Non melanoma skin cancer (NMSC) can be seen as a multifaceted problem, considered primarily as a public health problem whose impact on society considers the morbidity and cost aspects of the treatment. It is a social problem, affecting all those who depend exclusively on the Brazilian public health system and need to wait months to receive any type of treatment. From the economic point of view, to treat all patients diagnosed with NMSC, it is necessary a big investment. Finally, the problem is logistical, since the territorial extension of Brazil and its population distribution do not enable the adequate care in all the places, which requires reallocation of patients from small cities to reference centers. Based on these facts, PDT for small skin lesions may be one of the best solutions from an economic point of view. Being a treatment that is easy for the training of professionals and enables to be performed in an ambulatory environment, minimizing post-treatment effects, this study shows that the cost of implementing the procedure on a large scale is extremely adequate for the national public health service. Using a strategy involving companies, national bank and medical partners, equipment, medication and protocols were tested in a multicenter study. With results collected over 5 years from a national program to implement PDT for non melanoma skin cancer over the Brazilian territory, we could reach a great economic evaluation of advances concerning the use of PDT for skin cancer.
One of the limiting factors of photodynamic therapy is cutaneous permeation of a photosensitizer or precursor. Studies report that there is a strong relationship between temperature and porphyrin synthesis in biological tissue. The use of thermogenic and/or vasodilator substances may favor both ALA/methyl-ALA permeation and protoporphyrin IX (PpIX) production in the tissue. In this study, menthol, methyl nicotinate, and ginger extract were incorporated into either the ALA or methyl-ALA cream to investigate the PpIX production in rat skin. Fluorescence spectra were collected to quantify the PpIX present in tissues. The methyl nicotinate was the one with the highest optimization effect of PpIX production after three hours of incubation of the cream. Its association with methyl-ALA caused the production to be about 50% higher than that observed for methyl-ALA alone. These results are promising as a possible strategy for decreasing the incubation time of the precursor cream in various clinical protocols and increasing the photosensitizer production in lesions.
The photodynamic therapy (PDT) is a therapeutic modality that depends mostly on photosensitizer (PS), light and molecular oxygen species. However, there are still technical limitations in clinical PDT that are under constant development, particularly concerning PS and light delivery. Intense Pulsed Light (IPL) sources are systems able to generate pulses of high energy with polychromatic light. IPL is a technique mainly used in the cosmetic area to perform various skin treatments for therapeutic and aesthetic applications. The goals of this study were to determine temperature variance during the application of IPL in porcine skin model, and the PDT effects using this light source with PS delivery by a commercial high pressure, needle-free injection system. The PSs tested were Indocyanine Green (ICG) and Photodithazine (PDZ), and the results showed an increase bellow 10 °C in the skin surface using a thermographic camera to measure. In conclusion, our preliminary study demonstrated that IPL associated with needle-free injection PS delivery could be a promising alternative to PDT.
Phototherapies have been increasingly used in several applications such as the control of pain and inflammatory processes, photodynamic therapy, and even aesthetics uses. After many decades, the dosimetry for those techniques remains challenging. One of the key issues is the lack of homogeneity obtained for tissue illumination, which may limit adequate treatment. Especially concerning lesions, the surface tissue is usually irregular, and the light does not couple to the tissue efficiently to promote an effective treatment. A series of experiments have been performed using optical phantoms, in which coupling was improved by introducing a gel with a low concentration of scattering agents between the fiber and the phantom as an attempt to improve the homogeneity of light distribution within the phantoms. The effects promoted by roughness on phantom tissue surfaces are considerably attenuated when the coupling gel was introduced, resulting in a more uniform illumination pattern that may be used to promote better phototherapy treatments outcome.
Photodynamic therapy (PDT) is a technique used for several tumor types treatment. Light penetration on biological tissue
is one limiting factor for PDT applied to large tumors. An alternative is using interstitial PDT, in which optical fibers are
inserted into tumors. Cylindrical diffusers have been used in interstitial PDT. Light emission of different diffusers depends
on the manufacturing process, size and optical properties of fibers, which make difficult to establish an adequate light
dosimetry, since usually light profile is not designed for direct tissue-fiber contact. This study discusses the relevance of
light distribution by a cylindrical diffuser into a turbid lipid emulsion solution, and how parts of a single diffuser contribute
to illumination. A 2 cm-long cylindrical diffuser optical fiber was connected to a diode laser (630 nm), and the light spatial
distribution was measured by scanning the solution with a collection probe. From the light field profile generated by a 1
mm-long intermediary element of a 20 mm-long cylindrical diffuser, recovery of light distribution for the entire diffuser
was obtained. PDT was performed in rat healthy liver for a real treatment outcome analysis. By using computational tools,
a typical necrosis profile generated by the irradiation with such a diffuser fiber was reconstructed. The results showed that
it was possible predicting theoretically the shape of a necrosis profile in a healthy, homogeneous tissue with reasonable
accuracy. The ability to predict the necrosis profile obtained from an interstitial illumination by optical diffusers has the
potential improve light dosimetry for interstitial PDT.
Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.
Photodynamic therapy (PDT) is a treatment modality that can be indicated for several cancer types and pre-cancer lesions. One of the main applications of PDT is the treatment of superficial skin lesions such as basal cell carcinoma, Bowen’s disease and actinic keratosis. Three elements are necessary in PDT, a photosensitizer (PS); light at specific wavelength to be absorbed by the PS, and molecular oxygen. A typical PS used for skin lesion is protoporphyrin IX (PpIX), which is an intrinsic PS; its production is stimulated by a pro-drug, such as 5-aminolevulinic acid (ALA). Before starting a treatment, it is very important to follow up the PpIX production (to ensure that enough PS was produced prior to a PDT application) and, during a PDT session, to monitor its photodegradation (as it is evidence of the photodynamic effect taking place). The aim of this paper is to present a unique device, LINCE (MMOptics - São Carlos, Brazil), that brings together two probes that can, respectively, allow for fluorescence imaging and work as a light source for PDT treatment. The fluorescence probe of the system is optically based on 400 nm LED (light emitting diodes) arrays that allow observing the fluorescence emission over 450 nm. The PDT illumination probe options are constituted of 630 nm LED arrays for small areas and, for large areas, of both 630 nm and 450 nm LED arrays. Joining both functions at the same device makes PDT treatment simpler, properly monitorable and, hence, more clinically feasible. LINCE has been used in almost 1000 PDT treatments of superficial skin lesions in Brazil, with 88.4% of clearance of superficial BCC.
Optical images have been used in several medical situations to improve diagnosis of lesions or to monitor
treatments. However, most systems employ expensive scientific (CCD or CMOS) cameras and need computers
to display and save the images, usually resulting in a high final cost for the system. Additionally, this sort of
apparatus operation usually becomes more complex, requiring more and more specialized technical knowledge
from the operator. Currently, the number of people using smartphone-like devices with built-in high quality
cameras is increasing, which might allow using such devices as an efficient, lower cost, portable imaging system
for medical applications. Thus, we aim to develop methods of adaptation of those devices to optical medical
imaging techniques, such as fluorescence. Particularly, smartphones covers were adapted to connect a
smartphone-like device to widefield fluorescence imaging systems. These systems were used to detect lesions in
different tissues, such as cervix and mouth/throat mucosa, and to monitor ALA-induced protoporphyrin-IX
formation for photodynamic treatment of Cervical Intraepithelial Neoplasia. This approach may contribute
significantly to low-cost, portable and simple clinical optical imaging collection.
Liver transplantation is a well-established treatment for liver failure. However, the success of the transplantation procedure depends on liver graft conditions. The tissue function evaluation during the several transplantation stages is relevant, in particular during the organ harvesting, when a decision is made concerning the viability of the graft. Optical fluorescence spectroscopy is a good option because it is a noninvasive and fast technique. A partial normothermic hepatic ischemia was performed in rat livers, with a vascular occlusion of both median and left lateral lobes, allowing circulation only for the right lateral lobe and the caudate lobe. Fluorescence spectra under excitation at 532 nm (doubled frequency Nd:YAG laser) were collected using a portable spectrometer (USB2000, Ocean Optics, USA). The fluorescence emission was collected before vascular occlusion, after ischemia, and 24 hours after reperfusion. A morphometric histology analysis was performed as the gold standard evaluation ─ liver samples were analyzed, and the percentage of necrotic tissue was obtained. The results showed that changes in the fluorescence emission after ischemia can be correlated with the amount of necrosis evaluated by a morphometric analysis, the Pearson correlation coefficient of the generated model was 0.90 and the root mean square error was around 20%. In this context, the laser-induced fluorescence spectroscopy technique after normothermic ischemia showed to be a fast and efficient method to differentiate ischemic injury from viable tissues.
Evaluating transplantation grafts at harvest is essential for its success. Laser-induced fluorescence spectroscopy (LIFS) can help monitoring changes in metabolic/structural conditions of tissue during transplantation. The aim of the present study is to correlate LIFSobtained spectra of human hepatic grafts during liver transplantation with post-operative patients' mortality rate and biochemical parameters, establishing a method to exclude nonviable grafts before implantation. Orthotopic liver transplantation, piggyback technique was performed in 15 patients. LIFS was performed under 408nm excitation. Collection was performed immediately after opening donor’s abdominal cavity, after cold perfusion, end of back-table period, and 5 min and 1 h after warm perfusion at recipient. Fluorescence information was compared to lactate, creatinine, bilirubin and INR levels and to survival status. LIFS was sensitive to liver changes during transplantation stages. Study-in-progress; initial results indicate correlation between fluorescence and life/death status of patients.
The concern with the hydrogen penetration towards the pulp can be observed on the literature by the great number of papers published on this topic; Those measurements often uses chemical agents to quantify the concentration of the bleaching agent that cross the enamel and dentin. The objective of this work was the quantification of oxygen free radicals by fluorescence that are located in the interface between enamel and dentin. It was used to accomplish our objectives a Ruthenium probe (FOXY R - Ocean Optics) a 405nm LED, a bovine tooth and a portable diagnostic system (Science and support LAB - LAT - IFSC/USP). The fluorescence of the probe is suppressed in presence of oxygen free radicals in function of time. The obtained results
clearly shows that the hydrogen peroxide when not catalyzed should be kept in contact with the tooth for longer periods of time.
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