A photoacoustic 3D tomographic breast imager - Bench & bedside experiences
Sjoukje Schoustra is a PhD student in the research group Biomedical Photonic Imaging (BMPI). Supervisors are prof.dr.ir. W. Steenbergen and prof.dr. S. Manohar from the Faculty of Science & Technology (S&T).
Medical breast imaging is an important aid in diagnosing and guiding treatment of breast cancer, the cancer type with the highest incidence and mortality rates in females worldwide. Currently used clinical imaging techniques are x-ray mammography, ultrasonography and magnetic resonance (MR) imaging. Each of these modalities has its advantages but also drawbacks, and often multiple modalities are employed to assess the suspicious lesion of a patient. On top of imaging, invasive tissue sampling (histopathological examination) remains the gold standard up to this day in assessing a lesion and confirming the diagnosis. Research goes into the development of new modalities to image the breast in order to detect and/or diagnose tumors, of which photoacoustics is one. Photoacoustic imaging aims to make use of the strong optical contrast of the tumor-related environment, and combines this with the relatively high resolution of ultrasonic detection. The optical contrast originates from the often highly vascularized tumor and tumoral region. The blood in these vessels contains hemoglobin, a protein with a high optical absorption coefficient in the near-infrared wavelength region. Upon illuminating the breast with nanosecond light pulses, optical energy is transferred through the photoacoustic effect to ultrasound waves, detectable outside the body. Many research groups around the world have developed and tested photoacoustic breast imaging systems, with different system characteristics, geometries and designs. The main goal of this work has been to assess the feasibility of photoacoustic breast imaging, specifically with our second generation Twente Photoacoustic Mammoscope (PAM 2): a three-dimensional (3D) tomographic prototype system.
Chapter 2 shows the characterization of the PAM 2 system and its performance. A detailed description of the system and its components is provided. As part of a preliminary study to assess the system’s in vivo performance, the breasts of two healthy volunteers were imaged. The obtained three-dimensional images showed the breast contour, the nipple and the vascular anatomy within the breast. The design, development and added value of breast-supporting cups to immobilize and position the breast are described in Chapter 3. The use of cups to support and position the breast provided higher quality images, compared to images of the same breast measured without support. This was achieved by reducing movement during the measurement and by enabling the use of a more detailed reconstruction through a two-speed of sound model. Moreover, the cups ensured central positioning of the breast within the imaged volume. Multiple sizes of the cups accommodated a range of breast sizes. A clinical study was set up at the center for breast care at the local hospital. Chapter 4 describes clinical measurements on breast cancer patients. Obtained photoacoustic images were compared to conventional clinical images: x-ray, ultrasound, and if available, MR imaging. A selection of patients was made to study in detail. Reconstructed photoacoustic images were processed to enhance visibility of vascular structures and decrease background noise. After locating the tumoral region in the photoacoustic images, we searched for markers indicative of malignancy in this region. In a few cases, photoacoustic image features indicative of malignancy were seen, such as spotty high-intensity signals and a relatively high level of entropy in the tumoral region. Chapter 5 describes the first steps towards longitudinal photoacoustic imaging, investigating the influence of the menstrual cycle on photoacoustic breast appearance. A literature survey on the hormonal responsiveness of breast tissue was provided, based on optical characterization studies as well as imaging studies employing dynamic contrast-enhanced (DCE) MR imaging, both on the premenopausal breast. A first step was made to assess PAM 2 system repeatability with phantom measurements. Intraclass correlation coefficients of calculated contrast values in scans on five phantoms indicated good to excellent system repeatability. Next to phantom measurements, the breast of one healthy subject was scanned multiple times, where positioning variations between scans were apparent, hampering accurate longitudinal assessment.
With PAM 2, we were able to visualize detailed vasculature, both in healthy volunteers as well as in breast cancer patients. Given the pathophysiological target of the imaging method (detecting enhanced tumor-related vasculature) this suggests that the technique might potentially add value in breast cancer management as a noninvasive, harmless imaging technique. Chapter 6 considers potential areas of application, alongside a general discussion of the work. The chapter starts with discussing the topic of full-breast imaging, focusing on the illumination scheme and imaging depth of PAM 2 and comparable systems. Next, the photoacoustic appearance of a breast tumor is discussed. Multiple research groups have attempted to find image descriptors of malignancy, which are summarized and compared. More research is needed to learn about the varying reported tumor appearances and the cause of these variations. Then, some recommendations for developing an improved next generation photoacoustic breast imaging system are listed. An outlook is presented, discussing steps towards future implementation of a photoacoustic breast imaging system in the clinic. The interdependence of technical design choices and the foreseen application is underlined. A few potential areas for clinical application are considered, as are their respective system requirements. It is advised to apply early health technology assessment (HTA), to assist in making informed choices regarding future system design, considering the potential value of the method.
