Category: Publications

source: © 2010 Journal of Biomedical Optics

New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.  [Read more…]

Fig 1. Catheter prototype for intravascular sensing of NIR fluorescence signals. (a) The NIRF catheter consists of a 0.36-mm∕0.014-in. floppy radiopaque tip with a maximum outer diameter of 0.48mm∕0.019in.. The arrow highlights the focal spot (40±15μm) for the 90-deg arc-sensing catheter at a distance of 2±1mm (arrow). (b) Phantom experiment to measure NIR light attenuation in the presence of whole blood. Plaque (P) consists of 1% Intralipid plus India ink 50ppm plus AF750 (an NIR fluorochrome, concentration 300nmol∕L); tissue (T: fibrous cap) consists of polyester casting resin plus titanium dioxide plus India ink; a container (gray shaded area) was filled with fresh rabbit blood or saline. The catheter was immersed in fresh rabbit blood and positioned at variable distance (D) from a fluorescent phantom representing the plaque (P). To mimic the presence of a fibrous cap, a solid tissue phantom of thickness T was interposed between the plaque and the lumen. (c) Plot of detected NIRF signal as a function of distance D in presence of blood compared to saline, showing only modest attenuation by blood. Inset, fluorescence signal decay in saline at distance of up to 10mm. (d) Plot of the detected NIRF signal in blood in the presence of a tissue phantom (T) of thickness 500μm shows modest NIRF signal attenuation (<35%) vs the case in (c) where T=0. Reproduced by permission from Ref. 22.

Marcella A. Calfon, Claudio Vinegoni, Vasilis Ntziachristos, Farouc A. Jaffer, “Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques,” J. of Biomedical Optics, 15(1), 011107 (2010)

source: © 2011 Applied Physics Letters

Neuroscience investigations may significantly benefit from the availability of accurate imaging methods of brain parameters in small animals. In this letter, we investigate the imaging performance of the recently introduced interpolated model-matrix inversion (IMMI), in quantitative optoacoustic imaging of the mouse head. We compare the findings of the method against back-projection inversion methods that have more commonly been considered. We find that cross-sectional images of the mouse head accurately match anatomical structures seen on cryosliced head images serving as the gold standard. Moreover, superior imaging performance is found for IMMI compared to previously reported optoacoustic imaging of the mouse head.  [Read more…]

Fig 2.Several cross-sectional slices of the head region of a mouse back projection based reconstructions of (a) head region, (b) lower part of the head, (c) and (d) corresponding IMMI reconstructions, (e) and (f) corresponding IMMI high-pass filtered images, and (g) and (h) cryoslices. Anatomical structure: 1, 3, 4, 6—eye sockets 2, 5, 7, 8—blood vessels.

Thomas Jetzfellnera, Amir Rosenthal, K.-H. Englmeier, Alexander Dima, Miguel Ángel Araque Caballero, Daniel Razansky, and Vasilis Ntziachristos, “Interpolated model-matrix optoacoustic tomography of the mouse brain,” Appl. Phys. Lett. 98, 163701 (2011)

source: © 2011 American Association of Physicists in Medicine

Purpose:
Optoacoustic imaging enables mapping the optical absorption of biological tissue using optical excitation and acoustic detection. Although most image‐reconstruction algorithms are based on the assumption of a detector with an isotropic sensitivity, the geometry of the detector often leads to a response with spatially dependent magnitude and bandwidth. This effect may lead to attenuation or distortion in the recorded signal and, consequently, in the reconstructed image.

Methods:
Herein, an accurate numerical method for simulating the spatially dependent response of an arbitrary‐shape acoustic transducer is presented. The method is based on an analytical solution obtained for a two‐dimensional line detector. The calculated response is incorporated in the forward model matrix of an optoacoustic imaging setup using temporal convolution, and image reconstruction is performed by inverting the matrix relation.  [Read more…]

Fig. 8 Experimental reconstructions of a point optoacoustic source detected by a flat detector with a width of 1.3 cm obtained using (a) the back‐projection algorithm (b) IMMI modeled with a point detector (c) IMMI modeled with a 1.3‐mm flat detector using spatial convolution and (d) IMMI modeled with a 1.3‐mm flat detector using temporal convolution. The point source was obtained by applying plane‐selective illuminating on a black hair embedded in a clear agar phantom, as shown in Fig. 6(a). Although both the spatial‐ and temporal‐convolution methods managed enhancing the reconstruction resolution, the temporal‐convolution method yielded a more accurate reconstruction with less background texture.

Results:
The method was numerically and experimentally demonstrated in two dimensions for both flat and focused transducers and compared to the spatial‐convolution method. In forward simulations, the developed method did not suffer from the numerical errors exhibited by the spatial‐convolution method. In reconstruction simulations and experiments, the use of both temporal‐convolution and spatial‐convolution methods lead to an enhancement in resolution compared to a reconstruction with a point detector model. However, because of its higher modeling accuracy, the temporal‐convolution method achieved a noise figure approximated three times lower than the spatial‐convolution method.

Conclusions:
The demonstrated performance of the spatial‐convolution method shows it is a powerful tool for reducing reconstruction artifacts originating from the detector finite size and improving the quality of optoacoustic reconstructions. Furthermore, the method may be used for assessing new system designs. Specifically, detectors with nonstandard shapes may be investigated.

Amir Rosenthal Vasilis Ntziachristos Daniel Razansky, “Model‐based optoacoustic inversion with arbitrary‐shape detectors,” Medical Physics Volume38, Issue7,July 2011,Pages 4285-4295

source: © 2011 Optics Letters

Quantification of biomarkers using multispectral optoacoustic tomography can be challenging due to photon fluence variations with depth and spatially heterogeneous tissue optical properties. Herein we introduce a spectral ratio approach that accounts for photon fluence variations. The performance and imaging improvement achieved with the proposed method is showcased both numerically and experimentally in phantoms and mice.  [Read more…]

Fig. 3 (a) Optoacoustic image of a mouse with ICG filled tubes at 800 nm . (b) Sketch of the mouse and the implanted tubes. (c) Spectral difference. (d) Spectral ratio. (e) Profiles along the dashed lines of (b) for spectral ratio and spectral difference. (f) Superimposed image of (d) on (a) after application of a threshold at 𝐼=0.5 .

Thomas Jetzfellner, Amir Rosenthal, Andreas Buehler, Karl-Hans Englmeier, Daniel Razansky, and Vasilis Ntziachristos, “Multispectral optoacoustic tomography by means of normalized spectral ratio,” Opt. Lett. 36, 4176-4178 (2011)

source: © 2012 Optics express

Advances in fabrication of high-finesse optical resonators hold promise for the development of miniaturized, ultra-sensitive, wide-band optical sensors, based on resonance-shift detection. Many potential applications are foreseen for such sensors, among them highly sensitive detection in ultrasound and optoacoustic imaging. Traditionally, sensor interrogation is performed by tuning a narrow linewidth laser to the resonance wavelength. Despite the ubiquity of this method, its use has been mostly limited to lab conditions due to its vulnerability to environmental factors and the difficulty of multiplexing – a key factor in imaging applications. In this paper, we develop a new optical-resonator interrogation scheme based on wideband pulse interferometry, potentially capable of achieving high stability against environmental conditions without compromising sensitivity. Additionally, the method can enable multiplexing several sensors. The unique properties of the pulse-interferometry interrogation approach are studied theoretically and experimentally. Methods for noise reduction in the proposed scheme are presented and experimentally demonstrated, while the overall performance is validated for broadband optical detection of ultrasonic fields. The achieved sensitivity is equivalent to the theoretical limit of a 6 MHz narrow-line width laser, which is 40 times higher than what can be usually achieved by incoherent interferometry for the same optical resonator.  [Read more…]

Fig. 4 (a) The schematic of the system used to evaluate the effect of ASE on the noise in the detection scheme. The visibility and noise level were measured for OPDs varying from 0 to 15 mm (b) The noise at the differential amplifier for wideband pulsed (blue square markers) and CW (red circle markers) sources as function of OPD obtained when the source is filtered to a bandwidth of 0.3 nm. The noise at OPD = 0 was mostly a result of electronic noise and was similar for both optical sources. (c) the noise data of Fig. 4(b) scaled to the same level for better visualization displayed with the measured fringe visibility (dashed curve). The similar dependency of noise for both cases indicates that the ASE noise is dominant in the pulse interferometry scheme. (d) The system used to test the effect of ASE rejection on noise reduction in the pulse interferometry setup. The saturable absorber (SA) added to the system had a transmission approximately 2.8 higher for the pulses compared to CW. (e) The noise recorded with the SA (solid-blue curve) and with an attenuator replacing the SA to ensure the same signal level (dashed-red curve). A reduction of 2.3 in the noise was observed, in correspondence with the SA rejection ratio.

Amir Rosenthal, Daniel Razansky, and Vasilis Ntziachristos,”Wideband optical sensing using pulse interferometry,” Optics express Vol. 20, Issue 17, pp. 19016-19029 (2012)

source: © 2012 IEEE Photonics Technology Letters

We report on a robust scheme for wideband variable-phase interferometer stabilization based on active modulation. In contrast to previous schemes, the correction signal is generated without using second harmonics, whose low amplitude often requires employing narrowband lock-in amplifiers. Resonances in the element modulating the phase are attenuated to enable high gain without high-frequency oscillations. Operation over a 3-kHz bandwidth is demonstrated.  [Read more…]

Fig. 2 (a) Schematic description of the analog feedback circuit. PS: phase shifter. BSF: band-stop filter. HPF: high-pass filter. FB: feedback. (b) Measured combined response of the electronic filter and optical system. The figure shows a decrease in the strength of the PZT resonance.

Amir Rosenthal , Stephan Kellnberger , George Sergiadis , Vasilis Ntziachristos,”Wideband Fiber-Interferometer Stabilization With Variable Phase,” IEEE Photonics Technology Letters ( Volume: 24 , Issue: 17 , Sept.1, 2012 )

source: © 2013 IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control

The characterization of the spatial and frequency response of acoustic detectors is important for enabling accurate optoacoustic imaging. In this work, we developed a hybrid method for the characterization of the spatially dependent response of ultrasound detectors. The method is based on the experimental determination of the receive-mode electrical impulse response (EIR) of the sensor, which is subsequently convolved with the corresponding spatial impulse response (SIR), computed numerically. The hybrid method is shown to have superior performance over purely experimental techniques in terms of accurate determination of the spatial and temporal responses of ultrasonic detectors, in high as well as low sensitivity regions of the sensor.  [Read more…]

Fig. 1 Effect of the spatial impulse response (SIR) on an optoacoustic signal. (a) Optoacoustic waves emanating from the source at r ′ reach the different points of the transducer, r d1 and r d2 , at different times t1 and t2(c represents the speed of sound). (b) Geometry for the numerical example: the sensor is 1.8 mm along the y direction, 15 mm along the z direction (here the sensor is shown from the side) and it is cylindrically focused to 40 mm. The source is located at 33 mm from the sensor along its median axis x . The relative dimensions have been exaggerated for ease of representation. (c) Simulated optoacoustic signal (solid blue curve) and the distorted signal (dashed red curve) that results after convolution with the SIR at a point out of focus. Inset: SIR used for convolution. (d) Frequency spectra of the simulated signal (solid blue curve) and the signal convolved with the SIR (dashed red curve). Inset: spectrum of the SIR.

Miguel Angel Araque Caballero , Amir Rosenthal , Andreas Buehler , Daniel Razansky , Vasilis Ntziachristos,”Optoacoustic determination of spatio-temporal responses of ultrasound sensors,” IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control ( Volume: 60 , Issue: 6 , June 2013 )

source: © 2013 Journal of Biomedical Optics

Cross sectional tomographic systems based on cylindrically focused transducers are widely used in optoacoustic (photoacoustic) imaging due to important advantages they provide such as high-cross sectional resolution, real-time imaging capacity, and high-throughput performance. Tomographic images in such systems are commonly obtained by means of two-dimensional (2-D) reconstruction procedures assuming point-like detectors, and volumetric (whole-body) imaging is performed by superimposing the cross sectional images for different positions along the scanning direction. Such reconstruction strategy generally leads to in-plane and out-of-plane artifacts as well as significant quantification errors. Herein, we introduce two equivalent full three-dimensional (3-D) models capable of accounting for the shape of cylindrically focused transducers. The performance of these models in 3-D reconstructions considering several scanning positions is analyzed in this work. Improvements of the results rendered with the introduced reconstruction procedure as compared with the 2-D-based approach are described and discussed for simulations and experiments with phantoms and biological tissues.  [Read more…]

Fig. 2 Full-view tomographic geometry for the simulations and experiments. The ROI is depicted by the red cuboid. The blue points represent the positions of the centers of the cylindrically focused detectors. All the transducer positions lie on the surface of a cylinder with radius 2.54 cm.

Daniel Queirós, Xose Luis Dean-Ben, Andreas Buehler, Daniel Razansky, Amir Rosenthal, Vasilis Ntziachristos,”Modeling the shape of cylindrically focused transducers in three-dimensional optoacoustic tomography,” J. of Biomedical Optics, 18(7), 076014 (2013)

source: © 2013 Physics in Medicine & Biology

Model-based optoacoustic inversion methods are capable of eliminating image artefacts associated with the widely adopted back-projection reconstruction algorithms. Yet, significant image artefacts might also occur due to reflections and scattering of optoacoustically-induced waves from strongly acoustically-mismatched areas in tissues. Herein, we modify the model-based reconstruction methodology to incorporate statistically-based weighting in order to minimize these artefacts. The method is compared with another weighting procedure termed half-image reconstruction, yielding generally better results. The statistically-based weighting is subsequently verified experimentally, attaining quality improvement of the optoacoustic image reconstructions in the presence of acoustic mismatches in tissue phantoms and small animals ex-vivo.  [Read more…]

Fig. 5 Tomographic reconstructions of the zebrafish obtained with the IMMI algorithm (a)–(c), with the statistically-based weighted IMMI algorithm (d)–(f) and with the half-time weighted IMMI algorithm (g)–(i). The reconstructions are done by considering all the measuring locations in a full-view scenario (a), (d), (g), or for a limited-view case by taking measuring locations along an arc covering an angle of 270° (b), (e), (h) or 180° (c), (f), (i). For the limited-view case, the centre of the detection arc is located above the images. (j) and (k) show a comparison of the reconstructions obtained with the IMMI algorithm and the statistically-based IMMI algorithm for several slices. The area A is taken as the as the area inside the dashed circumferences and the weighting parameter ω = 1 for all cases.

X Luís Deán-Ben, Rui Ma, Amir Rosenthal, Vasilis Ntziachristos and Daniel Razansky,”Weighted model-based optoacoustic reconstruction in acoustic scattering media,” Physics in Medicine & Biology, Volume 58, Number 16 (2013)

source: © 2014 The Journal of the Acoustical Society of America

In this study a theoretical framework for calculating the acoustic response of optical fiber-based ultrasound sensors is presented. The acoustic response is evaluated for optical fibers with several layers of coating assuming a harmonic point source with arbitrary position and frequency. First, the fiber is acoustically modeled by a layered cylinder on which spherical waves are impinged. The scattering of the acoustic waves is calculated analytically and used to find the normal components of the strains on the fiber axis. Then, a strain-optic model is used to calculate the phase shift experienced by the guided mode in the fiber owing to the induced strains. The framework is showcased for a silica fiber with two layers of coating for frequencies in the megahertz regime, commonly used in medical imaging applications. The theoretical results are compared to experimental data obtained with a sensing element based on a pi-phase-shifted fiber Bragg grating and with photoacoustically generated ultrasonic signals.  [Read more…]

Fig. 1 Problem statement: Spherical waves generated from a point source scatter from the optical fiber which is located at a distance of d from the source. The radii of the glass fiber and the coatings are 62.5, 110, and 130 μm, respectively.

István A. Veres, Peter Burgholzer, Thomas Berer, Amir Rosenthal, Georg Wissmeyer, and Vasilis Ntziachristos,”Characterization of the spatio-temporal response of optical fiber sensors to incident spherical waves,” The Journal of the Acoustical Society of America 135, 1853 (2014)