title: Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.
abstract: Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.
authors.affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, San Donato Milanese, Milan, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Zaccagnini
authors.affiliation: Preclinical Imaging Facility, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Palmisano
authors.affiliation: Preclinical Imaging Facility, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Canu
authors.affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, San Donato Milanese, Milan, Italy.
authors.forename: Biagina
authors.initials: B
authors.lastname: Maimone
authors.affiliation: Preclinical Imaging Facility, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Lo Russo
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Ambrogi
authors.affiliation: Division of Cardiovascular Epigenetics, Department of Cardiology, Internal Medicine Clinic III, Goethe University, Frankfurt am Main, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.affiliation: Preclinical Imaging Facility, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Cobelli
authors.affiliation: Preclinical Imaging Facility, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Del Maschio
authors.affiliation: Preclinical Imaging Facility, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, San Donato Milanese, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
mesh_terms: D000818:Animals; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D005263:Femoral Artery; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology / Q000502:physiology; D007511:Ischemia / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology* / Q000502:physiology; D012038:Regeneration / Q000502:physiology*