D. Piras

Visualizing breast cancer using the Twente photoacoustic mammoscope: what do we learn from twelve new patient measurements?

We acquired images of breast malignancies using the Twente photoacoustic mammoscope (PAM), to obtain more information about the clinical feasibility and limitations of photoacoustic mammography. Results were compared with conventional imaging and histopathology. Ten technically acceptable measurements on patients with malignancies and two measurements on patients with cysts were performed. In the reconstructed volumes of all ten malignant lesions, a confined region with high contrast with respect to the background could be seen. In all malignant cases, the PA contrast of the abnormality was higher than the contrast on x-ray mammography. The PA contrast appeared to be independent of the mammographically estimated breast density and was absent in the case of cysts. Technological improvements to the instrument and further studies on less suspicious lesions are planned to further investigate the potential of PAM.

Photoacoustic Imaging of the Breast Using the Twente Photoacoustic Mammoscope: Present Status and Future Perspectives

The Twente photoacoustic mammoscope (PAM) uses pulsed light at 1064 nm to excite PA signals. Detection is using a planar 590-element ultrasound (US) sensor matrix. Image reconstruction uses a delay-and-sum beamforming algorithm. Measurements are performed in the forward mode, with mild compression of the breast against the detector with US coupling gel. We consolidate the most important specifications of the system. Furthermore, we discuss in detail the results of imaging two cases of infiltrating ductal carcinoma and one case of a cyst. We critically discuss the features of the present embodiment and present plans for its improvement.

Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology

Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images, and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies, and first insights were gained into the relationship with tumor vascularity.

Photoacoustic needle: minimally invasive guidance to biopsy

Abstract. We introduce a needle probe based on photoacoustics (PA) to extend the scope of optical needle methods in guiding biopsies. Pulsed light is coupled to an optical fiber in a needle to be inserted in tissue, and PA signals are detected using an ultrasound imager used for needle guidance. This PA needle samples large volumes and possesses an imaging component so that sites forward and off-axis of the fiber are surveyed. This allows navigation of those regions for optical characterization and direct biopsy in a subsequent step. The concept is explored on simple phantoms and biological specimens.

An optimized ultrasound detector for photoacoustic breast tomography

PURPOSE Photoacoustic imaging has proven to be able to detect vascularization-driven optical absorption contrast associated with tumors. In order to detect breast tumors located a few centimeter deep in tissue, a sensitive ultrasound detector is of crucial importance for photoacoustic mammography. Further, because the expected photoacoustic frequency bandwidth (a few MHz to tens of kHz) is inversely proportional to the dimensions of light absorbing structures (0.5-10+ mm), proper choices of materials and their geometries and proper considerations in design have to be made to implement optimal photoacoustic detectors. In this study, we design and evaluate a specialized ultrasound detector for photoacoustic mammography. METHODS Based on the required detector sensitivity and its frequency response, a selection of active material and matching layers and their geometries is made leading to functional detector models. By iteration between simulation of detector performances, fabrication and experimental characterization of functional models an optimized implementation is made and evaluated. For computer simulation, we use 1D Krimholtz-Leedom-Matthaei and 3D finite-element based models. RESULTS The experimental results of the designed first and second functional detectors matched with the simulations. In subsequent bare piezoelectric samples the effect of lateral resonances was addressed and their influence minimized by subdicing the samples. Consequently, using simulations, a final optimized detector was designed, with a center frequency of 1 MHz and a -6 dB bandwidth of 0.4-1.25 MHz (fractional bandwidth of ~80%). The minimum detectable pressure was measured to be 0.5 Pa. CONCLUSIONS A single-element, large-aperture, sensitive, and broadband detector is designed and developed for photoacoustic tomography of the breast. The detector should be capable of detecting vascularized tumors with 1-2 mm resolution. The minimum detectable pressure is 0.5 Pa, which will facilitate deeper imaging compared to the current systems. Further improvements by proper electrical grounding and shielding and implementation of this design into an arrayed detector will pave the way for clinical applications of photoacoustic mammography.

Poly(vinyl alcohol) gels as photoacoustic breast phantoms revisited.

A popular phantom in photoacoustic imaging is poly(vinyl alcohol) (PVA) hydrogel fabricated by freezing and thawing (F-T) aqueous solutions of PVA. The material possesses acoustic and optical properties similar to those of tissue. Earlier work characterized PVA gels in small test specimens where temperature distributions during F-T are relatively homogeneous. In this work, in breast-sized samples we observed substantial temperature differences between the shallow regions and the interior during the F-T procedure. We investigated whether spatial variations were also present in the acoustic and optical properties. The speed of sound, acoustic attenuation, and optical reduced scattering coefficients were measured on specimens sampled at various locations in a large phantom. In general, the properties matched values quoted for breast tissue. But while acoustic properties were relatively homogeneous, the reduced scattering was substantially different at the surface compared with the interior. We correlated these variations with gel microstructure inspected using scanning electron microscopy. Interestingly, the phantoms reduced scattering spatial distribution matches the optical properties of the standard two-layer breast model used in x ray dosimetry. We conclude that large PVA samples prepared using the standard recipe make excellent breast tissue phantoms.

Design and evaluation of a laboratory prototype system for 3D photoacoustic full breast tomography

Photoacoustic imaging can visualize vascularization-driven optical absorption contrast with great potential for breast cancer detection and diagnosis. State-of-the-art photoacoustic breast imaging systems are promising but are limited either by only a 2D imaging capability or by an insufficient imaging field-of-view (FOV). We present a laboratory prototype system designed for 3D photoacoustic full breast tomography, and comprehensively characterize it and evaluate its performance in imaging phantoms. The heart of the system is an ultrasound detector array specifically developed for breast imaging and optimized for high sensitivity. Each detector element has an acoustic lens to enlarge the acceptance angle of the large surface area detector elements to ensure a wide system FOV. We characterized the ultrasound detector array performance in terms of frequency response, directional sensitivity, minimum detectable pressure and inter-element electrical and mechanical cross-talk. Further we evaluated the system performance of the laboratory prototype imager using well-defined breast mimicking phantoms. The system possesses a 2 mm XY plane resolution and a 6 mm vertical resolution. A vasculature mimicking object was successfully visualized down to a depth of 40 mm in the breast phantom. Further, tumor mimicking spherical objects with 5 and 10 mm diameter at 20 mm and 40 mm depths are recovered, indicating high system sensitivity. The system has a 170 × 170 × 170 mm(3) FOV, which is well suited for full breast imaging. Various recommendations are provided for performance improvement and to guide this laboratory prototype to a clinical version in future.

A new acoustic lens material for large area detectors in photoacoustic breast tomography.

Objectives We introduce a new acoustic lens material for photoacoustic tomography (PAT) to improve lateral resolution while possessing excellent acoustic acoustic impedance matching with tissue to minimize lens induced image artifacts. Background A large surface area detector due to its high sensitivity is preferable to detect weak signals in photoacoustic mammography. The lateral resolution is then limited by the narrow acceptance angle of such detectors. Acoustic lenses made of acrylic plastic (PMMA) have been used to enlarge the acceptance angle of such detectors and improve lateral resolution. However, such PMMA lenses introduce image artifacts due to internal reflections of ultrasound within the lenses, the result of acoustic impedance mismatch with the coupling medium or tissue. Methods A new lens is proposed based on the 2-component resin Stycast 1090SI. We characterized the acoustic properties of the proposed lens material in comparison with commonly used PMMA, inspecting the speed of sound, acoustic attenuation and density. We fabricated acoustic lenses based on the new material and PMMA, and studied the effect of the acoustic lenses on detector performance comparing finite element (FEM) simulations and measurements of directional sensitivity, pulse-echo response and frequency response. We further investigated the effect of using the acoustic lenses on the image quality of a photoacoustic breast tomography system using k-Wave simulations and experiments. Results Our acoustic characterization shows that Stycast 1090SI has tissue-like acoustic impedance, high speed of sound and low acoustic attenuation. These acoustic properties ensure an excellent acoustic lens material to minimize the acoustic insertion loss. Both acoustic lenses show significant enlargement of detector acceptance angle and lateral resolution improvement from modeling and experiments. However, the image artifacts induced by the presence of an acoustic lens are reduced using the proposed lens compared to PMMA lens, due to the minimization of internal reflections. Conclusions The proposed Stycast 1090SI acoustic lens improves the lateral resolution of photoacoustic tomography systems while not suffering from internal reflection-induced image artifacts compared a lens made of PMMA.

Appearance of breast cysts in planar geometry photoacoustic mammography using 1064-nm excitation

Abstract. In the search for improved imaging modalities for detection and diagnosis of breast cancer, a high negative prediction value is also important. Photoacoustic (optoacoustic) imaging is a relatively new technique that has high potential for visualizing breast malignancies, but little is known about the photoacoustic appearance of benign lesions. In this work, we investigate the visibility of benign breast cysts in forward-mode photoacoustic mammography using 1064-nm light, as currently applied in the Twente photoacoustic mammoscope. Results from (Monte Carlo and k-wave) simulations and phantom measurements were used to interpret results from patient measurements. There was a strong agreement among the results from simulations, phantom, and patient measurements. Depending on the absorption contrast between cyst and breast tissue, cysts were visible as either one or two confined high-contrast areas representing the front and the back of the cyst, respectively. This edge enhancement is most likely the consequence of the local sudden change in the absorbed energy density and Grüneisen coefficients. Although the current forward-mode single-wavelength photoacoustic mammoscope cannot always unambiguously discriminate cysts from malignancies, this study reveals specific features of cysts compared to malignancies, which can be exploited for discrimination of the two abnormalities in future modifications of the imager.

Photoacoustic imaging of breast tumor vascularization: a comparison with MRI and histopathology

Breast cancer is the most common form of cancer and the leading cause of cancer death among females. Early diagnosis improves the survival chances for the disease and that is why there is an ongoing search for improved methods for visualizing breast cancer. One of the hallmarks of breast cancer is the increase in tumor vascularization that is associated with angiogenesis: a crucial factor for survival of malignancies. Photoacoustic imaging can visualize the malignancyassociated increased hemoglobin concentration with optical contrast and ultrasound resolution, without the use of ionizing radiation or contrast agents and is therefore theoretically an ideal method for breast imaging. Previous clinical studies using the Twente Photoacoustic Mammoscope (PAM), which works in forward mode using a single wavelength (1064 nm), showed that malignancies can indeed be identified in the photoacoustic imaging volume as high contrast areas. However, the specific appearance of the malignancies led to questions about the contrast mechanism in relation to tumor vascularization. In this study, the photoacoustic lesion appearance obtained with an updated version of PAM is compared with the lesion appearance on Magnetic Resonance Imaging (MRI), both in general (19 patients) and on an individual basis (7 patients). Further, in 3 patients an extended histopathology protocol is being performed in which malignancies are stained for vascularity using an endothelial antibody: CD31. The correspondence between PAM and MRI and between PAM and histopathology makes it likely that the high photoacoustic contrast at 1064 nm is indeed largely the consequence of the increased tumor vascularization.