Clinical experiences with photoacoustic breast imaging: the appearance of suspicious lesions

This thesis describes photoacoustic (PA) imaging of suspicious breast lesions. In PA imaging, the tissue of interest is illuminated by short pulses of laser light, usually in the near infrared (NIR) regime. Upon absorption by primarily the tumor vasculature, the light causes a small temperature increase, which is converted into a pressure wave by the process of thermoelastic expansion. This pressure wave can be detected by ultrasound detectors with the appropriate frequency and bandwidth. The low scattering of ultrasound in tissue overcomes the poor resolution of pure optical techniques. PA mammography is therefore theoretically an ideal technique for visualizing breast cancer, without the use of ionizing radiation, contrast agents and painful breast compression. The Twente Photoacoustic Mammoscope (PAM) applies the technique in forward mode, using 1064 nm light illumination in combination with a 1 MHz (130% bandwidth) unfocused ultrasound detector array. A study in ten patients with malignancies and two patients with cysts, showed that PAM can visualize breast malignancies with high imaging contrast. Moreover, the PA contrast was independent of the mammographically estimated breast density. The outcomes of the study led to improvements in the system in terms of scan area and scan duration. Subsequently, the appearance of benign breast cysts was investigated using simulations (Monte Carlo and K-wave), phantom and patient measurements. Breast cysts were shown to be visible using PAM, but could not always unambiguously be discriminated from (multiple) malignancies. The signature appearance of cysts suggests that they might be differentiable from malignancies in a system using tomographic multi-wavelength imaging. For proper definition of the wavelengths to use, it is important to answer the question into what extent the PA appearance and contrast can be related to the tumor vascularity. A first comparison between PA images, MRI and vascularity stained histopathology slides, indicated that the PA appearance and contrast are indeed largely the consequence of tumor vascularity, but that the contribution of other chromophores cannot be excluded. With the improved system, 32 of 33 malignancies were visible with high imaging contrast, which was confirmed by a good co-localization with the lesions in x-ray and/or MR images. The contrast was independent of the mammographically estimated breast density. However, in an non-negligible number of patients, high intensity regions were observed that could not be related to the presence of known structures in the breast. The results reported in this thesis, show the potential of PA mammography for the visualization of malignancies, but also indicate that the current system requires improvements. Recommendations for such a system and future studies are provided in the concluding chapter of the thesis.