Everolimus-eluting stents stabilize plaque inflammation in vivo: assessment by intravascular fluorescence molecular imaging.

source: © 2016 European Heart Journal

Inflammation drives atherosclerosis complications and is a promising therapeutic target for plaque stabilization. At present, it is unknown whether local stenting approaches can stabilize plaque inflammation in vivo. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity in vivo using intravascular near-infrared fluorescence (NIRF) molecular imaging.
Methods and results
Balloon-injured, hyperlipidaemic rabbits with atherosclerosis received non-overlapping EES and bare metal stents (BMS) placement into the infrarenal aorta (n = 7 EES, n = 7 BMS, 3.5 mm diameter x 12 mm length). Four weeks later, rabbits received an injection of the cysteine protease-activatable NIRF imaging agent Prosense VM110. Twenty-four hours later, co-registered intravascular 2D NIRF, X-ray angiography and intravascular ultrasound imaging were performed. In vivo EES-stented plaques contained substantially reduced NIRF inflammatory protease activity compared with untreated plaques and BMS-stented plaques (P = 0.006). Ex vivo macroscopic NIRF imaging of plaque protease activity corroborated the in vivo results (P = 0.003). Histopathology analyses revealed that EES-treated plaques showed reduced neointimal and medial arterial macrophage and cathepsin B expression compared with unstented and BMS-treated plaques.
EES-stenting stabilizes plaque inflammation as assessed by translational intravascular NIRF molecular imaging in vivo. These data further support that EES may provide a local approach for stabilizing inflamed plaques.[Read more…]

FRI of plaque

Fig. Ex vivo FRI analyses of plaque inflammatory cysteine protease activity in BMS-, EES-treated, and unstented plaque zones. (A–C) Ex vivo FRI alignments from three representative animals. All NIRF images were obtained with a one second exposure. Image windows optimized for individual images.

Marcella A. Calfon Press, Georgios Mallas, Amir Rosenthal, Tetsuya Hara, Adam Mauskapf, R. Nika Nudelman, Alexander Sheehy, Igor V. Polyakov, Frank Kolodgie, Renu Virmani, J. Luis Guerrero, Vasilis Ntziachristos, Farouc A. Jaffer.European Heart Journal – Cardiovascular Imaging, Volume 18, Issue 5, 1 May 2017, Pages 510–518.

Optoacoustic image reconstruction and system analysis for finite-aperture detectors under the wavelet-packet framework.

Schematic illustration

source: © 2016 J. of Biomedical Optics

In optoacoustic tomography, detectors with relatively large areas are often employed to achieve high detection sensitivity. However, spatial-averaging effects over large detector areas may lead to attenuation of high acoustic frequencies and, subsequently, loss of fine features in the reconstructed image. Model-based reconstruction algorithms improve image resolution in such cases by correcting for the effect of the detector’s aperture on the detected signals. However, the incorporation of the detector’s geometry in the optoacoustic model leads to a significant increase of the model matrix memory cost, which hinders the application of inversion and analysis tools such as singular value decomposition (SVD). We demonstrate the use of the wavelet-packet framework for optoacoustic systems with finite-aperture detectors. The decomposition of the model matrix in the wavelet-packet domain leads to sufficiently smaller model matrices on which SVD may be applied. Using this methodology over an order of magnitude reduction in inversion time is demonstrated for numerically generated and experimental data. Additionally, our framework is demonstrated for the analysis of inversion stability and reveals a new, nonmonotonic dependency of the system condition number on the detector size. Thus, the proposed framework may assist in choosing the optimal detector size in future optoacoustic systems.[Read more…]

Optoacoustic reconstructions of a mouse

Fig.Optoacoustic reconstructions of a mouse’s head from limited view (180 deg) experimental data obtained using (a) BP, (b) IMMI, (c) IMMI-FAD, and (d) GWP-IMMI-FAD.

Yiyong Han, Vasilis Ntziachristos, Amir Rosenthal. J. of Biomedical Optics, 21(1), 016002 (2016). https://doi.org/10.1117/1.JBO.21.1.016002

High-Throughput Sparsity-Based Inversion Scheme for Optoacoustic Tomography

source: © 2016 IEEE Transactions on Medical Imaging

The concept of sparsity is extensively exploited in the fields of data acquisition and image processing, contributing to better signal-to-noise and spatio-temporal performance of the various imaging methods. In the field of optoacoustic tomography, the image reconstruction problem is often characterized by computationally extensive inversion of very large datasets, for instance when acquiring volumetric multispectral data with high temporal resolution. In this article we seek to accelerate accurate model-based optoacoustic inversions by identifying various sources of sparsity in the forward and inverse models as well as in the single- and multi-frame representation of the projection data. These sources of sparsity are revealed through appropriate transformations in the signal, model and image domains and are subsequently exploited for expediting image reconstruction. The sparsity-based inversion scheme was tested with experimental data, offering reconstruction speed enhancement by a factor of 40 to 700 times as compared with the conventional iterative model-based inversions while preserving similar image quality. The demonstrated results pave the way for achieving real-time performance of model-based reconstruction in multi-dimensional optoacoustic imaging.[Read more…..]

Fingers us samples

Fig.3d maximum intensity projections of the volumetric dataset showing a 3d angiogram of a human finger obtained by cross-sectional scan in the z direction. (a) Photograph of the finger and reconstructions obtained with (b) LSQR-15, (c) WP-o, and (d) PCA-wp-T are shown.

Christian Lutzweiler, Stratis Tzoumas, Amir Rosenthal, Vasilis Ntziachristos, Daniel Razansky. Published in: IEEE Transactions on Medical Imaging ( Volume: 35 , Issue: 2 , Feb. 2016 ).

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

source: © 2016 European Heart Journal

(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.
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 image

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.

All-optical optoacoustic microscope based on wideband pulse interferometry

Microscopy scans of (a)–(c) a mouse ear and (d)–(f) a zebrafish larva ex vivo.

source:© 2016 Optical Society of America

Optical and optoacoustic (photoacoustic) microscopy have been recently joined in hybrid implementations that resolve extended tissue contrast compared to each modality alone. Nevertheless, the application of the hybrid technique is limited by the requirement to combine an optical objective with ultrasound detection collecting signal from the same micro-volume. We present an all-optical optoacoustic microscope based on a pi-phase-shifted fiber Bragg grating (?-FBG) with coherence-restored pulsed interferometry (CRPI) used as the interrogation method. The sensor offers an ultra-small footprint and achieved higher sensitivity over piezoelectric transducers of similar size. We characterize the spectral bandwidth of the ultrasound detector and interrogate the imaging performance on phantoms and tissues. We show the first optoacoustic images of biological specimen recorded with ?-FBG sensors. We discuss the potential uses of ?-FBG sensors based on CRPI.
[Read More…]

Fig. 1. Schematic of the all-optical optoacoustic microscope. ND, neutral density filter; L, lens; M, mirror; PH, pinhole; xyz, motorized translation stages; DAQ, data acquisition system; EDFA, erbium-doped optical amplifier; PZ, piezoelectric fiber stretcher.

G. Wissmeyer, D. Soliman, R. Shnaiderman, A. Rosenthal, and V. Ntziachristos, “All-optical optoacoustic microscope based on wideband pulse interferometry,” Opt. Lett. Vol. 41, pp. 1953-1956 (2016).

Magnetoacoustic sensing of magnetic nanoparticles

Magnetic fluid heating and magnetoacoustic signal induction

source: © 2016 Physical Review Letters

The interaction of magnetic nanoparticles and electromagnetic fields can be determined through electrical signal induction in coils due to magnetization. However, the direct measurement of instant electromagnetic energy absorption by magnetic nanoparticles, as it relates to particle characterization or magnetic hyperthermia studies, has not been possible so far. We introduce the theory of magnetoacoustics, predicting the existence of second harmonic pressure waves from magnetic nanoparticles due to energy absorption from continuously modulated alternating magnetic fields. We then describe the first magnetoacoustic system reported, based on a fiber-interferometer pressure detector, necessary for avoiding electric interference. The magnetoacoustic system confirmed the existence of previously unobserved second harmonic magnetoacoustic responses from solids, magnetic nanoparticles, and nanoparticle-loaded cells, exposed to continuous wave magnetic fields at different frequencies. We discuss how magnetoacoustic signals can be employed as a nanoparticle or magnetic field sensor for biomedical and environmental applications.
[Read More…]

Figure 1
Concept of magnetoacoustic signal induction. (a) Components of the magnetoacoustic setup. Power supply (PS), modulator (M), water chiller (W), driver (D). (b) Magnetoacoustic sensing using a PZT transducer. The sample comprises a steel rod located within the coil. (c) rf-free magnetoacoustic sensing employing a fiber-Bragg-based interferometric ultrasound sensor in a horizontally arranged solenoid (water tank not displayed). The optical sensor comprises optical filters (F), an erbium-doped fiber amplifier (EFDA), a 99/1optical splitter (S), a demodulator (Demod), and the π-shifted FBG sensing unit. (d) Magnetoacoustic sensing of a steel rod specimen using PZT based ultrasound detection. rf interference due to the nonlinearity of the rf amplifier (blue dotted line) and experimental confirmation of the second harmonic magnetoacoustic signal (red line) induced in conducting material at f_MA=2f_rf. Inset shows the quadratic increase of detected magnetoacoustic signal (red crosses) as a function of the linearly rising B field compared to the expected theory (dashed black curve) and a linear relationship (dotted green line).

Kellnberger, A. Rosenthal, A. Myklatun, G. G. Westmeyer, G. Sergiadis, and V. Ntziachristos, ” Magnetoacoustic sensing of magnetic nanoparticles,” Phys. Rev. Lett., Vol. 116, 108103 (2016).