Molecular MRI of Collagen Enables Evaluation of Fibrosis and Therapeutic Response in Venous Thrombosis

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dc.catalogadorjlo
dc.contributor.authorGao, Ling
dc.contributor.authorChaher, Nadia
dc.contributor.authorSerralha, Joana C.
dc.contributor.authorBertolaccini, Laura
dc.contributor.authorVelasco, Carlos
dc.contributor.authorCruz, Gastão
dc.contributor.authorMorrell, Alexander P.
dc.contributor.authorPrieto Vásquez, Claudia Del Carmen
dc.contributor.authorBotnar, René Michael
dc.contributor.authorSmith, Alberto
dc.contributor.authorSaha, Prakash
dc.contributor.authorPhinikaridou, Alkystis
dc.date.accessioned2025-12-17T19:22:30Z
dc.date.available2025-12-17T19:22:30Z
dc.date.issued2025
dc.description.abstractBackground: Fibrosis, with accumulation of type I collagen, is a hallmark of postthrombotic change after deep vein thrombosis (DVT), but tools for its direct detection are lacking. Here, we investigate whether molecular magnetic resonance imaging (MRI) using a collagen-specific gadolinium-based probe can detect and measure changes in collagen during thrombus resolution and in response to treatment in a mouse model of DVT.Methods:Venous thrombus was induced in the inferior vena cava of BALB/c mice (n=45), and MRI was performed at day 2 (n=3) and weeks 1, 2, and 3 post-surgery using the collagen-specific probe, EP-3533 (10 μmol/kg; n=11–13/group). A subgroup of mice with DVT (n=7) was treated with pravastatin in drinking water (40 mg/kg per d) for 3 weeks post-DVT. Pre- and post-EP-3533 MRI scans were performed. Magnetic resonance venography was used to measure thrombus volume. Inversion recovery T1-weighted images and T1 maps, pre- and post-contrast, were used to calculate the percent change (%) in Δ contrast-to-noise ratio, Δ signal-to-noise ratio, and Δ relaxation rate. Tissues were used for ex vivo analyses.Results:EP-3533 uptake increased during thrombus organization and resolution, resulting in MRI signal enhancement, with % Δ contrast-to-noise ratio, % Δ signal-to-noise ratio, and % Δ relaxation rate peaking at 3 weeks after DVT. MRI measurements of collagen accumulation quantified as an increase in % Δ contrast-to-noise ratio (ρ=0.89; P=0.012) and % Δ relaxation rate (ρ=0.80; P=0.029) correlated positively with collagen histology. The spatial distribution of gadolinium in the tissue colocalized with collagen type I based on immunohistochemistry (ρ=0.95; P<0.001). Statin treatment decreased both collagen accumulation and vein wall thickness, without affecting thrombus size.Conclusions:Molecular MRI using a collagen-targeting probe made collagenous thrombus visible on MRI and detected changes in collagen content during thrombus resolution.
dc.fechaingreso.objetodigital2025-12-17
dc.format.extent13 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1161/CIRCIMAGING.125.018784
dc.identifier.eissn1942-0080
dc.identifier.urihttps://doi.org/10.1161/CIRCIMAGING.125.018784
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/107439
dc.information.autorucEscuela de Ingeniería; Prieto Vásquez, Claudia Del Carmen; 0000-0003-4602-2523; 14195
dc.information.autorucEscuela de Ingeniería; Botnar, René Michael; 0000-0003-2811-2509; 1015313
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaCirculation: Cardiovascular Imaging
dc.rightsacceso abierto
dc.subjectCollagen
dc.subjectGadolinium
dc.subjectPhlebography
dc.subjectVena cava, inferior
dc.subject.ddc610
dc.titleMolecular MRI of Collagen Enables Evaluation of Fibrosis and Therapeutic Response in Venous Thrombosis
dc.typeartículo
sipa.codpersvinculados14195
sipa.codpersvinculados1015313
sipa.trazabilidadORCID;2025-12-15
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