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We have developed the ultrasound (US)-guided diffuse optical tomography technique to assist US diagnosis of breast cancer and to predict neoadjuvant chemotherapy response of patients with breast cancer. The technique was implemented using a hand-held hybrid probe consisting of a coregistered US transducer and optical source and detector fibers which couple the light illumination from laser diodes and photon detection to the photomultiplier tube detectors. With the US guidance, diffused light measurements were made at the breast lesion site and the normal contralateral reference site which was used to estimate the background tissue optical properties for imaging reconstruction. However, background optical properties were affected by the chest wall underneath the breast tissue. We have analyzed data from 297 female patients, and results have shown statistically significant correlation between the fitted optical properties (μa and μs') and the chest wall depth. After subtracting the background μa at each wavelength, the difference of computed total hemoglobin (tHb) between malignant and benign lesion groups has improved. For early stage malignant lesions, the area-under-the- receiver operator characteristic curve (AUC) has improved from 88.5% to 91.5%. For all malignant lesions, the AUC has improved from 85.3% to 88.1%. Statistical test has revealed the significant difference of the AUC improvements after subtracting background tHb values. [ABSTRACT FROM AUTHOR]

We present a photoacoustic tomography-guided diffuse optical tomography approach using a hand-held probe for detection and characterization of deeply-seated targets embedded in a turbid medium. Diffuse optical tomography guided by coregistered ultrasound, MRI, and x ray has demonstrated a great clinical potential to overcome lesion location uncertainty and to improve light quantification accuracy. However, due to the different contrast mechanisms, some lesions may not be detectable by a nonoptical modality but yet have high optical contrast. Photoacoustic tomography utilizes a short-pulsed laser beam to diffusively penetrate into tissue. Upon absorption of the light by the target, photoacoustic waves are generated and used to reconstruct, at ultrasound resolution, the optical absorption distribution that reveals optical contrast. However, the robustness of optical property quantification of targets by photoacoustic tomography is complicated because of the wide range of ultrasound transducer sensitivity, the orientation and shape of the targets relative to the ultrasound array, and the uniformity of the laser beam. We show in this paper that the relative optical absorption map provided by photoacoustic tomography can potentially guide the diffuse optical tomography to accurately reconstruct target absorption maps. [ABSTRACT FROM AUTHOR]

Ovarian cancer has the highest mortality of all gynecologic cancers, with a five-year survival rate of only 30 or less. Current imaging techniques are limited in sensitivity and specificity in detecting early stage ovarian cancer prior to its widespread metastasis. New imaging techniques that can provide functional and molecular contrasts are needed to reduce the high mortality of this disease. One such promising technique is photoacoustic imaging. We develop a 1280-element coregistered 3-D ultrasound and photoacoustic imaging system based on a 1.75-D acoustic array. Volumetric images over a scan range of 80 deg in azimuth and 20 deg in elevation can be achieved in minutes. The system has been used to image normal porcine ovarian tissue. This is an important step toward better understanding of ovarian cancer optical properties obtained with photoacoustic techniques. To the best of our knowledge, such data are not available in the literature. We present characterization measurements of the system and compare coregistered ultrasound and photoacoustic images of ovarian tissue to histological images. The results show excellent coregistration of ultrasound and photoacoustic images. Strong optical absorption from vasculature, especially highly vascularized corpora lutea and low absorption from follicles, is demonstrated. [ABSTRACT FROM AUTHOR]

We present the application of a curved array photoacoustic tomographic imaging system that can provide rapid, high-resolution photoacoustic imaging of small animal brains. The system is optimized to produce a B-mode, 90-degfield-of-view image at sub-200-mresolution at a frame rate of ∼1 framesecondwhen a 10-Hzpulse repetition rate laser is employed. By rotating samples, a complete 360-degscan can be achieved within 15 s. In previous work, two-dimensional (2-D) ex vivomouse brain cortex imaging has been reported. We report three-dimensional (3-D) small animal brain imaging obtained with the curved array system. The results are presented as a series of 2-D cross-sectional images. Besides structural imaging, the blood oxygen saturation of the animal brain cortex is also measured in vivo. In addition, the system can measure the time-resolved relative changes in blood oxygen saturation level in the small animal brain cortex. Last, ultrasonic gel coupling, instead of the previously adopted water coupling, is conveniently used in near-real-time 2-D imaging. [ABSTRACT FROM AUTHOR]

The chest wall underneath the breast tissue affects near-infrared (NIR) diffusive waves measured with reflection geometry. With the assistance of a co-registered ultrasound, the depth and the tilting angle of the chest wall can be determined and are used to model the breast as a two-layer medium. Finite element method (FEM) is suitable for modeling complex boundary conditions and is adapted to model the breast tissue and chest wall. Four parameters of bulk absorption and reduced scattering coefficients of these two layers are estimated and used for imaging reconstruction. Using a two-layer model, we have systematically investigated the effect of the chest wall on breast lesion reconstruction. Results have shown that chest-wall depth, titling angle, and difference between optical properties of two layers of lesion and reference sites affect the lesion reconstruction differently. Our analysis will be valuable and informative to researchers who are using reflectance geometry for breast imaging. The analysis can also provide guidelines for imaging operators to minimize image artifacts and to produce the best reconstruction results. [ABSTRACT FROM AUTHOR]

We develop a new tomographic imaging reconstruction algorithm for a two-layer tissue structure. Simulations and phantom experiments show more accurate reconstruction of target optical properties compared with those results obtained from a semi-infinite tissue model for layered structures. This improvement is mainly attributed to the more accurate estimation of background optical properties and more accurate estimation of weight matrix for imaging reconstruction by considering the light propagation effect in the second layer. Clinical results of breast lesions are also presented to demonstrate the utility of this new imaging algorithm. [ABSTRACT FROM AUTHOR]

Shallow lesions less than 1.5-cm deep are frequently seen in breast patients when they are scanned in reflection geometry. Two boundary conditions are compared for imaging shallow lesions, and a new probe design is introduced. A partial reflection boundary condition is suitable for imaging shallow lesions less than 1.0-cm deep; whereas an absorption boundary condition is desirable for imaging lesions more than 1.5-cm deep. Our new probe design incorporates either a partial reflection boundary or an absorption boundary based on a priori knowledge of lesion depth provided by coregistered real-time ultrasound images. An angled source is introduced to further improve the illumination of the region between 1.0- to 1.5-cm depths. Simulation, phantom, and freshly excised mouse tumor experiments demonstrate that targets located at different depths can be uniformly reconstructed. A clinical example is given to demonstrate the utility of this new approach for optimally probing lesions located at different depths. [ABSTRACT FROM AUTHOR]

We present systematic characterization of a photoacoustic imaging system optimized for rapid, high-resolution tomographic imaging of small animals. The system is based on a 128-element ultrasonic transducer array with a 5-MHz center frequency and 80% bandwidth shaped to a quarter circle of 25 mm radius. A 16-channel data-acquisition module and dedicated channel detection electronics enable capture of a 90-deg field-of-view image in less than 1 s and a complete 360-deg scan using sample rotation within 15 s. Measurements on cylindrical phantom targets demonstrate a resolution of better than 200 μm and high-sensitivity detection of 580-μm blood tubing to depths greater than 3 cm in a turbid medium with reduced scattering coefficient μs′=7.8 cm−1. The system is used to systematically investigate the effects of target size, orientation, and geometry on tomographic imaging. As a demonstration of these effects and the system imaging capabilities, we present tomographic photoacoustic images of the brain vasculature of an ex vivo mouse with varying measurement aperture. For the first time, according to our knowledge, resolution of sub-200-μm vessels with an overlying turbid medium of greater than 2 cm depth is demonstrated using only intrinsic biological contrast. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the second most common malignancy diagnosed globally. Critical gaps exist in diagnostic and surveillance imaging modalities for colorectal neoplasia. Although prior studies have demonstrated the capability of photoacoustic imaging techniques to differentiate normal from neoplastic tissue in the gastrointestinal tract, evaluation of deep tissue with a fast speed and a large field of view remains limited. To investigate the ability of photoacoustic technology to image deeper tissue, we conducted a pilot study using a real-time co-registered photoacoustic tomography (PAT) and ultrasound (US) system. A total of 23 ex vivo human colorectal tissue samples were imaged immediately after surgical resection. Co-registered photoacoustic images of malignancies showed significantly increased PAT signal compared to normal regions of the same sample. The quantitative relative total hemoglobin (rHbT) concentration computed from four optical wavelengths, the spectral features, such as the mean spectral slope, and 0.5-MHz intercept extracted from PAT and US spectral data, and image features, such as the first- and second-order statistics along with the standard deviation of the mean radon transform of PAT images, have shown statistical significance between untreated colorectal tumors and the normal tissue. Using either a logistic regression model or a support vector machine, the best set of parameters of rHbT and PAT intercept has achieved area-under-the-curve (AUC) values of 0.97 and 0.95 for both training and testing data sets, respectively, for prediction of histologically confirmed invasive carcinoma. [ABSTRACT FROM AUTHOR]

Near-infrared diffuse optical tomography (DOT) has demonstrated a great potential as an adjunct modality for differentiation of malignant and benign breast lesions and for monitoring treatment response in patients with locally advanced breast cancers. The path toward commercialization of DOT techniques depends upon the improvement of robustness and user-friendliness of this technique in hardware and software. In this study, we introduce our recently developed ultrasound-guided DOT system, which has been improved in system compactness, robustness, and user-friendliness by custom-designed electronics, automated data preprocessing, and implementation of a new two-step reconstruction algorithm. The system performance has been tested with several sets of solid and blood phantoms and the results show accuracy in reconstructed absorption coefficients as well as blood oxygen saturation. A clinical example of a breast cancer patient, who was undergoing neoadjuvant chemotherapy, is given to demonstrate the system performance. [ABSTRACT FROM AUTHOR]

Diffuse optical tomography (DOT) has demonstrated huge potential in breast cancer diagnosis and treatment monitoring. DOT image reconstruction guided by ultrasound (US) improves the diffused light localization and lesion reconstruction accuracy. However, DOT reconstruction depends on tumor geometry provided by coregistered US. Experienced operators can manually measure these lesion parameters; however, training and measurement time are needed. The wide clinical use of this technique depends on its robustness and faster imaging reconstruction capability. This article introduces a semiautomated procedure that automatically extracts lesion information from US images and incorporates it into the optical reconstruction. An adaptive thresholdbased image segmentation is used to obtain tumor boundaries. For some US images, posterior shadow can extend to the chest wall and make the detection of deeper lesion boundary difficult. This problem can be solved using a Hough transform. The proposed procedure was validated from data of 20 patients. Optical reconstruction results using the proposed procedure were compared with those reconstructed using extracted tumor information from an experienced user. Mean optical absorption obtained from manual measurement was 0.21 ± 0.06 cm−1 for malignant and 0.12 ± 0.06 cm−1 for benign cases, whereas for the proposed method it was 0.24 ± 0.08 cm−1 and 0.1 ± 0.05 cm−1, respectively. [ABSTRACT FROM AUTHOR]