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January 29, 2019September 30, 2019

Quantitative intravascular biological fluorescence-ultrasound imaging of coronary and peripheral arteries in vivo.

Aims
(i) to evaluate a novel hybrid near-infrared fluorescence—intravascular ultrasound (NIRF-IVUS) system in coronary and peripheral swine arteries in vivo; (ii) to assess simultaneous quantitative biological and morphological aspects of arterial disease.
Methods and results
Two 9F/15MHz peripheral and 4.5F/40MHz coronary near-infrared fluorescence (NIRF)-IVUS catheters were engineered to enable accurate co-registrtation of biological and morphological readings simultaneously in vivo. A correction algorithm utilizing IVUS information was developed to account for the distance-related fluorescence attenuation due to through-blood imaging. Corrected NIRF (cNIRF)-IVUS was applied for in vivo imaging of angioplasty-induced vascular injury in swine peripheral arteries and experimental fibrin deposition on coronary artery stents, and of atheroma in a rabbit aorta, revealing feasibility to intravascularly assay plaque structure and inflammation. The addition of ICG-enhanced NIRF assessment improved the detection of angioplasty-induced endothelial damage compared to standalone IVUS. In addition, NIRF detection of coronary stent fibrin by in vivo cNIRF-IVUS imaging illuminated stent pathobiology that was concealed on standalone IVUS. Fluorescence reflectance imaging and microscopy of resected tissues corroborated the in vivo findings.
Conclusions
Integrated cNIRF-IVUS enables simultaneous co-registered through-blood imaging of disease related morphological and biological alterations in coronary and peripheral arteries in vivo. Clinical translation of cNIRF-IVUS may significantly enhance knowledge of arterial pathobiology, leading to improvements in clinical diagnosis and prognosis, and helps to guide the development of new therapeutic approaches for arterial diseases.[Read more…]

Intravascular cNIRF-IVUS imaging with the 4.5F/40MHz catheter reveals the value of IVUS-based distance correction of the NIRF signal in blood. In vivo cNIRF-IVUS imaging of a swine carotid artery was performed following local injection of an NIR fluorophore into the artery wall. Panels (A), (B) and (C) illustrate the in vivo cNIRF image, the corresponding longitudinal IVUS image, and the FRI image of the resected artery, respectively. (D) A 3D representation of the lumen and arterial wall NIR fluorescence signal rendered based on the in vivo cNIRF-IVUS image stack. Insets (C1–C3) show representative examples of the cross-sectional cNIRF-IVUS images corresponding to pullback positions C1, C2, and C3 in (B), (C), and (D). The cNIRF signal in C1, C2, and C3 is fused onto the interior of the IVUS catheter and also replicated at the exterior (outlined with red dotted lines) of the IVUS image. (E) Serial imaging of the same vessel region demonstrates that the raw NIRF signal (top row) is affected by variable intraluminal catheter position that changes the distance between the NIR fluorescence source and imaging catheter detector, leading to fluctuations in the measured NIRF signal. Note that applying the NIRF distance correction (bottom row) substantially improved the reproducibility of the NIRF image and reduced the variability due to changes in catheter position. (F) Quantitative assessment of the improvement of the reproducibility by NIRF distance correction: black dots correspond to the maximum NIRF signal vs. pullback position, and the blue line indicates the average distribution function. Distance correction improved the correspondence between NIRF signals from all three pullbacks from R2 = 0.89 to R2 = 0.96.

Dmitry Bozhko, Eric A Osborn, Amir Rosenthal, Johan W Verjans, Tetsuya Hara, Stephan Kellnberger, Georg Wissmeyer, Saak V Ovsepian, Jason R McCar. European Heart Journal – Cardiovascular Imaging, Volume 18, Issue 11, 1 November 2017, Pages 1253–1261.

February 17, 2019September 30, 2019

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.

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….]

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 µm (upper row) and 50 µm (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, Łukasz 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

January 28, 2019September 30, 2019

Sensitive interferometric detection of ultrasound for minimally invasive clinical imaging applications.

Miniaturized optical detectors of ultrasound represent a promising alternative to piezoelectric technology and may enable new minimally invasive clinical applications, particularly in the field of optoacoustic imaging. However, the use of such detectors has so far been limited to controlled lab environments, and has not been demonstrated in the presence of mechanical disturbances, common in clinical imaging scenarios. Additionally, detection sensitivity has been inherently limited by laser noise, which hindered the use of sensing elements such as optical fibers, which exhibit a weak response to ultrasound. In this work, coherence‐restored pulse interferometry (CRPI) is introduced – a new paradigm for interferometric sensing in which shot‐noise limited sensitivity may be achieved alongside robust operation. CRPI is implemented with a fiber‐based resonator, demonstrating over an order of magnitude higher sensitivity than that of conventional 15 MHz intravascular ultrasound probes. The performance of the optical detector is showcased in a miniaturized all‐optical optoacoustic imaging catheter.[Read more….]

Fig1. Experimental demonstration of ultrasound detection in turbulent water using coherence restored pulse interferometry (CRFI) with passive demodulation. (a) Schematic description of the setup used to test CRPI for detecting ultrasound under a strong external disturbance. (b) The resonance shift measured with the passive‐demodulation scheme when the water pump was on. The inset shows one of the ultrasound signals measured under the volatile environmental conditions.

Amir Rosenthal, Stephan Kellnberger, Dmitry Bozhko, Andrei Chekkoury, Murad Omar, Daniel Razansky, Vasilis Ntziachristos. Volume8, Issue3, May 2014, Pages 450-457

January 8, 2020January 8, 2020

Multiple resonance grating

Project supervisor: Yoav Hazan

yoav.hazan@campus.technion.ac.il

Optical detection of ultrasound is mostly done with high-Q factor optical resonators. These optical resonators can be manufactured in Silicon wafers, where a common design is of π-phase shift Bragg grating producing a single resonator. Complex grating designs with multiple resonators could enable simultaneous measurement in several positions, accelerating acquisition time.

Coherence-restored pulse interferometry (CRPI) is a recently developed method for optical detection of ultrasound that achieves shot-noise-limited sensitivity and high dynamic range. Today, the CRPI, implemented in free space Fabry-Perot, required a manual calibration process of the feedback circuit to lock the CRPI in operating state. This project core is the automation of the calibration procedure using Arduino microcontroller platform.

Project Status: Available

Project requirements:

Design and simulation of complex grating designs to produce a multiple resonance transmission function.
Optimization of grating dimensions for narrow resonance and high transmission efficiency.

Recommended readings:

Painchaud, Y., Poulin, M., Latrasse, C., Ayotte, N., Picard, M.J. and Morin, M., 2012, June. “Bragg grating notch filters in silicon-on-insulator waveguides”. In Bragg Gratings, Photosensitivity, and Poling in Glass Waveguides (pp. BW2E-3). Optical Society of America.
Rosenthal, A., Razansky, D., & Ntziachristos, V. (2011). “High-sensitivity compact ultrasonic detector based on a pi-phase-shifted fiber Bragg grating”. Optics letters, 36(10), 1833-1835.

February 17, 2019September 30, 2019

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

The schematic of the optoacoustic imaging system

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……]

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.

March 21, 2019September 30, 2019

Measuring the structure of highly reflecting fiber Bragg gratings

We demonstrate a new technique that enables us to measure the structure of highly reflecting fiber Bragg gratings. The impulse response function is measured from both sides of the grating using a low-coherence spectral interferometry technique. An inverse scattering algorithm is used to extract the refractive-index profiles from the measured impulse responses. The reconstruction of the grating is performed by combining the refractive-index profiles, measured from both sides of the grating. The transfer function of the optical spectrum analyzer is measured and used to correct the measured results. The interrogation of an apodized grating with a reflectivity of 99.91% is demonstrated. [Read more…]

Fig. 1. Schematic description of the experimental setup used to measure the structure of highly reflecting fiber Bragg gratings. The interference spectrum of a wave reflected from the grating and a wave reflected from a reference mirror is measured from both sides of the grating by changing the state of the optical switches. PC is a polarization controller.

S. Keren, A. Rosenthal, M. Horowitz, “Measuring the structure of highly reflecting fiber Bragg gratings,” IEEE Photonics Technology Letters ( Volume: 15 , Issue: 4 , April 2003 )

March 21, 2019September 30, 2019

Measuring temperature profiles in high-power optical fiber components

We demonstrate a new method for measuring changes in temperature distribution caused by coupling a high-power laser beam into an optical fiber and by splicing two fibers. The measurement technique is based on interrogating a fiber Bragg grating by using low-coherence spectral interferometry. A large temperature change is found owing to coupling of a high-power laser into a multimode fiber and to splicing of two multimode fibers. Measurement of the temperature profile rather than the average temperature along the grating allows study of the cause of fiber heating. The new measurement technique enables us to monitor in real time the temperature profile in a fiber without the affecting system operation, and it might be important for developing and improving the reliability of high-power fiber components. [Read more…]

Fig. 1 Schematic description of the experimental setup used to measure the temperature profile caused (a) by coupling a high-power argon-ion laser beam into a fiber and (b) by splicing two optical fibers.

Vladimir Goloborodko, Shay Keren, Amir Rosenthal, Boris Levit, and Moshe Horowitz, “Measuring temperature profiles in high-power optical fiber components,” Appl. Opt. 42, 2284-2288 (2003)

March 21, 2019September 30, 2019

Inverse scattering algorithm for reconstructing strongly reflecting fiber Bragg gratings

We demonstrate a new inverse scattering algorithm for reconstructing the structure of highly reflecting fiber Bragg gratings. The method, called integral layer-peeling (ILP), is based on solving the Gel’fand-Levitan-Marchenko (GLM) integral equation in a layer-peeling procedure. Unlike in previously published layer-peeling algorithms, the structure of each layer in the ILP algorithm can have a nonuniform profile. Moreover, errors due to the limited bandwidth used to sample the reflection coefficient do not rapidly accumulate along the grating. Therefore, the error in the new algorithm is smaller than in previous layer peeling algorithms. The ILP algorithm is compared to two discrete layer-peeling algorithms and to an iterative solution to the GLM equation. The comparison shows that the ILP algorithm enables one to solve numerically difficult inverse scattering problems, where previous algorithms failed to give an accurate result. The complexity of the ILP algorithm is of the same order as in previous layer peeling algorithms. When a small error is acceptable, the complexity of the ILP algorithm can be significantly reduced below the complexity of previously published layer-peeling algorithms.. [Read more…]

Fig. 1. Reconstructed modulation index n1(z) of a uniform grating with a refractive index modulation amplitude n1=6.5×10−4, a length of 4 mm, and a maximum reflectivity of 99.99%, calculated using the ILP algorithm (solid line), the FDLP algorithm (dashed line), and iterative solution to the GLM equation with 70 iterations (dotted line). The reflection spectrum was sampled over a bandwidth of 40 nm with a resolution of 0.01 nm. The figure shows that an excellent reconstruction of the grating was obtained using the ILP algorithm, while the FDLP algorithm and the iterative solution to the GLM equation gave a large error. The inset of the figure shows a zoom on the profile close to the input end of the grating.

Amir Rosenthal and Moshe Horowitz, “Inverse scattering algorithm for reconstructing strongly reflecting fiber Bragg gratings,” IEEE Journal of Quantum Electronics ( Volume: 39 , Issue: 8 , Aug. 2003 )

March 21, 2019September 30, 2019

Inverse scattering algorithm for reconstructing lossy fiber Bragg gratings

We demonstrate an inverse scattering algorithm for reconstructing the structure of lossy fiber Bragg gratings. The algorithm enables us to extract the profiles of the refractive index and the loss coefficient along the grating from the grating transmission spectrum and from the reflection spectra, measured from both sides of the grating. Such an algorithm can be used to develop novel distributed evanescent-wave fiber Bragg sensors that measure the change in both the refractive index and the attenuation coefficient of the medium surrounding the grating. The algorithm can also be used to analyze and to design fiber Bragg gratings written in fiber amplifiers. A novel method to overcome instability problems in extracting the parameters of the lossy grating is introduced. The new method also makes it possible to reduce the spectral resolution needed to accurately extract the grating parameters. [Read more…]

Fig. 1 Reconstruction of a grating with a chirped Gaussian coupling coefficient, 𝑞(𝑧)=600 exp[−105(𝑧−𝐿/2)2(2.5+20𝑖)] m−1 and with a sinusoidal loss profile 𝛼=70[1−cos(10𝜋𝑧/𝐿)] m−1 written in the region [0, L=1 cm]. The reconstructed parameters (solid curves) are compared with the original parameters (dashed curves). The reflection spectra, obtained from both sides of the grating, and the transmission spectrum were sampled over a bandwidth of 10 nm with a spectral resolution of 0.02 nm.

Amir Rosenthal and Moshe Horowitz, “Inverse scattering algorithm for reconstructing lossy fiber Bragg gratings,” J. Opt. Soc. Am. A 21, 552-560 (2004)

March 21, 2019September 30, 2019

New technique to accurately interpolate the complex reflection spectrum of fiber Bragg gratings

We demonstrate theoretically a new method to accurately interpolate the complex reflection spectrum of fiber Bragg gratings with a finite length at any desired frequency resolution. The required sampling resolution is significantly smaller than can be expected by directly using the sampling theorem for obtaining a low-error characterization of the reflection spectrum. A further decrease in the required sampling resolution by a factor of two is obtained by sampling both the complex reflection and the complex transmission functions. The new reconstruction technique may enable to significantly reduce the time needed to characterize fiber Bragg gratings and to interrogate fiber Bragg sensors. [Read more…]

Fig. 1 (a) The reflectivity and (b) the impulse response function of a uniform fiber Bragg grating with a maximum reflectivity of 99% and a length of L=4 mm . The sampled points used to characterize the reflection function with a sampling period of Δλ=0.1 nm are marked in the figure.

Amir Rosenthal and Moshe Horowitz, “New technique to accurately interpolate the complex reflection spectrum of fiber Bragg gratings,” IEEE Journal of Quantum Electronics ( Volume: 40 , Issue: 8 , Aug. 2004 )