<b>A:</b> Short axis high resolution, high field cardiac MRI of a FXIII^−/− mouse 2 days after coronary ligation.

<div><p>Arrows: intrathoracic hematoma adjacent to experimental anterolateral infarction.</p> <p> <b>B:</b> Autopsy confirms a blood clot (asterisk) originating from myocardial rupture at the border zone (arrow) of the myocardial infarct.</p> <p> <b>C:</b> Histology of 1A shows rupture channel (arrows), filled with blood.</p> <p> <b>D:</b> In patients with ruptured MI, FXIII levels were significantly reduced (*p<0.01).</p> <p> <b>E:</b> Color Doppler echo of patient with new ventricular septum defect 7 days after myocardial infarction (arrow).</p> <p> <b>F:</b> MRI after VSD repair with patch (arrows).</p> <p> <b>G–I:</b> Explantation site of saphenous veins for CABG surgery displays delayed healing.</p> <p> <b>J:</b> 73 days after initial surgery, 3 revisions and 2 weeks after i.v. FXIII augmentation, the wound is closed.</p></div

Time evolution of cathepsin activity in response to injected materials fluorescently imaged.

<p><i>In vivo</i> fluorescence imaging using ProSense 680 for cathepsin activity at various time points for a) saline, b) polystyrene, and c) alginate. The scale bar ranges 0–6×10⁻⁴ in fluorescence efficiency. The quantified fluorescence efficiencies of cathepsin activities are shown for d) polystyrene and e) alginate as the mean with standard deviation. Symbols represent data points and lines represent linear regressions.</p

Subcutaneous Injection arrays.

<p>Three array formats used for injecting saline and polymers subcutaneously in mice where A is 30 µl, B is 50 µl, C is 70 µl, and D is 100 µl.</p

Quantification of probe activity in infarct area.

<p>(A) Cylindrical (left) and Bull's Eye (right) maps of molecular probe and bead distribution of an excised heart at day 5 after myocardial infarction. High cathepsin B and phagocytic activity, are evident in the proximity of the injured area with a high degree of colocalization. Fluorescently labeled (FITC) microbeads, injected in vivo into the left ventricle before harvesting, are homogeneously distributed across the whole heart, with the exception of the non-perfused infarct area. The white dotted line indicates the border of the necrotic infarct scar, localized in apical and lateral segments. Continuous white line indicates the border of the interventricular septum. (B) Axial reconstructions of probe activities at the indicated plane. (C) Cylindrical (left) and Bull's Eye (right) representation of reparative (Ly6C^lo, green) and inflammatory (Ly6C^hi, red) monocyte subsets together with the an axial (D) and tomographic (E) reconstruction.</p

Validation of tomographic reconstructions.

<p>Comparison between OPT reconstructions and histological sections of molecular probe activity distribution (Prosense-680) in the inflamed heart after MI. Comparisons between reconstructions obtained with fluorescence OPT (A), Bornnormalized OPT (B), and the corresponding histological section (C). Born normalization preserves the molecular distributions in the reconstructed fluorescence channels. This is particularly evident for the papillary muscles located deep within the left ventricle, which appear less fluorescent without normalization, and the epicardium, which always shows bright fluorescent signal in absence of normalization. Born-normalized OPT reconstructions were obtained on the whole heart. The histological section (500 µm) belongs to the same specimen.</p

Time evolution of macrophage response to injected materials fluorescently imaged.

<p><i>In vivo</i> fluorescence imaging of F4/80 pan macrophage antibody at various time points for a) saline, b) polystyrene, and c) alginate. The scale bar ranges 0–1.5×10⁻⁴ in fluorescence efficiency. The quantified fluorescence efficiency of F4/80 pan macrophage responses are shown for d) polystyrene and e) alginate as the mean with standard deviation. Symbols represent data points and lines represent linear regressions.</p

Histological comparison.

<p>Born-normalized fluorescence OPT reconstructions (A) of the two molecular imaging agents Prosense-680 and CLIO-750 are compared with immune-reactive staining of the imaging target protease Cathepsin B (B) and for the Mac3 macrophage antigen (C).</p

Probe activity distribution maps in inflamed left ventricle.

<p>(A) Bull's Eye (top) and cylindrical (right) maps of molecular probe activity at day 5 post myocardial infarction. Inflammation is accentuated along the border of the injured tissue, while the core of the infarct displays low signal. Continuous white line indicates the border of the interventricular septum. (B) One-dimensional plots showing the intensities of the probes activity, along the directions indicated in the maps (white faded bands). Signal plots indicate a high correlation in probe activities. (C) Axial reconstructions of cell-associated probe activity along the indicated plane, with their corresponding co-localization maps. (D) Overlapping cross correlation functions (CCF) are calculated for the two channels, taking into account both translational and rotational shifts. Overall, a high degree of correlation is present, however there are distinct differences in each channel reflecting the different spatial distribution of the molecular target.</p

Tomographic reconstructions.

<p>Coronal (top), saggital (middle), and axial (bottom) tomographic reconstructions of enzyme (A) and phagocytic cell (B) distributions. After permanent occlusion of the coronary artery, both probes are primarily confined to the infarct scar area. This area is associated with a strong localized near-infrared fluorescence (NIRF) signal, whereas only weak fluorescence intensity is observed in the basal part of the ventricle.</p

Born-normalized molecular optical projection tomography of inflamed hearts.

<p>(A) Dual channel imaging. A cocktail containing two different molecular imaging agents is administered intravenously. (B) Dual channel Born-normalized near-infrared transillumination fluorescence image on day 5 after myocardial infarction (MI), 24 hours after probe injection. High signal in both the 680 nm (left) and 750 nm (right) fluorescence channels can be observed in the heart region, indicating elevated protease and phagocytic activity. (C) A narrow bandwidth light source excites the fluorophores attached to a molecular probe located within the sample, and fluorescent light is then emitted. Both excitation and emission light are, in part, absorbed by the sample on the way to and from the fluorophore, respectively. Using a Born-normalized approach, fluorescence tomographic reconstructions can be obtained, after correcting for the sample's absorption map. (D) Image processing algorithms are applied to tomographically obtain signal distribution reconstructions in whole hearts and to remove noise and artifacts contributions.</p