F.M. van den Engh

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 image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology

Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images, and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies, and first insights were gained into the relationship with tumor vascularity.

Imaging Tumor Vascularization for Detection and Diagnosis of Breast Cancer

Breast cancer is one of the major causes of morbidity and mortality in western women. Current screening and diagnostic imaging modalities, like x-ray mammography and ultrasonography, focus on morphological changes of breast tissue. However, these techniques still miss some cancers and often falsely detect cancer. The sensitivity and specificity for detecting the disease can probably be improved by focusing on the consequences of tumor angiogenesis: the increased microvessel density with altered vascular characteristics. In this review, various techniques for imaging breast tumor vasculature are discussed. Dynamic contrast enhanced magnetic resonance imaging is the most-used imaging modality in this field. It has a proven high sensitivity, but a low specificity and cannot be applied in all women. Moreover, it has problems with detecting ductal carcinoma in situ (DCIS). On the contrary, contrast enhanced digital mammography can detect DCIS, but requires the use of ionizing radiation. Contrast enhanced ultrasound provides real-time information about true intravascular blood volume and flow. However, this technique still has difficulties with discriminating benign from malignant tissue. Moreover, these three imaging modalities all require the injection of contrast agents. Two relatively new techniques that do not use external contrast agents are diffuse optical imaging and photoacoustic imaging. Both visualize the increased concentration of hemoglobin in malignant tissue and thereby provide a high intrinsic contrast.

In vivo determination of scattering properties of healthy and malignant breast tissue by use of multi-diameter-single fiber reflectance spectroscopy (MDSFR)

Elastic scattering of light in tissue offers a natural biologic contrast that can be used to classify tissue for diagnostic purposes. For a single fiber reflectance spectroscopy setup, which uses a single multimode optical fiber with diameter dfib for both illumination and detection, our group has previously reported a relationship between the single fiber reflectance (SFR) signal and the dimensionless scattering (μ′sdfib). Based on this relationship, the multi-diameter single fiber reflectance method (MDSFR), was developed. This method allows the extraction of μ′S and a phase function dependent parameter γ=(1-g2) / (1-g1) from tissue by taking multiple SFR measurements with different fiber diameters. Limitations and the sensitivity of the MDSFR method have been discussed previously based on an in silico analysis and the feasibility of the method has been proven experimentally during measurements in scattering phantoms containing polystyrene spheres. In the current study we will present data from an in-vivo clinical study utilizing MDSFR to determine tissue scattering properties of healthy and malignant breast tissue, on patients undergoing biopsy of a suspicious lesion found during mammographic breast imaging. Here MDSFR measurements are performed with a custom made disposable probe, incorporating two fiber diameters (0.4 and 0.8 mm), which is inserted through the biopsy needle before the biopsy is taken, allowing in vivo spectroscopic measurements of tumor center and healthy tissue.

Imaging breast lesions using the Twente Photoacoustic Mammoscope: ongoing clinical experience

Current imaging modalities are often not able to detect early stages of breast cancer with high imaging contrast. Visualizing malignancy-associated increased hemoglobin concentrations might improve breast cancer diagnosis. Photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound resolution, which makes it potentially ideal for breast imaging. The Twente Photoacoustic Mammoscope (PAM) has been designed specifically for this purpose. Based on a successful pilot study in 2007, a large clinical study using PAM has been started in December 2010. PAM uses a pulsed Q-switched Nd:YAG laser at 1064 nm to illuminate a region of interest on the breast. Photoacoustic signals are detected with a 1MHz, unfocused ultrasound detector array. Three dimensional data are reconstructed using an acoustic backprojection algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study, the goal was to optimize the visualization of malignancies. We performed sixteen technically acceptable measurements on confined breast malignancies. In the reconstructed volumes of all malignancies, a confined high contrast region could be identified at the expected lesion depth. After ten successful measurements, the illumination area was increased and the fluence was substantially decreased. This caused a further significant increase in PAM lesion contrast.