Wiendelt Steenbergen

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.

Measurement of depth of burns by laser Doppler perfusion imaging

Laser Doppler perfusion imaging (LDPI), is a further development in laser Doppler flowmetry (LDF). Its advantage is that it enables assessment of microvascular blood flow in a predefined skin area rather than, as for LDF, in one place. In many ways this method seems to be more promising than LDF in the assessment of burn wounds. However, several methodological issues that are inherent in the LDPI technique, and are relevant for the assessment of burn depth, must be clarified. These include the effect of scanning distance, curvature of the tissue, thickness of topical wound dressings, and pathophysiological effects of skin colour, blisters, and wound fluids. Furthermore, we soon realised that to examine the perfusion image generated by LDPI adequately the process of analysis was appreciably improved by the simultaneous use of digital photography. In the present investigation we used both in vitro and in vivo models and also examined burned patients, and found that the listed factors all significantly affected the LDPI output signal. However, if these factors are known to the examiner, most of them can be adjusted for. If the technique is further improved by minimizing such effects and by reducing the practical difficulties of applying it to a burned patient in the burns unit, the technique may find uses in everyday clinical decision-making.

Review of laser speckle contrast techniques for visualizing tissue perfusion

When a diffuse object is illuminated with coherent laser light, the backscattered light will form an interference pattern on the detector. This pattern of bright and dark areas is called a speckle pattern. When there is movement in the object, the speckle pattern will change over time. Laser speckle contrast techniques use this change in speckle pattern to visualize tissue perfusion. We present and review the contribution of laser speckle contrast techniques to the field of perfusion visualization and discuss the development of the techniques.

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.

Laser Doppler perfusion monitoring and imaging: novel approaches

Laser Doppler flowmetry (LDF) is a non invasive method enabling the monitoring of microvascular blood flow, a very important marker of tissue health. This article gives an overview on the concept of LDF for microvascular perfusion monitoring and imaging. It first describes the theoretical background of the technique. Then, the benefits of LDF signal processing are shown through clinical examples: use of time–frequency representations and wavelets. Afterwards, the paper introduces novel approaches of velocity components. For that purpose, a work providing the determination of the velocities relative contribution in physiologically relevant units (mm/s) is presented. Imaging perfusion is also reviewed through methods based on laser speckle. The most prominent disadvantage of the latter devices being the time needed to produce a perfusion image, solutions are proposed in the last part of the paper.

In vivo photoacoustic imaging of blood vessels using an extreme-narrow aperture sensor

We applied photoacoustics for noninvasive two-dimensional imaging of blood vessels in vivo, using near infrared light. This study was undertaken to develop photoacoustic tomography of tissue for the detection of embedded blood vessels using a newly developed piezoelectric double ring detector, featuring an extremely narrow aperture.

Laser speckle contrast imaging: theoretical and practical limitations

Abstract. When laser light illuminates a diffuse object, it produces a random interference effect known as a speckle pattern. If there is movement in the object, the speckles fluctuate in intensity. These fluctuations can provide information about the movement. A simple way of accessing this information is to image the speckle pattern with an exposure time longer than the shortest speckle fluctuation time scale—the fluctuations cause a blurring of the speckle, leading to a reduction in the local speckle contrast. Thus, velocity distributions are coded as speckle contrast variations. The same information can be obtained by using the Doppler effect, but producing a two-dimensional Doppler map requires either scanning of the laser beam or imaging with a high-speed camera: laser speckle contrast imaging (LSCI) avoids the need to scan and can be performed with a normal CCD- or CMOS-camera. LSCI is used primarily to map flow systems, especially blood flow. The development of LSCI is reviewed and its limitations and problems are investigated.

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.

Review of methodological developments in laser Doppler flowmetry

Laser Doppler flowmetry is a non-invasive method of measuring microcirculatory blood flow in tissue. In this review the technique is discussed in detail. The theoretical and experimental developments to improve the technique are reviewed. The limitations of the method are elaborated upon, and the research done so far to overcome these limitations is critically assessed.