During neoadjuvant chemotherapy for breast cancer, little information is available on the response or non-response of the tumor to the treatment. Pathologic complete response is correlated with survival, but patients and clinicians both must wait until after the patient undergoes surgery and the resected tissue is analyzed in order to assign pathologic response. Because structural imaging modalities and clinical palpation are poor predictors of pathologic response, there is need for an inexpensive imaging method which is sensitive to the changing physiology of the tumor. Such a method should be noninvasive, to permit frequent monitoring during therapy. Near-infrared optical imaging has already shown promise for monitoring neoadjuvant chemotherapy, with measurement of hemodynamics providing additional information over baseline chromophore concentrations. These contrasts rely on the highly vascularized nature of most breast tumors, as well as the abnormal vasculature, which can produce a different response to perturbations than healthy tissue. Here we describe the development of a new held-held spatial-frequency domain imaging (SFDI) device, to be used for measuring the response of breast tissue to local compression. Device design is described, as well as validation on optical phantoms, and in vivo. Compression studies were performed in soft optical phantoms containing stiff, tumor-mimicking inclusions, which indicate the potential for compression to be used to bring stiff lesions within a depth which can be measured with SFDI. Additionally, the hemodynamic response of pressure cuff venous occlusion is described, measured on the forearm, and this response is contrasted with the hemodynamic response to local tissue compression.
In breast cancer diagnosis and therapy monitoring, there is a need for frequent, noninvasive disease progression evaluation. Breast tumors differ from healthy tissue in mechanical stiffness as well as optical properties, which allows optical methods to detect and monitor breast lesions noninvasively. Spatial frequency-domain imaging (SFDI) is a reflectance-based diffuse optical method that can yield two-dimensional images of absolute optical properties of tissue with an inexpensive and portable system, although depth penetration is limited. Since the absorption coefficient of breast tissue is relatively low and the tissue is quite flexible, there is an opportunity for compression of tissue to bring stiff, palpable breast lesions within the detection range of SFDI. Sixteen breast tissue-mimicking phantoms were fabricated containing stiffer, more highly absorbing tumor-mimicking inclusions of varying absorption contrast and depth. These phantoms were imaged with an SFDI system at five levels of compression. An increase in absorption contrast was observed with compression, and reliable detection of each inclusion was achieved when compression was sufficient to bring the inclusion center within ∼12 mm of the phantom surface. At highest compression level, contrasts achieved with this system were comparable to those measured with single source–detector near-infrared spectroscopy.
We describe a novel approach for monitoring breast lesions, utilizing spatial frequency domain imaging, a diffuse optical imaging method to detect hemoglobin contrast, in combination with mechanical compression of the tissue. The project is motivated by the growing rate of unnecessary breast biopsies, caused by uncertainty in X-ray mammographic diagnoses. We believe there is a need for an alternate means of tracking the progression palpable lesions exhibiting probably benign features, that can be performed non-invasively and hence frequently: at home or in the clinic. The proposed approach capitalizes on two distinguishing properties of cancerous lesions, namely the relative stiffness with respect to surrounding tissue and the optical absorption due to the greater vascularization, hence hemoglobin concentration. The current research project is a pilot study to evaluate the principle on soft, breast tissue-mimicking phantoms containing stiffer, more highly absorbing inclusions. Spatial frequency domain imaging was performed by projecting onto the phantom a series of wide-field patterns at multiple spatial frequencies. Image analysis then was performed to map absorption and scattering properties. The results of the study demonstrate that compression significantly increases the optical contrast observed for inclusions located 10 and 15 mm beneath the surface. In the latter case, the inclusion was not detectable without compression.