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In JoVE (1)
Other Publications (22)
- Applied Optics
- Journal of the Optical Society of America. A, Optics, Image Science, and Vision
- Journal of the Optical Society of America. A, Optics, Image Science, and Vision
- Optics Letters
- Journal of the Optical Society of America. A, Optics, Image Science, and Vision
- Optics Letters
- Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics
- Optics Letters
- Journal of the Optical Society of America. A, Optics, Image Science, and Vision
- Optics Letters
- Journal of the Optical Society of America. A, Optics, Image Science, and Vision
- IEEE Transactions on Medical Imaging
- IEEE Transactions on Medical Imaging
- Optics Express
- Journal of the Optical Society of America. A, Optics, Image Science, and Vision
- IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
- Medical Physics
- Optics Letters
- Journal of the American College of Cardiology
- Medical Physics
- Optics Letters
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
Articles by Amir Rosenthal in JoVE
JoVE Clinical and Translational Medicine
In vivo Near Infrared Fluorescence (NIRF) Intravascular Molecular Imaging of Inflammatory Plaque, a Multimodal Approach to Imaging of Atherosclerosis
1Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 2Institute for Biological and Medical Imaging, Helmholtz Zentrum München und Technische Universität München, 3Department of Electrical and Computer Engineering, Northeastern University
We detail a new near-infrared fluorescence (NIRF) catheter for 2-dimensional intravascular molecular imaging of plaque biology in vivo. The NIRF catheter can visualize key biological processes such as inflammation by reporting on the presence of plaque-avid activatable and targeted NIR fluorochromes. The catheter utilizes clinical engineering and power requirements and is targeted for application in human coronary arteries. The following research study describes a multimodal imaging strategy that utilizes a novel in vivo intravascular NIRF catheter to image and quantify inflammatory plaque in proteolytically active inflamed rabbit atheromata.
Other articles by Amir Rosenthal on PubMed
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.
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.
Reconstruction of a Fiber Bragg Grating from Noisy Reflection Data
We develop a novel method that enables one to reconstruct the structure of highly reflecting fiber Bragg gratings from noisy reflection spectra. When the reflection spectrum is noisy and the grating reflectivity is high, noise in the Bragg zone of the reflection spectrum is amplified by the inverse scattering algorithms and prevents the reconstruction of the grating. Our method is based on regularizing the reflection spectrum in frequencies inside the Bragg zone by using the data on the grating spectrum outside the Bragg zone. The regularized reflection spectrum is used to reconstruct the grating structure by means of inverse scattering. Our method enables one to analyze gratings with a high reflectivity from a spectrum that contains a high level of noise. Such gratings could not be analyzed by using methods described in previous work [IEEE J. Quantum Electron. 39, 1238 (2003)].
Experimental Reconstruction of a Long-period Grating from Its Core-to-core Transmission Spectrum
We demonstrate, for the first time to our knowledge, reconstruction of the structure of a long-period grating from its measured core-to-core transmission spectrum intensity. The reconstruction is obtained by writing an auxiliary grating in cascade to the interrogated grating. Our reconstruction technique is based on using the Hilbert transform and a phase-retrieval algorithm. Using our method, we have reconstructed the structure of a uniform long-period grating with a 47% coupling efficiency.
Reconstruction of Long-period Fiber Gratings from Their Core-to-core Transmission Function
In order to reconstruct the structure of a long-period grating, both the complex core-to-core transmission function and the complex core-to-cladding transmission function should be known. However, in practice, only the core-to-core transmission function of the grating can be measured. We demonstrate theoretically the reconstruction of long-period gratings from only the core-to-core transmission function. The reconstruction is performed by extracting the complex core-to-cladding transmission function of the grating from its core-to-core transmission function. Generally, the extraction is not unique; however, we show that by writing an additional grating in cascade to the interrogated grating, a unique reconstruction can be obtained. In weak long-period gratings, only the amplitude of the core-to-core transmission function is needed to reconstruct the grating. The results of our work can enable the experimental reconstruction of long-period gratings from their transmission function as well as the development of novel distributed sensors.
Analysis and Design of Nonlinear Fiber Bragg Gratings and Their Application for Optical Compression of Reflected Pulses
We demonstrate a novel split-step solution for analyzing nonlinear fiber Bragg gratings. The solution is used for designing nonlinear fiber Bragg gratings with a low reflectivity. The structure of the grating is designed according to the profiles of the incident and reflected pulses. We demonstrate our method for nonlinear compression of a pulse reflected from a fiber Bragg grating. The method allows us to obtain compressed pulses with a very low wing intensity.
Bragg-soliton Formation and Pulse Compression in a One-dimensional Periodic Structure
We present a method for efficiently exciting a Bragg soliton with a spectral content located mostly within the bandgap of a one-dimensional periodic structure. The method is based on a new interaction between Bragg solitons and on a high intensity enhancement, caused owing to the reduced propagation velocity inside periodic structures. Our method can also be used for efficient compression of optical pulses. We have theoretically demonstrated pulse compression with a compression ratio of 2800--over two orders of magnitude higher than previously reported. The results open new possibilities for experimental demonstration of Bragg soliton propagation and for pulse compression in one-dimensional periodic structures.
Extracting the Structure of Highly Reflecting Fiber Bragg Gratings by Measuring Both the Transmission and the Reflection Spectra
We demonstrate a novel method that enables one to measure the structure of highly reflecting fiber Bragg gratings. The method is based on measuring both the transmission and reflection spectra of the grating and applying an inverse-scattering algorithm. The use of the transmission spectrum significantly reduces the sensitivity of the reconstruction to measurement noise, and therefore it significantly decreases the measurement duration. We experimentally demonstrate our method for reconstructing the structure of an apodized grating with a reflectivity of 99.91%.
Experimental Reconstruction of a Highly Reflecting Fiber Bragg Grating by Using Spectral Regularization and Inverse Scattering
We demonstrate experimentally, for the first time to our knowledge, a reconstruction of a highly reflecting fiber Bragg grating from its complex reflection spectrum by using a regularization algorithm. The regularization method is based on correcting the measured reflection spectrum at the Bragg zone frequencies and enables the reconstruction of the grating profile using the integral-layer-peeling algorithm. A grating with an approximately uniform profile and with a maximum reflectivity of 99.98% was accurately reconstructed by measuring only its complex reflection spectrum.
Efficient Method for Launching In-gap Solitons in Fiber Bragg Gratings Using a Two-segment Apodization Profile
We theoretically demonstrate what is a new method for efficient launching of in-gap solitons in fiber Bragg gratings. The method is based on generating a soliton outside the grating bandgap. Then, the soliton is adiabatically coupled into the bandgap by using its particlelike behavior. We compare our method to a previously published launching scheme that is based on generating the soliton directly within the grating bandgap. When using low-intensity incident pulses, the transmission efficiency of our method is three times higher than that of the previously published scheme.
Multirate Asynchronous Sampling of Sparse Multiband Signals
Because optical systems have a huge bandwidth and are capable of generating low-noise short pulses, they are ideal for undersampling multiband signals that are located within a very broad frequency range. We propose a new scheme for reconstructing multiband signals that occupy a small part of a given broad frequency range under the constraint of a small number of sampling channels. The scheme, which we call multirate sampling (MRS), entails gathering samples at several different rates whose sum is significantly lower than the Nyquist sampling rate. The number of channels does not depend on any characteristics of a signal. In order to be implemented with simplified hardware, the reconstruction method does not rely on the synchronization between different sampling channels. Also, because the method does not solve a system of linear equations, it avoids one source of lack of robustness of previously published undersampling schemes. Our simulations indicate that our MRS scheme is robust both to different signal types and to relatively high noise levels. The scheme can be implemented easily with optical sampling systems.
Quantitative Optoacoustic Signal Extraction Using Sparse Signal Representation
We report on a new quantification methodology of optoacoustic tomographic reconstructions under heterogeneous illumination conditions representative of realistic whole-body imaging scenarios. Our method relies on the differences in the spatial characteristics of the absorption coefficient and the optical energy density within the medium. By using sparse-representation based decomposition, we exploit these different characteristics to extract both the absorption coefficient and the photon density within the imaged object from the optoacoustic image. In contrast to previous methods, this algorithm is not based on the solution of theoretical light transport equations and it does not require explicit knowledge of the illumination geometry or the optical properties of the object and other unknown or loosely defined experimental parameters, leading to highly robust performance. The method was successfully examined with numerically and experimentally generated data and was found to be ideally suited for practical implementations in tomographic schemes of varying complexity, including multiprojection illumination systems and multispectral optoacoustic tomography (MSOT) studies of tissue biomarkers.
Fast Semi-analytical Model-based Acoustic Inversion for Quantitative Optoacoustic Tomography
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.
Near-infrared Fluorescence Catheter System for Two-dimensional Intravascular Imaging in Vivo
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.
Optoacoustic Tomography with Varying Illumination and Non-uniform Detection Patterns
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.
Optoacoustic Methods for Frequency Calibration of Ultrasonic Sensors
The frequency response of ultrasonic detectors is commonly calibrated by finding their sensitivity to incident plane waves at discrete frequencies. For certain applications, such as the emerging field of optoacoustic tomography, it is the response to point sources emitting broadband spectra that needs to be found instead. Although these two distinct sensitivity characteristics are interchangeable in the case of a flat detector and a point source at infinity, it is not the case for detectors with size considerably larger than the acoustic wavelength of interest or those having a focused aperture. Such geometries, which are common in optoacoustics, require direct calibration of the acoustic detector using a point source placed in the relevant position. In this paper, we report on novel cross-validating optoacoustic methods for measuring the frequency response of wideband acoustic sensors. The approach developed does not require pre-calibrated hydrophones and therefore can be readily adopted in any existing optoacoustic measurement configuration. The methods are successfully confirmed experimentally by measuring the frequency response of a common piezoelectric detector having a cylindrically focused shape.
Model-based Optoacoustic Inversions with Incomplete Projection Data
Optoacoustic imaging is an emerging noninvasive imaging modality that can resolve optical contrast through several millimeters to centimeters of tissue with diffraction-limited resolution of ultrasound. Yet, quantified reconstruction of tissue absorption maps requires optoacoustic signals to be collected from as many locations around the object as possible. In many tomographic imaging scenarios, however, only limited-view or partial projection data are available, which has been shown to generate image artifacts and overall loss of quantification accuracy.
High-sensitivity Compact Ultrasonic Detector Based on a Pi-phase-shifted Fiber Bragg Grating
A highly sensitive compact hydrophone, based on a pi-phase-shifted fiber Bragg grating, has been developed for the measurement of wideband ultrasonic fields. The grating exhibits a sharp resonance, whose centroid wavelength is pressure sensitive. The resonance is monitored by a continuous-wave (CW) laser to measure ultrasound-induced pressure variations within the grating. In contrast to standard fiber sensors, the high finesse of the resonance--which is the reason for the sensor's high sensitivity--is not associated with a long propagation length. Light localization around the phase shift reduces the effective size of the sensor below that of the grating and is scaled inversely with the resonance spectral width. In our system, an effective sensor length of 270 μm, pressure sensitivity of 440 Pa, and effective bandwidth of 10 MHz were achieved. This performance makes our design attractive for medical imaging applications, such as optoacoustic tomography, in which compact, sensitive, and wideband acoustic detectors are required.
Two-dimensional Intravascular Near-infrared Fluorescence Molecular Imaging of Inflammation in Atherosclerosis and Stent-induced Vascular Injury
This study sought to develop a 2-dimensional (2D) intravascular near-infrared fluorescence (NIRF) imaging strategy for investigation of arterial inflammation in coronary-sized vessels.
Model-based Optoacoustic Inversion with Arbitrary-shape Detectors
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.
Multispectral Optoacoustic Tomography by Means of Normalized Spectral Ratio
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.
Progress on Multimodal Molecular / Anatomical Intravascular Imaging of Coronary Vessels Combining Near Infrared Fluorescence and Ultrasound
The use of intravascular imaging modalities for the detection and assessment of atherosclerotic plaque is becoming increasingly useful. Current clinical invasive modalities assess the presence of plaque using anatomical information and include Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT). However, such modalities cannot take into account underlying functional biological information, which can however be revealed with the use of molecular imaging. Consequently, intravascular molecular imaging is emerging as a powerful approach. We have developed such a Near-Infrared Fluorescence (NIRF) imaging system and showcased, in both phantom and in-vivo (rabbit) experiments, its potential to successfully detect inflamed atherosclerotic plaques, using appropriate fluorescent probes. Here, we discuss some limitations of the current system and suggest the combined use of the NIRF and IVUS imaging systems as a means for more accurate assessment of atherosclerotic plaque. We include some results and models that showcase the potential power of this kind of hybrid imaging.
