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We demonstrate a novel fiber endface photoacoustic (PA) generator using infrared (IR) 144 laser dye dispersed within an ultraviolet adhesive. The generator provides a wide acoustic bandwidth in the transducer frequency range of 2–7 MHz, high thermal conversion efficiency ( > 90 % ), good PA signal controllability (well-controlled IR 144 concentration), and high feasibility (simple procedures). Through a series of experimental validations, we show that this fiber-based endface PA generator can be a useful tool for a broad range of biomedical applications such as calibrating the local absorption coefficient of biological tissue for quantitative PA tomography.

Benefitting from advantages of optical and ultrasound imaging, photoacoustic imaging (PAI) has demonstrated potentials in a wide range of medical applications. In order to facilitate clinical applications of PAI and encourage its application in low-resource settings, research on low-cost photoacoustic imaging with inexpensive optical sources has gained attention. Here, we review the advances made in photoacoustic imaging with low-cost sources. Keywords: Photoacoustic imaging, Low-cost, Laser diode, Light emitting diode, Medical imaging

Homogeneous laser illumination is critical for side view photoacoustic tomography. In this paper, two homogeneous fiber side illumination methods are proposed by utilizing diffuser coating made of ultraviolet adhesive mixed with silica microspheres. One method is the gradient side diffuser, manufactured by dip coating fiber core with consecutive diffuser sections of different silica microsphere concentrations. The other method is the partially peeled-off diffuser, generated by peeling off part of the diffuser coating section on a single concentration fiber diffuser. Both methods show homogeneous laser side illumination according to simulation and experiment, with adjustable illumination length by design.

In diffuse optical tomography (DOT) and spectroscopy (DOS) using handheld probes, tissue curvature can cause bad fiber-to-tissue contact. Understanding and minimizing image artifacts caused by these coupling errors would significantly improve DOT and DOS image quality. In this work, we utilized Monte Carlo simulations and experiments with gelatin-Intralipid phantoms to systematically study the influence of source or detector (optode) coupling errors. Optode coupling errors can increase the amplitude and decrease the phase of the measured diffuse reflectance, creating artifacts in the reconstructed absorption maps, such as hot spots on the edges. We propose an outlier removal algorithm that can correct these image artifacts, and we demonstrate its performance using simulations, phantom experiments, and breast patient data acquired with bad probe contact due to a dense or small breast. Further, we designed and implemented a new resistance-type thin-film force sensor array that provides real-time optode coupling feedback and guides the outlier removal to minimize optode coupling errors. Our approaches and study results have significant implications for reducing image artifacts arising from handheld probes, which are commonly used with mobile and wearable DOT and DOS devices.

The laser illumination delivery method is important in designing probes that achieve high imaging quality and deep tissue penetration. Here we present a novel, to the best of our knowledge, fiber diffuser tip using microspheres dispersed within an ultraviolet adhesive to scatter light. This diffuser keeps the skin surface fluence under the maximum permissible exposure, while enabling higher laser energy injection to enhance the photoacoustic (PA) signal generated from the tissue. We compare the light diffusion effects of different microsphere materials, sizes, and concentrations, and find that 10 µm silica microspheres provide the best light scattering with minimal 5% output energy loss. With the Zemax simulation and experimental validation, we show that this fiber diffuser tip is a valuable tool for endo-cavity PA imaging.

A finite element method (FEM) and experiment on phantoms were used to study the influence of breast contour mismatch and probe-tissue coupling mismatch in ultrasound-guided diffuse optical tomography for breast cancer imaging.

The development of low-cost and fast photoacoustic microscopy systems enhances the clinical applicability of photoacoustic imaging systems. To this end, we present a laser scanning laser diode-based photoacoustic microscopy system. In this system, a 905 nm, 325 W maximum output peak power pulsed laser diode with 50 ns pulsewidth is utilized as the light source. A combination of aspheric and cylindrical lenses is used for collimation of the laser diode beam. Two galvanometer scanning mirrors steer the beam across a focusing aspheric lens. The lateral resolution of the system was measured to be ∼21 μm using edge spread function estimation. No averaging was performed during data acquisition. The imaging speed is ∼370 A-lines per second. Photoacoustic microscopy images of human hairs, ex vivo mouse ear, and ex vivo porcine ovary are presented to demonstrate the feasibility and potentials of the proposed system. Keywords: Photoacoustic imaging, Diode lasers, Medical imaging, Biological imaging, Low-cost sources

Ultrasound (US) guided diffuse optical tomography has demonstrated great potential for breast cancer diagnosis, treatment monitoring, and chemotherapy response prediction. Optical measurements of four different wavelengths are used to reconstruct unknown optical absorption maps, which are then used to calculate the hemoglobin concentration distribution of the US visible lesion. Reconstructed absorption maps are prone to image artifacts from outliers in measurement data from tissue heterogeneity, bad coupling between tissue and light guides, and motion by patient or operator. We propose an automated iterative perturbation correction algorithm to reduce image artifacts based on the structural similarity index (SSIM) of absorption maps of four optical wavelengths. The initial image is estimated from the truncated pseudoinverse solution. The SSIM was calculated for each wavelength to assess its similarity with other wavelengths. An absorption map is repeatedly reconstructed and projected back into measurement space to quantify projection error. Outlier measurements with highest projection errors are iteratively removed until all wavelength images are structurally similar with SSIM values greater than a threshold. Clinical data demonstrate statistically significant improvement in image artifact reduction.

Adenocarcinoma is a type of cancers that forms in mucus-secreting glands throughout the body. For example, adenocarcinomas make up around 96% of colorectal cancers and some cervical cancers (10%). Depth of invasion for early adenocarcinoma is generally around 1-7 mm. In this report, we propose an optimal design, implementation, and evaluation of an optical fiber-based transvaginal photoacoustic/ultrasound prototype imaging probe for endo-cavity imaging of adenocarcinoma with ball-shaped fiber tips (refractive index = 1.517, radius 0.75 mm), to improve the light illumination homogeneity and increase the light delivery fluence on the central imaging area of the tissue surface. The light delivery system consists of light coupling optics, a custom-made transducer sheath, four 1-mm-core multimode optical fibers with the ball-shaped fiber tip arranged around the transducer. The probe design was optimized by simulating the light fluence distribution of the fibers with and without ball-shaped tips using a 3D model in Zemax for different design parameters such as fiber effective numerical aperture, fiber displacement from the probe base, sheath taper angle, ball-shaped fiber tips’ diameter and refractive index, etc. The laser fluence profiles were experimentally recorded through calibrated intralipid solution by camera at various imaging depths. The output power on the central imaged areas were experimentally measured by calculating the PAT signal strengths from the black threads buried inside chicken breast tissue at various depths and in-vivo photoacoustic imaging of one palmar vein proximal to the human wrist.

We present a low-cost, compact, and multispectral spatial frequency domain imaging prototype. Illumination components, including 9 LEDs (660 nm - 950 nm) placed on a custom-designed printed circuit board, linear and rotational motors, a printed sinusoidal pattern, and collimation and projection optics as well as the detection components are incorporated in a compact custom-designed 3D-printed probe. Reconstruction of absorption and reduced scattering coefficients is evaluated via imaging tissue mimicking phantoms and potentials of the probe for biological tissue imaging are evaluated via imaging human ovarian tissue ex vivo.

In this abstract a calibration method based on depth and size information provided from ultrasound images is introduced. The method utilizes the forward data simulated by finite element method to calibrate the reconstructed absorption map.

Initial feasibility of a spatial frequency domain imaging system was studied consisting of a hand held miniaturized projector and a rigid endoscope. Three wavelengths and two spatial frequencies were used for imaging. The system was calibrated using tissue mimicking phantoms. In vivo imaging was performed on five live mouse tumor models, and the absorption, scattering, hemoglobin oxygen saturation was measured. The initial promising results indicate that the spatial frequency domain imaging can a very useful tool for quantitative wide field tissue evaluation during minimally invasive image guided surgery.

We present a low-cost laser scanning photoacoustic microscopy system with a pulsed laser diode as the excitation source. The system utilizes a 905 nm pulsed laser diode with 120 ns pulse width and 1 KHz repetition rate. No averaging is performed in data acquisition, resulting in a short image acquisition time. The maximum field of view is 4.6 mm × 3.7 mm and the lateral resolution is 71 μm. Images of human hairs and mouse ear are presented to demonstrate the feasibility of the system in imaging biological tissue.

Imaging of tissue with Ultrasound-guided diffuse optical tomography (DOT) is a rising imaging technique to map hemoglobin concentrations within tissue for breast cancer detection and diagnosis. Near-infrared optical imaging received a lot of attention in research as a possible technique to be used for such purpose especially for breast tumors. Since DOT images contrast is closely related to oxygenation and deoxygenating of the hemoglobin, which is an important factor in differentiating malignant and benign tumors. One of the optical imaging modalities used is the diffused optical tomography (DOT); which probes deep scattering tissue (1-5cm) by NIR optical source-detector probe and detects NIR photons in the diffusive regime. The photons in the diffusive regime usually reach the detector without significant information about their source direction and the propagation path. Because of that, the optical reconstruction problem of the medium characteristics is ill-posed even with the tomography and Back-projection techniques. The accurate recovery of images requires an effective image reconstruction method. Here, we illustrate a method in which ultrasound images are encoded as prior for regularization of the inversion matrix. Results were evaluated using phantom experiments of low and high absorption contrasts. This method improves differentiation between the low and the high contrasts targets. Ultimately, this method could improve malignant and benign cases by increasing reconstructed absorption ratio of malignant to benign. Besides that, the phantom results show improvements in target shape as well as the spatial resolution of the DOT reconstructed images.

We present a laser diode-based photoacoustic microscopy (PAM) system with a minimized light intensity loss for ovarian tissue imaging. A 905 nm, 650 W output peak power pulsed laser diode (PLD) is utilized as the light source. The intrinsic properties and the construction of this PLD typically make it challenging to focus its beam to a small spot size with a lowloss optical system. An optical system comprising a combination of aspheric and cylindrical lenses is presented that allows a low-loss collimation and tight focusing of the light beam. The lateral resolution of this PAM system is measured to be 40 μm using edge spread function estimation. Images of black human hairs, polyethylene tubes filled with rat blood, ex vivo mouse ear and ex vivo porcine ovary are presented.

This paper reports a method of estimating an approximate closed-form solution to the light diffusion equation for any type of geometry involving Dirichlet's boundary condition with known source location. It is based on estimating the optimum locations of multiple imaginary point sources to cancel the fluence at the extrapolated boundary by constrained optimization using a genetic algorithm. The mathematical derivation of the problem to approach the optimum solution for the direct-current type of diffuse optical systems is described in detail. Our method is first applied to slab geometry and compared with a truncated series solution. After that, it is applied to hemispherical geometry and compared with Monte Carlo simulation results. The method provides a fast and sufficiently accurate fluence distribution for optical reconstruction.

Diffuse Optical Tomography reconstruction is divided into coarse mesh for background region and finer mesh for target region using NIRFAST. The results show the spatial resolution of the reconstructed images and target shape are improved.

Purpose: A new frequency-domain estimation algorithm has been developed that uses a priori information to simultaneously improve imaging quality and time resolution in photoacoustic tomography with incomplete data sets. Methods: The method involves application of a single-stage Wiener optimal filter to augment data sets by interpolation between measurement locations using relationships determined in a reference scan. The filter can be applied in real-time using FFT methods using either fixed or dynamic references and used with any imaging algorithm. The performance of the method is compared to a modified version of constrained backprojection algorithms using simulations and experimental investigations. Results: Simulations demonstrate the effectiveness of the approach for tracking dynamic photoacoustic activity for data sets with limited views (90°) or tomographic views with a reduced number of acquisition angles at any given time (≤32). Experimental data of contrast uptake and washout using a 512-element curved transducer with 8:1 electronic multiplexing with the algorithm demonstrate full two-dimensional tomographic imaging with a temporal resolution better than 130 ms. Conclusions: The estimation algorithm enables high spatial resolution, real-time imaging of dynamic physiological events or volumetric regions for photoacoustic systems employing multiplexing or scanning.

Due to the correlated nature of diffused light, the problem of reconstructing optical properties using diffuse optical tomography (DOT) is ill-posed. US-, MRI- or x-ray-guided DOT approaches can reduce the total number of parameters to be estimated and improve optical reconstruction accuracy. However, when the target volume is large, the number of parameters to estimate can exceed the number of measurements, resulting in an underdetermined imaging model. In such cases, accurate image reconstruction is difficult and regularization methods should be employed to obtain a useful solution. In this manuscript, a simple two-step reconstruction method that can produce useful image estimates in DOT is proposed and investigated. In the first step, a truncated Moore-Penrose Pseudoinverse solution is computed to obtain a preliminary estimate of the image that can be reliably determined from the measured data; subsequently, this preliminary estimate is incorporated into the design of a penalized least squares estimator that is employed to compute the final image estimate. By use of phantom data, the proposed method was demonstrated to yield more accurate images than those produced by conventional reconstruction methods. The method was also evaluated with clinical data that included 10 benign and 10 malignant cases. The capability of reconstructing high contrast malignant lesions was demonstrated to be improved by use of the proposed method.

A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer.

Near infrared (NIR) diffuse optical tomography has demonstrated great potential in the initial diagnosis of tumor and in the assessment of tumor vasculature response to neoadjuvant chemotherapy. To reconstruct the absorption map of a breast lesion, perturbation is needed which is the normalized difference between the measurements of lesion-side breast and contralateral reference breast. However, the heterogeneity in the reference breast can produce unwanted perturbation which will result in distortion of the reconstructed target absorption map. This report introduces a filtering method to overcome the reference heterogeneity. This method corrects affected source-detector measurements obtained from the reference side by using averages of unaffected measurements. As a result, the filtered perturbation has decreased the effect of heterogeneity on the reconstructed absorption maps. To evaluate the performance of this filtering method, we have compared the reconstructed results with and without the filtering algorithm using simulated heterogeneous reference with heterogeneous absorbers ranging from 0.05 to 0.20 cm -1 and heterogeneous scatters ranging from 10 to 20cm -1 . The results show that the algorithm can improve the maximum reconstructed target value up to 99% of the value with homogeneous reference. In the worst case of high absorption heterogeneity in reference breast, the maximum reconstructed value was around 30.85% of the true absorption without filtering correction and was improved to 60.4% of the true absorption value, which is 95% of the reconstructed value when using the homogeneous reference.

Optical-resolution photoacoustic microscopy (OR-PAM) has demonstrated the capability of mapping microvasculature and is promising for biomedical applications. However, the popularity of the PAM system is limited due to the use of expansive and bulky laser sources. In this paper, a compact and cost-efficient OR-PAM system with a laser diode excitation has been developed. The black threads, phantom made of polyethylene tubes filled with rat blood, and a mouse ear were imaged to evaluate the PAM and demonstrate its capability of imaging biological tissue.

We have estimated the micro-mechanical properties of ovarian tissue using phase-sensitive swept source optical coherence tomography. Ovary samples were mechanically excited by periodical vibration of an ultrasound transducer. The displacement and strain of the tissues were calculated during loading. Significant difference in strain was observed between the normal and malignant ovary groups, which indicates much softer and heterogeneous tissue structure for malignant ovaries. The initial results show that the phase sensitive swept source optical coherence elastography (OCE) can be an effective tool for characterization of stiffness and other micro-mechanical properties of normal and malignant ovarian tissue.

A high-throughput ultrasound/photoacoustic probe for delivering high contrast and signal-to-noise ratio images was designed, constructed, and tested. The probe consists of a transvaginal ultrasound array integrated with four 1mm-core optical fibers and a sheath. The sheath encases transducer and is lined with highly reflecting aluminum for high intensity light output and uniformity while at the same time remaining below the maximum permissible exposure (MPE) recommended by the American National Standards Institute (ANSI). The probe design was optimized by simulating the light fluence distribution in Zemax. The performance of the probe was evaluated by experimental measurements of the fluence and real-time imaging of polyethylene-tubing filled with blood. These results suggest that our probe has great potential for in vivo imaging and characterization of ovarian cancer.

In this paper, a cover layer is introduced to reduce the artifact in small animal experiments when monitoring the exogenous contrast agent, indocyanine green, uptake and washout using diffuse optical tomography and photoacoustic tomography.

A novel illumination setup for compact pulse-echo/photoacoustic transvaginal probe is presented. Hemoglobin oxygen-saturation of mouse tumor was imaged in vivo. The results suggest that it has great potential for in vivo ovarian cancer imaging.

LEDs are also available in near infrared. In this study, we introduce a continuous-wave diffuse optical tomography system using 8 groups of LEDs of four wavelengths. Phantom experiments showed its potential to image deep targets.

Using a fluorescence imager we studied the biodistribution of a new hypoxia probe, piperazine-2-nitroimidazole-ICG in murine tumor models. It showed much higher fluorescence intensity and tumor retention in comparison with its predecessors

Techniques for the correction of ultrasonic wavefront distortion are compared using measured pulse transmission through human breast specimens. The measured data were obtained by recording the pulse signals on each element of a linear array that was moved in elevation to synthesize a two-dimensional aperture. The one-way point spread functions were reconstructed using matched filtering technique, phase conjugation, time-delay compensation, and backpropagation followed by phase conjugation, each with and without amplitude compression. Two measures of performance were compared, the mainlobe diffraction shape and the ratio of the energy outside the mainlobe to the energy inside the mainlobe. Matched filtering, which compensates the phase distortion but also increases the variation in the modulus, performs more poorly than other techniques with respect to both measures. Phase conjugation and time-delay compensation, which leave the magnitude of the wavefront unchanged, have similar beamwidths but phase conjugation is consistently superior with respect to energy ratio. The backpropagation method, which models wavefront distortion using a phase screen at a computed position between the source and aperture, is shown to perform better. The use of a novel amplitude compression that approaches inverse filtering improves the performance of the compensation techniques significantly. This is because inverse filtering optimizes image fidelity, in contrast, for example, to matched filtering, which optimizes SNR. With the amplitude compression method, the results of the one-way experiments show that the mainlobe shape can be recovered down to -30 dB.

To overcome the intensive light scattering in biological tissue, diffuse optical tomography (DOT) in the near-infrared range for breast lesion detection is usually combined with other imaging modalities, such as ultrasound, x-ray, and magnetic resonance imaging, to provide guidance. However, these guiding imaging modalities may depend on different contrast mechanisms compared to the optical contrast in the DOT. As a result, they cannot provide reliable guidance for DOT because some lesions may not be detectable by a nonoptical modality but may have a high optical contrast. An imaging modality that relies on optical contrast to provide guidance is desirable for DOT. We present a system that combines a frequency-domain DOT and real-time photoacoustic tomography (PAT) systems to detect and characterize deeply seated targets embedded in a turbid medium. To further improve the contrast, the exogenous contrast agent, indocyanine green (ICG), is used. Our experimental results show that the combined system can detect a tumor-mimicking phantom, which is immersed in intralipid solution with the concentrations ranging from 100 to 10 μM and with the dimensions of 0.8 cm×0.8 cm×0.6 cm , up to 2.5 cm in depth. Mice experiments also confirmed that the combined system can detect tumors and monitor the ICG uptake and washout in the tumor region. This method can potentially improve the accuracy to detect small breast lesions as well as lesions that are sensitive to background tissue changes, such as the lesions located just above the chest wall.

A photoacoustic contrast agent that is based on bis-carboxylic acid derivative of indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT) is presented. 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 a mouse tumor model is demonstrated in vivo by our custom-built photoacoustic imaging system. The summation of the photoacoustic tomography (PAT) beam envelope, referred to as the "PAT summation," is used to demonstrate the postinjection light absorption of tumor areas in ICG- and ICG/SWCNT-injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 min peak response time with reference to the preinjection PAT level, while ICG/SWCNT provides 128% enhancement at 80 min and even higher enhancement of 196% at the end point of experiments (120 min on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery, which was 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 to achieve clean tumor margins to improve surgical resection of tumors.

Chen Xu, Patrick D. Kumavor, Yan Xu, and Quing Zhu Electrical and Computer Engineering Department, Uni versity of Connecticut, 371 Fairfield Road, Unit 2157, Storrs, CT 06269-215 7 Tel: (860) 486-3344; Fax: (860) 486-2447; E-mail: cxu@engr.uconn.edu Abstract: To overcome the intensive light scattering in the b iological tissue, diffuse optical tomography (DOT) in the near infrared range for breast lesion detection usually is combined with other imaging modalities such as ultrasound, X-ray, and M RI, to provide guidance. However, the guided imaging modalities may depend on different c ontrast mechanics compared to the optical contrast in the DOT. As a result, they can’t provid e reliable guidance for diffuse optical tomography because some lesions may not be detectab le by a non-optical modality but yet have high optical contrast. An imaging modality which ca n provide the guidance from optical contrast is desirable for DOT. In this paper, we pr esent a system that combines diffuse optical tomography and photoacoustic tomography (PAT), to d etect and characterize the deeply-seated targets embedded in a turbid medium. Photoacoustic tomography utilizes a short-pulsed laser beam to penetrate into tissue diffusively. Upon absorption of the light by the target, photoacoustic waves are generated and used to recon struct, at ultrasound resolution, the optical absorption distribution that reveals optical contra st. The combined system used in the experiment combines a 64-channel photoacoustic syst em with a frequency-domain diffused optical system. To further improve the contrast, th e exogenous contrast agent, indocyanine green (ICG) is used. Our experiment results show th at the combined system can detect a tumor-mimicking phantom up to 2.5 cm in depth and 10 µM i n concentration. Mice experiments also confirmed that the combined system can detect the t umor region and monitor the ICG uptake and washout in the tumor region. This method can po tentially improve the accuracy to detect the small breast lesions or any lesions which are s ensitive to the reference change, such as the lesions located on the chest wall. Keywords: Diffuse optical tomography , Photoacoustic tomography, absorption coefficient, exogenous contrast agent 1. Introduction Diffuse optical tomography (DOT) in the near infrar ed spectrum (NIR) provides a unique approach for functional diagnostic imaging, which can detect endogenous absorbers, such as the tumor hemoglobin concentration and oxygen saturatio n.

We characterized ovarian tissue by using polarization-sensitive optical coherence tomography (PS-OCT). Phase retardation changing rate along with optical scattering coefficient and phase retardation were extracted from 33 ex vivo human ovaries from 18 patients. By using phase retardation changing rate as a classifier, we could achieve 71% sensitivity and 100% specificity. Combining those three parameters together, we could achieve 100% sensitivity and 100% specificity. These initial results showed that the quantitative analysis of PS-OCT could be a useful tool to characterize normal and malignant ovarian tissue.

Angle-resolved optical scattering properties of ovarian tissue on different optical coherence tomography (OCT) imaging planes were quantitatively measured by fitting the compounded OCT A-lines into a single scattering model. Higher cross correlation value of angle-resolved scattering coefficients between different OCT imaging planes was found in normal ovaries than was present in malignant ovaries. The mean cross correlation coefficient (MCC) was introduced in this pilot study to characterize and differentiate normal and malignant ovaries. A specificity of 100% and a sensitivity of 100% were achieved by setting MCC threshold at 0.6 in the limited sample population. The collagen properties such as content, structure and directivity were found to be different within OCT imaging penetration depth between normal and malignant ovarian tissue. The homogeneous three-dimensional collagen fiber network observed in the normal ovary effectively explains the stronger cross correlation of angle-resolved scattering properties on different imaging planes while the heterogeneity observed in the malignant ovary suggests a weaker correlation.

Ultrasound-guided diffuse optical tomography (DOT) is a promising method for characterizing malignant and benign lesions in the female breast. We introduce a new two-step algorithm for DOT inversion in which the optical parameters are estimated with the global optimization method, genetic algorithm. The estimation result is applied as an initial guess to the conjugate gradient (CG) optimization method to obtain the absorption and scattering distributions simultaneously. Simulations and phantom experiments have shown that the maximum absorption and reduced scattering coefficients are reconstructed with less than 10% and 25% errors, respectively. This is in contrast with the CG method alone, which generates about 20% error for the absorption coefficient and does not accurately recover the scattering distribution. A new measure of scattering contrast has been introduced to characterize benign and malignant breast lesions. The results of 16 clinical cases reconstructed with the two-step method demonstrates that, on average, the absorption coefficient and scattering contrast of malignant lesions are about 1.8 and 3.32 times higher than the benign cases, respectively.

Traditional Photoacoustic tomography provides the distribution of absorbed optical energy densities which are the products of the optical absorption coefficients and fluences. However, the absorption coefficient is the only functional parameter that is related to disease diagnosis, such as cancer. In this paper, we report the experimental investigation of an improved fitting procedure which can quantitatively characterize optical absorption coefficients of multiple targets. The original fitting procedure was proposed by us and used for a single target. 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 target information from the PAT images and the background information from diffuse optical measurements (DOM), the fitting method minimizes the photoacoustic measurements and forward model data and recovers the target absorption coefficient quantitatively. The fitting errors in the absorption coefficients can reach 20% to 100% if the original fitting procedure is directly used on multiple targets. In our improved fitting method, the ratio between the photoacoustic intensities is introduced and served as extra input to the fitting procedure. As a result, the total number of unknown parameters is reduced and fitting accuracy is improved. The hybrid system used in the experiment combines a 64-channel photoacoustic system with a frequency-domain diffused optical system. The experiment was performed in the reflection geometry suitable for breast imaging. Phantom experiments include the combination of high contrast and low contrast targets with absorption coefficients ranging from 0.07 to 0.28 cm -1 and with different spatial separations. The phantoms were inserted into a chicken breast tissue. The fitting errors of multiple targets were reduced to less than 20% for both high and low contrast targets. These results illustrate the potential application of this quantitative DOM-assisted photoacoustic fitting procedure to image and diagnose breast cancer having multiple and complex tumor distribution.

Optical scattering coefficient from ex-vivo unfixed normal and malignant ovarian tissue was quantitatively extracted by fitting optical coherence tomography (OCT) A-line signals to a single scattering model. 1097 average A-line measurements at a wavelength of 1310nm were performed at 108 sites obtained from 18 ovaries. The average scattering coefficient obtained from normal group consisted of 833 measurements from 88 sites was 2.41 mm-1 (±0.59), while the average coefficient obtained from malignant group consisted of 264 measurements from 20 sites was 1.55 mm-1 (±0.46). Using a threshold of 2 mm-1 for each ovary, a sensitivity of 100% and a specificity of 100% were achieved. The amount of collagen within OCT imaging depth was analyzed from the tissue histological section stained with Sirius Red. The average collagen area fraction (CAF) obtained from normal group was 48.4% (±12.3%), while the average CAF obtained from malignant group was 11.4% (±4.7%). Statistical significance of the collagen content was found between the two groups (p < 0.001). The preliminary data demonstrated that quantitative extraction of optical scattering coefficient from OCT images could be a potential powerful method for ovarian cancer detection and diagnosis.

High-energy and short-duration outputs from lasers are desirable to improve the photoacoustic image quality when imaging deeply-seated lesions. In many clinical applications, optical fibers are used to couple the high-energy laser pulse to tissue. These high peak intensity pulses can damage an optical fiber input face if the damage threshold is exceeded. It is necessary to reduce the peak intensity to minimize the fiber damage and to delivery sufficient light for imaging. In this paper, a laser-pulse-stretching technique is introduced to reduce the peak intensity of laser pulses. To demonstrate the technique, an initial 17ns pulse was stretched to 37ns by a ring-cavity laser-pulse-stretching system, and the laser peak power reduced to 42%. The stretched pulse increased the fiber damage threshold by 1.5-fold. Three ultrasound transducers centered at 1.3MHz, 3.5MHz, 6MHz frequencies were simulated and the results showed that the photoacoustic signal of 0.5mm-diameter target obtained with 37ns pulse was about 98%, 91% and 80% respectively using the same energy as with the 17ns pulse. Simulations were validated using a broadband hydrophone. Quantitative comparisons of photoacoustic images obtained with three corresponding ultrasound transducers showed that the image quality was not affected by stretching the pulse.

Optical Coherence Tomography is an imaging technique characterized by high spatial resolution and noninvasive subsurface detection1. OCT started as an interferometric technique utilizing the newly emerged low coherence or partial coherence light source and time-domain gating to achieve the depth resolution. With additional lateral scans, 2-D or 3D tomographic images can be obtained. The instrumental development of OCT has experienced several phases. It goes from free space architectures to fiber-based systems, from intensity-based structural imaging to multiple functional extensions of polarization sensitive, Doppler, and spectroscopic OCT. Since the beginning of this century, a Fourier domain OCT infrastructure has been introduced that resulted in a new revolution in OCT technology2, 3. Not only was the new technology bringing a hundred times more sensitivity, it was also technically more convenient for the design of a higher speed scanning system structures. Nowadays, FD-OCT are implemented with either a spectrometer or a tunable laser design. Modern OCT is more accurately defined as a broadband rather than lowcoherence interferometric technology. And the outcome is a true 3D imaging modality4-9 with high data speed for real-time clinical diagnosis, free from the degradation of motion artifacts.

We systemically evaluated the sensitivity of the hypoxia targeted 2-nitroimidazole-ICG conjugate using piperazine linker in in-vivo tumor models, which showed hypoxia can be targeted with twice higher signal strength than that of untargeted ICG.

We report the existence of polarization memory effect (PME) in optical coherence tomography and investigate its potential applications in dental imaging. We performed the study in three steps. First, microsphere scattering phantoms of different sizes were imaged in order to validate experimental results with PME theory. Both linearly and circularly polarized light were used to probe the samples. Second, healthy tooth samples were scanned and polarization memory effect was identified in dentin. In this step, specific verification and signal processing were performed to rule out possible image interpretation by birefringence effect. Third, we evaluated dentin demineralization with PME. Results show polarization memory can be useful to characterize this dynamic mineralization process for early caries detection and rehabilitation. C 2011 Society of Photo-Optical Instrumentation Engineers

Optical quantification of large lesions imaged with diffuse optical tomography in reflection geometry is depth dependence due to the exponential decay of photon density waves. We introduce a depth-correction method that incorporates the target depth information provided by coregistered ultrasound. It is based on balancing the weight matrix, using the maximum singular values of the target layers in depth without changing the forward model. The performance of the method is evaluated using phantom targets and 10 clinical cases of larger malignant and benign lesions. The results for the homogenous targets demonstrate that the location error of the reconstructed maximum absorption coefficient is reduced to the range of the reconstruction mesh size for phantom targets. Furthermore, the uniformity of absorption distribution inside the lesions improve about two times and the median of the absorption increases from 60 to 85% of its maximum compared to no depth correction. In addition, nonhomogenous phantoms are characterized more accurately. Clinical examples show a similar trend as the phantom results and demonstrate the utility of the correction method for improving lesion quantification.

In this report, we present a novel 3D photoacoustic computed tomography (PACT) system for small-animal whole-body imaging. The PACT system, based on a 512-element full-ring transducer array, received photoacoustic signals primarily from a 2-mm-thick slice. The light was generated by a pulse laser, and can either illuminate from the top or be reshaped to illuminate the sample from the side, using a conical lens and an optical condenser. The PACT system was capable of acquiring an in-plane image in 1.6 s; by scanning the sample in the elevational direction, a 3D tomographic image could be constructed. We tested the system by imaging a cylindrical phantom made of human hairs immersed in a scattering medium. The reconstructed image achieved an in-plane resolution of 0.1 mm and an elevational resolution of 1 mm. After deconvolution in the elevational direction, the 3D image was found to match well with the phantom. The system was also used to image a baby mouse in situ; the spinal cord and ribs can be seen easily in the reconstructed image. Our results demonstrate that the PACT system has the potential to be used for fast small-animal whole-body tomographic imaging.

Due to the exponential decay of the photon density wave, the accuracy of quantifying deeper portion of the large lesions by diffuse optical tomography in reflection geometry is much lower than that of the top portion. In this study, we introduce a modified depth correction method that incorporates the target depth information provided by co-registered ultrasound. Phantom experiments and clinical example will be presented to demonstrate the utility of the method in improving light quantification of large lesions.

We present a multi-wavelength DC system using Light Emitting Diode (LED) sources of four wavelengths in the near infrared range. These LEDs are commercially available, much cheaper than laser diodes, and have adequate power to probe deeply seated lesions. In our system, 8 groups of LEDs of four wavelengths were deployed on a hand-held probe and 10 PMT detectors were fiber coupled to the probe. A co-registered ultrasound (US) array located in the middle of the probe provided lesion location and morphology, which were used for assisting near infrared imaging reconstruction. Experiments evaluated the performance of the LED based DC system using phantom targets.

Photoacoustic imaging and optical coherence tomography are two emerging imaging modalities which provide complementary optical absorption and scattering contrasts for biological tissues. While photoacoustic imaging provides tissue vasculature information, optical coherence tomography offers micron-scale morphological imaging with penetration depths of 1~3 mms. Pulse-echo ultrasound is readily available from photoacoustic system and it provides tissue structure information at deeper depths with resolutions scalable with the transducer frequency. We present a prototype endoscope that consists of a ball lensed optical coherence tomography probe, a right-angled multimode fiber for delivering the laser beam for photoacoustic imaging, and a high frequency ultrasound transducer of 35 MHz center frequency. The overall diameter is 5mms. Porcine ovaries were imaged ex vivo to demonstrate the capability of this new combined endoscopy. The microvascular and high resolution structural images at subsurface and deeper tissue range demonstrate the synergy of the combined endoscopy over each modality alone.

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.

A fiber optical coherence tomography (OCT) probe is used for three dimensional dental imaging. The probe has a lightweight miniaturized design with a size of a pen to facilitate clinic in vivo diagnostics. The probe is interfaced with a swept-source / Fourier domain optical coherence tomography at 20K axial scanning rate. The tooth samples were scanned from occlusal, buccal, lingual, mesial, and distal orientations. Three dimensional imaging covers tooth surface area up to 10 mm x 10 mm with a depth about 5 mm, where a majority of caries affection occurs. OCT image provides better resolution and contrast compared to gold standard dental radiography (X-ray). In particular, the technology is well suited for occlusal caries detection. This is complementary to X-ray as occlusal caries affection is difficult to be detected due to the X-ray projectile scan geometry. The 3D topology of occlusal surface as well as the dentin-enamel junction (DEJ) surface inside the tooth can be visualized. The lesion area appears with much stronger back scattering signal intensity.

For part I, see ibid., vol.40, no.6, p.747-753 (1993). In vivo measurements of the rise of the sidelobe level in a single-source image obtained through the female breast as a function of the distortion of the wavefront amplitude are described. The measured sidelobe levels are the average sidelobe floor (ASF) and the peak sidelobe level (PSL). The ASF is shown to be proportional to the variance of the modulus of the wavefront normalized to the square of its mean value, with a proportionality constant close to the value predicted by theory. The PSL similarly increases linearly. The average ratio of PSL to ASF is 5 (7 dB). >