend to be a bit too aggressive. We propose the application of a noninvasive MRI method, Arterial Spin Labeling Perfusion MRI to this problem. Arterial spin-labeling sequences have been developed to study micro-vascular blood flow in the calf and foot. We intend to further the development and application of this technique at high field MRI where improved signal and resolution are likely. We also propose to develop flow indices for the foot, calf, and forearm and compare them with recognized diagnostic standards. Finally, we will apply them prospectively to predict graft patency and wound healing after amputation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL075649-02
Application #
6803027
Study Section
Special Emphasis Panel (ZHL1-CSR-I (S1))
Program Officer
Reid, Diane M
Project Start
2003-09-22
Project End
2008-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$396,250
Indirect Cost
Name
University of Pennsylvania
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Englund, Erin K; Rodgers, Zachary B; Langham, Michael C et al. (2018) Simultaneous measurement of macro- and microvascular blood flow and oxygen saturation for quantification of muscle oxygen consumption. Magn Reson Med 79:846-855
Magland, Jeremy F; Li, Cheng; Langham, Michael C et al. (2016) Pulse sequence programming in a dynamic visual environment: SequenceTree. Magn Reson Med 75:257-65
Englund, Erin K; Rodgers, Zachary B; Langham, Michael C et al. (2016) Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL). J Magn Reson Imaging 44:929-39
Langham, Michael C; Desjardins, Benoit; Englund, Erin K et al. (2016) Rapid High-resolution, Self-registered, Dual Lumen-contrast MRI Method for Vessel-wall Assessment in Peripheral Artery Disease:: A Preliminary Investigation. Acad Radiol 23:457-67
Englund, Erin K; Langham, Michael C; Ratcliffe, Sarah J et al. (2015) Multiparametric assessment of vascular function in peripheral artery disease: dynamic measurement of skeletal muscle perfusion, blood-oxygen-level dependent signal, and venous oxygen saturation. Circ Cardiovasc Imaging 8:
Langham, Michael C; Li, Cheng; Englund, Erin K et al. (2013) Vessel-wall imaging and quantification of flow-mediated dilation using water-selective 3D SSFP-echo. J Cardiovasc Magn Reson 15:100
Englund, Erin K; Langham, Michael C; Li, Cheng et al. (2013) Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg. J Cardiovasc Magn Reson 15:70
Langham, Michael C; Floyd, Thomas F; Mohler 3rd, Emile R et al. (2010) Evaluation of cuff-induced ischemia in the lower extremity by magnetic resonance oximetry. J Am Coll Cardiol 55:598-606
Langham, Michael C; Magland, Jeremy F; Epstein, Charles L et al. (2009) Accuracy and precision of MR blood oximetry based on the long paramagnetic cylinder approximation of large vessels. Magn Reson Med 62:333-40
Langham, Michael C; Magland, Jeremy F; Floyd, Tom F et al. (2009) Retrospective correction for induced magnetic field inhomogeneity in measurements of large-vessel hemoglobin oxygen saturation by MR susceptometry. Magn Reson Med 61:626-33

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