We developed an eight-channel scanning time-domain fluorescence mammograph capable of imaging the distribution of
a non-specific fluorescent contrast agent in the female breast, besides imaging intrinsic absorption and scattering
properties of healthy breast tissue and tumors. The apparatus is based on the PTB multi-channel laser pulse
mammograph, originally designed for measurements of absorption and scattering coefficients at four selected
wavelengths (&lgr; = 652 nm, 684 nm, 797nm, and 830 nm). It was upgraded for time-resolved detection of fluorescence,
excited at 735 nm by a ps diode laser with 10 mW output power and detected at wavelengths &lgr; ⩾ 780 nm. Cooled PMTs
with GaAs photocathodes are used to detect laser and fluorescence photons at five positions in transmission and three
positions in reflection. Measurements are performed with the breast being slightly compressed between two parallel
glass plates. The transmitting and receiving fiber bundles are scanned synchronously over the breast in steps of typically
2.5 mm. At each scan position, distributions of times of flight of laser photons are measured by time-correlated single
photon counting at eight detector positions, followed by measurements of distributions of times of arrival of
fluorescence photons. The performance of the fluorescence mammograph was investigated by using breast-like
phantoms with a fluorescent inhomogeneity with dye enrichment varying between 2:1 and 10:1 over background values.
Optical techniques based on photon migration are rapidly emerging as a promising alternative and/or augmentation of existing medical imaging modalities. For example, real time studies of hemodynamic changes in brain tissue are possible as a step towards optical functional brain imaging. Time-resolved implementations of these techniques allow for discrimination between scattering and absorption and for depth resolution. They require sub-nanosecond pulsed light sources with high repetition rate and sufficient power for deep enough tissue penetration. Picosecond diode lasers satisfy the clinical demands of economy, compact size, and reliability almost perfectly. Today multi-channel diode laser devices are commercially available and are widely used in diffuse optical imaging and spectroscopy, in particular in optical tomography and breast cancer detection. However, the output powers of these devices are just about sufficient for moderate tissue penetration depths. An improvement that does not compromise the advantages of the diode laser sources is amplification of the diode laser output by means of solid state tapered amplifiers. We present an amplified light source for use in NIR diffuse optical spectroscopy and imaging, providing pulse widths as short as 100 ps, adjustable repetition rates up to 80 MHz, and peak power levels as high as 7 Watts, corresponding to average power levels exceeding 100 mW. In combination with time-resolved photon counting electronics matching the high throughput demands in conjunction with the new source, state-of-the-art systems for diffuse optical imaging can be built. System design features and possible application examples are presented.
We present a newly developed optical mammograph for concurrent diffuse optical and MR imaging of the compressed breast. A home-built MR coil allows optical measurements to be carried out along mediolateral as well as craniocaudal projections. Preliminary in-vivo experimental data are presented.
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.
We investigate correlations of the intensity fluctuations of two-dimensional arrays of non-identical, locally-coupled lasers, numerically and experimentally. We find evidence of a power-law dependence of spatial correlations as a function of laser pair distance (or coupling strength) near the phase-locking threshold.
Two time-domain scanning optical mammographs are presently tested in clinical trials within the EU project "OPTIMAMM" supported by the EC. To assess their performance (e.g., accuracy, sensitivity, stability), systematic measurements were performed on breast-like phantoms. Both, estimation of optical properties and acquisition of good contrast images for diagnostic purposes were considered. The proposed
assessment procedure can be applied to characterize and improve other novel and existing instruments for photon migration imaging and spectroscopy.
We present a newly developed scanning time-resolved optical mammograph for breast cancer detection featuring four wavelengths for enhanced spectroscopic information, up to 6 off-axis detection channels for improved depth localisation and novel attenuation and imaging optics for improved response reproducibility and photon collection efficiency. First results on the characterisation and on performance tests of this mammograph are shown.
NIRS signals measured on the adult head contain contributions from the brain and from overlying tissue. It was shown recently that measured distributions of times of flight (DTOF) of photons allow to deduce absorption changes occurring in different layers of the head. This method relies on time-dependent mean partial pathlengths calculated by Monte Carlo simulations for assumed background optical properties of the various tissues. Deconvolution of the measured
DTOF is required using the instrumental response function. We propose an alternative method to estimate absorption changes in various tissue layers by analyzing changes of moments of DTOFs (integral, mean time of flight and variance) recorded at various source-detector separations. The sensitivity factors corresponding to integral, mean time of flight and variance were obtained by Monte Carlo simulations for a layered model of the head. From experimentally derived mean time of flight and variance the contributions of the instrumental response function were subtracted. The proposed method was applied to multi-distance time-domain measurements during functional stimulation of the brain of healthy volunteers.
A new method for measurement, documentation and visualization of fast repetitive processes is presented. The method extends the principle of sampling--as is currently used in measuring fast repetitive electrical signals--to video recording; using a fast external shutter in front of an unmodified, free running, standard CCIR or EIA video camera. The result is a slow-motion display that can be viewed continuously, recorded on standard video equipment or further processed like any other video signal. In a number of experiments in the field of nonlinear optics, exposure intervals of down to 100 nanoseconds at a full-frame repetition rate of 25 Hz were used, thus slowing down the time scale by a factor of 400,000. Additional features increase the efficiency, which is otherwise limited by the short exposure time, increase the maximum time-scaling factor and facilitate polarization-resolved measurements.