Previous dosimetric studies during PDT of superficial cavitary lesions such as Barret’s esophagus, trachea and nasopharyngeal malignancies demonstrated significant intra- and inter-patient variations in fluence rate build up as a result of tissue surface re-emitted and reflected photons. The total fluence rate at the cavity surface consists of a direct incident term, i.e. photons directly from the source entering the tissue and a scatter term and will therefore affect the response to PDT as a result of the number of photons available for photosensitizer absorption. The build-up factor depends on the optical properties and geometry. Recently a Foscan™ mediated PDT study of tumors in the paranasal sinuses after partial maxillectomy and/or endoscopic sinus surgery was initiated. These geometries are complex in shape, and have spatially varying optical properties, therefor pre-planning and in-vivo dosimetry to ensure a steady and effective light dose delivered to the tumor while securing the vital structures is required.
For this purpose, two 3D mesh based light transport models were developed. An empirical model that utilizes a linear function that determines the build-up factor as function of the source to surface distance, and an analytical model based on Lambert’s cosine law and an average diffuse reflectance. Both models were evaluated by means of 3D printed tissue optical phantoms, and a porcine tissue model. The models are within ± 20% accurate and have the potential to determine the optimal source location (OSL) along with the output power settings. EM navigation can be used to guide the source to the OSL.
This ex vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy oral tissue, with the aim to develop a technique that can be used to determine a complete excision of tumor through intraoperative margin assessment.
DRS spectra were acquired on fresh surgical specimens from patients with an oral squamous cell carcinoma. The spectra represent a measure of diffuse light reflectance (wavelength range of 400-1600 nm), detected after illuminating tissue with a source fiber at 1.0 and 2.0 mm distances from a detection fiber. Spectra were obtained from 23 locations of tumor tissue and 16 locations of healthy muscle tissue. Biopsies were taken from all measured locations to facilitate an optimal correlation between spectra and pathological information.
The area under the spectrum was used as a parameter to classify spectra of tumor and healthy tissue. Next, a receiver operating characteristics (ROC) analysis was performed to provide the area under the receiver operating curve (AUROC) as a measure for discriminative power.
The area under the spectrum between 650 and 750 nm was used in the ROC analysis and provided AUROC values of 0.99 and 0.97, for distances of 1 mm and 2 mm between source and detector fiber, respectively.
DRS can discriminate tumor from healthy oral tissue in an ex vivo setting. More specimens are needed to further evaluate this technique with component analyses and classification methods, prior to in vivo patient measurements.
The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan®-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy–induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan® absorption.
In-vivo optical spectroscopy and the determination of tissue absorption and scattering properties have a central role in the development of novel optical diagnostic and therapeutic modalities in medicine. A number of techniques are available for the optical characterization of tissue in the visible near-IR region of the spectrum. An important consideration for many of these techniques is the reliability of the absorption spectrum of the various constituents of tissue. The availability of accurate absorption spectra in the range 600 to 1100 nm may allow for the determination of the concentration of key tissue constituents such as oxy- and deoxy-hemoglobin, water, and lipids. The objective of the current study is the determination of a reliable absorption spectrum of lipid(s) that can be used for component analysis of in-vivo spectra. We report the absorption spectrum of a clear purified oil obtained from pig lard. In the liquid phase above 36°C, the oil is transparent and thus suitable for collimated transmission measurements. At room temperature, the oil is a solid grease that is highly scattering. The absorption and scattering properties in this solid phase are measured using time- and spatially resolved diffuse reflectance spectroscopy. Using these three independent measurement techniques, we have determined an accurate estimate for the absorption spectrum of mammalian fat.
We use spatially resolved diffuse remittance spectroscopy (DRS) for the measurement of absorption (µa) and reduced scattering (µ) coefficients of normal and malignant breast tissue in vivo during surgery. Prior to these measurements, the linearity of the measurement technique was evaluated on liquid optical phantoms. In addition, the reproducibility of in-vivo tissue measurements was determined on a healthy volunteer. We present results of the in-vivo measurement of optical properties in the wavelength range from 600 to 1100 nm performed during radical mastectomy. A total of 24 patients were included in the study. Both the absorption and reduced scattering properties show large variations. Significant differences in optical properties between normal (glandular plus lipid rich tissue) and tumor tissues are present in 74% of all patients. However, in some cases the tumor showed lower values than normal tissue, and in other cases this was the other way around. Thus, a general trend in optical properties is not observed. However, the average absorption contrast of all patients as a function of wavelength reveals an optimal contrast peak at 650 nm. We believe that this relates to a difference in vascular saturation between tumor and adjacent normal tissue.
Absorption and reduced scattering coefficients calculated from spatially resolved diffuse reflectance measurements are usually assumed to be unreliable for wavelengths lower than approximately 600 nm. A correction factor was developed for non-homogenous distribution of absorbers concentrated in discrete cylindrical blood vessels. The concept of an effective absorption coefficient extends the applicability of diffusion theory too much lower wavelength regions.
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