title: Microstructural impact of ischemia and bone marrow-derived cell therapy revealed with diffusion tensor magnetic resonance imaging tractography of the heart in vivo.
abstract: BACKGROUND
  The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, with the use of serial diffusion tensor magnetic resonance imaging tractography of the heart in vivo, is presented.
  
  
  RESULTS
  Validation of the approach was performed in normal (n=6) and infarcted mice (n=6) as well as healthy human volunteers. Mice (n=12) were then injected with bone marrow mononuclear cells 3 weeks after coronary ligation. In half of the mice the donor and recipient strains were identical, and in half the strains were different. A positive response to cell injection was defined by a decrease in mean diffusivity, an increase in fractional anisotropy, and the appearance of new myofiber tracts with the correct orientation. A positive response to bone marrow mononuclear cell injection was seen in 1 mouse. The response of the majority of mice to bone marrow mononuclear cell injection was neutral (9/12) or negative (2/12). The in vivo tractography findings were confirmed with histology.
  
  
  CONCLUSIONS
  Diffusion tensor magnetic resonance imaging tractography was able to directly resolve the ability of injected cells to generate new myofiber tracts and provided a fundamental readout of their regenerative capacity. A highly novel and translatable approach to assess the efficacy of cell therapy in the heart is thus presented.
authors.affiliation: From Martinos Center for Biomedical Imaging, Department of Radiology (D.E.S., C.M., S.H., H.H.C., G.D., R.W., W.J.K., V.J.W.), and Cardiovascular Research Center, Cardiology Division (D.E.S., H.H.C., W.J.K.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (C.T.S., S.K.); Cardiac Muscle Research Laboratory, Divisions of Cardiology and Genetics, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA (S.N., J.G., R.L.); and Department of Computer Science, Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil (M.P.J.).
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
authors.forename: Choukri
authors.initials: C
authors.lastname: Mekkaoui
authors.forename: Shuning
authors.initials: S
authors.lastname: Huang
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chen
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.forename: Christian T
authors.initials: CT
authors.lastname: Stoeck
authors.forename: Soeun
authors.initials: S
authors.lastname: Ngoy
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Wang
authors.forename: William J
authors.initials: WJ
authors.lastname: Kostis
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Jackowski
authors.forename: Van J
authors.initials: VJ
authors.lastname: Wedeen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kozerke
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
mesh_terms: D000818:Animals; D051379:Mice; D016880:Anisotropy; D016026:Bone Marrow Transplantation / Q000379:methods; D056324:Diffusion Tensor Imaging / Q000379:methods; D004195:Disease Models, Animal; D064368:Healthy Volunteers; D021621:Imaging, Three-Dimensional / Q000379:methods; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D017202:Myocardial Ischemia / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D006801:Humans
keywords: diffusion tensor imaging; diffusion tractography; ischemia; magnetic resonance imaging; myocardium; stem cell transplantation