title: Surface-enhanced Raman spectral biomarkers correlate with Ankle Brachial Index and characterize leg muscle biochemical composition of patients with peripheral arterial disease.
abstract: Peripheral arterial disease (PAD) is characterized by atherosclerotic blockages of the arteries supplying the lower extremities, which cause a progressive accumulation of ischemic injury to the skeletal muscles of the lower limbs. This injury includes altered metabolic processes, damaged organelles, and compromised bioenergetics in the affected muscles. The objective of this study was to explore the association of Raman spectral signatures of muscle biochemistry with the severity of atherosclerosis in the legs as determined by the Ankle Brachial Index (ABI) and clinical presentation. We collected muscle biopsies from the gastrocnemius (calf muscle) of five patients with clinically diagnosed claudication, five patients with clinically diagnosed critical limb ischemia (CLI), and five control patients who did not have PAD. A partial least squares regression (PLSR) model was able to predict patient ABI with a correlation coefficient of 0.99 during training and a correlation coefficient of 0.85 using a full cross-validation. When using the first three PLS factor scores in combination with linear discriminant analysis, the discriminant model was able to correctly classify the control, claudicating, and CLI patients with 100% accuracy, using a full cross-validation procedure. Raman spectroscopy is capable of detecting and measuring unique biochemical signatures of skeletal muscle. These signatures can discriminate control muscles from PAD muscles and correlate with the ABI and clinical presentation of the PAD patient. Raman spectroscopy provides novel spectral biomarkers that may complement existing methods for diagnosis and monitoring treatment of PAD patients.
authors.affiliation: Bioengineering, Wichita State University, Wichita, Kansas.
authors.forename: Kim
authors.initials: K
authors.lastname: Cluff
authors.affiliation: Biological Systems Engineering, University of Nebraska, Lincoln, Nebraska.
authors.forename: Abby M
authors.initials: AM
authors.lastname: Kelly
authors.affiliation: Division of General Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Koutakis
authors.affiliation: Department of Electrical Engineering, University of Nebraska, Lincoln, Nebraska.
authors.forename: Xiang N
authors.initials: XN
authors.lastname: He
authors.affiliation: Department of Electrical Engineering, University of Nebraska, Lincoln, Nebraska.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Electrical Engineering, University of Nebraska, Lincoln, Nebraska.
authors.forename: Yong Feng
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Division of General Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska Department of Surgery and VA Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska.
authors.forename: Iraklis I
authors.initials: II
authors.lastname: Pipinos
authors.affiliation: Division of General Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: George P
authors.initials: GP
authors.lastname: Casale
authors.affiliation: Biological Systems Engineering, University of Nebraska, Lincoln, Nebraska Food Science and Technology, University of Nebraska, Lincoln, Nebraska.
authors.forename: Jeyamkondan
authors.initials: J
authors.lastname: Subbiah
keywords: Linear discriminant analysis; Raman spectroscopy; muscle biochemistry; partial least squares regression; peripheral arterial disease