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This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found.

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Proton range verification (PRV) in proton therapy by means of prompt-gamma detection is a promising but challenging approach. High count rates, energies ranging between 1 MeV and 7 MeV, and a strong background complicate the detection of such particles. In this work, the Cherenkov light generated by prompt-gammas in the pure Cherenkov emitters TlBr, TlCl and PbF2 was studied. Cherenkov light in these crystals can provide a very fast timing signal with the potential to achieve very high count rates and to discern between prompt-gammas and background signals. Crystals of 1×1 cm2 and thicknesses of 1 cm, 2 cm, 3 cm and 4 cm were simulated. Different photodetector configurations were studied for 2.3 MeV, 4.4 MeV, and 6.1 MeV prompt-gammas. TlCl achieved the greatest number of detected Cherenkov photons for all energies, detector dimensions, and photodetector efficiency modeling. For the highest prompt-gamma energy simulated, TlCl yielded approximately 250 Cherenkov detected photons, using a hypothetical high-performance photodetector. Results show the crystal blocks of 1 cm × 1 cm × 1 cm have greater prompt-gamma detection efficiency per volume and a comparable average number of detected Cherenkov photons per event.

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Radiotherapy-related medical accidents are frequently caused by planning problems, excessive irradiation during radiotherapy, or patient movement. This is partly because the local exposure dose cannot be directly monitored during radiotherapy. This article discusses the development of our recent real-time radiation exposure dosimetry system that uses a synthetic ruby for radiation therapy. Background noise was observed before the measurement of the short-term characteristic features. Regarding the relationship between the number of photons and dose rate, using 100 monitor units (MU)/min as the measurement value, the counts decreased by approximately 10% at 600 MU/min. A clear correlation was observed between the MU value and the number of photons (R2 = 0.9987). The coefficient of variation (%CV) was less than ± 1.0% under all the irradiation conditions. Slight differences were observed between the ion chamber and the synthetic ruby dosimeters in the measurement of the percentage depth dose. However, this difference was almost matched by correcting for the Cherenkov light. Although some problems were observed with the synthetic ruby dosimeter system, our results indicate that the developed dosimeter can be used to measure the irradiation dose of patients in real time, with no significant impact on the data, as any effect would be masked by the larger effect of the ruby; however, the impact requires a detailed assessment in the future.

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Possible enhancements of DNA damage with light of different wavelengths and ionizing radiation (Rhenium-188-a high energy beta emitter (Re-188)) on plasmid DNA and FaDu cells via psoralen were investigated. The biophysical experimental setup could also be used to investigate additional DNA damage due to photodynamic effects, resulting from Cherenkov light. Conformational changes of plasmid DNA due to DNA damage were detected and quantified by gel electrophoresis and fluorescent staining. The clonogene survival of the FaDu cells was analyzed with colony formation assays. Dimethyl sulfoxide was chosen as a chemical modulator, and Re-188 was used to evaluate the radiotoxicity and light (UVC: λ = 254 nm and UVA: λ = 366 nm) to determine the phototoxicity. Psoralen did not show chemotoxic effects on the plasmid DNA or FaDu cells. After additional treatment with light (only 366 nm-not seen with 254 nm), a concentration-dependent increase in single strand breaks (SSBs) was visible, resulting in a decrease in the survival fraction due to the photochemical activation of psoralen. Whilst UVC light was phototoxic, UVA light did not conclude in DNA strand breaks. Re-188 showed typical radiotoxic effects with SSBs, double strand breaks, and an overall reduced cell survival for both the plasmid DNA and FaDu cells. While psoralen and UVA light showed an increased toxicity on plasmid DNA and human cancer cells, Re-188, in combination with psoralen, did not provoke additional DNA damage via Cherenkov light.

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OBJECTIVE: Dose distribution measurements of high-energy X-rays from medical linear accelerators (LINAC) in water are important for quality control (QC) of the system. Although Cherenkov-light imaging is a useful method for measuring the high-energy X-ray dose distribution, depth profiles have an underestimated dose at increased depths due to the angular dependency of the Cherenkov light generated in water. In this study, we use a linear polarizer to separate the majority of polarized components from the majority of unpolarized components of Cherenkov-light images in water and then use this information to correct for angular dependencies. METHODS: A water phantom, a cooled charge-coupled device (CCD) camera, and a polarizer were installed in a black box. Then, the water phantom was irradiated from the upper side with 6 or 10 MV X-rays, and the Cherenkov light generated in water was imaged with the polarizer axis at both parallel and perpendicular orientations to the beam. By using these images from the two orientations relative to the beam, we corrected the angular dependency of the Cherenkov light. RESULTS: By subtracting the images measured with the polarizer perpendicular to the beams from the images measured with the polarizer parallel to the beams, we could obtain images with only the polarized components. Using these images, we could calculate the images with non-polarized components that had similar depth profiles to those calculated with a planning system. The average difference between corrected depth profiles and those calculated with the planning system was less than 1%, while that between uncorrected depth profiles and the planning system was more than 8.3% in depths of water from 20 to 100 mm. CONCLUSION: We conclude that the use of the polarizer has the potential to improve the accuracy of dose distribution in Cherenkov-light imaging of water using high-energy X-rays.

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PURPOSE: Although the imaging of luminescence emitted in water during irradiation of protons and carbon ions is a useful method for range and dose estimations, the intensity of the images is relatively low due to the low photon production of the luminescence phenomenon. Therefore, a relatively long time is required for the imaging. Since a fluorescent dye, fluorescein, may increase the intensity of the optical signal, we measured the luminescence images of water with different concentrations of fluorescein during irradiation of protons and carbon ions and compared the results with those by measurements with water. METHODS: A cooled charge-coupled device (CCD) camera was used for imaging a water phantom with different concentrations of fluorescein from 0.0063 to 0.025 mg/cm3 , in addition to a water phantom without fluorescein during irradiation of 150-MeV protons and 241.5-MeV/n carbon ions. RESULTS: For both protons and carbon ions, the intensity of the luminescence images increased as the concentration of fluorescein increased. With a fluorescein concentration of 0.025 mg/cm3 , the intensities increased to more than 10 times those of water for both protons and carbon ions. Although the shape of the depth profiles of luminescence images of water with fluorescein appeared similar to that of water for protons, those for carbon ions were different from those of water due to the increase in the Cherenkov light component at shallow depths by the decrease in the angular dependencies of the Cherenkov light. CONCLUSION: We confirmed the increase in intensity of the luminescence of water by adding fluorescein for particle ions. With a small amount of Cherenkov light contamination in the images, such as protons, the relative distributions of the luminescence images with fluorescein were similar to that of water and will be used for range or dose determination in a short time.

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It is widely believed that light is not emitted in water during irradiation of radiation at energies lower than the Cherenkov light threshold. Contrary to this consensus, we discovered that light (luminescence) is emitted in water during irradiation of radiation, and imaging of this luminescence was possible. In this review, the author describes the optical images obtained for various types of radiation, their characteristics and origins, and potential applications of the luminescence of water during irradiation at a lower energy than the Cherenkov light threshold. The author also describes the luminescence of other transparent materials and future prospects of the discovered luminescence.

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PURPOSE: The luminescence image of water during the irradiation of carbon ions showed higher intensity at shallow depths than dose distribution due to the contamination of Cerenkov light from secondary electrons. Since Cerenkov light is coherent and polarized for the light produced during the irradiation of carbon ions to water, the reduction of Cerenkov light may be possible with a polarizer. In addition, there is no information on the polarization of the luminescence of water. To clarify these points, we measured the optical images of water during the irradiation of carbon ions with a polarizer by changing the directions of the transmission axis. METHODS: Imaging was conducted using a cooled charge-coupled device (CCD) camera during the irradiation of 241.5 MeV/n energy carbon ions to a water phantom with a polarizer in front of the lens by changing the transmission axis parallel and perpendicular to the carbon-ion beam. RESULTS: With the polarizer parallel to the carbon-ion beam, the intensity at the shallow depth was ~26% higher than that measured with the polarizer perpendicular to the beam. We found no significant intensity difference between these two images at deeper depths where the Cerenkov light was not included. The difference image of the parallel and perpendicular directions showed almost the same image as the simulated Cerenkov light distribution. Using the measured difference image, correction of the Cerenkov component was possible from the measured luminescence image of water during the irradiation of carbon ions. CONCLUSION: We could measure the difference of the Cerenkov light component by changing the transmission axis of the polarizer. Also we clarified that there was no difference in the luminescence of water by changing the transmission axis of the polarizer.

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Different applications require different customizations of silicon photomultiplier (SiPM) technology. We present a review on the latest SiPM technologies developed at Fondazione Bruno Kessler (FBK, Trento), characterized by a peak detection efficiency in the near-UV and customized according to the needs of different applications. Original near-UV sensitive, high-density SiPMs (NUV-HD), optimized for Positron Emission Tomography (PET) application, feature peak photon detection efficiency (PDE) of 63% at 420 nm with a 35 um cell size and a dark count rate (DCR) of 100 kHz/mm². Correlated noise probability is around 25% at a PDE of 50% at 420 nm. It provides a coincidence resolving time (CRT) of 100 ps FWHM (full width at half maximum) in the detection of 511 keV photons, when used for the readout of LYSO(Ce) scintillator (Cerium-doped lutetium-yttrium oxyorthosilicate) and down to 75 ps FWHM with LSO(Ce:Ca) scintillator (Cerium and Calcium-doped lutetium oxyorthosilicate). Starting from this technology, we developed three variants, optimized according to different sets of specifications. NUV-HD⁻LowCT features a 60% reduction of direct crosstalk probability, for applications such as Cherenkov telescope array (CTA). NUV-HD⁻Cryo was optimized for cryogenic operation and for large photosensitive areas. The reference application, in this case, is the readout of liquid, noble-gases scintillators, such as liquid Argon. Measurements at 77 K showed a remarkably low value of the DCR of a few mHz/mm². Finally, vacuum-UV (VUV)-HD features an increased sensitivity to VUV light, aiming at direct detection of photons below 200 nm. PDE in excess of 20% at 175 nm was measured in liquid Xenon. In the paper, we discuss the specifications on the SiPM related to different types of applications, the SiPM design challenges and process optimizations, and the results from the experimental characterization of the different, NUV-sensitive technologies developed at FBK.