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Biomedical subjects

Robert Weersink

Publications and source records attributed to Robert Weersink.

5 recordsLinked to original sources

Towards conformal light delivery using tailored cylindrical diffusers: attainable light dose distributions.

Interstitial light delivery for therapeutic applications requires the use of fibre-based light diffusers. Such diffusers are presently manufactured to emit with a flat longitudinal power profile. Recently, diffusers with tailored longitudinal emission profiles have become available opening an avenue to improve conformal light delivery. This paper explores the ability of tailored diffusers to improve light dose confinement to the target volume. A formalism to calculate the light dose from an arbitrary source distribution is presented based on the convolution with an appropriate point source function. By choosing a source distribution corresponding to a cylindrical diffuser emitting with a sinusoidal profile, the set of attainable light dose distributions is characterized via a relationship between the diffuser's spatial frequency, the radial distance and the amplitude of the isodose contour.

Biophysical Phenomena↗

Photodynamic therapy for urological malignancies: past to current approaches.

PURPOSE: Modern PDT for urological tumors is a potentially selective approach in which in situ photosensitization by a nontoxic drug, locally activated by light, generates cytotoxic reactive oxygen species, causing cell death. While urological clinical experience with PDT is largely limited to treatment for superficial bladder cancer, the advent of novel photosensitizers and technologies for treatment planning, light delivery and dosimetry, PDT for prostate and other urological cancers appears increasingly realistic. MATERIALS AND METHODS: We reviewed the current literature on PDT for urological tumors, in addition to recent emerging data from our laboratory and elsewhere. RESULTS: Remarkable progress has been made in the field of photochemistry and photobiology. Together with improved optical delivery and imaging systems PDT holds promise as an alternative, minimally invasive and potentially curative treatment for localized solid tumors as well as for palliative treatment for isolated, clinically problematic metastases. CONCLUSIONS: Current experience with photodynamic therapy using contemporary photosensitizing agents and light sources is mainly restricted to in vivo experimental models and early phase clinical trails. However, ongoing preclinical work and clinical trials indicate that safer and effective PDT treatments in uro-oncology are imminent.

Genital Neoplasms, Male↗

Partial least squares based decomposition of five spectrally overlapping factors.

The development of a multi-sensory fiber-optic based fluence rate probe (MSP) for light monitoring and dosimetry during photodynamic therapy (PDT) created the need for a robust multivariate signal analysis algorithm capable of quantifying the intensity of five component spectra, representing the sensors, which display a large degree of spectral overlap. Partial least squares (PLS) analysis, as an option for such an analysis algorithm, was evaluated through simulations in the presence of three types of noise, which experimentally may limit the accuracy of PLS quantification of component spectra contributions. Random, or white noise, background was varied over a range of 0-15% relative intensity. A non-random (Gaussian) background vector was simulated, as an experimentally relevant spectral interferent, over a range of 0-7% relative intensity. Spectral variation was modeled by a spectral shift of +/-1-5 nm. Procedures for selecting preferred combinations of fluorophores, with minimum possible spectral overlap, were developed. To illustrate the importance of this selection process, PLS performance results were compared for two possible combinations of five fluorophores, as well as for the combination of three fluorophores currently in experimental use with MSPs. Experimentally anticipated worst-case quantifications were identified for all three types of simulated noise (5% random background, 0.5% Gaussian background, and +/-2 nm spectral shift). The effects of single and combined types of noise were evaluated by independently varying each type of simulated noise over the experimentally relevant range. The mean percentage error in determining the fluorophore contributions and hence quantification of the fluence rate were compared with the required performance standard of better than 10% error for optical power meters in medical use. The PLS algorithm provided an accuracy of 7 +/- 2% for five fluorophores and 3.3 +/- 0.8% for three fluorophores, indicating that PLS is an appropriate choice for this application.

Algorithms↗

Lethal photosensitization of periodontal pathogens by a red-filtered Xenon lamp in vitro.

BACKGROUND: The ability of Helium-Neon (He-Ne) laser irradiation of a photosensitizer to induce localized phototoxic effects that kill periodontal pathogens is well documented and is termed photodynamic therapy (PDT). OBJECTIVES: We investigated the potential of a conventional light source (red-filtered Xenon lamp) to activate toluidine blue O (TBO) in vitro and determined in vitro model parameters that may be used in future in vivo trials. MATERIALS AND METHODS: Porphyromonas gingivalis 381 was used as the primary test bacterium. RESULTS: Treatment with a 2.2 J/cm2 light dose and 50 micro g/ml TBO concentration resulted in a bacterial kill of 2.43 +/- 0.39 logs with the He-Ne laser control and 3.34 +/- 0.24 logs with the lamp, a near 10-fold increase (p = 0.028). Increases in light intensity produced significantly higher killing (p = 0.012) that plateaued at 25 mW/cm2. There was a linear relationship between light dose and bacterial killing (r2 = 0.916); as light dose was increased bacterial survival decreased. No such relationship was found for the drug concentrations tested. Addition of serum or blood at 50% v/v to the P. gingivalis suspension prior to irradiation diminished killing from approximately 5 logs to 3 logs at 10 J/cm2. When serum was washed off, killing returned to 5 logs for all species tested except Bacteroides forsythus (3.92 +/- 0.68 logs kill). CONCLUSIONS: The data indicate that PDT utilizing a conventional light source is at least as effective as laser-induced treatment in vitro. Furthermore, PDT achieves significant bactericidal activity in the presence of serum and blood when used with the set parameters of 10 J/cm2, 100 mW/cm2 and 12.5 micro g/ml TBO.

Aggregatibacter actinomycetemcomitans↗

Photodynamic therapy for the treatment of metastatic lesions in bone: studies in rat and porcine models.

This study represents the first reported use of photodynamic therapy (PDT) for metastatic bone lesions and specifically, as a treatment for spinal metastases. A model of bone metastasis in rat confirmed the efficacy of benzoporphyrin derivative-monoacid-mediated PDT for treating lesions within the spine and appendicular bone. Fluorimetry confirmed the selective accumulation of drug into the tumor(s) at 3 h post-injection. 48 h post-light delivery into the vertebral body of the rat spine loss of bioluminescent signal and histological analyses of sectioned spine confirmed MT-1 tumor cell kill in vivo as previously confirmed in vitro using an established cell viability assay. Porcine vertebrae provided a model comparable to that of human for light propagation and PDT response. Histological examination of vertebrae 48 h post-PDT revealed a necrotic radius of 0.6 cm with an average fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident up to 2 cm out from the treatment fiber. Results support the application of PDT to the treatment of primary or metastatic lesions within bone.

Animals↗