Browsing by Author "Smith, Alberto"

Now showing 1 - 6 of 6
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    Increased vascular permeability is a surrogate marker of atherosclerotic plaque instability
    (2015) Phinikaridou, Alkystis; Andía Kohnenkampf, Marcelo Edgardo; Plaza, Begona L.; Saha, Prakash; Smith, Alberto; Botnar, René Michael
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    Molecular MRI of Collagen Enables Evaluation of Fibrosis and Therapeutic Response in Venous Thrombosis
    (2025) Gao, Ling; Chaher, Nadia; Serralha, Joana C.; Bertolaccini, Laura; Velasco, Carlos; Cruz, Gastão; Morrell, Alexander P.; Prieto Vásquez, Claudia Del Carmen; Botnar, René Michael; Smith, Alberto; Saha, Prakash; Phinikaridou, Alkystis
    Background: 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.
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    Multiparametric Contrast-Free MRI Successfully Identifies Venous Thrombus Responsive to Lytic Therapy: From Mice to Humans
    (2025) Silickas, Justinas; Smith, Alberto; Andía Kohnenkampf, Marcelo Edgardo; Botnar, René Michael; Modarai, Bijan; Karunanithy, Narayan; Patel, Ashish S.; Black, Stephen; Saha, Prakash; Phinikaridou, Alkystis
    Background:Randomized trials of venous thrombolysis to prevent postthrombotic syndrome have produced mixed results. A method to identify patients most likely to benefit from interventional treatment is needed. This study evaluated a contrast-free, magnetic resonance-based multisequence thrombus imaging (MSTI) technique to characterize deep venous thrombi and predict susceptibility to thrombolysis.Methods:Venous thrombosis was induced in the inferior vena cava of BALB/C mice (n=56, male), which were imaged up to 28 days postsurgery and 24 hours after systemic thrombolysis (Actilyse, 10 mg/kg, IV). The prelysis MSTI protocol included 3-dimensional T1 mapping, 3-dimensional magnetization transfer, and 2-dimensional diffusion-weighted imaging. Thrombolysis was defined as successful if inferior vena cava blood flow increased by ≥50% compared with prelysis values. In a clinical cohort, 41 patients with acute iliofemoral deep venous thrombi underwent MSTI before catheter-directed thrombolysis. Imaging parameters were analyzed against postintervention outcomes.Results:MSTI identified thrombi susceptible to thrombolysis in both mice and humans. In mice, lysed thrombi showed lower T1 (723 [667–782] versus 874 [799–1000] ms; P<0.001) and higher apparent diffusion coefficient values (1.02 [0.96–1.14] versus 0.78 [0.62–0.88]×10-³ mm²/s; P<0.001) than nonlysable thrombi, with no difference in magnetization transfer. In patients, lysed thrombi demonstrated lower T1 (606 [543–656] versus 765 [630–909] ms; P<0.001), lower apparent diffusion coefficient (0.67 [0.5–1.1] versus 1.23 [0.69–1.74]×10-³ mm²/s; P=0.001), and similar magnetization transfer rates. Combining MSTI parameters optimized prediction, achieving 88% sensitivity and 97% specificity in mice, and 86% sensitivity and 91% specificity in humans.Conclusions:MSTI enables noninvasive, contrast-free characterization of thrombus composition and predicts thrombolytic susceptibility. This technique has the potential to guide patient selection for invasive therapies and should be incorporated into future trials of venous thrombosis treatment.
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    Noninvasive Magnetic Resonance Imaging Evaluation of Endothelial Permeability in Murine Atherosclerosis Using an Albumin-Binding Contrast Agent
    (LIPPINCOTT WILLIAMS & WILKINS, 2012) Phinikaridou, Alkystis; Andia, Marcelo E.; Protti, Andrea; Indermuchle, Andreas; Shah, Ajay; Smith, Alberto; Warley, Alice; Botnar, Rene M.
    Backgound-Endothelial dysfunction promotes atherosclerosis and precedes acute cardiovascular events. We investigated wether in vivo magnetic resonance imaging with the use of an albumin-binding contrast agent, gadofosveset, could detect endothelial damage associated with atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. Furthermore, we tested whether magnetic resonance imaging could noninvasively assess endothelial function by measuring the endothelial-dependent vasolidation in response to acetycholine.
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    Tropoelastin: A Novel Marker for Plaque Progression and Instability
    (2018) Phinikaridou, Alkystis; Lacerda, Sara; Lavin, Begona; Andía Kohnenkampf, Marcelo Edgardo; Smith, Alberto; Saha, Prakash; Botnar, René Michael
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    Venous Thrombosis Accelerates Atherosclerosis in Mice
    (2023) Saha, Prakash; Gutmann, Clemens; Kingdon, Jack; Dregan, Alexandru; Bertolaccini, Laura; Grover, Steven P.; Patel, Ashish S.; Modarai, Bijan; Lyons, Oliver; Schulz, Christian; Andía Kohnenkampf, Marcelo Edgardo; Phinikaridou, Alkystis; Botnar, René Michael; Smith, Alberto