Efficient algorithm to calculate the optical properties of breast tumors by high-order perturbation theory.

An efficient algorithm to obtain the solutions for n-th order terms of perturbation expansions in absorption, scattering, and cross-coupling for light propagating in human tissue is presented. The proposed solution is free of any approximations and makes possible fast and efficient estimates of mammographic, optical tomographic, and fluorescent images, applying a perturbation order of 30 and more. The presented analysis sets the general limits for the applicability of the perturbation approach as a function of tumor size and optical properties of the human tissue. The convergence tests of the efficient calculations for large absorbing objects show excellent agreement with the reference data from finite element method calculations. The applicability of the theory is demonstrated in experiments on breast-like phantoms with high absorbing and low-scattering lesions.

Oxidation-Sensitive Core-Multishell Nanocarriers for the Controlled Delivery of Hydrophobic Drugs.

A synthetic route for oxidation-sensitive core-multishell (osCMS) nanocarriers was established, and their drug loading and release properties were analyzed based on their structural variations. The nanocarriers showed a drug loading of 0.3-3 wt % for the anti-inflammatory drugs rapamycin and dexamethasone and the photosensitizer meso-tetra-hydroxyphenyl-porphyrin (mTHPP). Oxidative processes of the nanocarriers were probed in vitro by hydrogen peroxide, and the degradation products were identified by infrared spectroscopy supported by ab initio calculations, yielding mechanistic details on the chemical changes occurring in redox-sensitive nanocarriers. Oxidation-triggered drug release of the model drug Nile Red measured and assessed by time-dependent fluorescence spectroscopy showed a release of up to 80% within 24 h. The drug delivery capacity of the new osCMS nanocarriers was tested in ex vivo human skin with and without pretreatments to induce local oxidative stress. It was found that the delivery of mTHPP was selectively enhanced in skin under oxidative stress. The number and position of the thioether groups influenced the physicochemical as well as drug delivery properties of the carriers.

Adsorption of Mono- and Divalent 4-(Dimethylamino)pyridines on Gold Surfaces: Studies by Surface-Enhanced Raman Scattering and Density Functional Theory.

The adsorption thermodynamics of 4-(dimethylamino)pyridine (DMAP) and its five divalent derivatives di-DMAP- n (2 ≤ n ≤ 6) with gradually increasing methylene-spacer lengths n binding to planar gold surfaces has been studied by surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT). SERS intensities of the totally symmetrical breathing mode of the pyridine ring at approximately 1007 cm-1 are used to monitor the surface coverage of the DMAP and di-DMAP- n ligands on gold surfaces at different concentrations. The equilibrium constant as a measure of the binding affinity is obtained from these measurements by using a modified Langmuir isotherm. Due to multivalent binding to the gold substrate, a characteristic enhancement of the binding affinity of di-DMAP- n compared to the monovalent DMAP is observed for all divalent species. First principles calculations of the di-DMAP- n ligands on an ideal Au(111) surface model as well as step terrace models have been performed to understand the adsorption structures and the multivalent binding enhancements. Furthermore, Raman spectra of the adsorbed molecules have been studied by first principles calculations to correlate the binding affinities to experimentally determined adsorption constants. The joint experimental and theoretical investigation of an oscillatory behavior of the binding affinity as a function of the methylene-spacer length in mono- and divalent 4-(dimethylamino)pyridines reveals that the molecular architecture plays an important role for the structure-function interplay of multivalently bound adsorbates.

Charge Effects on the Efflorescence in Single Levitated Droplets.

The influence of electrical excess charges on the crystallization from supersaturated aqueous sodium chloride solutions is reported. This is accomplished by efflorescence studies on single levitated microdroplets using optical and electrodynamic levitation. Specifically, a strong increase in efflorescence humidity is observed as a function of the droplet's negative excess charge, ranging up to -2.1 pC, with a distinct threshold behavior, increasing the relative efflorescence humidity, at which spontaneous nucleation occurs, from 44% for the neutral microparticle to 60%. These findings are interpreted by using molecular dynamics simulations for determining plausible structural patterns located near the particle surface that could serve as suitable precursors for the formation of critical clusters overcoming the nucleation barrier. These results, facilitating heterogeneous nucleation in the case of negatively charged microparticles, are compared to recent work on charge-induced nucleation of neat supercooled water, where a distinctly different nucleation behavior as a function of droplet charge has been observed.

Control of coherent excitation of neon in the extreme ultraviolet regime.

Coherent excitation of a superposition of Rydberg states in neon by the 13th harmonic of an intense 804 nm pulse and the formation of a wave packet is reported. Pump-probe experiments are performed, where the 3d-manifold of the 2p6-->2p5 (2P3/2) 3d [1/2]1- and 2p6-->2p5 (2P3/2) 3d [3/2]1-transitions are excited by an extreme ultraviolet (XUV) radiation pulse, which is centered at 20.05 eV photon energy. The temporal evolution of the excited state population is probed by ionization with a time-delayed 804 nm pulse. Control of coherent transient excitation and wave packet dynamics in the XUV-regime is demonstrated, where the spectral phase of the 13th harmonic is used as a control parameter. Modulation of the phase is achieved by propagation of the XUV-pulse through neon of variable gas density. The experimental results indicate that phase-shaped high-order harmonics can be used to control fundamental coherent excitation processes in the XUV-regime.

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.

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.

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.

Controlled low-temperature molecular manipulation of sexiphenyl molecules on Ag111 using scanning tunneling microscopy.

A novel scanning tunneling microscope manipulation scheme for a controlled molecular transport of weakly adsorbed molecules is demonstrated. Single sexiphenyl molecules adsorbed on a Ag(111) surface at 6 K are shot towards single silver atoms by excitation with the tip. To achieve atomically straight shooting paths, an electron resonator consisting of linear standing-wave fronts is constructed. The sexiphenyl manipulation signals reveal a pi ring flipping as the molecule moves from the hcp to fcc site. Ab initio calculations show an incorporation of the Ag atom below the center of a pi ring.

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.