Louise C. Enfield

Diffuse optical imaging of the healthy and diseased breast: A systematic review

Screening X-ray mammography is limited by false positives and negatives leading to unnecessary physical and psychological morbidity. Diffuse Optical Imaging using harmless near infra red light, provides lesion detection based on functional abnormalities and represents a novel diagnostic arm that could complement traditional mammography. Reviews of optical breast imaging have not been systematic, are focused mainly on technological developments, and have become superseded by rapid technological advancement. The aim of this study is to review clinically orientated studies involving approximately 2,000 women in whom optical mammography has been used to evaluate the healthy or diseased breast. The results suggest that approximately 85% of breast lesions are detectable on optical mammography. Spectroscopic resolution of tissue haemoglobin composition and oxygen saturation may improve the detectability of breast diseases. Results suggest that breast lesions contain approximately twice the haemoglobin concentration of background tissue. Current evidence suggests that it is not possible to distinguish benign from malignant disease using optical imaging techniques in isolation. Methods to improve the performance of Diffuse Optical Imaging, such as better spectral coverage with additional wavelengths, improved modelling of light transport in tissues and the use of extrinsic dyes may augment lesion detection and characterisation. Future research should involve large clinical trials to determine the overall sensitivity and specificity of optical imaging techniques as well as to establish patient satisfaction and economic viability.

Three-dimensional time-resolved optical mammography of the uncompressed breast

Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.

Time-resolved optical mammography using a liquid coupled interface

A method has been devised for generating three-dimensional optical images of the breast using a 32-channel time-resolved system and a liquid-coupled interface. The breast is placed in a hemispherical cup surrounded by sources and detectors, and the remaining space is filled with a fluid with tissue-like optical properties. This approach has three significant benefits. First, cups can accommodate a large range of breast sizes, enabling the entire volume of the breast to be sampled. Second, the coupling of the source and detector optics at the surface is constant and independent of the subject, enabling intensity measurements to be employed in the image reconstruction. Third, the external geometry of the reconstructed volume is known exactly. Images of isolated targets with contrasting absorbing and scattering properties have been acquired, and the performance of the system has been evaluated in terms of the contrast, spatial resolution, and localization accuracy. These parameters were strongly dependent on the location of the targets within the imaged volume. Preliminary images of a healthy human subject are also presented, which reveal subtle heterogeneity, particularly in the distribution of scatter. The ability to detect an absorbing target adjacent to the breast is also demonstrated.

Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography

Abstract. Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment.

Monitoring the response to primary medical therapy for breast cancer using three- dimensional time-resolved optical mammography.

Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months.

A tissue equivalent phantom for simultaneous near-infrared optical tomography and EEG

We describe a phantom which enables EEG and near-infrared optical tomography to be performed simultaneously over the same volume. The phantom provides a surface electrical contact impedance comparable to that of the human scalp, whilst also possessing an optical scattering coefficient and electrical conductivity equivalent to that of brain tissue. The construction of the phantom is described, as is the resulting simultaneous EEG and near infrared optical tomography experiment, which, to our knowledge, is the first performed on a scale comparable to that of the infant human brain. This imaging experiment successfully shows the suitability of this phantom construction for the assessment of simultaneous EEG and near infrared optical tomography systems.

A Review of Mechanisms of Contrast for Diffuse Optical Imaging of Cancer

Diffuse optical imaging and spectroscopy have been extensively used to detect, diagnose and monitor cancer. This paper is a review not of cancer in general, but of the biological changes that occur that can provide contrast for near infrared (NIR) techniques. Cancer is defined by characteristics such as the development of new blood vessels, changes in metabolism and the ability to invade surrounding tissue. The sensitivity of NIR techniques to haemoglobin, water and lipid concentrations, tissue oxygen saturation and cell density means that the pathological changes that occur in malignant tissues can provide contrast between healthy and pathological tissue. Each of these contrast mechanisms are discussed in turn, with a short introduction to the physiological changes that occur, and then a review of the NIR techniques that can be used to investigate these changes and findings from published papers. The role of exogenous contrast agents with NIR techniques in cancer diagnosis and assessment are also discussed. By understanding the characteristics of cancer and the changes that occur, we can interpret our results from NIR with greater confidence and accuracy and develop new techniques that target these characteristics. Information on angiogenesis or hypoxia can be clinically useful, especially when planning treatment (hypoxia) or predicting outcome to chemotherapy (haemoglobin concentration can be used as a measure of vessel density). By understanding the characteristics of cancer and the changes that occur, we can interpret our results from NIR with greater confidence and accuracy and develop new techniques that target these characteristics.

Three-Dimensional Time-Resolved Optical Mammography of the Uncompressed Breast

Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.