Whole field laser Doppler imaging of the microcirculation in psoriasis and clinically unaffected skin.

BACKGROUND: Angiogenesis represents a key phenomenon in psoriasis. Insights in the microcirculation within psoriatic lesions in a whole field are lacking. Recently, the Twente Optical Perfusion Camera (TOPCam) was developed, which provides the possibility of evaluating the superficial cutaneous microcirculation in a whole field. OBJECTIVES: This pilot study aims to examine whether the TOPCam can be used to visualize the microcirculation within and around psoriatic lesions, and whether it is capable of revealing vascular changes during topical treatment. METHODS: Five patients with chronic plaque psoriasis were included. The superficial microcirculation and clinical local scores (SUM score) were analyzed in two comparable lesions within one patient. At baseline and after 2, 4, 6, and 8 weeks the disease's natural course was evaluated in one plaque versus topical treatment in the other. RESULTS: The TOPCam was able to visualize an increased microcirculation within psoriatic lesions and perfusion variability due to the heartbeat. Whole field images demonstrated heterogeneity in perfusion intensity (hot and cold spots) within clinically homogeneous-looking plaques. Topical therapy induced a decrease in overall perfusion and a significant decrease in SUM score. CONCLUSION: The TOPCam is the first noninvasive technique to visualize the microcirculation of psoriatic lesions in a whole field, to correct images for the heartbeat, and to reveal heterogeneity in perfusion intensity.

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.

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.

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.

Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics.

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.

The Twente Photoacoustic Mammoscope: system overview and performance.

We present PAM, the Photoacoustic Mammoscope developed at the University of Twente, intended for initial retrospective clinical studies on subjects with breast tumours. A parallel plate geometry has been adopted and the breast will be gently compressed between a glass plate and a flat ultrasound detector matrix. Pulsed light (5 ns) from an Nd:YAG laser will impinge the breast through the glass plate in regions of interest; an appropriate number of the 590 elements of the detector matrix will be activated in succession to record photoacoustic signals. Three-dimensional image reconstruction employs a delay-and-sum beamforming algorithm. We discuss various instrumental aspects and the proposed imaging protocol. Performance studies of the ultrasound detector are presented in terms of sensitivity, frequency response and resolution. Details of the patient-instrument interface are provided. Finally some imaging results on well-characterized breast tissue phantoms with embedded tumour simulating inserts are shown.

Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms.

We present a laboratory version of a photoacoustic mammoscope, based on a parallel plate geometry. The instrument is built around a flat high-density ultrasound detector matrix. The light source is a Q-switched Nd:YAG laser with a pulse duration of 5 ns. To test the instrument, a novel photoacoustic phantom is developed using poly(vinyl alcohol) gel, prepared by a simple procedure that imparts optical scattering suggestive of breast tissue to it without the requirement for extraneous scattering particles. Tumor simulating poly(vinyl alcohol) gel spheres appropriately dyed at the time of preparation are characterized for optical absorption coefficients. These are then embedded in the phantom to serve as tumors with absorption contrasts ranging from 2 to 7, with respect to the background. Photoacoustic studies in transmission mode are performed, by acquiring the laser-induced ultrasound signals from regions of interest in the phantom. Image reconstruction is based on a delay-and-sum beamforming algorithm. The results of these studies provide an insight into the capabilities of the prototype. Various recommendations that will guide the evolving of our laboratory prototype into a clinical version are also discussed.