Scopic light delivery systems. Laser light can be focused into thin optical fibers for delivery of light into deeper and difficult to access treatment sites. For example, in a recent clinical study by Jerjes et. al., [18] multiple fibers were placed underFigure 3: Examples of image-guided interstitial PDT for deeply situated tumors. A. Photograph of surgeon inserting needles under ultrasound-guidance for placing fibers in deep tissue. B. Light delivered to the heamangioma of the left infraorbital region through multiple fibers. Photographs of solid skin tumor in the ear with 6 fibers implanted under ultrasound guidance. C. One fiber is used for illumination while other 5 fibers are used for diagnostic purposes to evaluate light fluence, sensitizer concentration and tissue oxygenation. D. All the fibers are used in “transmit” mode to illuminate the whole tumor for PDT. Images adapted with permission from Jerjes et al [18] and Svanberg et al. [21]http://www.thno.orgTheranostics 2016, Vol. 6, Issueattractive feature of interstitial PDT is that it also facilitates efficient dosimetric planning. Because fibers are placed in predetermined locations within the target site, they can not only be used to deliver light, but can simultaneously act as diagnostic sensors that can gauge important PDT parameters that critically impact the therapeutic response, such as the fluence rate, PS concentration, PS purchase Stattic photobleaching, and the tissue oxygenation status [21, 22]. The low adverse event rates that have been reported in PDT treated PD173074 dose patients, who were otherwise unsuitable for surgery or resistant to chemotherapy, point to the potentially important role that PDT can play in treating pathologies such as cancer. Furthermore, it should be noted that these studies were performed by coupling laser light into optical fibers. Indeed, coupling non-collimated light sources into fibers, though feasible, leads to a significant loss in the power at the fiber output, and has generally not been considered. Recent advances in LED light source technology have led to their ability to output hundreds of Watts. Along with enhanced portability stemming from battery powered sources and precision optical fiber coupling, these non-collimated and less expensive light sources will ease the translation of PDT to clinical procedures.irradiance [30]. On the contrary, another study by Grecco et. al. demonstrated that a femtosecond laser irradiation produced twice as deep a necrotic zone compared to a CW laser at an equivalent dose (150 J/cm2) using the first-generation PDT sensitizer hemoatoporphyrin derivative (HpD) [31, 32]. Several differences, such as the type of PS and interval between irradiations etc, have made the comparison between pulsed and continuous PDT inconclusive. To determine factors that affect or increase the necrotic depth in a pulsed-PDT regime, Pogue et al simulated the deposited dose and reported that the pulsed laser irradiation can be beneficial for deep tissue PDT [33]; however, these results are modest and strongly depend on the PS, the laser pulse width, the pulse energy, and the repetition rate. In another study by Sterenborg et al [34], the simulations concluded that pulsed excitation in PDT is identical to CW for fluence rates below 4 ?108 Wm-2. At higher fluence rates, the effectiveness of pulse PDT drops significantly [34]. Despite promise for deep tissue PDT and the debate on the advantages of pulsed irradiation versus CW irradiation to produce optim.Scopic light delivery systems. Laser light can be focused into thin optical fibers for delivery of light into deeper and difficult to access treatment sites. For example, in a recent clinical study by Jerjes et. al., [18] multiple fibers were placed underFigure 3: Examples of image-guided interstitial PDT for deeply situated tumors. A. Photograph of surgeon inserting needles under ultrasound-guidance for placing fibers in deep tissue. B. Light delivered to the heamangioma of the left infraorbital region through multiple fibers. Photographs of solid skin tumor in the ear with 6 fibers implanted under ultrasound guidance. C. One fiber is used for illumination while other 5 fibers are used for diagnostic purposes to evaluate light fluence, sensitizer concentration and tissue oxygenation. D. All the fibers are used in “transmit” mode to illuminate the whole tumor for PDT. Images adapted with permission from Jerjes et al [18] and Svanberg et al. [21]http://www.thno.orgTheranostics 2016, Vol. 6, Issueattractive feature of interstitial PDT is that it also facilitates efficient dosimetric planning. Because fibers are placed in predetermined locations within the target site, they can not only be used to deliver light, but can simultaneously act as diagnostic sensors that can gauge important PDT parameters that critically impact the therapeutic response, such as the fluence rate, PS concentration, PS photobleaching, and the tissue oxygenation status [21, 22]. The low adverse event rates that have been reported in PDT treated patients, who were otherwise unsuitable for surgery or resistant to chemotherapy, point to the potentially important role that PDT can play in treating pathologies such as cancer. Furthermore, it should be noted that these studies were performed by coupling laser light into optical fibers. Indeed, coupling non-collimated light sources into fibers, though feasible, leads to a significant loss in the power at the fiber output, and has generally not been considered. Recent advances in LED light source technology have led to their ability to output hundreds of Watts. Along with enhanced portability stemming from battery powered sources and precision optical fiber coupling, these non-collimated and less expensive light sources will ease the translation of PDT to clinical procedures.irradiance [30]. On the contrary, another study by Grecco et. al. demonstrated that a femtosecond laser irradiation produced twice as deep a necrotic zone compared to a CW laser at an equivalent dose (150 J/cm2) using the first-generation PDT sensitizer hemoatoporphyrin derivative (HpD) [31, 32]. Several differences, such as the type of PS and interval between irradiations etc, have made the comparison between pulsed and continuous PDT inconclusive. To determine factors that affect or increase the necrotic depth in a pulsed-PDT regime, Pogue et al simulated the deposited dose and reported that the pulsed laser irradiation can be beneficial for deep tissue PDT [33]; however, these results are modest and strongly depend on the PS, the laser pulse width, the pulse energy, and the repetition rate. In another study by Sterenborg et al [34], the simulations concluded that pulsed excitation in PDT is identical to CW for fluence rates below 4 ?108 Wm-2. At higher fluence rates, the effectiveness of pulse PDT drops significantly [34]. Despite promise for deep tissue PDT and the debate on the advantages of pulsed irradiation versus CW irradiation to produce optim.