Wenfeng Xia

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.

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.

Performance characteristics of an interventional multispectral photoacoustic imaging system for guiding minimally invasive procedures

Abstract. Precise device guidance is important for interventional procedures in many different clinical fields including fetal medicine, regional anesthesia, interventional pain management, and interventional oncology. While ultrasound is widely used in clinical practice for real-time guidance, the image contrast that it provides can be insufficient for visualizing tissue structures such as blood vessels, nerves, and tumors. This study was centered on the development of a photoacoustic imaging system for interventional procedures that delivered excitation light in the ranges of 750 to 900 nm and 1150 to 1300 nm, with an optical fiber positioned in a needle cannula. Coregistered B-mode ultrasound images were obtained. The system, which was based on a commercial ultrasound imaging scanner, has an axial resolution in the vicinity of 100  μm and a submillimeter, depth-dependent lateral resolution. Using a tissue phantom and 800 nm excitation light, a simulated blood vessel could be visualized at a maximum distance of 15 mm from the needle tip. Spectroscopic contrast for hemoglobin and lipids was observed with ex vivo tissue samples, with photoacoustic signal maxima consistent with the respective optical absorption spectra. The potential for further optimization of the system is discussed.

Interventional multispectral photoacoustic imaging with a clinical ultrasound probe for discriminating nerves and tendons: an ex vivo pilot study

Accurate and efficient identification of nerves is an essential component of peripheral nerve blocks. While ultrasound (US) imaging is increasingly used as a guidance modality, it often provides insufficient contrast for identifying nerves from surrounding tissues such as tendons. Electrical nerve stimulators can be used in conjunction with US imaging for discriminating nerves from surrounding tissues, but they are insufficient to reliably prevent neural punctures, so that alternative methods are highly desirable. In this study, an interventional multispectral photoacoustic (PA) imaging system was used to directly compare the signal amplitudes and spectra acquired from nerves and tendons ex vivo, for the first time. The results indicate that the system can provide significantly higher image contrast for discriminating nerves and tendons than that provided by US imaging. As such, photoacoustic imaging could be valuable as an adjunct to US for guiding peripheral nerve blocks.

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.

In-plane ultrasonic needle tracking using a fiber-optic hydrophone

PURPOSE Accurate and efficient guidance of needles to procedural targets is critically important during percutaneous interventional procedures. Ultrasound imaging is widely used for real-time image guidance in a variety of clinical contexts, but with this modality, uncertainties about the location of the needle tip within the image plane lead to significant complications. Whilst several methods have been proposed to improve the visibility of the needle, achieving accuracy and compatibility with current clinical practice is an ongoing challenge. In this paper, the authors present a method for directly visualizing the needle tip using an integrated fiber-optic ultrasound receiver in conjunction with the imaging probe used to acquire B-mode ultrasound images. METHODS Needle visualization and ultrasound imaging were performed with a clinical ultrasound imaging system. A miniature fiber-optic ultrasound hydrophone was integrated into a 20 gauge injection needle tip to receive transmissions from individual transducer elements of the ultrasound imaging probe. The received signals were reconstructed to create an image of the needle tip. Ultrasound B-mode imaging was interleaved with needle tip imaging. A first set of measurements was acquired in water and tissue ex vivo with a wide range of insertion angles (15°-68°) to study the accuracy and sensitivity of the tracking method. A second set was acquired in an in vivo swine model, with needle insertions to the brachial plexus. A third set was acquired in an in vivo ovine model for fetal interventions, with insertions to different locations within the uterine cavity. Two linear ultrasound imaging probes were used: a 14-5 MHz probe for the first and second sets, and a 9-4 MHz probe for the third. RESULTS During insertions in tissue ex vivo and in vivo, the imaged needle tip had submillimeter axial and lateral dimensions. The signal-to-noise (SNR) of the needle tip was found to depend on the insertion angle. With the needle tip in water, the SNR of the needle tip varied with insertion angle, attaining values of 284 at 27° and 501 at 68°. In swine tissue ex vivo, the SNR decreased from 80 at 15° to 16 at 61°. In swine tissue in vivo, the SNR varied with depth, from 200 at 17.5 mm to 48 at 26 mm, with a constant insertion angle of 40°. In ovine tissue in vivo, within the uterine cavity, the SNR varied from 46.4 at 25 mm depth to 18.4 at 32 mm depth, with insertion angles in the range of 26°-65°. CONCLUSIONS A fiber-optic ultrasound receiver integrated into the needle cannula in combination with single-element transmissions from the imaging probe allows for direct visualization of the needle tip within the ultrasound imaging plane. Visualization of the needle tip was achieved at depths and insertion angles that are encountered during nerve blocks and fetal interventions. The method presented in this paper has strong potential to improve the safety and efficiency of ultrasound-guided needle insertions.

Interventional Photoacoustic Imaging of the Human Placenta with Ultrasonic Tracking for Minimally Invasive Fetal Surgeries

Image guidance plays a central role in minimally invasive fetal surgery such as photocoagulation of inter-twin placental anastomosing vessels to treat twin-to-twin transfusion syndrome (TTTS). Fetoscopic guidance provides insufficient sensitivity for imaging the vasculature that lies beneath the fetal placental surface due to strong light scattering in biological tissues. Incomplete photocoagulation of anastamoses is associated with postoperative complications and higher perinatal mortality. In this study, we investigated the use of multi-spectral photoacoustic (PA) imaging for better visualization of the placental vasculature. Excitation light was delivered with an optical fiber with dimensions that are compatible with the working channel of a fetoscope. Imaging was performed on an ex vivo normal term human placenta collected at Caesarean section birth. The photoacoustically-generated ultrasound signals were received by an external clinical linear array ultrasound imaging probe. A vein under illumination on the fetal placenta surface was visualized with PA imaging, and good correspondence was obtained between the measured PA spectrum and the optical absorption spectrum of deoxygenated blood. The delivery fiber had an attached fiber optic ultrasound sensor positioned directly adjacent to it, so that its spatial position could be tracked by receiving transmissions from the ultrasound imaging probe. This study provides strong indications that PA imaging in combination with ultrasonic tracking could be useful for detecting the human placental vasculature during minimally invasive fetal surgery.