Author: Main Administrator of this WP

Posted on

Optoacoustic tomography: Systems and theory

optoacoustic

Optoacoustic tomography (OAT), also known as photoacoustic tomography, is a hybrid imaging modality that enables the visualization of optical contrast with high resolution at tissue depths in which light propagation is diffusive. In OAT, high-energy laser pulses are sent into the tissue, leading to local energy deposition and (almost) instantaneous thermal expansion of optically absorbing tissue constituents. This rapid expansion propagates outwards in the form of acoustic waves. To form an image of the optical absorption in the tissue, one needs to measure the acoustic waves emanating from the imaged object in a tomographic fashion and apply acoustic inversion. In multi-spectral optoacoustic tomography (MSOT), the optical excitation is performed in several wavelengths, enabling the detection of various chromophores based on their spectral signature and quantifying oxygen saturation in tissue. The additional dimension offered by MSOT makes it a highly promising technique for pre-clinical research and clinical applications.

The design of MSOT systems is a multi-facet problem that requires an understanding of the physics of light and ultrasound propagation in tissue, characteristics of ultrasound detectors, the mathematical properties of the inverse problems involved, and the technical constraints of the imaging scenario. At LBIS, our goal is to develop new system designs and algorithmic tools that enable imaging applications.

Fig (1): Experimental reconstruction of an optoacoustic point source when (a) the deterctor’s geometry is not modelled and (b) when it is. (taken from A. Rosenthal et al., Med. Phys., 2011)

Posted on

Fiber interferometer for hybrid optical and optoacoustic intravital microscopy

source: © 2017 Optical Society of America

The addition of optoacoustic sensing to optical microscopy may supplement fluorescence contrast with label-free measurements of optical absorption, enhancing biological observation. However, the physical dimensions of many optoacoustic systems have restricted the implementation of hybrid optical and optoacoustic (O2A) microscopy to imaging thin samples in transmission mode or to ex-vivo investigations. Here we describe a miniaturized optoacoustic sensor, based on a ?-phase-shifted fiber Bragg grating embedded in an acoustic cavity, which is virtually invisible to the optical path and can be seamlessly integrated into any conventional optical microscope. The new sensor enables, for the first time to our knowledge, entirely optical O2A intravital microscopy in epi-illumination mode, demonstrated by label-free optoacoustic and second-harmonic generation images of a mouse abdomen and ear. Our technique greatly simplifies the integration of acoustic detection in standard microscopes and could therefore make optoacoustic microscopy more accessible to the biomedical community. [Read More…]

Fig. 5. Schematic depiction of the O2A microscopy setup: A standard inverted microscope with laser sources for optoacoustic and non-linear optical imaging is combined with galvanometric mirrors for fast laser raster scanning. The sensor is mounted on the microscope objective, with a tunable CW laser coupled to the embedded ?-FBG. The inset shows the 3D printed platform supporting an anesthetized mouse and mounted on a ??? positioning stage. DM, dichroic mirror; BP, bandpass filter; PH, pinhole; ND, neutral density filter; BS, beam splitter; PMT, photomultiplier tube; OA, optoacoustic; DAQ, data acquisition card.

Authors: Rami Shnaiderman, Georg Wissmeyer, Markus Seeger, Dominik Soliman, Hector Estrada, Daniel Razansky, Amir Rosenthal, and Vasilis Ntziachristos, “Fiber interferometer for hybrid optical and optoacoustic intravital microscopy,” Optica 4, 1180-1187 (2017)

Posted on

Quantitative Intravascular Fluorescence-Ultrasound Imaging In Vivo

Figure 1. Concurrent cNIRF- IVUS imaging in the intravascular arterial environment in vivo.

source:© 2017 Optical Society of America

To enable quantitative molecular and morphological readings in vivo, a near-infrared fluorescence (NIRF)-IVUS catheter and a novel correction algorithm were engineered. Hybrid imaging was validated in atherosclerotic rabbit model in vivo.[Read More…]

Fig 2. In vivo cNIRF-IVUS imaging of inflammation in atherosclerosis.cNIRF-IVUS in vivo imaging of atherosclerosis-related inflammation inside a rabbit aorta revealed two areas (12-30mm and 38-50mm at Fig. 2a, c) of elevated NIR fluorescence activity with a 7mm lower NIRF signal in between. The same fluorescence distribution was observed on the ex vivo FRI image (Fig. 2b). Representative cross-sectional cNIRF-IVUS images at pullback position 1 and 2 (at Fig. 2a) are shown in Fig. 2d and e.

D. Bozhko, E. A. Osborn, A. Rosenthal, J. W. H. Verjans, T. Hara, J. R. McCarthy, S. Kellnberger, G. Wissmeyer, A. Mauskapf, A. F. Stein, F. A. Jaffer, and V. Ntziachristos, “Quantitative Intravascular Fluorescence-Ultrasound Imaging In Vivo,” in Optics in the Life Sciences Congress, OSA Technical Digest (online) (Optical Society of America, 2017), paper OmM2D.3.

Posted on

EOM-PI low bandwidth demodulation and sampling -Taken

Project supervisor: Yoav Hazan

yoav.hazan@campus.technion.ac.il

In the development of Electro-Optic Modulated Pulse Interferometry (EOM-PI) emerged the need for the development of a technique for sampling the EOM-PI signal with low bandwidth sampler (~10MHz) rather than the 1.5GHz sampling bandwidth implemented today. Furthermore, a development of demodulation algorithm for the sampled signals to retrieve signal’s phase.

Project Status: Finished

Project requirements:

  1. Development of signal analysis process to achieve 2-channel sampling of low bandwidth of ~10MHz from a 1-channel 1.5GHz original signal. The two sampling channels are in the surrounding of the DC and the EOM frequency (125MHz).
  2. Development of signal demodulation algorithm to retrieve the signal’s phase from the 2-channel sampling, where the two signals will be in the form of: and .  The demodulation algorithm should be able to handle either DC-coupled measurement and AC-couple measurement.

Advancement options:

  1. Designing an electrical circuit that will operate as developed in the first project requirement.

Recommended readings:

  1. Hazan, Yoav, and Amir Rosenthal. “Passive-demodulation pulse interferometry for ultrasound detection with a high dynamic range.” Optics letters5 (2018): 1039-1042.
  2. Rosenthal, Amir, Daniel Razansky, and Vasilis Ntziachristos. “Wideband optical sensing using pulse interferometry.” Optics Express17 (2012): 19016-19029.
Posted on

Laser Speckle Contrast Imaging on RaspberryPi -Done

Project supervisor: Yoav Hazan

yoav.hazan@campus.technion.ac.il

Laser Speckle Contrast Imaging (LSCI) is an imaging method used in diffusive media. This method maps the regions of dynamic scatters, i.e. blood flowing in blood vessels. Due to developments in both cameras and miniaturized computers, LSCI systems may be implemented in a small cost efficient system, such as a RaspberryPi platform.

Project Status: Taken

Raw image of part of a rat cortex (a) and its LSCI version (b). Briers et al., 2013

Project requirements:

  1. Implementing stand-alone LSCI system on a RaspberryPi platform.
  2. Researching LSCI from high frame rate video. Theoretical analysis and modeling of the new measured field mapped by high frame rate LSCI.

Advancement options:

  1. Researching bi-spectral LSCI.

Recommended readings:

  1. Richards, Lisa M., SM Shams Kazmi, Janel L. Davis, Katherine E. Olin, and Andrew K. Dunn. “Low-cost laser speckle contrast imaging of blood flow using a webcam.” Biomedical optics express, vol. 4, no. 10 (2013): 2269-2283.
  2. Briers, David, Donald D. Duncan, Evan R. Hirst, Sean J. Kirkpatrick, Marcus Larsson, Wiendelt Steenbergen, Tomas Stromberg, and Oliver B. Thompson. “Laser speckle contrast imaging: theoretical and practical limitations.” Journal of biomedical optics, vol. 18, no. 6 (2013): 066018.
  3. Boas, David A., and Andrew K. Dunn. “Laser speckle contrast imaging in biomedical optics.” Journal of biomedical optics, vol. 15, no. 1 (2010): 011109.
Posted on

TM Beam Propagation in Photonic Integrated Circuits -Done

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 the resonators spectra are highly sensitive to the polarization state of the propagating beam. TM polarized beam can potentially increase manufacturing yield as well as sensing sensitivity by an order of magnitude.

Project Status: Available

Y. Painchaud, et al.,2012

Project requirements:

  1. Simulations comparing TE and TM beam propagations through phase-shifted Bragg grating resonators in Silicon waveguide.
  2. Optimization of waveguide dimensions for narrow resonance and high transmission efficiency.

Advancement options:

  1. Simulations of different resonator structures, and the sensitivity for the two difference polarization states.

Recommended readings:

  1. 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.
Posted on

Arduino controlled Fabry-Perot -Available

Project supervisor: Yoav Hazan

yoav.hazan@campus.technion.ac.il

This project is an Arduino based project that combines both simple circuit design and fabrication along with algorithm implementation on the Arduino. This project will integrate into a real research system, in the laboratory for biomedical imaging and sensing, that develop for optical detection of ultrasound.

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:

  1. Design and manufacture amplifier and potentiometer PCB for the Arduino-Feedback circuit interface.
  2. Automation of the startup calibration of the CRPI feedback circuit using an Arduino Due microcontroller.
  3. Monitoring the CRPI locking state and stability during operation and modifying the calibration parameters if necessary.

Recommended readings:

  1. O. Volodarsky, Y. Hazan, and A. Rosenthal. “Ultrasound detection via low-noise pulse interferometry using a free-space Fabry-PĂ©rot.” Optics Express 26, no. 17 (2018): 22405-22418.
Posted on

Model-based image reconstruction in optoacoustic tomography

The effect of limited tomographic coverage on the quality of the reconstructed image [13]. (a) A reconstruction of a cylindrical phantom with a square inclusion from full-view experimental data. (b) Model-based reconstruction with no regularizarion when only 130Âş of the projection data is used. (c) Back-projection reconstruction of the phantom in the limited-view scenario. (d) Regularized model-based reconstruction of the phantom in the limited-view scenario.

source:© 2014 Computer Vision in Medical Imaging

Optoacoustic tomography is a powerful hybrid bioimaging method which retains rich optical contrast and diffraction-limited ultrasonic resolution at depths of varying from millimeters to several centimeters in biological tissue irrespective of photon scattering. Optoacoustic imaging is commonly performed with high power optical pulses whose absorption leads to instantaneous temperature increase, thermal expansion and, subsequently, to the generation of a pressure field proportional to the distribution of the absorbed energy. For tomographic data acquisition, the optoacoustically generated waves are detected on a surface surrounding the imaged region. Recovery of the initially generated pressure distribution from the detected tomographic projections, and hence of the optical energy deposition in the tissue, constitutes the inverse problem of optoacoustic tomography, which is often solved using closed-form inversion formulae. However, those closed-form solutions are only exact for ideal detection geometries, which often do not accurately represent the experimental conditions. Model-based image-reconstruction techniques represent an alternative approach to solving the inverse problem that can significantly reduce image artifacts associated with approximated analytical formulae and significantly enhance image quality in non-ideal imaging scenarios. In the model-based reconstruction, a linear forward model is constructed to accurately describe the experimental conditions of the imaging setup. Inversion is performed numerically and may include regularization when the projection data is insufficient. This chapter demonstrates the benefits of the model-based reconstruction approach and describes numerically efficient methods for its implementation.
[Read More…]

Fig. 5 A comparison between back-projection and model-based reconstructions of a mouse heart in a 3D limited view scenario. The reduction of streak aritifacts in the model-based reconstruction
is readily seen in the images.

A. Rosenthal, D. Razansky, V. Ntziachristos, „Model-based image reconstruction in optoacoustic tomography,“ in Computer Vision in Medical Imaging, edited by C.H. Chen; World Scientific Publishing, October 2013.

Posted on

Improving quantification of intravascular fluorescence imaging using structural information

iNIRF system schematic. Excitation and emission light are coupled into a fibre which can be inserted in a catheter system through a rotational and translational stage, to allow fibre rotation and pull-back. The front end of the fibre is modified using a 45° prism so that fluorescence readings are obtained perpendicular to the translation axis.

source:© 2012 Physics in Medicine & Biology

Intravascular near-infrared fluorescence (iNIRF) imaging can enable the in vivo visualization of biomarkers of vascular pathology, including high-risk plaques. The technique resolves the bio-distribution of systemically administered fluorescent probes with molecular specificity in the vessel wall. However, the geometrical variations that may occur in the distance between fibre-tip and vessel wall can lead to signal intensity variations and challenge quantification. Herein we examined whether the use of anatomical information of the cross-section vessel morphology, obtained from co-registered intravascular ultrasound (IVUS), can lead to quantification improvements when fibre-tip and vessel wall distance variations are present. The algorithm developed employs a photon propagation model derived from phantom experiments that is used to calculate the relative attenuation of fluorescence signals as they are collected over 360° along the vessel wall, and utilizes it to restore accurate fluorescence readings. The findings herein point to quantification improvements when employing hybrid iNIRF, with possible implications to the clinical detection of high-risk plaques or blood vessel theranostics.
[Read More…]

Fig. 3 Experiment for validation of the algorithm: (a) phantom schematic: two straws containing the same concentration of fluorescent dye at different distances from the catheter; (b) iNIRF longitudinal image of the straws A and B and cross-section formation of a particular pullback position of interest; (c) corresponding IVUS cross-section of the straws and their corresponding edges; (d) iNIRF cross-section overlaid on the segmented IVUS cross-section is used for the correction of the iNIRF signal; (e) correction of the iNIRF image along the entire pullback.

G.Mallas, D. H. Brooks, A. Rosenthal, R.N.Nudelman, A. Mauskapf, F.A.Jaffer and V. Ntziachristos, “Improving quantification of intravascular fluorescence imaging using structural information,” Phys. Med. Biol. Vol. 57, pp. 6395–6406 (2012).

Posted on

Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges

Intravascular optoacoustic imaging of lipids in human aorta using the 1210 nm wavelength

source:©2012 Imaging Med.

The progression of atherosclerosis involves complex changes in the structure, composition and biology of the artery wall. Currently, only anatomical plaque burden is routinely characterized in living patients, whereas compositional and biological changes are mostly inaccessible. However, anatomical imaging alone has proven to be insufficient for accurate diagnostics of the disease. Multispectral optoacoustic tomography offers complementary data to anatomical methods and is capable of imaging both tissue composition and, via the use of molecular markers, the biological activity therein. In this paper we review recent progress in multispectral optoacoustic tomography imaging of atherosclerosis with specific emphasis on intravascular applications. The potential capabilities of multispectral optoacoustic tomography are compared with those of established intravascular imaging techniques and current challenges on the road towards a clinically viable imaging modality are discussed.
[Read More…]

Fig. 1 Intravascular multispectral optoacoustic tomography of gold nanoparticle-bearing macrophages in rabbit aorta.
(A) Intravascular ultrasound image and (B) optoacoustic image acquired at 700 nm of an atherosclerotic rabbit aorta injected with gold nanoparticle-bearing macrophages. The arrows indicate the locations where injection was performed. (C) The normalized spectral optoacoustic response obtained in a small section on the aorta, where injection was performed. (D) Multispectral optoacoustic tomography image corresponding to the recovered spectrum overlaid onto the intravascular ultrasound image revealing the injected regions.

A. Rosenthal, F. A. Jafferand V. Ntziachristos, „Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges,” Imaging Med., Vol. 4, pp. 299-310 (2012).