Near-infrared fluorescence catheter system for two-dimensional intravascular imaging in vivo

Phantom schematics: (a) phantom with two thin NIR fluorescent tubes lying parallel to the main tube, representing a blood vessel; (b) transverse phantom consisting of 4 thin tubes filled with NIR fluorochromes attached at different angles to the vessel-mimicking tube; (c) resolution phantom with two thin tubes crossed on the vessel surface; (d) SNR phantom; (e) sensitivity phantom.

source:©2010 Optical Society of America

Detection of high-risk coronary arterial plaques prior to rupture remains an unmet clinical challenge, in part due to the stringent resolution and sensitivity requirements for in vivo human coronary arterial imaging. To address this need, we have developed a near-infrared (NIR) fluorescence imaging catheter system for intra-vascular molecular imaging of atherosclerosis in coronary artery-sized vessels, capable of resolving two-dimensional fluorescence activity in hollow organs, such as blood vessels. Based on a rotational fiber design, the catheter system illuminates and detects perpendicular to the rotational axis, while an automated pullback mechanism enables visualization along blood vessels with a scan speed of up to 1.5 mm/sec. We demonstrate the previously undocumented capacity to produce intravascular NIR fluorescence images of hollow organs in vivo and showcase the performance metrics of the system developed using blood vessel mimicking phantoms. This imaging approach is geared toward in vivo molecular imaging of atherosclerotic biomarkers and is engineered to allow seamless integration into the cardiac catheterization laboratory.
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Fig. 1 NIR fluorescence imaging system catheter. Schematics of the experimental setup: laser light propagated through the optical cube into multimodal (MM) fiber, travels through rotational coupler and, finally, propagate into MM fiber that has angle-polished, mirror-coated front end. The delivered light excites fluorochromes in the ROI and collects corresponding emission signal, which propagates through the same MM fiber to the detection cube and measured by two PMTs. Signal is then digitized, stored and analyzed.

R. N. Razansky, A. Rosenthal, G. Mallas, D. Razansky, F. A. Jaffer, and V. Ntziachristos, “Near-infrared fluorescence catheter system for two-dimensional intravascular imaging in vivo,” Opt. Express, Vol. 18, pp. 11372-11381 (2010).

Fast semi-analytical model-based acoustic inversion for quantitative optoacoustic tomography

Reconstructions of three homogeneous scattering and absorbing cylindrical insertions

© 2010 IEEE Transactions on Medical Imaging

We present a fast model-based inversion algorithm for quantitative 2-D and 3-D optoacoustic tomography. The algorithm is based on an accurate and efficient forward model, which eliminates the need for regularization in the inversion process while providing modeling flexibility essential for quantitative image formation. The resulting image-reconstruction method eliminates stability problems encountered in previously published model-based techniques and, thus, enables performing image reconstruction in real time. Our model-based framework offers a generalization of the forward solution to more comprehensive optoacoustic propagation models, such as including detector frequency response, without changing the inversion procedure. The reconstruction speed and other algorithmic performances are demonstrated using numerical simulation studies and experimentally on tissue-mimicking optically heterogeneous phantoms and small animals. In the experimental examples, the model-based reconstructions manifested correctly the effect of light attenuation through the objects and did not suffer from the artifacts which usually afflict the commonly used filtered backprojection algorithms, such as negative absorption values.
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Fig.3 Description:(a) A simulated high-resolution optoacoustic source image, representing a map of local laser energy deposition; (b) The acoustic signal that is obtained at a distance of 4 cm from the center of the source image with (dashed-red curve) and without (solid-blue curve) noise; (c) the reconstruction obtained using a model-based inversion for the noise-free data and (d) the difference between the reconstructed and originating image; (e) the reconstruction obtained using a model-based inversion for the noisy data and (f) the difference between the reconstructed and originating image.

A. Rosenthal, D. Razansky, and V. Ntziachristos, “Fast semi-analytical model-based acoustic inversion for quantitative optoacoustic tomography”, IEEE Trans. Med. Imag., Vol. 29, pp. 1275-1285 (2010).

Multirate Synchronous Sampling of Sparse Multiband Signals

source: © 2010 IEEE Transactions on Signal Processing

Recent advances in electro-optical systems make them ideal for undersampling multiband signals with very high carrier frequencies. In this paper, we propose a new scheme for sampling and reconstructing of a multiband sparse signals that occupy a small part of a given broad frequency range under the constraint of a small number of sampling channels. The locations of the signal bands are not known a priori. The scheme, which we call synchronous multirate sampling (SMRS), entails gathering samples synchronously at few different rates whose sum is significantly lower than the Nyquist sampling rate. The signals are reconstructed by finding a solution of an underdetermined system of linear equations by applying a pursuit algorithm and assuming that the solution is composed of a minimum number of bands. The empirical reconstruction success rate is higher than obtained using previously published multicoset scheme when the number of sampling channels is small and the conditions for a perfect reconstruction in the multicoset scheme are not fulfilled. The practical sampling system which is simulated in our work consists of three sampling channels. Our simulation results show that a very high empirical success rate is obtained when the total sampling rate is five times higher than the total signal support of a complex signal with four bands. By comparison, a multicoset sampling scheme obtains a very high empirical success rate with a total sampling rate which is three times higher than the total signal support. However, the multicoset scheme requires 14 channels.  [Read more…]

Fig. 2 Empirical success percentages for four-band complex signals calculated by using the SMRS reconstruction scheme (circles) and by using SBR4 in 7 as a function of the spectral support (BW) for FNyquist= 20 GHz and a total sampling rate Ftotal= 3 GHz. The number of sampling channels is equal to 3 in the SMRS scheme and is equal to p=58 in the equivalent multicoset sampling scheme.

Michael Fleyer, Alexander Linden, Moshe Horowitz, Amir Rosenthal, “Multirate Synchronous Sampling of Sparse Multiband Signals,” IEEE Transactions on Signal Processing ( Volume: 58 , Issue: 3 , March 2010 )

Optoacoustic tomography with varying illumination and non-uniform detection patterns

source: © 2010 Optical Society of America

Quantification of tissue morphology and biomarker distribution by means of optoacoustic tomography is an important and longstanding challenge, mainly caused by the complex heterogeneous structure of biological tissues as well as the lack of accurate and robust reconstruction algorithms. The recently introduced model-based inversion approaches were shown to mitigate some of reconstruction artifacts associated with the commonly used back-projection schemes, while providing an excellent platform for obtaining quantified maps of optical energy deposition in experimental configurations of various complexity. In this work, we introduce a weighted model-based approach, capable of overcoming reconstruction challenges caused by per-projection variations of object’s illumination and other partial illumination effects. The universal weighting procedure is equally shown to reduce reconstruction artifacts associated with other experimental imperfections, such as non-uniform transducer sensitivity fields. Significant improvements in image fidelity and quantification are showcased both numerically and experimentally on tissue phantoms and mice.  [Read more…]

Fig. 1 Optoacoustic imaging configurations with partial or variable tomographic data. (a) Circular scanning with narrow laser beam and a rotating object. Illumination and detector are static; (b) circular scanning with ultrasonic detector having limited angular view. The imaged object and illumination are static; (c) optoacoustic microscopy (B-mode) imaging with confocal illumination-detection geometry and linear translation.

Thomas Jetzfellner, Amir Rosenthal, Andreas Buehler, Alexander Dima, Karl-Hans Englmeier, Vasilis Ntziachristos, and Daniel Razansky, “Optoacoustic tomography with varying illumination and non-uniform detection patterns,” J. Opt. Soc. Am. A 27, 2488-2495 (2010)

Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

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)