Diffuse-reflectance spectroscopy from 500 to 1060 nm by correction for inhomogeneously distributed absorbers

Diffuse-reflectance spectroscopy for measurement of the absorption and scattering coefficients of biological tissue produces reliable results for wavelengths from 650 to 1050 nm. Implicitly, this approach assumes homogeneously distributed absorbers. A correction factor is introduced for inhomogeneous distribution of blood concentrated in discrete cylindrical vessels. This factor extends the applicability of diffusion theory to lower wavelengths. We present measurements of in vivo optical properties in the wavelength range 500-1060 nm.     

Combinatorial Chemistry for Ligand Development in Catalysis: Synthesis and Catalysis Screening of Peptidosulfonamide Tweezers on the Solid Phase

On the basis of a pyrrolidine tweezer 1, a library of peptidosulfonamide tweezers (15a-e, 16a-e) was synthesized on the solid phase. This library was screened in a simultaneous substrate screening procedure for the ability to enantioselectively catalyze the Ti(O-i-Pr)(4)-mediated addition of diethylzinc to aldehydes. One of the best solid-phase tweezer catalyst (i.e., 16d, giving an ee of 32% in solid-phase catalysis) was resynthesized in solution (compounds 20 and 21). The now homogeneous solution-phase catalysis showed even better enantioselectivity (i.e., up to 66%).     

White-light toxicity, resulting from systemically administered 5-aminolevulinic acid, under normal operating conditions

This study has investigated damage to the intraperitoneal organs of the rat after systemic (intraperitoneal and intravenous) administration of low doses of 5-aminolevulinic acid (ALA) and illumination with a standard white-light operating-room (o.r.) lamp. The study has been done within the framework of a larger study in which the possibility of using ALA for localization of small-volume macroscopically nonvisible peritoneal metastasis of ovarian tumors is being investigated. Fluorescence diagnostics are done in addition to the standard staging and localization procedures, either through a laparoscope or during laparotomy. In these circumstances, fluorescence diagnostics involve some risk of photosensitization of critical organs since a broad-band (o.r.) light source is used during the surgical procedures for illumination of the operating area. The drug dose and the time interval between administration of ALA and illumination are varied and normal tissues are examined both macroscopically and microscopically for damage. A relationship is demonstrated between the maximum tolerable dose (MTD) of ALA (defined as the dose that does not cause any tissue damage) and the time interval between administration and illumination. The white light that is used for illumination of the operating area is sufficient to induce damage to the peritoneal organs at relatively low ALA doses. The MDTs for 2, 6 and 16 h intervals are found to be respectively 1, 10 and 100 mg kg⁻¹. The results are similar for both intraperitoneal and intravenous administration.     

Gamma-ray spectroscopy with relativistic exotic heavy-ions

Feasibility of gamma-ray spectroscopy at relativistic energies with exotic heavy-ions and new generation of germanium detectors (segmented Clover) is discussed. An experiment with such detector array and radioactive is discussed.     

Zur Theorie der Gammafunction

Ohne Zusammenfassung Vergl. meine Abhandlung:Om en ny klass af transcendenta functioner, hvilka ?ro n?ra besl?gtade med gammafunktionen, Acta soc. scient. Fennic?, Tom. XIV, XV; 1885, 1886.     

An efficient step size control for continuation methods

In solving a nonlinear equation by the use of a continuation method one of the crucial problems is the choice of the step sizes. We present a model for the total computational cost of a standard numerical continuation process and solve the problem of optimal step size control for this model. Using the theoretical results as a basis, we develop an adaptive step size algorithm for Newton's method. This procedure is computationally inexpensive and it gives quite satisfactory results compared to some other numerical experiments found in the literature.     

Monitoring ALA-induced PpIX photodynamic therapy in the rat esophagus using fluorescence and reflectance spectroscopy

The presence of phased protoporphyrin IX (PpIX) bleach kinetics has been shown to correlate with esophageal response to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) in animal models. Here we confirm the existence of phased PpIX photobleaching by increasing the temporal resolution of the fluorescence measurements using the therapeutic illumination and long wavelength fluorescence detection. Furthermore fluorescence differential pathlength spectroscopy (FDPS) was incorporated to provide information on the effects of PpIX and tissue oxygenation distribution on the PpIX bleach kinetics during illumination. ALA at a dose of 200 mg kg(-1) was orally administered to 15 rats, five rats served as control animals. PDT was performed at an in situ measured fluence rate of 75 mW cm(-2) using a total fluence of 54 J cm(-2). Forty-eight hours after PDT the esophagus was excised and histologically examined for PDT-induced damage. Fluence rate and PpIX photobleaching at 705 nm were monitored during therapeutic illumination with the same isotropic probe. A new method, FDPS, was used for superficial measurement on saturation, blood volume, scattering characteristics and PpIX fluorescence. Results showed two-phased PpIX photobleaching that was not related to a (systematic) change in esophageal oxygenation but was associated with an increase in average blood volume. PpIX fluorescence photobleaching measured using FDPS, in which fluorescence signals are only acquired from the superficial layers of the esophagus, showed lower rates of photobleaching and no distinct phases. No clear correlation between two-phased photobleaching and histologic tissue response was found. This study demonstrates the feasibility of measuring fluence rate, PpIX fluorescence and FDPS during PDT in the esophagus. We conclude that the spatial distribution of PpIX significantly influences the kinetics of photobleaching and that there is a complex interrelationship between the distribution of PpIX and the supply of oxygen to the illuminated tissue volume.     

Protoporphyrin IX fluorescence photobleaching and the response of rat Barrett's esophagus following 5-aminolevulinic acid photodynamic therapy

Barrett's esophagus (BE) can experimentally be treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT), in which ALA, the precursor of the endogenous photosensitizer protoporphyrin IX (PpIX) and subsequent irradiation with laser light are applied to destroy the (pre)malignant tissue. Accurate dosimetry is critical for successful ALA-PDT. Here, in vivo dosimetry and kinetics of PpIX fluorescence photobleaching were studied in a rat model of BE. The fluence and fluence rate were standardized in vivo and PpIX fluorescence was measured simultaneously at the esophageal wall during ALA-PDT and plotted against the delivered fluence rather than time. Rats with BE were administered 200 mg kg(-1) ALA (n = 17) or served as control (n = 4). Animals were irradiated with 633 nm laser light at a measured fluence rate of 75 mW cm(-2) and a fluence of 54 J cm(-2). Large differences were observed in the kinetics of PpIX fluorescence photobleaching in different animals. High PpIX fluorescence photobleaching rates corresponded with tissue ablation, whereas low rates corresponded with no damage to the epithelium. Attempts to influence tissue oxygenation by varying balloon pressure and ventilation were shown not to be directly responsible for the differences in effect. In conclusion, in vivo dosimetry is feasible in heterogeneous conditions such as BE, and PpIX fluorescence photobleaching is useful to predict the tissue response to ALA-PDT.     

Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval

We have previously shown that light fractionation during topical aminolevulinic acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a significant increase in efficacy in both pre-clinical and clinical PDT. However this fractionated illumination scheme required an extended overall treatment time. Therefore we investigated the relationship between the dark interval and PDT response with the aim of reducing the overall treatment time without reducing the efficacy. Five groups of mice were treated with ALA-PDT using a single light fraction or the two-fold illumination scheme with a dark interval of 30 min, 1, 1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during illumination. Visual skin response was monitored in the first seven days after PDT and assessed as PDT response. The PDT response decreases with decreasing length of the dark interval. Only the dark interval of 2h showed significantly more damage compared to all the other dark intervals investigated (P<0.05 compared to 1.5h and P<0.01 compared to 1h, 30 min and a single illumination). No relationship could be shown between the utilized PpIX fluorescence during the two-fold illumination and the PDT response. The rate of photobleaching was comparable for the first and the second light fraction and not dependent of the length of dark interval used. We conclude that in the skin of the hairless mouse the dark interval cannot be reduced below 2h without a significant reduction in PDT efficacy.