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Understanding user challenges with light dosimeters is crucial for designing more acceptable devices and advancing light exposure research. We systematically evaluated the usability and acceptability of a light dosimeter (lido) with 29 participants who wore the dosimeter near the corneal plane of the eye for 5 days. Common reasons for not wearing the dosimeter included exercise, recharging, wet environments, public places, and discomfort. Despite these issues, participants adhered to using the dosimeter with high compliance (89% of recording time). Our findings revealed a significant discrepancy between mean (300 lxmEDI) and median (51 lxmEDI) melanopic equivalent daylight illuminance. This discrepancy indicates that the participants were exposed to significantly lower light levels most of the time. Specifically, participants were exposed to light levels above 250 lxmEDI for only 14% of their wearing time. This highlights the need for increased exposure to recommended light levels. In the evening, participants were exposed to less than the recommended 10 lxmEDI for 58% of their wearing time, which is in line with the guidelines for reducing light exposure before sleep. This study highlights the urgent need for strategies to increase daily light exposure that are more in line with circadian health recommendations. [ABSTRACT FROM AUTHOR]

Background: Erythropoietic protoporphyria (EPP) causes painful light sensitivity, limiting quality of life. Our objective was to develop and validate a wearable light exposure device and correlate measurements with light sensitivity in EPP to predict and prevent symptoms. Methods: A wearable light dosimeter was developed to capture light doses of UVA, blue, and red wavelengths. A prospective observational pilot study was performed in which five EPP patients wore two light dosimeters for 3 weeks, one as a watch, and one as a shirt clip. Results: Standard deviation (SD) increases from the mean in the daily blue light dose increased the odds ratio (OR) for symptom risk more than the self‐reported outdoor time (OR 2.76 vs. 2.38) or other wavelengths, and a one SD increase from the mean in the daily blue light wristband device dose increased the OR for symptom risk more than the daily blue light shirt clip (OR 2.45 vs. 1.62). The area under the receiver operator curve for the blue light wristband dose was 0.78, suggesting 78% predictive accuracy. Conclusion: These data demonstrate that wearable blue light dosimetry worn as a wristband is a promising method for measuring light exposure and predicting and preventing symptoms in EPP. [ABSTRACT FROM AUTHOR]

The multifaceted nature of photodynamic therapy (PDT) requires a throughout evaluation of a multitude of parameters when devising preclinical protocols. In this study, we constructed MCF‐7 human breast tumor spheroid assays to infer PDT irradiation doses at four gradient levels for violet light at 408 nm and red light at 625 nm under normal and hypoxic oxygen conditions. The compacted three‐dimensional (3D) tumor models conferred PDT resistance as compared to monolayer cultures due to heterogenous distribution of photosensitizers along with the presence of internal hypoxic region. Cell viability results indicated that the violet light was more efficient to kill cells in the spheroids under normal oxygen conditions, while cells exposed to the hypoxic microenvironment exhibited minimal PDT‐induced death. The combination of 3D tumor spheroid assays and the multiparametric screening platform presented a solid framework for assessing PDT efficacy across a wide range of different physiological conditions and therapeutic regimes. [ABSTRACT FROM AUTHOR]

Cylindrical light diffusers (CLDs) are often employed for the treatment of large tumors by interstitial photodynamic therapy (iPDT) and photoimmunotherapy (PIT), which involves careful treatment planning to maximize therapeutic dose coverage while minimizing the number of CLDs used. There is, however, a lack of general guidelines regarding optimal positioning of CLDs, in particular when they are inserted in parallel to treat head and neck squamous cell cancer (HNSCC). Therefore, the purpose of this study is to determine the CLD-CLD distances maximizing the necrosis for different geometries of CLD positions and shed light on the influence of different optical parameters on this distance, in particular when HNSCCs are treated by interstitial PIT with cetuximab–IR700 using up to seven CLDs. To that end, Monte-Carlo simulations of the light propagation around CLDs inserted perpendicularly in a semi-infinite tumor were performed to determine the volume receiving a fluence larger than a therapeutic threshold. An optimization algorithm was then used to calculate and maximize the necrosed tumor volumes. Tumor optical properties were derived from published data. Our findings suggest that optimal CLD positioning maximizing the volume of necrosed tumor during interstitial PIT for typical HNSCC optical properties corresponds to a CLD-CLD distance between 11.5- and 13-mm. Variations of the absorption and reduced scattering coefficients have the greatest influence on CLD placements, while tissue anisotropy factor, CLD insertion geometry, CLD length, and the angular dependence of the radiance emitted by the CLDs have minimal influence. At first approximation the influence of these optical parameters on optimal CLD-CLD distance are independent. Our data also suggests it is possible to derive new treatment plans using knowledge of previous treatment plans. [ABSTRACT FROM AUTHOR]

Photodynamic Therapy (PDT) is a medical approach method based on the interaction between photosensitive agents and light to generate reactive oxygen species to selectively eliminate malignant cells. To optimize PDT effectiveness while minimizing side effects, precise light dosimetry is important. In this talk I will provide an insight into the central role of PDT light dosimetry, elucidating its principles, importance, and practical applications. This presentation commences by laying the foundation of light dosimetry principles, highlighting the critical elements of the light source, the computation of light parameters, and the determination of the therapeutic light dose. The interdependence of these factors in influencing PDT outcomes is emphasized. Furthermore, challenges inherent in light dosimetry, including tissue optical properties and light distribution, are explored, underscoring the necessity for optimized dosimetry strategies, such as Monte Carlo simulations. Studies performed by our group in Brazil are examples of what is possible to do to optimize PDT outcomes. Emerging trends and research focus areas that promise to expand PDT's therapeutic potential and clinical applications are also considered. In conclusion, this presentation highlights the fundamental role of light dosimetry in PDT. Showing that precision, safety, and knowledge concerning light interaction with tissues are essential for the establishment of a personalized PDT dosimetry and hence therapeutic success. [ABSTRACT FROM AUTHOR]

Controllable and effective irradiation of lesions is among the key factors that affect the potency of photodynamic therapy (PDT). An optimization method for the irradiance distribution of treatment was proposed which can be used to improve the efficacy of PDT and allow more lesions to receive the desired irradiance level in a single therapy session. With the proposed digital illumination binocular treatment system, the preferred surface normal vectors, irradiation angles, as well as area and weight coefficients of lesions can be achieved and used as characteristic parameters to optimize the irradiation direction. Two port-wine stain phantom experiments were performed. The comparison of the illumination area between preoptimization and postoptimization showed that the proposed method can effectively guide the light source control, improve the distribution of light dose, and increase the effective treatment area. [ABSTRACT FROM AUTHOR]

Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT624 induced more apoptosis than HAL-PDT410 and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) for the treatment of prostate cancer has been demonstrated to be a safe treatment option capable of inducing tissue destruction and decreasing prostate specific antigen (PSA) levels. However, prostate-PDT results in large intra- and interpatient variations in treatment response, possibly due to biological variations in tissue composition and short-term response to the therapeutic irradiation. Within our group, an instrument for interstitial PDT on prostate tissue has been developed that combines therapeutic light delivery and monitoring of light transmission via numerous bare-ended optical fibers. Here, we present algorithms that utilize data on the light distribution within the target tissue to provide realtime treatment feedback based on a light dose threshold model for PDT. This realtime dosimetry module is implemented to individualize the light dose and compensate for any treatment-induced variations in light attenuation. More specifically, based on the light transmission signals between treatment fibers, spatially resolved spectroscopy is utilized to assess the effective attenuation coefficient of the tissue. These data constitute input to a block-Cimmino optimization algorithm, employed to calculate individual fiber irradiation times provided the requirement to deliver a predetermined light dose to the target tissue while sparing surrounding sensitive organs. By repeatedly monitoring the light transmission signals during the entire treatment session, optical properties and individual fiber irradiation times are updated in realtime. The functionality of the algorithms is tested on diffuse light distribution data simulated by means of the finite element method (FEM). The feasibility of utilizing spatially resolved spectroscopy within heterogeneous media such as the prostate gland is discussed. Furthermore, we demonstrate the ability of the block-Cimmino algorithm to discriminate between target tissue and organs at risk (OAR). Finally, the realtime dosimetry module is evaluated for treatment scenarios displaying spatially and temporally varying light attenuation levels within the target tissue. We conclude that the realtime dosimetry module makes it possible to deliver a certain light dose to the target tissue despite spatial and temporal variations of the target tissue optical properties at the therapeutic wavelength. [ABSTRACT FROM AUTHOR]

Objective To develop an interstitial laser light delivery system using multiple optical fibres for photodynamic therapy (PDT) in the treatment of prostate cancer. Patients and methods A laser beam was divided equally with a 1×4 fibre splitter to deliver PDT simultaneously through four 2-cm long, flexible cylindrical optical diffusers. Biplanar transrectal ultrasonography (TRUS) and a template were used to position the optical fibres percutaneously. In vivo measurements of light penetration depth (1/μeff ) in prostate tissue were made in seven patients, using a sheathed isoprobe to measure light fluence rates at varying radial distances from the diffuser. The prostate was fixed with stabilization needles to minimize displacement during needle placement. Results The mean (sd, range) μeff in the prostates of the seven patients was 0.35 (0.07, 0.22–0.44) mm-1 , which produced closely parallel slopes of light attenuation. However, there was up to a 10-fold variation in absolute light levels at the same diffuser–detector separation distances amongst the seven patients, probably caused by blood pooling around the diffuser light source. A similar problem around the isoprobe detector was overcome by sheathing the probe in clear plastic tubing. By stabilizing the prostate, the optical fibre positioning was precise to within 2 mm. Conclusion Although this light delivery and TRUS assembly were developed for clinical PDT in the prostate, the same instrumentation can be used reliably for in vivo light-penetration studies. Haemorrhage was unpredictable and highlighted one of the main problems which needs to be overcome. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is currently being evaluated as a minimally invasive procedure for endometrial ablation not requiring anaesthesia. Light penetration depths at 630, 660 and 690 nm and the optimal configuration of intrauterine light-diffusing fibres were determined in 14 human uteri to assist in the design of a light intrauterine device. Post-menopausal ex-vivo uteri showed a significantly lower light penetration depth than pre-menopausal uteri. With a single central diffusing fibre inserted, the fluence rate measured in the uterine wall at the most remote point of the cavity decreased to 1.1 ± 0.4% of that measured at closest proximity, whereas it decreased to only 40.0 ± 9.0% with three fibres. Distension of the uterine cavity with 2 ml of an optically clear fluid increased the fluence rate at the fundus between the fibres at a depth of 2 mm by a factor of 4. We conclude that in normal-sized pre-menopausal uterine cavities, three diffusing fibres will deliver an optical dose above the photodynamic threshold level at a depth of 4 mm, even in the most remote areas, in <30 min without causing thermal damage. For distorted and elongated cavities, either slight distension of the cavity or the insertion of a fourth diffusing fibre is required. [ABSTRACT FROM PUBLISHER]

This paper presents a design of an applicator for light delivery and light dosimetry during endobronchial photodynamic therapy (EB-PDT). The design incorporates a linear diffuser that is fixed in the centre of the lumen by a steel spring basket that does not block air flow. An isotropic light detector is included in this design, to measure the light fluence actually delivered to the bronchial mucosa surface. The applicator is designed for use with common bronchoscopy equipment, and can be used with bronchoscopes with a large biopsy channel ( approximately 3 mm). The first clinical measurements were performed and caused no additional discomfort to the (nonphotosensitized) patients. The data showed considerable inter-patient variability of the light fluence rate measured as a result of fixed output power of the diffuser. This fact and the expected strong dependence of the fluence rate on the lumen diameter stress the importance of in situ fluence rate measurement for a proper evaluation of the relationship between light fluence and the biological response of EB-PDT. [ABSTRACT FROM AUTHOR]

There have been few studies to date of clinical photodynamic therapy (PDT) with tetra(m-hydroxyphenyl)chlorin (mTHPC). This paper describes the results of the authors' experience with this second-generation photosensitizer, used in the treatment of 40 early cancers of the oesophagus and the bronchi. Surface illumination of the tumour was performed, in most cases, 4 days after intravenous injection of 0.15 mg kg of mTHPC, using 652 nm or 514 nm continuous wave laser light. Endoscopic follow-up with biopsies and brushings was possible for 35 tumours: 27 (77%) showed no recurrence after disease-free follow-ups that ranged from 3 to 38 months. Major complications, all of which were after red light illumination, included one bronchial stenosis, one oesophagotracheal fistula and two probable occult perforations of the oesophagus. Photodynamic therapy with green light renders such perforations of the oesophageal wall essentially impossible at the applied conditions, and appears not to reduce the efficacy of the treatment. Skin photosensitization, which was never observed later than the first week after injection, occurred in 12 patients. Hence, PDT with mTHPC is a safe and effective treatment for early carcinomas of the oesophagus and the tracheobronchial tree. [ABSTRACT FROM AUTHOR]

Under identical conditions (drug and light dose, timing), the results of photodynamic therapy (PDT) of carcinomas of the bronchi with tetra(meta-hydroxyphenyl)chlorin (mTHPC) show large variations between patients. Before patients underwent PDT treatment, the mTHPC level was measured in the lesion, the normal surrounding tissue and the oral cavity, with an apparatus based on fluorescence spectroscopy. The fluctuations in degree of tissue reaction and tumour destruction between patients could be explained by individual variations in the mTHPC level in the mucosa of the bronchi. The patients who showed the highest mTHPC fluorescence signal also had the strongest response to PDT. In addition, a correlation between the mTHPC level in the oral cavity and bronchial mucosa was found. It is concluded that PDT can be improved by measuring the mTHPC level in the bronchi or the oral cavity before treatment by fluorescence spectroscopy, and then by adjusting the light dose to be applied to the observed mTHPC level. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a treatment modality with potential application for premalignant lesions and squamous cell carcinoma of the oral mucosa. PDT in principle has dual selectivity. This may result from a 'preferential' retention of the photosensitizer in target tissue. In addition, the photodynamic activity will be limited to the irradiated area because PDT will not affect tissues in the absence of excitation light. The specificity of PDT is limited by the fact that normal tissues also retain the photosensitizer to some degree, which makes these tissues susceptible to PDT damage. To optimize PDT for oral malignancies, a study was undertaken on normal tissue to investigate the responses in rat palatal mucosa and surrounding anatomical structures. Eighty male Wistar rats were used in the study. Photofrin was administered i.v. at four doses (0, 2.5, 5 or 10 mg kg body weight). Irradiation for PDT was performed 24 h later. An argon pumped dye laser system was used to produce light of two different treatment wavelengths (514.5 and 625 nm), and various energy density levels (0, 25, 50, 100 or 200 J cm). Early effects of PDT were studied at 2 days and late effects at 2 months after treatment. Twenty-four hours after i.v. administration of Photofrin, it was found that PDT affects normal tissues of the oral cavity both macroscopically and microscopically. Combinations of photosensitizer doses ≥5 mg kg and light doses≥100 J cm caused severe and permanent damage to the palatal mucosa and adjacent normal structures such as palatal bone and dentition. Light scattering and internal reflection usually raise the fluence rate in tissue above the irradiance of the incident beam. In an additional study using six male Wistar rats, the energy fluence rate at two treatment wavelengths (514.5 and 625 nm) was measured ex vivo in the palatal mucosa and adjacent anatomical structures. As expected, the energy fluence rates were wavelength, tissue and depth dependent. At the air-mucosa boundary, light of 625 nm was found to have a three-times higher fluence rate than the primary incident beam. Under similar conditions, the fluence rate of 514.5 nm was found to be less, but still twice as high as the primary incident beam. At deeper levels of the rat maxilla, fluence rates were still elevated compared with the incident beam. For 625 nm light, this phenomenon was observed up to the level of the nasal cavity. These increased fluence rates could largely explain the pattern of damage to normal mucosa and surrounding anatomical structures. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) using 5-aminolaevulinic-acid-(ALA)-induced protoporphyrin IX (PPIX) increases survival in hamsters with pancreatic cancer. However, experiments with other photosensitizers on this model show a high risk of duodenal perforation. In this paper, the pharmacokinetics and PDT effects of ALA on normal tissues in the pancreatobiliary region are presented. Using quantitative fluorescence microscopy, maximum PPIX fluorescence was seen in the bile ducts, less in the duodenal mucosa and least in the muscularis propria and pancreas. For PDT, light was delivered either using a bare fibre touching the tissue (single-point illumination), or irradiating a 1.5 cm diameter circular area. Single-point PDT (50 J) produced only localized reversible damage without perforation. Surface irradiation of the whole periampullary region (50 J cm) caused extensive damage, sometimes with perforation. Before PDT can be used safely to treat tumours of the pancreas and bile duct, further studies are necessary to understand its effect on larger areas of normal tissue. [ABSTRACT FROM AUTHOR]

We describe the calibration of fibre optic probes used to perform in vivo light dosimetry studies during the treatment of skin lesions by photodynamic therapy. Results from six individual detectors show that the linearity of the calibration and the calculated radiant energy fluence rate within a liquid phantom are independent of the type and sensitivity of the probe. The method of calibration is also shown to yield the optical interaction coefficients of the phantom. [ABSTRACT FROM AUTHOR]

Accurate measurement of light distribution in tissue can improve the knowledge of in vivo tissue optical properties, which is essential for precise dosimetry calculations during photodynamic therapy (PDT). In our application of PDT, superficial skin lesions are treated by topical administration of 5-aminolaevulinic acid followed by surface illumination using 630 nm laser light. Several small detector probes inserted under the skin surface prior to illumination record the light intensity at different depths throughout the treatment. Results from 11 patients are presented. These results indicate light distributions described by the diffusion theory for light transport in tissue. The accumulated data do not imply one specific set of optical parameters for the skin, but indicate that although the depth of light penetration is constant for all patients, the variation in skin colour is significant when performing dosimetry calculations. The average value of effective attenuation coefficient was found to be 0.359 mm (±9.5%) and the coefficient k that is used to quantify the build-up of subsurface fluence rate varies between 0.12 and 8.23. [ABSTRACT FROM AUTHOR]

For precise light dosimetry in photodynamic therapy (PDT), the light penetration characteristics of the tissue concerned need to be assessed. Several attenuation coefficients have so far been measured using 633 nm wavelength red light and human tissue obtained from autopsy or surgery. However, the validity of such ex vivo derived values remains uncertain, and hence is evaluated further in this study. Using a rat thigh muscle model, the tissue transmittance of 633 nm red light was compared between in vivo and ex vivo. Transmittance (in vivo) following preliminary injection of 40 mg kg haematoporphyrin derivative (HPD) was also measured in muscle and liver. The effective attenuation coefficient (⌆) ex vivo in muscle was 0.98±0.06 mm and in vivo 0.97 ± 0.05 mm. Values agreed within experimental error indicating that in this tissue, changes from in vivo to post-mortem produced no alteration in optical penetration at 633 nm. Preliminary injection of HPD did not influence the penetration depth in muscle although significant changes were observed in an organ of high porphyrin avidity, the liver (0.68±0.08 mm vs 0.40±0.08 mm with HPD). Until techniques for in vivo measurements of light attenuation coefficient become available, the use of ex vivo derived values with 633 nm wavelength light would seem appropriate. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has attracted attention because it was considered to be a selective form of cancer treatment causing minimal damage to normal tissues. This is not exactly true, because the ratio between the photosensitizer concentrations in tumour and surrounding normal tissues is not always much more than one. Nevertheless, tumour destruction by PDT with relatively little damage to normal tissue is possible in many cases. This requires sophisticated light delivery and/or light dosimetry techniques. In this respect the limited penetration of light into biological tissues can sometimes be useful. In this paper a qualitative and sometimes quantitative discussion is given of the physical phenomena determining the energy fluence in a biological tissue. Most important is light scattering, the contribution of which depends on the geometrical conditions. Finite beam surface irradiation, irradiation of hollow organs (bladder) and interstitial irradiation are discussed separately. The emphasis is on light 'dose' and light dose distribution. It is emphasized that PDT dosimetry in general is complicated by photosensitizer distribution (which is usually not known), by photobleaching of the sensitizer, by possible effects of hyperthermia, and by changes in optical properties during and as a result of PDT. [ABSTRACT FROM AUTHOR]

Optimal delivery of light to the tumour is of considerable importance in photodynamic therapy. The most effective way of delivering laser light to the tumour tissue is through an implanted optical fibre. In order to investigate the possible effects taking place at the tips of fibres implanted in tissue, fibres were used to deliver light to human blood and the transmission of light by the blood was measured at different power levels. The maximum power level which could be delivered without charring or coagulation at the fibre tip was measured for five different fibres. Three plane cut fibres and two with 1.5 cm long diffusing tips were studied. Charring and coagulation, which resulted in practically no light being delivered more than 0.5 mm from the fibre tip, were observed at relatively low-output powers (70-130 mW) for all the plane-cut fibres. This is less than the level required to deliver a clinically useful dose in a reasonable time. In contrast, neither charring nor coagulation was observed at the diffusing tips for output powers up to 1.1 W and consequently these should be the fibres of choice for interstitial photodynamic therapy. Observed changes in light transmission through the blood with increasing output power indicate that, for accurate light dosimetry, a means of monitoring delivered light in vivo during photodynamic therapy is essential. [ABSTRACT FROM AUTHOR]

Knowledge of the radiant energy fluence rate in tissues during laser irradiation is important for the understanding and improvement of the results of preclinical as well as clinical treatments. Quantitative data are extremely rare, however. In this paper, quantitative measurements of energy fluence rates are reported, in vitro as well as in vivo, with emphasis on light dosimetry for photodynamic therapy. Examples are given of fluence rate distributions that may occur during surface irradiation, intracavity irradiation of hollow organs (bladder) and interstitial irradiation. For the same incident irradiance, the energy fluence rate in tissue may vary considerably, depending on type of tissue, wavelength and geometry. During experimental and clinical interstitial PDT-treatments a considerable decrease in light penetration into tumours was observed, apparently indicating changes in optical properties as a result of treatment. This demonstrates the importance of in vivo light dosimetry. [ABSTRACT FROM AUTHOR]