[Show abstract][Hide abstract] ABSTRACT: In the present contribution we investigate the images of CW diffusely reflected light for a point-like source, registered by a CCD camera imaging a turbid medium containing an absorbing lesion. We show that detection of μa variations (absorption anomalies) is achieved if images are normalized to background intensity. A theoretical analysis based on the diffusion approximation is presented to investigate the sensitivity and the limitations of our proposal and a novel procedure to find the location of the inclusions in 3D is given and tested. An analysis of the noise and its influence on the detection capabilities of our proposal is provided. Experimental results on phantoms are also given, supporting the proposed approach.
[Show abstract][Hide abstract] ABSTRACT: We investigate the correction of fluorescence intensities in epi-illumination imaging by normalization to absorption images. Experiments on custom lymph node phantoms reveal improved estimation of dye concentration for superficial nodes.
[Show abstract][Hide abstract] ABSTRACT: Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.
Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 01/2013; 187:331-50.
[Show abstract][Hide abstract] ABSTRACT: To assess early- and late-fluorescence near-infrared imaging, corresponding to the vascular (early-fluorescence) and extravascular (late-fluorescence) phases of indocyanine green (ICG) enhancement, for breast cancer detection and benign versus malignant breast lesion differentiation.
The study was approved by the ethical review board; all participants provided written informed consent. Twenty women with 21 breast lesions were examined with near-infrared imaging before, during, and after intravenous injection of ICG. Absorption and fluorescence projection mammograms were recorded simultaneously on a prototype near-infrared imaging unit. Two blinded readers independently assessed the images and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence mammograms. Imaging results were compared with histopathologic findings. Lesion contrast and diameter on the fluorescence mammograms were measured, and Cohen κ, Mann-Whitney U, and Spearman ρ tests were conducted.
The absorption-corrected fluorescence ratio mammograms showed high contrast (contrast value range, 0.25-0.64) between tumors and surrounding breast tissue. Malignant lesions were correctly defined in 11 (reader 1) and 12 (reader 2) of 13 cases, and benign lesions were correctly defined in six (reader 1) and five (reader 2) of eight cases with late-fluorescence imaging. Lesion visibility scores for malignant and benign lesions were significantly different on the fluorescence ratio mammograms (P = .003) but not on the absorption mammograms (P = .206). Mean sensitivity and specificity reached 92% ± 8 (standard error of mean) and 75% ± 16, respectively, for fluorescence ratio imaging compared with 100% ± 0 and 25% ± 16, respectively, for conventional mammography alone.
Preliminary data suggest that early- and late-fluorescence ratio imaging after ICG administration can be used to distinguish malignant from benign breast lesions.
[Show abstract][Hide abstract] ABSTRACT: We present a scanning time-domain fluorescence mammograph capable to image the distribution of a fluorescent contrast agent within a female breast, slightly compressed between two parallel glass plates, with high sensitivity. Fluorescence of the contrast agent is excited using a near infrared picosecond diode laser module. Four additional picosecond diode lasers with emission wavelengths between 660 and 1066 nm allow to measure the intrinsic optical properties of the breast tissue. By synchronously moving a source fiber and seven detection fiber bundles across the breast, distributions of times of flight of photons are recorded simultaneously for selected source-detector combinations in transmission and reflection geometry either at the fluorescence wavelength or at the selected laser wavelengths. To evaluate the performance of the mammograph, we used breastlike rectangular phantoms comprising fluorescent and absorbing objects using the fluorescent dye Omocyanine as contrast agent excited at 735 nm. We compare two-dimensional imaging of the phantom based on transmission and reflection data. Furthermore, we developed an improved tomosynthesis algorithm which permits three-dimensional reconstruction of fluorescence and absorption properties of lesions with good spatial resolution. For illustration, we present fluorescence mammograms of one patient recorded 30 min after administration of the contrast agent indocyanine green showing the carcinoma at high contrast originating from fluorescence of the extravasated dye, excited at 780 nm.
The Review of scientific instruments 02/2011; 82(2):024302. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have investigated twenty patients with suspicious breast lesions by fluorescence mammography using ICG as contrast agent. Differences in early and late fluorescence mammograms offer the chance to distinguish malignant from benign lesions.
[Show abstract][Hide abstract] ABSTRACT: We have developed a prototype mammograph for simultaneous acquisition of tomographic and time-resolved data at fluorescence and laser wavelengths in slab geometry. System performance was tested on phantoms and on a volunteer.
[Show abstract][Hide abstract] ABSTRACT: We report on the nonlinear reconstruction of local absorption and fluorescence contrast in tissuelike scattering media from measured time-domain diffuse reflectance and transmittance of laser as well as laser-excited fluorescence radiation. Measurements were taken at selected source-detector offsets using slablike diffusely scattering and fluorescent phantoms containing fluorescent heterogeneities. Such measurements simulate in vivo data that would be obtained employing a scanning, time-domain fluorescence mammograph, where the breast is gently compressed between two parallel glass plates, and source and detector optical fibers scan synchronously at various source-detector offsets, allowing the recording of laser and fluorescence mammograms. The diffusion equations modeling the propagation of the laser and fluorescence radiation were solved in frequency domain by the finite element method simultaneously for several modulation frequencies using Fourier transformation and preprocessed experimental data. To reconstruct the concentration of the fluorescent contrast agent, the Born approximation including higher-order reconstructed photon densities at the excitation wavelength was used. Axial resolution was determined that can be achieved by various detection schemes. We show that remission measurements increase the depth resolution significantly.
[Show abstract][Hide abstract] ABSTRACT: Using scanning time-domain instrumentation we recorded fluorescence projection mammograms on few breast cancer patients prior, during and after infusion of indocyanine green (ICG), while monitoring arterial ICG concentration by transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after ICG had been largely cleared from the blood by the liver, showed invasive carcinomas at high contrast over a rather homogeneous background, whereas benign lesions did not produce (focused) fluorescence contrast. During infusion, tissue concentration contrast and hence fluorescence contrast is determined by intravascular contributions, whereas late-fluorescence mammograms are dominated by contributions from protein-bound ICG extravasated into the interstitium, reflecting relative microvascular permeabilities of carcinomas and normal breast tissue. We simulated intravascular and extravascular contributions to ICG tissue concentration contrast within a two-compartment unidirectional pharmacokinetic model.
[Show abstract][Hide abstract] ABSTRACT: We developed a method to record artifact-free diffuse reflectance in a parallel plate scanning fluorescence mammograph and used reflection data together with transmission data for reconstruction based fluorescence imaging at improved axial resolution.
[Show abstract][Hide abstract] ABSTRACT: We present a new method to reconstruct arbitrary large volumes in (fluorescence) diffuse optical tomography by splitting the volume of reconstruction into sub-volumes. This allows to perform nonlinear reconstruction on large grids with a larger number of measurement data and more grid nodes than conventional reconstruction schemes, where images are reconstructed on a single grid. We investigate how the reconstructed spatial distributions of diffusion and absorption coefficients using the new method depend on the size of the sub-volumes, compare the convergence to the conventional nonlinear approach, and present an error estimation.
[Show abstract][Hide abstract] ABSTRACT: Time-domain perturbation theory of photon diffusion up to third order was evaluated for its accuracy in deducing optical properties of breast tumors using simulated and physical phantoms and by analyzing 141 projection mammograms of 87 patients with histology-validated tumors that had been recorded by scanning time-domain optical mammography. The slightly compressed breast was modeled as (partially) homogeneous diffusely scattering infinite slab containing a scattering and absorbing spherical heterogeneity representing the tumor. Photon flux densities were calculated from densities of transmitted photons, assuming extended boundary conditions. Explicit formulas are provided for second-order changes in transmitted photon density due to the presence of absorbers or scatterers. The results on phantoms obtained by perturbation theory carried up to third order were compared with measured temporal point spread functions, with numerical finite-element method (FEM) simulations of transmitted photon flux density, with results obtained from the diffraction of diffuse photon density waves, and from Padé approximants. The breakdown of first-, second-, and third-order perturbation theory is discussed for absorbers and a general expression was derived for the convergence of the Born series in this case. Taking tumor optical properties derived by the diffraction model as reference we conclude that estimates of tumor absorption coefficients by perturbation theory agree with reference values within +/-25% in only 65% (first order), 66% (second order), and 77% (third order) of all mammograms analyzed. In the remaining cases tumor absorption is generally underestimated due to the breakdown of perturbation theory. On average the empirical Padé approximants yield tumor absorption coefficients similar to third-order perturbation theory, yet at noticeable lower computational efforts.
[Show abstract][Hide abstract] ABSTRACT: In this study we have theoretically and experimentally investigated the behavior of first order approximation contrast function when purely scattering inhomogeneities located at different depths inside a turbid thick slab are considered. Results of model predictions have been compared with Finite element method simulations and tested on phantoms. To this aim, we have developed for the first time to our knowledge a fitting algorithm for estimating both the scattering perturbation parameter and the shift of the inhomogeneity from the middle plane, allowing one to reduce the uncertainties due to depth. This is important for optical mammography because effects of the depth can cause uncertainties in the derived tumor optical properties that are above 20% and the scattering properties of tumors differ from those of the sourrounding healthy tissue by a comparable extent. OCIS codes: (170.3660) light propagation in tissues; (170.5280) photon migration; (170.6510) spectroscopy, tissue diagnostics; (290.1990) diffusion; (290.7050) turbid media., "In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time-domain mammograms,-resolved contrast function and optical char-acterization of spatially varying absorptive inclusions at different depths in diffusing media," Phys. Rev. E 69, 031901 (2004).
[Show abstract][Hide abstract] ABSTRACT: We studied the free precession of the nuclear magnetization of hyperpolarized
129Xe gas in external magnetic fields as low as B0 = 4.5 nT, using
SQUIDs as magnetic flux detectors.
The transverse relaxation was mainly caused by the restricted diffusion of
129Xe in the presence of ambient magnetic field gradients.
Its pressure dependence was measured in the range from 30mbar to 850mbar and
compared quantitatively to theory.
Motional narrowing was observed at low pressure, yielding transverse relaxation
times of up to 8000s.
The European Physical Journal D 04/2007; 42(2):197-202. · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on the reconstruction of absorption and fluorescence from measured time-domain diffuse reflectance and transmittance of laser and fluorescence radiation. Measurements were taken on slab-like, diffusely scattering and fluorescent phantoms containing fluorescent inhomogeneities, using fs laser pulses (lambda = 730 nm) and time correlated single photon counting. The source was scanned across the entrance face of the phantom, and at each source position data were collected in transmission and reflection at various detector positions. These measurements simulate in vivo data that will be obtained employing a scanning, time-domain fluorescence mammograph, where the breast is gently compressed between two parallel glass plates, and source and detector optical fibers scan synchronously at various source-detector offsets, allowing to record laser and fluorescence mammograms. The diffusion equations for the propagation of the laser and fluorescence radiation were solved in frequency domain by the finite element method. Measured time-resolved phantom data were Fourier-transformed to frequency domain prior to image reconstruction. Signal-to-noise ratios were high enough to use several data sets simultaneously in the reconstruction process belonging to various modulation frequencies up to several hundred MHz. To obtain the spatial distribution of the fluorescent contrast agent the Born approximation of the fluorescence diffusion equation was used.
[Show abstract][Hide abstract] ABSTRACT: We have carried out phantom studies for optimizing the design of a fluorescence mammograph employing time-domain and cw measurements, for improving data analysis and methods of reconstruction. By scanning pulsed (100 fs) laser radiation across a fluorescent, rectangular breast-like phantom with a spherical inhomogeneity simulating a tumor bearing breast slightly compressed between two parallel glass plates, distributions of times of flight of laser and fluorescence photons were measured in transmission and reflection for various detector arrangements. Absorption coefficients and dye concentrations were reconstructed using perturbation solutions of the diffusion equation at the laser and fluorescence wavelengths. We additionally employed a CCD camera to measure time-integrated intensity of fluorescence and laser radiation transmitted through the phantom. The increased number of projection angles entering the reconstruction improved spatial resolution. Further improvements were obtained when combined cw data and time-resolved remission data were used in the reconstruction.
[Show abstract][Hide abstract] ABSTRACT: 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 (lambda = 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 lambda >= 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Technology in cancer research & treatment 11/2005; 4(5):483-96. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.