title: Baseline assessment and comparison of arterial anatomy, hyperemic flow, and skeletal muscle perfusion in peripheral artery disease: The Cardiovascular Cell Therapy Research Network "Patients with Intermittent Claudication Injected with ALDH Bright Cells" (CCTRN PACE) study.
abstract: BACKGROUND
  Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies.
  
  
  METHODS
  The PACE study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow-derived ALDHbrstem cells. The primary MRI end points of the study are as follows: (1) total collateral count, (2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and (3) peak hyperemic popliteal flow by phase-contrast MRI (PC-MRI).
  
  
  RESULTS
  The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8% vs 5.6%) and peak hyperemic popliteal flow (4.1 vs 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization.
  
  
  CONCLUSIONS
  Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Bharath Ambale
authors.initials: BA
authors.lastname: Venkatesh
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Victor
authors.initials: V
authors.lastname: Nauffal
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Chikara
authors.initials: C
authors.lastname: Noda
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Yang
authors.affiliation: University of Texas Houston Health Science Center, School of Public Health, Houston, TX.
authors.forename: Judy
authors.initials: J
authors.lastname: Bettencourt
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Erin P
authors.initials: EP
authors.lastname: Ricketts
authors.affiliation: Indiana University School of Medicine, Bloomington, IN.
authors.forename: Michael
authors.initials: M
authors.lastname: Murphy
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Leeper
authors.affiliation: University of Texas Houston Health Science Center, School of Public Health, Houston, TX. Electronic address: lemmoye@msn.com.
authors.forename: Lem
authors.initials: L
authors.lastname: Moyé
authors.affiliation: NIH, National Heart, Lung, and Blood Institute, Bethesda, MD.
authors.forename: Ray F
authors.initials: RF
authors.lastname: Ebert
authors.affiliation: Texas Heart Institute, Houston, TX.
authors.forename: Raja
authors.initials: R
authors.lastname: Muthupillai
authors.affiliation: NIH, National Heart, Lung, and Blood Institute, Bethesda, MD.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: Texas Heart Institute, Houston, TX.
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.affiliation: University of Minnesota Medical School, Minneapolis, MN.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Hirsch
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: João A C
authors.initials: JA
authors.lastname: Lima
mesh_terms: D064592:Autografts; D004311:Double-Blind Method; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007273:Injections, Intramuscular; D007383:Intermittent Claudication / Q000503:physiopathology / Q000628:therapy*; D007866:Leg / Q000098:blood supply* / Q000000981:diagnostic imaging; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D058729:Peripheral Arterial Disease / Q000503:physiopathology* / Q000628:therapy*; D012039:Regional Blood Flow