Laser Optoacoustic Ultrasonic Imaging System (LOUIS) and Methods of Use

Abstract

Provided herein are the systems, methods, components for a three-dimensional tomography system. The system is a dual-modality imaging system that incorporates a laser ultrasonic system and a laser optoacoustic system. The dual-modality imaging system generates tomographic images of a volume of interest in a subject body based on speed of sound, ultrasound attenuation and/or ultrasound backscattering and for generating optoacoustic tomographic images of distribution of the optical absorption coefficient in the subject body based on absorbed optical energy density or various quantitative parameters derivable therefrom. Also provided is a method for increasing contrast, resolution and accuracy of quantitative information obtained within a subject utilizing the dual-modality imaging system. The method comprises producing an image of an outline boundary of a volume of interest and generating spatially or temporally coregistered images based on speed of sound and/or ultrasonic attenuation and on absorbed optical energy within the outlined volume.

What is claimed is: 
     
         1 . A dual-modality imaging system, comprising:
 a) first subsystem comprising a laser ultrasonic imaging system having an ultrawide-band ultrasonic transducer array sensitive within a range of ultrasonic frequencies from 50 KHz to 30 MHz positioned for acoustic detection of transient pressure waves resulting from delivery of the laser generated ultrasound to a subject body and configured to produce tomographic images of a volume of interest in the subject body utilizing parameters comprising one or more of the speed of sound, ultrasound attenuation or ultrasound backscattering; and   b) second subsystem comprising a laser optoacoustic imaging system having one or more arrays of ultrawide-band ultrasonic transducers sensitive within the range of ultrasonic frequencies from 50 KHz to 30 MHz positioned for acoustic detection of transient pressure waves resulting from delivery of short laser pulses of nanoseconds duration for generating optoacoustic tomographic images of distribution of the optical absorption coefficient in the subject body utilizing parameters of the absorbed optical energy density or various quantitative parameters that can be derived from the optical absorption.   
     
     
         2 . The dual-modality imaging system of  claim 1 , wherein the images generated by the laser-generated ultrasound are tomographic images of tissue anatomy, morphology and structure. 
     
     
         3 . The dual-modality imaging system of  claim 1 , wherein the images generated by the laser-generated optoacoustics are tomographic images of tissue functional molecules of hemoglobin, oxyhemoglobin, water, lipids, proteins. 
     
     
         4 . The dual-modality imaging system of  claim 1 , wherein the images generated by the laser-generated optoacoustics are tomographic images of proteins, nucleic acids, and enzymes comprising tissue of biomedical interest targeted with exogenous contrast agents or images of a spatial distribution of the exogenous contrast agents, said contrast agents increasing contrast or characterizing molecules, cells or tissues. 
     
     
         5 . The dual-modality imaging system of  claim 4 , wherein said exogenous contrast agents are optical, optoacoustic, acoustic ultrasonic or dual optoacoustic-ultrasonic contrast agents and said contrast agents are either molecules or nanoparticles. 
     
     
         6 . The system of  claim 5 , wherein all images are spatially coregistered or temporally coregistered. 
     
     
         7 . An imaging method for increasing contrast, resolution and accuracy of quantitative information obtained within a subject, comprising the steps of:
 a) producing a laser ultrasound of an outline boundary of a volume of interest within the subject using the dual-modality imaging system of  claim 1 ;   b) generating a spatially or temporally coregistered image of at least one of speed of sound and an image of ultrasonic attenuation within the outlined volume boundary from information contained in the laser ultrasound; and   c) generating a spatially or temporally coregistered optoacoustic image based on absorbed optical energy using at least one of distribution of the speed of sound and ultrasound attenuation within the outlined volume boundary.   
     
     
         8 . A laser optoacoustic ultrasound imaging system (LOUIS), comprising:
 a) a dual laser source switchable between a laser ultrasonic mode and a laser optoacoustic mode, said laser source configured to emit either short optical pulses with high repetition rate for the illumination of the ultrasonic emitters in the ultrasonic mode or short optical pulses with lower repetition rate but higher pulse energy for the illumination of the volume of interest in the optoacoustic mode;   b) an imaging module comprising one or more ultrawide-band ultrasonic transducers configured to detect, through a coupling medium, optoacoustic and ultrasonic signals propagated as transient pressure waves from said volume of interest within a subject body;   c) means to rotate and/or translate said imaging module relative to the volume of interest in the subject body to create multiple pressure waves, said means computer controllable or manually controllable;   d) means for processing said detected laser optoacoustic and laser ultrasonic signals and reconstructing processed signals into one or more of anatomical and functional/molecular images of the volume of interest in the subject body; and   e) means for displaying the one or more images or superimposed coregistered images of the subject body or the volume of interest therein.   
     
     
         9 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein laser optoacoustic illumination is performed in orthogonal mode, backward mode forward mode relative to the subject body or the volume of interest therein. 
     
     
         10 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein laser ultrasonication is performed in transmission or forward mode or in reflection or backward mode relative to the subject body or the volume of interest therein or in a combination of said modes. 
     
     
         11 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein the transducer array is interchangeable for acquisition of various types of images in order to achieve greater contrast, resolution, or quantitative accuracy of either optoacoustic or ultrasonic images or both. 
     
     
         12 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein the rotating means is configured to rotate said imaging module, wherein the detecting array of transducers comprises an arc-shaped array or linear flat array or combination of said array shapes comprising ultrawide-band ultrasonic transducers with wide angular directivity. 
     
     
         13 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein the translating means is configured to translate said imaging module, wherein the detecting array of transducers comprises an arc-shaped array or linear flat array or combination of said array shapes comprising finite size ultrasonic transducers with narrow angular directivity. 
     
     
         14 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein the means for processing and reconstructing said detected ultrasonic signals comprises one or more of:
 electronic amplifiers with time-gain-control circuits;   multichannel analog-to-digital-converter with a field programmable gate array; and   imaging module design and tomography algorithms configured to reconstruct quantitatively accurate volumetric images.   
     
     
         15 . The laser optoacoustic ultrasound imaging system of  claim 8 , wherein said imaging module comprises a hand-held probe configured for acquisition, reconstruction and display of real-time two-dimensional or three-dimensional images. 
     
     
         16 . A method for imaging a subject's body or a volume of interest within, comprising the steps of:
 a) positioning the subject body within or proximate to the imaging module of the laser optoacoustic ultrasound imaging system of  claim 8 ;   b) delivering a laser-generated pulses of ultrasonic energy to a volume of interest in the subject body;   c) detecting the transmitted or reflected ultrasonic pressure waves while measuring one or more parameters comprising a difference between the time of emission and a time of arrival, a difference between emitted amplitude and detected amplitude, and a difference between ultrasonic frequency spectrum of emitted and detected ultrasonic pulses;   d) delivering a laser-generated pulse of optical energy to a volume of interest in the subject body, wherein the pulse of optical energy has a duration shorter than the time of pressure wave propagation through the distance in the subject body or volume thereof equal to a desired spatial resolution;   e) detecting the ultrasonic pressure waves generated through optical absorption inside the subject body while measuring one or more parameters comprising a time of arrival relative to a time of generation, an amplitude of detected optoacoustic signals, and an ultrasonic frequency spectrum of detected optoacoustic signals;   f) scanning the subject body or volume of interest therein with a detecting array of ultrawide-band ultrasonic transducers by repeating steps b) to e) at multiple positions around the subject body or volume of interest while simultaneously scanning the sources of optical energy and sources of ultrasonic energy such that relative position of the detecting array of ultrasonic transducers and the sources of optical or ultrasonic energy can change or remain constant during the scans;   g) processing the detected ultrasonic signals to remove distortions of detected signals; and   h) reconstructing one or more volumetric images via mathematical tomography algorithms using data of the processed signals.   
     
     
         17 . The method of  claim 16 , wherein the scanning step comprises:
 a) scanning the whole subject subject body with a first array of ultrasonic transducers in a rotational configuration to determine at least one volume-of-interest and its characteristics related to absorbed optical energy;   b) replacing the first array with a second array of ultrasonic transducers in a translational configuration; and   c) scanning through said at least one volume-of-interest with a high resolution sufficient to acquire quantitative information related to distribution and concentration of functional molecules therein.   
     
     
         18 . The method of  claim 16 , wherein the one or more volumetric images are three-dimensional images of the volume of interest or of the subject body, or two-dimensional slices through the three-dimensional volume of interest or one-dimensional profiles of molecules of interest within the volume. 
     
     
         19 . The method of  claim 16 , wherein at least one volume of interest is a tumor, a lymph node, a vascular circulation network, or a brain. 
     
     
         20 . The optoacoustic imaging method of  claim 16 , wherein the step of delivering pulsed optical energy is performed at multiple wavelengths of light, whether in sequence or toggling.