Optical Tomography and Spectroscopy of Tissue X, 2013
ABSTRACT In this paper, we have synthesized a second generation tumor hypoxia targeted 2-nitroimi... more ABSTRACT In this paper, we have synthesized a second generation tumor hypoxia targeted 2-nitroimidazole-ICG conjugate using piperazine linker (2-nitro-ICG-p) and validated its performance in in vivo tumor targeting. The results have shown that tumor hypoxia can be targeted with twice higher signal strength beyond three hours post-injection while the un-targeted ICG has completely washed out. The improvement of the second generation 2-nitro-ICG-p dyes is 1.2-1.3 times over the first generation 2-nitro-ICG dyes using ethanol linker beyond 3 hours post-injection which is the optimal time-window for evaluating tumor hypoxia.
Photons Plus Ultrasound: Imaging and Sensing 2008: The Ninth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, 2008
ABSTRACT We report the first experimental investigations of photoacoustic guidance of diffusive o... more ABSTRACT We report the first experimental investigations of photoacoustic guidance of diffusive optical tomography for detection and characterization of optical contrast targets. The hybrid system combined an 8-source, 10-detector reflection mode frequency domain DOT imager with either orthogonal and reflection-geometry photoacoustic systems. The PAT subsystems imaged two-dimensional cross-sections to define centers and radii of regions of interest for a dual-zone mesh DOT imaging algorithm. Phantom absorbers, 1 cm in diameter, of high and low contrast, were spaced 1.5 to 2.5 cm apart at depths ranging from 1 to 2 cm in a turbid medium. Without PAT guidance, the absorber DOT images in many cases were merged and indistinguishable. With PAT guidance, the two targets were well resolved and the reconstructed absorption coefficients improved to 86-130% of the true values. In addition, using both pulse-echo and photoacoustic image detection, the photoacoustic guidance correctly distinguished mechanical from optical contrast providing more specific target information and reconstruction accuracy.
Photons Plus Ultrasound: Imaging and Sensing 2007: The Eighth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, 2007
ABSTRACT Photoacoustic imaging is a promising non-invasive imaging technology due to its ability ... more ABSTRACT Photoacoustic imaging is a promising non-invasive imaging technology due to its ability to combine the enhanced contrast of optical absorption with the spatial resolution of acoustic imaging. Co-registered three-dimensional (3-D) ultrasound and photoacoustic imaging takes advantage of both modalities to allow visualization of tissue structures within a volume using simultaneous structural and functional information. 1.75D acoustic arrays are well-suited for this application due to their ability to scan in 3-D volumes rapidly and accurately while maintaining a reasonable system complexity and cost. We have designed, fabricated, and tested a 1.75D 1280-ch ultrasound system for co-registered 3-D ultrasound and photoacoustic imaging. The system features a 1.75D 1280-channel ultrasound array with a center frequency of 5MHz and 80% bandwidth. The electronics includes 1280 high-voltage pulsers, 40 32-to-1 multiplexers, amplification circuitry, and a 40-channel data acquisition circuit. The system is able to drive the entire array simultaneously, and each array element independently, to scan a 3-D volume within +/- 40 degrees in azimuth direction and +/- 10 degrees in elevation respectively. System performance including axial and lateral resolution has been characterized and compared with simulations. Co-registered 3-D ultrasound and photoacoustic imaging has been successfully performed on phantoms with different geometries and contrast.
ABSTRACT In this study, we present a novel photoacoustic contrast agent which is based on bis-car... more ABSTRACT In this study, we present a novel photoacoustic contrast agent which is based on bis-carboxylic acid derivative of Indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT). Covalently attaching ICG to the functionalized SWCNT provides a more robust system that delivers much more ICG to the tumor site. The detection sensitivity of the new contrast agent in mouse tumor model is demonstrated in vivo by our custom built photoacoustic imaging system. PAT summation signal is defined to show the long-term light absorption of tumor areas in ICG injected mice and ICG/SWCNT injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 minutes peak response time referred to pre-injection PAT summation level, while ICG/SWCNT provides 128% enhancement at 80 minutes and even higher enhancement of 196% at the end point of experiments (120 minutes on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery as confirmed by fluorescence images of the tumor samples. This feature is highly valuable in guiding surgeons to assess tumor boundaries and dimensions in vivo and improve surgical resection of tumors for achieving clean tumor margins.
Currently, most of the cancers in the ovary are detected when they have already metastasized to o... more Currently, most of the cancers in the ovary are detected when they have already metastasized to other parts of the body. As a result, ovarian cancer has the highest mortality of all gynecological cancers with a 5-year survival rate of 30% or less [1]. The reason is the lack of reliable ...
ABSTRACT A method to reduce image artifacts arising from secondary ultrasound echoes during photo... more ABSTRACT A method to reduce image artifacts arising from secondary ultrasound echoes during photoacoustic imaging is presented. Experimental results presented indicate a significant improvement in the image quality by the use this technique.
ABSTRACT Unique features in co-registered ultrasound and photoacoustic images of ex vivo ovarian ... more ABSTRACT Unique features in co-registered ultrasound and photoacoustic images of ex vivo ovarian tissue are introduced, along with the hypotheses of how these features may relate to the physiology of tumors. The images are compressed with wavelet transform, after which the mean Radon transform of the photoacoustic image is computed and fitted with a Gaussian function to find the centroid of the suspicious area for shift-invariant recognition process. In the next step, 24 features are extracted from a training set of images by several methods; including features from the Fourier domain, image statistics, and the outputs of different composite filters constructed from the joint frequency response of different cancerous images. The features were chosen from more than 400 training images obtained from 33 ex vivo ovaries of 24 patients, and used to train a support vector machine (SVM) structure. The SVM classifier was able to exclusively separate the cancerous from the non-cancerous cases with 100% sensitivity and specificity. At the end, the classifier was used to test 95 new images, obtained from 37 ovaries of 20 additional patients. The SVM classifier achieved 76.92% sensitivity and 95.12% specificity. Furthermore, if we assume that recognizing one image as a cancerous case is sufficient to consider the ovary as malignant, then the SVM classifier achieves 100% sensitivity and 87.88% specificity.
Photons Plus Ultrasound: Imaging and Sensing 2009, 2009
ABSTRACT We report experimental investigations of photoacoustic guidance of diffusive optical tom... more ABSTRACT We report experimental investigations of photoacoustic guidance of diffusive optical tomography for detection and characterization of optical contrast targets. The hybrid system combined an 8-source, 10-detector frequency domain DOT with a clinical reflection geometry probe. For the photoacoustic tomography (PAT) functionality, a high-energy 1×7 optical fiber delivery system illuminated a 2 cm central region for localization of absorptive targets. Two-dimensional PAT images along one central axis of the probe defined of regions of interest for a dual-zone mesh DOT imaging algorithm. PVC Plastisol phantom absorbers, 1 cm on a side, with absorption coefficients ranging from 0.075 to 0.23 cm-1 were imaged at depths up to 2.5 cm. Pairs of absorbers simulating a multi-lobed heterogeneous tumor were also investigated. Without PAT guidance, the absorber location was not clear and lower contrast targets in the twoabsorber configurations were not distinguishable. With PAT guidance, the two targets were well resolved and the reconstructed absorption coefficients improved to within 15% of the true values.
ABSTRACT Co-registered Ultrasound and Photoacoustic images provide complimentary structure and fu... more ABSTRACT Co-registered Ultrasound and Photoacoustic images provide complimentary structure and functional information for cancer diagnosis and assessment of therapy response. In SPIE Photonics West 2011, we reported a system that acquires from 64 channels and displays up to 1 frame per second (fps) ultrasound pulse-echo images, 5 fps photoacoustic images, and 0.5 fps co-registered images. In this year, we report an upgraded system which acquires from 128 channels and displays up to 15 fps co-registered ultrasound and photoacoustic images limited by our laser pulse repetition rate. The system architecture is novel and it provides real-time co-registration of images, the ability of acquiring the channel RF data for both modalities, and the flexibility of adjusting every parameter involved in the imaging process for both modalities. The digital signal processor board is upgraded to an FPGA-based PCIe board that collects the data from the acquisition modules and transfers them to the PC memory at 2.5GT/s rate through an x8 DDR PCIe bus running at 100MHz clock frequency. The modules FPGA code is also upgraded to form a beam line in 90 microseconds and to communicate through ultrafast differential tracks with the PCIe board. Furthermore, the printed circuit board (PCB) design of the system was adjusted to provide a maximum of 80dB signal-to-noise ratio at 60dB gain, which is comparable to some commercial ultrasound machines. The real-time system allows capturing co-registered US/PAT images free of motion artifacts and also provides ultrafast dynamic information when a contrast agent is used. The system is built for clinical use to assist the diagnosis of ovarian cancer. However, the hardware is still under testing and evaluation stage, experimental and clinical results will be reported later.
Photons Plus Ultrasound: Imaging and Sensing 2011, 2011
In this paper, we report the experimental investigation of a novel fitting procedure which can de... more In this paper, we report the experimental investigation of a novel fitting procedure which can detect and quantitatively characterize the optical contrasts of targets using diffuse optical tomography (DOT)-assisted photoacoustic tomography. The hybrid system combines a 64-channel photoacoustic system with a 9-source, 14-detector frequency-domain DOT system. A white probe was used to house the ultrasound transducer, the optical sources and detectors. The experiment was performed in the reflection mode which is more realistic to clinical applications. The fitting procedure included a complete photoacoustic forward model, which incorporated an analytical model of light transport and a model of acoustic propagation. Using the structural information from the PAT images and the background information from DOT measurements, the photoacoustic forward model was used to recover the target absorption coefficient quantitatively. Phantom absorbers, 1 cm in diameter, with absorption coefficients ranging from 0.08 to 0.28 cm-1 were imaged at depths of up to 3.0 cm. The fitting results were at least 85% of their true values for both high and low contrast targets. Blood sample in a thin tube of radius 0.6 mm, that was simulating a blood vessel, was also imaged, and the reconstructed images and fitted absorption coefficients are presented. These results illustrate the promising application of this fitting procedure for tissue absorption coefficient characterization and consequently breast cancer diagnosis.
ABSTRACT We introduce a fitting procedure which can quantitatively recover the absorption coeffic... more ABSTRACT We introduce a fitting procedure which can quantitatively recover the absorption coefficient using DOT-assisted photoacoustic tomography. The background optical properties provided by DOT can significantly improve the accuracy of the fitting.
Optical Tomography and Spectroscopy of Tissue X, 2013
ABSTRACT In this paper, we have synthesized a second generation tumor hypoxia targeted 2-nitroimi... more ABSTRACT In this paper, we have synthesized a second generation tumor hypoxia targeted 2-nitroimidazole-ICG conjugate using piperazine linker (2-nitro-ICG-p) and validated its performance in in vivo tumor targeting. The results have shown that tumor hypoxia can be targeted with twice higher signal strength beyond three hours post-injection while the un-targeted ICG has completely washed out. The improvement of the second generation 2-nitro-ICG-p dyes is 1.2-1.3 times over the first generation 2-nitro-ICG dyes using ethanol linker beyond 3 hours post-injection which is the optimal time-window for evaluating tumor hypoxia.
Photons Plus Ultrasound: Imaging and Sensing 2008: The Ninth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, 2008
ABSTRACT We report the first experimental investigations of photoacoustic guidance of diffusive o... more ABSTRACT We report the first experimental investigations of photoacoustic guidance of diffusive optical tomography for detection and characterization of optical contrast targets. The hybrid system combined an 8-source, 10-detector reflection mode frequency domain DOT imager with either orthogonal and reflection-geometry photoacoustic systems. The PAT subsystems imaged two-dimensional cross-sections to define centers and radii of regions of interest for a dual-zone mesh DOT imaging algorithm. Phantom absorbers, 1 cm in diameter, of high and low contrast, were spaced 1.5 to 2.5 cm apart at depths ranging from 1 to 2 cm in a turbid medium. Without PAT guidance, the absorber DOT images in many cases were merged and indistinguishable. With PAT guidance, the two targets were well resolved and the reconstructed absorption coefficients improved to 86-130% of the true values. In addition, using both pulse-echo and photoacoustic image detection, the photoacoustic guidance correctly distinguished mechanical from optical contrast providing more specific target information and reconstruction accuracy.
Photons Plus Ultrasound: Imaging and Sensing 2007: The Eighth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, 2007
ABSTRACT Photoacoustic imaging is a promising non-invasive imaging technology due to its ability ... more ABSTRACT Photoacoustic imaging is a promising non-invasive imaging technology due to its ability to combine the enhanced contrast of optical absorption with the spatial resolution of acoustic imaging. Co-registered three-dimensional (3-D) ultrasound and photoacoustic imaging takes advantage of both modalities to allow visualization of tissue structures within a volume using simultaneous structural and functional information. 1.75D acoustic arrays are well-suited for this application due to their ability to scan in 3-D volumes rapidly and accurately while maintaining a reasonable system complexity and cost. We have designed, fabricated, and tested a 1.75D 1280-ch ultrasound system for co-registered 3-D ultrasound and photoacoustic imaging. The system features a 1.75D 1280-channel ultrasound array with a center frequency of 5MHz and 80% bandwidth. The electronics includes 1280 high-voltage pulsers, 40 32-to-1 multiplexers, amplification circuitry, and a 40-channel data acquisition circuit. The system is able to drive the entire array simultaneously, and each array element independently, to scan a 3-D volume within +/- 40 degrees in azimuth direction and +/- 10 degrees in elevation respectively. System performance including axial and lateral resolution has been characterized and compared with simulations. Co-registered 3-D ultrasound and photoacoustic imaging has been successfully performed on phantoms with different geometries and contrast.
ABSTRACT In this study, we present a novel photoacoustic contrast agent which is based on bis-car... more ABSTRACT In this study, we present a novel photoacoustic contrast agent which is based on bis-carboxylic acid derivative of Indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT). Covalently attaching ICG to the functionalized SWCNT provides a more robust system that delivers much more ICG to the tumor site. The detection sensitivity of the new contrast agent in mouse tumor model is demonstrated in vivo by our custom built photoacoustic imaging system. PAT summation signal is defined to show the long-term light absorption of tumor areas in ICG injected mice and ICG/SWCNT injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 minutes peak response time referred to pre-injection PAT summation level, while ICG/SWCNT provides 128% enhancement at 80 minutes and even higher enhancement of 196% at the end point of experiments (120 minutes on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery as confirmed by fluorescence images of the tumor samples. This feature is highly valuable in guiding surgeons to assess tumor boundaries and dimensions in vivo and improve surgical resection of tumors for achieving clean tumor margins.
Currently, most of the cancers in the ovary are detected when they have already metastasized to o... more Currently, most of the cancers in the ovary are detected when they have already metastasized to other parts of the body. As a result, ovarian cancer has the highest mortality of all gynecological cancers with a 5-year survival rate of 30% or less [1]. The reason is the lack of reliable ...
ABSTRACT A method to reduce image artifacts arising from secondary ultrasound echoes during photo... more ABSTRACT A method to reduce image artifacts arising from secondary ultrasound echoes during photoacoustic imaging is presented. Experimental results presented indicate a significant improvement in the image quality by the use this technique.
ABSTRACT Unique features in co-registered ultrasound and photoacoustic images of ex vivo ovarian ... more ABSTRACT Unique features in co-registered ultrasound and photoacoustic images of ex vivo ovarian tissue are introduced, along with the hypotheses of how these features may relate to the physiology of tumors. The images are compressed with wavelet transform, after which the mean Radon transform of the photoacoustic image is computed and fitted with a Gaussian function to find the centroid of the suspicious area for shift-invariant recognition process. In the next step, 24 features are extracted from a training set of images by several methods; including features from the Fourier domain, image statistics, and the outputs of different composite filters constructed from the joint frequency response of different cancerous images. The features were chosen from more than 400 training images obtained from 33 ex vivo ovaries of 24 patients, and used to train a support vector machine (SVM) structure. The SVM classifier was able to exclusively separate the cancerous from the non-cancerous cases with 100% sensitivity and specificity. At the end, the classifier was used to test 95 new images, obtained from 37 ovaries of 20 additional patients. The SVM classifier achieved 76.92% sensitivity and 95.12% specificity. Furthermore, if we assume that recognizing one image as a cancerous case is sufficient to consider the ovary as malignant, then the SVM classifier achieves 100% sensitivity and 87.88% specificity.
Photons Plus Ultrasound: Imaging and Sensing 2009, 2009
ABSTRACT We report experimental investigations of photoacoustic guidance of diffusive optical tom... more ABSTRACT We report experimental investigations of photoacoustic guidance of diffusive optical tomography for detection and characterization of optical contrast targets. The hybrid system combined an 8-source, 10-detector frequency domain DOT with a clinical reflection geometry probe. For the photoacoustic tomography (PAT) functionality, a high-energy 1×7 optical fiber delivery system illuminated a 2 cm central region for localization of absorptive targets. Two-dimensional PAT images along one central axis of the probe defined of regions of interest for a dual-zone mesh DOT imaging algorithm. PVC Plastisol phantom absorbers, 1 cm on a side, with absorption coefficients ranging from 0.075 to 0.23 cm-1 were imaged at depths up to 2.5 cm. Pairs of absorbers simulating a multi-lobed heterogeneous tumor were also investigated. Without PAT guidance, the absorber location was not clear and lower contrast targets in the twoabsorber configurations were not distinguishable. With PAT guidance, the two targets were well resolved and the reconstructed absorption coefficients improved to within 15% of the true values.
ABSTRACT Co-registered Ultrasound and Photoacoustic images provide complimentary structure and fu... more ABSTRACT Co-registered Ultrasound and Photoacoustic images provide complimentary structure and functional information for cancer diagnosis and assessment of therapy response. In SPIE Photonics West 2011, we reported a system that acquires from 64 channels and displays up to 1 frame per second (fps) ultrasound pulse-echo images, 5 fps photoacoustic images, and 0.5 fps co-registered images. In this year, we report an upgraded system which acquires from 128 channels and displays up to 15 fps co-registered ultrasound and photoacoustic images limited by our laser pulse repetition rate. The system architecture is novel and it provides real-time co-registration of images, the ability of acquiring the channel RF data for both modalities, and the flexibility of adjusting every parameter involved in the imaging process for both modalities. The digital signal processor board is upgraded to an FPGA-based PCIe board that collects the data from the acquisition modules and transfers them to the PC memory at 2.5GT/s rate through an x8 DDR PCIe bus running at 100MHz clock frequency. The modules FPGA code is also upgraded to form a beam line in 90 microseconds and to communicate through ultrafast differential tracks with the PCIe board. Furthermore, the printed circuit board (PCB) design of the system was adjusted to provide a maximum of 80dB signal-to-noise ratio at 60dB gain, which is comparable to some commercial ultrasound machines. The real-time system allows capturing co-registered US/PAT images free of motion artifacts and also provides ultrafast dynamic information when a contrast agent is used. The system is built for clinical use to assist the diagnosis of ovarian cancer. However, the hardware is still under testing and evaluation stage, experimental and clinical results will be reported later.
Photons Plus Ultrasound: Imaging and Sensing 2011, 2011
In this paper, we report the experimental investigation of a novel fitting procedure which can de... more In this paper, we report the experimental investigation of a novel fitting procedure which can detect and quantitatively characterize the optical contrasts of targets using diffuse optical tomography (DOT)-assisted photoacoustic tomography. The hybrid system combines a 64-channel photoacoustic system with a 9-source, 14-detector frequency-domain DOT system. A white probe was used to house the ultrasound transducer, the optical sources and detectors. The experiment was performed in the reflection mode which is more realistic to clinical applications. The fitting procedure included a complete photoacoustic forward model, which incorporated an analytical model of light transport and a model of acoustic propagation. Using the structural information from the PAT images and the background information from DOT measurements, the photoacoustic forward model was used to recover the target absorption coefficient quantitatively. Phantom absorbers, 1 cm in diameter, with absorption coefficients ranging from 0.08 to 0.28 cm-1 were imaged at depths of up to 3.0 cm. The fitting results were at least 85% of their true values for both high and low contrast targets. Blood sample in a thin tube of radius 0.6 mm, that was simulating a blood vessel, was also imaged, and the reconstructed images and fitted absorption coefficients are presented. These results illustrate the promising application of this fitting procedure for tissue absorption coefficient characterization and consequently breast cancer diagnosis.
ABSTRACT We introduce a fitting procedure which can quantitatively recover the absorption coeffic... more ABSTRACT We introduce a fitting procedure which can quantitatively recover the absorption coefficient using DOT-assisted photoacoustic tomography. The background optical properties provided by DOT can significantly improve the accuracy of the fitting.
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