Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium.

Histopathological evaluation

source: © 2015 European Heart Journal

Background
Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe.

Methods
Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin–eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen.

Results
Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm2 vs. late: 2485 ± 1778 per mm2; P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm2 vs. late: 1428 ± 1023 per mm2; P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents.

Conclusion
In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST.[Read more….]

eukocyte accumulation in stent thrombus specimens.

Fig. Leukocyte accumulation in stent thrombus specimens. (A) Leukocyte accumulation in human stent thrombus specimens. Left images: Haematoxylin–eosin staining (n = 253). Arrows indicate granulocytes, arrowheads indicate mononuclear cells. Right images: immunofluorescence staining of neutrophil elastase to identify neutrophils (n = 229). Nuclei are counterstained with Hoechst. Bars, 200 ”m (upper row) and 50 ”m (bottom row); (B) Quantification of leukocytes and neutrophils in early (n = 67) vs. late (n = 162) stent thrombosis (leukocytes: P = 0.44; neutrophils: P = 0.81); (C) Leukocytes and neutrophils in stent thrombosis from drug-eluting stents (n = 149) and bare metal stents (n = 73) and in thrombi aspirated from patients with spontaneous myocardial infarction (spont. myocardial infarction; n = 104) (P < 0.05 for drug-eluting stents vs. spont. myocardial infarction and bare metal stents vs. spont. myocardial infarction). Shown are mean + SD, each symbol in (B) and (C) represents one individual patient.

++These authors contributed equally to this work.
Julia Riegger, Robert A. Byrne, Michael Joner, Sue Chandraratne, Anthony H. Gershlick, Jurrien M. ten Berg, Tom Adriaenssens, Giulio Guagliumi, Thea C. Godschalk, Franz-Josef Neumann, Dietmar Trenk, Laurent J. Feldman, Philippe Gabriel, Steg Walter Desmet, Fernando Alfonso, Alison H. Goodall, Roman Wojdyla, Dariusz Dudek, Vanessa Philippi, Sheryl Opinaldo, Anna Titova, Nikesh Malik, James Cotton, Darshni A. Jhagroe, Antonius A.C.M. Heestermans, Peter Sinnaeve, Paul Vermeersch, Christian Valina, Christian Schulz, Adnan Kastrati, Steffen Massberg the Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort (PRESTIGE) Investigators On Behalf of the Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort (PRESTIGE) Investigators,Tom Adriaenssens, Ian Buysschaert, Mickaël Chausson, Dries De Cock, Jo Dens, Emanuele Barbato, Walter Desmet, Sandrine Gautier, Paul Vermeersch, Peter Sinnaeve, Helene Abergel, Laurent Feldman, Martine Jandrot-Perrus, Didier Letourneur, Pierre Mangin, Véronique Olivier, Caroline Roques, Robert A. Byrne, Sue Chandraratne, Matthias Gratz, Michael Joner, Adnan Kastrati, Elisabeth Kennerknecht, Ildiko Konrad, Tobias Koppara, Steffen Massberg, Franz-Josef Neumann, Vasilis Ntziachristos, Sheryl Opinaldo, Vanessa Philippi, Julia Riegger, Amir Rosenthal, Alexander Rzany, Christian Schulz, Kristin Steigerwald, Tomohiso Tada, Anna Titova, Dietmar Trenk, Christian Valina, Andreas Vogelsang, Erion Xhepa, Chiara Bernelli, Micol Coccato, Giulio Guagliumi, Kenichi Komukai, Vasile Sirbu, Garry Kerch, Giovanni Amoroso, Jurriën ten Berg, Willem J.M. Dewilde, Thea C. Godschalk, Antonius A.C.M. Heestermans, Darshni A. Jhagroe, Joanne J. Wykrzykowska, Mark H.M. Winkens, Dariusz Dudek, Ɓukasz Rzeszutko, Roman Wojdyla, Wojciech Zasada, Fernando Alfonso, Javier Cuesta, Miguel Medina, Colin Berry, James Cotton, Nick Curzen, Margaret McEntegart, Robert Gerber, Anthony Gershlick, Alison H. Goodall, Simon Hetherington, Jonathan Hill, Damian Kelly, Nikesh Malik, Keith Oldroyd, Helen Routledge, Joanne Shannon, Venkatesan Suresh, Azfar Zahman.

European Heart Journal, Volume 37, Issue 19, 14 May 2016, Pages 1538–1549, https://doi.org/10.1093/eurheartj/ehv419

Optical and optoacoustic model-based tomography: theory and current challenges for deep tissue imaging of optical contrast

A state of the art in hybrid optical molecular tomography

source:© 2015 IEEE Signal Processing Magazine

Light offers a range of interactions with tissue that give rise to an extensive list of methods to sense physical, chemical, or biological processes. Combined with using safe and nonionizing radiation, optical imaging is considered as a fundamental tool in the biomedical sciences.
[Read More…]ï»ż

Fig. 1 Principles of optical and optoacoustic tomography. (a) Themorelastic expansion of an optically absorbing object (black circle) within tissue (blue circle) upon illumination by pulsed laser beams. The object expands and contracts, due to temperature variation, and releases the absorbed energy as pressure waves (dotted circles). (b) Typical time-resolved optoacoustic signal detected using an ultrasound sensor. (c) A reconstructed transversal optoacoustic image of the abdominal region of a mouse, using a two-dimensional (2-D) circular measurement system geometry,. (d) The principles of fluorescence, as electrons are excited to higher energy levels upon absorbing photons. Fluorescence photons are then emitted as the excited electrons vibrationally relax to their base states. (e) Fluorescence image acquired with a CCD camera from the dorsal side of a mouse. (f) A three-dimensional (3-D) image of a pancreatic tumor model reconstructed with concurrent X-ray CT and fluorescence molecular tomography (FMT-XCT), in 360° transillumination geometry.

P. Mohajerani, S. Tzoumas, A. Rosenthal, and V. Ntziachristos “Optical and optoacoustic model-based tomography: theory and current challenges for deep tissue imaging of optical contrast,” IEEE Signal Processing Magazine, Vol. 32, pp. 88-100 (2015).

Sparsity‐based acoustic inversion in cross‐sectional multiscale optoacoustic imaging.

The schematic of the optoacoustic imaging system

source: © 2015  Medical physics & American Association of Physicists in Medicine

Purpose:
With recent advancement in hardware of optoacoustic imaging systems, highly detailed cross‐sectional images may be acquired at a single laser shot, thus eliminating motion artifacts. Nonetheless, other sources of artifacts remain due to signal distortion or out‐of‐plane signals. The purpose of image reconstruction algorithms is to obtain the most accurate images from noisy, distorted projection data.

Methods:
In this paper, the authors use the model‐based approach for acoustic inversion, combined with a sparsity‐based inversion procedure. Specifically, a cost function is used that includes the L1 norm of the image in sparse representation and a total variation (TV) term. The optimization problem is solved by a numerically efficient implementation of a nonlinear gradient descent algorithm. TV–L1 model‐based inversion is tested in the cross section geometry for numerically generated data as well as for in vivo experimental data from an adult mouse.

Results:
In all cases, model‐based TV–L1 inversion showed a better performance over the conventional Tikhonov regularization, TV inversion, and L1 inversion. In the numerical examples, the images reconstructed with TV–L1 inversion were quantitatively more similar to the originating images. In the experimental examples, TV–L1 inversion yielded sharper images and weaker streak artifact.

Conclusions:
The results herein show that TV–L1 inversion is capable of improving the quality of highly detailed, multiscale optoacoustic images obtained in vivo using cross‐sectional imaging systems. As a result of its high fidelity, model‐based TV–L1 inversion may be considered as the new standard for image reconstruction in cross‐sectional imaging. [Read more……]

Experimental data reconstructions in almost-completed-view

Fig. Experimental data reconstructions in almost-completed-view with (a) Tik–Lap, (b) TV, (c) L1, and (d) TV–L1; (e)–(h) zoomed images in the dash line rectangle region of (a), (d), (c), and (d); (i) comparison of FWHM of the vessel along the dashed lines in (e)–(h).

Yiyong Han, Stratis Tzoumas, Antonio Nunes, Vasilis Ntziachristos, Amir Rosenthal.  Medical physics.