HOUSTON, TX, United States

Tomowave Laboratories, Inc.

www.tomowave.com
HOUSTON, TX, United States
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We developed a 3D optoacoustic tomography (OAT) system* combining advantages of pulsed optical spectroscopy and high‐resolution ultrasonic detection, characterized the system and demonstrated that it produces high‐ contrast 3D maps of optical absorbance through the large volume of tissue from 20 to 500 mL with resolution better than 0.5 mm. Applications of this technology range from the whole body imaging of a small animal for purposes of preclinical research in oncology to the diagnostic imaging of breast cancer and angiography. An ultrawide‐band of ultrasonic frequencies present in optoacoustic signals contains wealth of information, which can be revealed through proper filtering and post‐processing. The excellent contrast of hemoglobin and oxyhemoglobin in tissue allows one not only to see the circulatory system, but also to visualize the internal organs. Application of exogenous contrast agents permits imaging of microvasculature of tumors, spine, bones and joints. We demonstrated that either larger anatomy, such as organs or major vessels, or the smaller structures (kidney medullas, ovarian arteries) and even microvasculature can be visualized in case of sufficient contrast depending on methods of signal and image processing. The most significant value of 3D tomography employing a rigorous solution for the image reconstruction is to provide quantitative information of the absorption coefficient that can be translated into concentrations of tissue chromophores while imaging at several laser wavelengths. This system was employed to generate functional images of blood distribution and molecular images of malignancy‐related protein receptors in the cells of cancerous tumors in vivo. The most important parameter that enables clinical application is the depth of imaging. We demonstrated that the depth of optoacoustic imaging in tissues exceeds 50 mm for small blood vessel structures. Based on the experimental evidence, translation of the developed preclinical system to clinical applications will be discussed. © 2011, American Association of Physicists in Medicine. All rights reserved.


Oraevsky A.,Tomowave Laboratories, Inc.
Optics InfoBase Conference Papers | Year: 2014

A review of our recent works advancing three-dimensional optoacoustic tomography systems and their applications in preclinical imaging using small animal models and clinical application in diagnostic imaging of breast cancer is presented. We also discuss benefits of the latest addition of the laser ultrasound tomography to the optoacoustic imaging system. Examples of preclinical and clinical images obtained with laser optoacoustic ultrasonic imaging system (LOUIS-3D are provided and challenges of achieving further progress are outlined. © 2014 OSA.


Petrova E.V.,Tomowave Laboratories, Inc. | Oraevsky A.A.,Tomowave Laboratories, Inc. | Ermilov S.A.,Tomowave Laboratories, Inc.
Applied Physics Letters | Year: 2014

Optoacoustic (photoacoustic) temperature imaging could provide improved spatial resolution and temperature sensitivity as compared to other techniques of non-invasive thermometry used during thermal therapies for safe and efficient treatment of lesions. However, accuracy of the reported optoacoustic methods is compromised by biological variability and heterogeneous composition of tissues. We report our findings on the universal character of the normalized temperature dependent optoacoustic response (ThOR) in blood, which is invariant with respect to hematocrit at the isosbestic point of hemoglobin. The phenomenon is caused by the unique homeostatic compartmentalization of blood hemoglobin exclusively inside erythrocytes. On the contrary, the normalized ThOR in aqueous solutions of hemoglobin showed linear variation with respect to its concentration and was identical to that of blood when extrapolated to the hemoglobin concentration inside erythrocytes. To substantiate the conclusions, we analyzed optoacoustic images acquired from the samples of whole and diluted blood as well as hemoglobin solutions during gradual cooling from +37 to -15°C. Our experimental methodology allowed direct observation and accurate measurement of the temperature of zero optoacoustic response, manifested as the sample's image faded into background and then reappeared in the reversed (negative) contrast. These findings provide a framework necessary for accurate correlation of measured normalized optoacoustic image intensity and local temperature in vascularized tissues independent of tissue composition. © 2014 AIP Publishing LLC.


Liopo A.,Tomowave Laboratories, Inc. | Su R.,Tomowave Laboratories, Inc. | Oraevsky A.A.,Tomowave Laboratories, Inc.
Photoacoustics | Year: 2015

We describe the synthesis and characterization of melanin-like nanoparticles (MNP) as novel contrast agents for optoacoustic tomography. Good dispersion stability of high concentration MNPs in different biological media was achieved with thiol-terminated methoxy-poly(ethylene glycol), which can be used for further functional conjugation. MNP-PEG were found biocompatible with human MCF-7 and 3T3 cells. Cell toxicity of MNPs was found lower than that of gold nanorods for concentrations that provide equal optical absorbance. Optoacoustic tomography images were obtained with Laser Optoacoustic Imaging System (LOIS-3D) from tubes filled with contrast agents and live mice. Imaging of tubes permitted verification of the system resolution <300μm and sensitivity δμa=0.03/cm under safe laser fluence of 20mJ/cm2. Water suspensions of MNP demonstrated optoacoustic efficiency that is about equal to that of gold nanorods under conditions of equal optical absorption. We conclude that MNPs have the potential for biomedical imaging applications as optoacoustic contrast agents. © 2015 The Authors.


Wang K.,Washington University in St. Louis | Su R.,Tomowave Laboratories, Inc. | Oraevsky A.A.,Tomowave Laboratories, Inc. | Anastasio M.A.,Washington University in St. Louis
Physics in Medicine and Biology | Year: 2012

Iterative image reconstruction algorithms for optoacoustic tomography (OAT), also known as photoacoustic tomography, have the ability to improve image quality over analytic algorithms due to their ability to incorporate accurate models of the imaging physics, instrument response and measurement noise. However, to date, there have been few reported attempts to employ advanced iterative image reconstruction algorithms for improving image quality in three-dimensional (3D) OAT. In this work, we implement and investigate two iterative image reconstruction methods for use with a 3D OAT small animal imager: namely a penalized least-squares (PLS) method employing a quadratic smoothness penalty and a PLS method employing a total variation norm penalty. The reconstruction algorithms employ accurate models of the ultrasonic transducer impulse responses. Experimental data sets are employed to compare the performances of the iterative reconstruction algorithms to that of a 3D filtered backprojection (FBP) algorithm. By the use of quantitative measures of image quality, we demonstrate that the iterative reconstruction algorithms can mitigate image artifacts and preserve spatial resolution more effectively than FBP algorithms. These features suggest that the use of advanced image reconstruction algorithms can improve the effectiveness of 3D OAT while reducing the amount of data required for biomedical applications. © 2012 Institute of Physics and Engineering in Medicine.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 131.67K | Year: 2012

DESCRIPTION (provided by applicant): Laser Ultrasound and Optoacoustic Endoscopy of Esophagus We propose development of a novel commercial dual-modality imaging system which will integrate laser ultrasound and optoacoustic imaging capabilities in a compact package suitable for endoscopy of esophagus. There is a pressing need for versatile and effective instrumentation capable of detecting deadly esophageal cancer in its early stages. Ultrasound imaging has been proven effective in identifying and staging of relatively advanced tumors in esophageal wall lining based on differences in their density and speed of sound (acoustic impedance) relative to normal tissues. Optoacoustic imaging is a novel complementary imaging modality which combines optics and high-resolution of ultrasound to generate images based on optical properties of tissues. Enhanced performance of the dual-mode optoacoustic-ultrasound imaging as compared to conventional ultrasound was clinically demonstrated in detection and staging of breast cancers, and the optoacoustic imaging technology have been commercialized. We reasonably expect that the proposed device will significantly improve diagnostic capability of ultrasound endoscopy and therefore be highly desired in clinical practice. The proposed optoacoustic/ultrasound imaging system will utilize a number of innovations which will allow us to achieve top-notch performance and versatility. Our first key innovation involves the use an off-axis parabolic reflector in conjunction with a flat transducer array for optoacoustic endoscopy. The reflector, as we demonstrated, provides and ideal conversion of a spherical wavefront into a plane wave without losses or distortions. The use of a transducer array will allow us to expand limited depth of view of the focused system using dynamic ultrasound focusing and wavefront corrections. With an array, approximately 10-fold larger volume can be imaged in a single step as compared to diffraction-limited volume of a focused system. Finally, we propose to addultrasound imaging capability to the optoacoustic endoscope using laser-generated ultrasound. A removable absorbing and acoustically transparent layer placed in the path of laser beam will generate strong and broadband pressure pulses propagating towardsa sample and the reflected signals will be used to recreate an ultrasound image. This innovation will eliminate the need for pulse-receive switches known to generate electronic interference and will allow optimization of the transducer design for detectionmode only, thereby simplifying and enhancing sensitivity of an imaging system. The PI is an internationally recognized leader in optoacoustic imaging technology and its commercialization and will guide the team of highly qualified experts in ultrasound imaging and optoacoustic tomography towards successful completion of a project. At present, no compact dual-mode optoacoustic-ultrasound imaging systems suitable for endoscopy applications have been either developed or commercialized. The proposed research will create a foundation towards development and future commercialization of a novel instrument. Our dual-modality optoacoustic-ultrasound imaging system is expected to have a high demand in clinic for functional endoscopy of esophagus. PUBLIC HEALTH RELEVANCE: Laser Ultrasound and Optoacoustic Endoscopy of Esophagus Efficient imaging technologies capable of early stage detection of deadly esophageal cancers are need in clinical practice. Here we proposed to enhance conventional ultrasound imaging used for detection and staging of tumors in esophageal lining by introducing a novel dual-mode optoacoustic-ultrasound imaging endoscopy system. The proposed design based on an off-axis parabolic reflector in conjunction with a transducer array will provide a significantly improved resolution, depth of focus, and the rate of data acquisition as compared to prior optoacoustic endoscopy designs. The use of laser-ultrasound to perform conventional ultrasound imaging will not complicate the probe design andwill significantly expand its utility fr detecting and staging of esophageal cancers. The proposed dual-modality optoacoustic-ultrasound imaging system is expected to have a high demand in clinic for functional endoscopy of esophagus.


Patent
Tomowave Laboratories, Inc. | Date: 2015-02-02

Provided herein are system and methods for monitoring and guiding thermal therapy procedures within a human or animal tissue. The system comprises a therapeutic module configured to apply thermal treatment to a subject; an ultrasound imaging module; an optoacoustic imaging module; a processing module connected to both ultrasound and optoacoustic based imaging module; and an operating controlling module connected with said processing module and configured to manipulate at least one of said therapeutic module, ultrasound imaging module or optoacoustic imaging module. The calibration method is able to eliminate the inconsistency of optoacoustic based temperature measurements caused by sample-to-sample and spatial variations of Gruneisen parameter for different tissues. The method for temperature-structure imaging is able to generate both two dimensional and three dimensional co-registered structure and temperature images for the tissues inside a region of interest of a subject.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 115.12K | Year: 2011

DESCRIPTION (provided by applicant): We propose novel application of optoacoustic tomography for non-invasive and quantitative analysis of nanoparticle biodistribution in preclinical research. Novel nanotechnology-based treatments of cancer and other diseases with increased specificity and enhanced therapeutic potential are being actively developed at present. There is a pressing need for low-cost and high-sensitivity instrumentation capable of monitoring proliferation and clearance of nanoparticles in vivoto perform health safety assessments and determine efficacy of disease treatments. Current non-invasive methods of nanoparticle detection, such as magnetic resonance imaging and radiological imaging (i.e. computer tomography and its variants) remain expensive and are not accessible to many businesses involved in advancing nanotechnology-based drugs and therapeutic strategies in clinical practice. Instead, tedious post-mortem analysis of numerous samples remains a common method to perform nanoparticle biodistribution studies. Optoacoustic tomography is a novel imaging technology based on optical absorptivity of tissues and high resolution of ultrasound to produce three-dimensional images of vasculature and internal organs in small animals. Since a wide variety of gold and carbon-based nanoparticles, as well as select biodegradable nano- complexes already exhibit or can be engineered to display strong optical resonances in a near-infrared spectral region, a so-called biological transparency window, their small quantities can be detected in vivo with optoacoustics. In this work, we propose to demonstrate feasibility of using optoacoustic technology to perform quantitative biodistribution analysis of gold nanorods and carbon nanotubes in mice. Our optoacoustic tomography system will detect small volumetric changes in absoprtivity corresponding to less than 1 % of an organ absorbance at a specific wavelength. We propose to establish a correlation between absorption increase and a concentration of nanoparticles ina particular organ to allow quantitative measurements of nanoparticles in vivo. This will allow us to define sensitivity limits of our method and demonstrate its benefits in terms of cost, versatility, sensitivity and resolution and assess its potential for a future commercialization. The PI is an internationally recognized leader in optoacoustic imaging technology and its commercialization and will guide the team of highly qualified experts in nanotechnology and optoacoustic tomography towards successfulcompletion of a project. The proposed technology will lead towards commercial instrumentation that will provide a significantly cheaper, safer and more versatile alternative to current non invasive imaging modalities, such as CT and MRI. Our imaging systemwill have a high demand in a nanotechnology-oriented bioengineering businesses and academic circles with applications in pharmacokinetics analysis, biodistribution studies and health risk assessments of novel nano-drugs and nano-devices. PUBLIC HEALTH RELEVANCE: Efficient and affordable imaging technologies capable of non-invasive and highly sensitive imaging of nanoparticles in vivo are needed to perform health risk assessment and biodistribution analysis of nanoparticles and novel nanotechnology-based drugs. Here we demonstrate that optoacoustic tomography is capable of detecting small quantities of carbon and gold nanoparticles and monitor their proliferation in vivo. We propose to define sensitivity of optoacoustic tomography and calibrate theimaging system to allow quantitave measurements of nanoparticle concentrations directly in small animals. Novel, inexpensive and reliable imaging modality is proposed to empower businesses and non-profit researchers interested in developing nanotechnology-based drugs and disease treatments, analyzing health risks presented by nanoparticles and developing strategies to reduce adverse effects associated with nanoparticle presence.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 200.81K | Year: 2014

Summary / Abstract The objective of this Phase-I SBIR project is to develop a novel transrectal optoacoustic-ultrasonic (OU) imaging system for guiding cryotherapy of prostate cancer via real-time monitoring of ice ball formation and temperature distribution within the area of healthy tissues adjacent to the rectal wall. The proposed system will be capable of (i) non-invasive monitoring of spatial temperature distribution in areas of important innervation around rectal wall during cryotherapy and (ii) monitoring of development of the ice ball boundary. After encouraging additional preliminary studies we decided to restructure our Research Strategy and resubmit this proposal for development of a commercial prototype of the image-guided cryotherapy system andits in vivo evaluation of two canine prostates in the course of treatment. The proposed system will operate in real time and will be capable of imaging the prostate gland and assist in computer-controlled treatment procedure. Current methods of prostate c


Provided herein are dual modality imaging systems and methods within displayed anatomical structures of placenta in real time. The imaging system comprises a dual modality laser optoacoustic and ultrasonic platform with a plurality of subsystems for delivering near infrared light, optoacoustic and ultrasonic pulses to the placenta and/or associated tissue and deep anatomic structures, for detecting ultrasonic pulses generated or reflected within the tissue using a multi-channel optoacoustic-ultrasound probe and associated transducers. The dual modality imaging system displays the results obtained as quantitative functional images of the parameters coregistered with anatomic tissue images. A multichannel electronic system comprising a computer tangibly storing software enables processor-executable instructions to calculate quantitative functional parameters of the placental blood within specific anatomical tissue structures and display quantitative functional optoacoustic images of the functional parameters within specific anatomical structures in the tissue that are visualized by ultrasound.

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