Jörg Mucke

Time-domain optical mammography: initial clinical results on detection and characterization of breast tumors.

Mammograms of 35 patients suspected of breast cancer were taken along craniocaudal and mediolateral projections with a dual-wavelength scanning laser pulse mammograph measuring time-resolved transmittance. Among 26 tumors known from routine clinical diagnostics, 17 tumors were detected retrospectively in optical mammograms. Effective tumor optical properties derived from a homogeneous model were used to deduce physiological information. All tumors exhibited increased total hemoglobin concentration and decreased or unchanged blood oxygen saturation compared with surrounding healthy tissue. Scatter plots based on a pixelwise analysis of individual mammograms were introduced and applied to represent corelations between characteristic quantities derived from measured distributions of times of flight of photons.

Time-domain scanning optical mammography : II. Optical properties and tissue parameters of 87 carcinomas

Within a clinical trial on scanning time-domain optical mammography reported on in a companion publication (part I), craniocaudal and mediolateral projection optical mammograms were recorded from 154 patients, suspected of having breast cancer. Here we report on in vivo optical properties of the subset of 87 histologically validated carcinomas which were visible in optical mammograms recorded at two or three near-infrared wavelengths. Tumour absorption and reduced scattering coefficients were derived from distributions of times of flight of photons recorded at the tumour site employing the model of diffraction of photon density waves by a spherical inhomogeneity, located in an otherwise homogeneous tissue slab. Effective tumour radii, taken from pathology, and tumour location along the compression direction, deduced from off-axis optical scans of the tumour region, were included in the analysis as prior knowledge, if available. On average, tumour absorption coefficients exceeded those of surrounding healthy breast tissue by a factor of about 2.5 (670 nm), whereas tumour reduced scattering coefficients were larger by about 20% (670 nm). From absorption coefficients at 670 nm and 785 nm total haemoglobin concentration and blood oxygen saturation were deduced for tumours and surrounding healthy breast tissue. Apart from a few outliers total haemoglobin concentration was observed to be systematically larger in tumours compared to healthy breast tissue. In contrast, blood oxygen saturation was found to be a poor discriminator for tumours and healthy breast tissue; both median values of blood oxygen saturation are the same within their statistical uncertainties. However, the ratio of total haemoglobin concentration over blood oxygen saturation further improves discrimination between tumours and healthy breast tissue. For 29 tumours detected in optical mammograms recorded at three wavelengths (670 nm, 785 nm, 843 nm or 884 nm), scatter power was derived from transport scattering coefficients. Scatter power of tumours tends to be larger than that of surrounding healthy breast tissue, yet the 95% confidence intervals of both medians overlap.

Concentration and oxygen saturation of haemoglobin of 50 breast tumours determined by time-domain optical mammography

Using a dual-wavelength (670 nm, 785 nm) time-domain scanning instrument we have recorded optical mammograms of 93 patients suspected of having breast cancer which was subsequently assessed histologically. Among 65 histologically confirmed carcinomas, 54 were detectable in at least one of two optical mammograms recorded of each tumour-bearing breast in craniocaudal and mediolateral projection. Optical mammograms were based on photon counts in selected time windows of measured distributions of times of flight of photons. Optical properties of 50 carcinomas investigated at both wavelengths were derived by modelling the breast as partially homogeneous infinite slab with an embedded spherical inhomogeneity representing the tumour and by calculating the diffraction of photon density waves. In selected cases, additional information about the location of the tumour along the compression direction was used that was obtained from scans at selected offsets between source and detector optical fibres. A correlation plot of haemoglobin concentration and blood oxygen saturation of tumours and healthy tissue shows good separation between both kinds of tissue. The majority of carcinomas exhibited increased total haemoglobin concentration compared to healthy tissue.

Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients

Using a triple wavelength (670 nm, 785 nm, 843/884 nm) scanning laser-pulse mammograph we recorded craniocaudal and mediolateral projection optical mammograms of 154 patients, suspected of having breast cancer. From distributions of times of flight of photons recorded at typically 1000-2000 scan positions, optical mammograms were derived displaying (inverse) photon counts in selected time windows, absorption and reduced scattering coefficients or total haemoglobin concentration and blood oxygen saturation. Optical mammograms were analysed by comparing them with x-ray and MR mammograms, including results of histopathology, attributing a subjective visibility score to each tumour assessed. Out of 102 histologically confirmed tumours, 72 tumours were detected retrospectively in both optical projection mammograms, in addition 20 cases in one projection only, whereas 10 tumours were not detectable in any projection. Tumour contrast and contrast-to-noise ratios of mammograms of the same breast, but derived from measured DTOFs by various methods were quantitatively compared. On average, inverse photon counts in selected time windows, including total photon counts, provide highest tumour contrast and contrast-to-noise ratios. Based on the results of the present study we developed a multi-wavelength, multi-projection scanning time-domain optical mammograph with improved spectral and spatial (angular) sampling, that allows us to record entire mammograms simultaneously at various offsets between the transmitting fibre and receiving fibre bundle and provides first results for illustration.

Scanning time-domain optical mammography : Detection and characterization of breast tumors in vivo

Optical mammography is one of several new techniques for breast cancer detection and characterization presently under development for clinical use that provide information other than morphologic, in particular on the biochemical and metabolic state of normal and diseased tissue. In breast tissue, scattering of red to near infrared (NIR) light dominates absorption and NIR light may penetrate several centimeters through the breast. Optical mammography avoids the use of ionizing radiation and offers the power of diffuse optical spectroscopy. However, because of strong light scattering, spatial resolution of optical mammography is generally low. The paper reviews the results of a clinical study on scanning time-domain optical mammography comprising 154 patients carrying a total of 102 carcinomas validated by histology. Ninety two of these tumors were detected in optical mammograms retrospectively and for 87 of the detected tumors optical properties and tissue parameters were derived. In addition developments on instrumentation and data analysis are covered and possible improvements of optical mammography are briefly discussed.

Detection and characterization of breast tumours by time-domain scanning optical mammography

The paper gives a short overview of various methods of optical mammography, emphasizing scanning time-domain mammography. The results of a clinical study on time-domain optical mammography are reviewed, comprising 154 patients carrying a total of 102 carcinomas validated by histology. A visibility score attributed to each carcinoma as qualitative measure of tumour detectability indicates acceptable sensitivity but poor specificity for discrimination between malignant and benign lesions. Likewise, a multi-variate statistical analysis yields sensitivity and specificity between 80% and 85% for tumour detection and discrimination with respect to normal (healthy) breast tissue, but values less than 70% for discrimination between malignant and benign breast lesions, being too low to be of clinical relevance. For 87 of the 88 tumours detected retrospectively in both projection optical mammograms, optical properties and tissue parameters were derived based on the diffraction of photon density waves by a spherical inhomogeneity as forward model. Following injection of a bolus of indocyanine green as non-targeted absorbing contrast agent, dynamic contrast-enhanced time-domain optical mammography was carried out on a small number of patients, but no differences in wash-out kinetics of indocyanine green between tumours and healthy breast tissue were observed.

In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time-domain mammograms.

A valuable method is described to analyze time-domain optical mammograms measured in the slab-like geometry of the slightly compressed female breast with a method based on linear perturbation theory including edge correction. Perturbations in scattering and absorption coefficients were mapped applying a computationally efficient point model.

Analysis of time-domain optical mammograms recorded from more than 150 patients

We used a scanning laser pulse mammograph to record craniocaudal and mediolateral projection optical mammograms of 154 patients suspected to have breast cancer. Optical mammograms were analyzed by comparing them with x-ray and MR mammograms, including results of histopathology. Out of 102 histologically confirmed carcinomas, 92 carcinomas were visible in at least one of the two projection mammograms. On average optical mammograms based on photon counts in a late time window exhibited the carcinomas with highest contrast compared to mammograms displaying absorption coefficients or hemoglobin concentration. Optical properties of carcinomas visible in optical mammograms were determined employing the model of diffraction of photon density waves by a spherical inhomogeneity, located in an otherwise homogeneous tissue slab. On average, tumor absorption coefficients exceeded those of surrounding healthy breast tissue by a factor of about 2.5 at the shortest wavelength used (670 nm), whereas tumor reduced scattering coefficients were larger by about 20% at this wavelength. Total hemoglobin concentration was observed to be systematically larger in tumors compared to healthy breast tissue. In contrast, blood oxygen saturation was found to be a poor discriminator for tumors and healthy breast tissue.