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PURPOSE: The goal of this study is to assess the utility of Cherenkov imaging (CI) and scintillation imaging (SI) as high-resolution techniques to measure CyberKnife® beam shape quantitatively at the irradiation surface in quality assurance (QA). METHODS: The EMCCD camera captured scintillation and Cherenkov photons arising from 6 MV x-ray dose deposition produced by the CyberKnife® VSI System. Two imaging methods were done at source to surface distance of 800 cm with the same field size, ranging from 10 to 60 mm using fixed cones and iris collimators. The output sensitivity and constancy were measured using the SI and CI, and benchmarked against an ionization chamber. Line profiles of each beam measured by optical imaging were compared with film measurement. Position shifts were introduced to test the sensitivity of SI and CI to small beam position deviations. To assess reproducibility, the beam measurements were tested three times on 5 consecutive days. RESULTS: Both systems exhibited comparable sensitivity to the ionization chamber in response to fluctuations in CyberKnife® output. The beam profiles in SI matched well with the measured film image, with accuracy in the range of ± 0.20 and ± 0.26 mm standard deviation for the circle and iris field, respectively. The corresponding accuracy measured by CI is in the range of ± 0.25 and ± 0.33 mm, respectively. These are all within the tolerance recommended by the guidelines of CyberKnife® QA. The accuracy measured by SI and CI for 1 mm beam position shift within 0.21 and 0.45 mm tolerance, respectively. Repeatability measurements of the beam have shown a standard deviation within 0.94 mm. CONCLUSIONS: SI and CI techniques are tested to provide a valid way to measure CyberKnife® beam shape in this study. Meanwhile, the systematic comparison of SI and CI also provides evidence for the measurement methods selection appropriately.

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High-energy gamma rays produced in inertial confinement fusion (ICF) experiments are crucial for studying implosion dynamics. These gamma rays, characterized by their extremely short durations, represent the least disturbed products of fusion, preserving vital birth information. To detect such γ-rays, ultrafast radiation detectors with high time resolution are necessary. This study introduces a newly developed Cherenkov optical image screen designed for ultra-fast gamma-ray imaging. Composed of pure quartz fiber material, the imaging screen features a single fiber pixel size of 0.6 mm and a thickness of 3 cm. Theoretical investigations explore the luminous time response and efficiency of the Cherenkov optical imaging screen under gamma-ray irradiation. Experimental validation was conducted using a steady-state gamma-ray source with an average energy of 1.25 MeV. Results demonstrate that the image screen achieves a spatial resolution limit of 0.75 mm. The temporal response exhibits a full width at half maximum of less than 0.4 ns when excited by a high-energy electron beam with a single pulse duration of several picoseconds.

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PURPOSE: This study investigates scintillation dosimetry coupled with Cherenkov imaging for in vivo dose monitoring during whole breast radiotherapy (WBRT). Given recent observations of excess dose to the contralateral breast (CB), in vivo dosimetry (IVD) could help ensure accurate dose delivery and decrease risks of secondary cancer. This work presents a rapid, streamlined alternative to traditional IVD, providing direct visualization of measurement location relative to the treatment field on the patient. METHODS AND MATERIALS: 10 WBRT patients consented under an IRB-approved protocol were monitored with scintillation dosimetry and always-on Cherenkov imaging, on both their treated and CB for one to three fractions. Scintillator dosimeters, small plastic discs 1mm thick and 15mm in diameter, were calibrated against optically-stimulated luminescent dosimeters (OSLDs) to generate an integral output-to-dose conversion, where integral output is measured in post-processing through a custom fitting algorithm. The discs have been extensively characterized in a previous study for various treatment conditions including beam energy and treatment geometry. RESULTS: N=44 dosimetry measurements were evaluated, including 22 treated breast and 22 CB measurements. Following integral output-to-dose calibration, in vivo scintillator dosimeters exhibited high linearity (R2=0.99) with paired OSLD readings across all patients. The difference between scintillation and OSLD dose measurements averaged 2.8% of the prescribed dose, or an absolute dose difference of approximately 7 cGy. CONCLUSIONS: Integration of scintillation dosimetry with Cherenkov imaging offers an accurate, rapid alternative for in vivo dose verification in WBRT, circumventing the limitations of conventional point dosimeters. The additional benefit of visualizing measurement locations relative to the treatment field provides users an enhanced understanding of results and allows for detection of high dose gradients. Future work will explore the applicability of this technique across a broader range of radiotherapy treatments, aiming to streamline IVD practices.

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The global challenge of on-site detection of highly enriched uranium (HEU), a substance with considerable potential for unauthorized use in nuclear security, is a critical concern. Traditional passive nondestructive assay (NDA) techniques, such as gamma-ray spectroscopy with high-purity germanium detectors, face significant challenges in detecting HEU when it is shielded by heavy metals. Addressing this critical security need, we introduce an on-site detection method for lead-shielded HEU employing a transportable NDA system that utilizes the 252Cf rotation method with a water Cherenkov neutron detector. This cost-effective NDA system is capable of detecting 4.17 g of 235U within a 12 min measurement period using a 252Cf source of 3.7 MBq. Integrating this system into border control measures can enhance the prevention of HEU proliferation significantly and offer robust deterrence against nuclear terrorism.

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This work reviews the progression of chemical analysis via Cherenkov emissions, i.e., Cherenkov Photometry and Cherenkov Emission Spectroscopy, from its introduction in the literature up to modern developments. In presenting the history of this field, we aim to consolidate the literature, both for reference and contextualization. We present an argument aiming to untangle why this corner of research has seen little progress while so many other directly related aspects of Cherenkov research have flourished, as well as speak to the progress of the field in recent years and prospective direction in years to come.

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This is an explanatory paper on Sun Il Kwon et al., Nat. Photon. 15: 914-918, 2021 and some parts of this manuscript are translated from the paper. Medical imaging modalities such as X-ray computed tomography, Magnetic resonance imaging, positron emission tomography (PET), and single photon emission computed tomography, require image reconstruction processes, consequently constraining them to form cylindrical shapes. However, among them, only PET can use additional information, so called time of flight, on an event-by-event basis. If coincidence time resolution (CTR) of PET detectors improved to 30 ps, which corresponds to spatial resolution of 4.5 mm, directly localizing electron-positron annihilation point is possible, allowing us to circumvent image reconstruction processes and free us from the geometric constraint. We call this concept direct positron emission imaging (dPEI). We have developed ultrafast radiation detectors by focusing on Cherenkov photon detection. Furthermore, the CTR of 32 ps being equivalent to 4.8 mm spatial resolution is achieved by combining deep learning-based signal processing with the detectors. In this article, we explain how we developed the detectors and demonstrated the first dPEI using different types of phantoms, how we will tackle limitations to be addressed to make the dPEI more practical, and how dPEI will emerge as an imaging modality in nuclear medicine.

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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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Objective. Very high energy electrons (VHEE) in the range of 50-250 MeV are of interest for treating deep-seated tumours with FLASH radiotherapy (RT). This approach offers favourable dose distributions and the ability to deliver ultra-high dose rates (UHDR) efficiently. To make VHEE-based FLASH treatment clinically viable, a novel beam monitoring technology is explored as an alternative to transmission ionisation monitor chambers, which have non-linear responses at UHDR. This study introduces the fibre optic flash monitor (FOFM), which consists of an array of silica optical fibre-based Cherenkov sensors with a photodetector for signal readout.Approach. Experiments were conducted at the CLEAR facility at CERN using 200 MeV and 160 MeV electrons to assess the FOFM's response linearity to UHDR (characterised with radiochromic films) required for FLASH radiotherapy. Beam profile measurements made on the FOFM were compared to those using radiochromic film and scintillating yttrium aluminium garnet (YAG) screens.Main results. A range of photodetectors were evaluated, with a complementary-metal-oxide-semiconductor (CMOS) camera being the most suitable choice for this monitor. The FOFM demonstrated excellent response linearity from 0.9 Gy/pulse to 57.4 Gy/pulse (R2= 0.999). Furthermore, it did not exhibit any significant dependence on the energy between 160 MeV and 200 MeV nor the instantaneous dose rate. Gaussian fits applied to vertical beam profile measurements indicated that the FOFM could accurately provide pulse-by-pulse beam size measurements, agreeing within the error range of radiochromic film and YAG screen measurements, respectively.Significance. The FOFM proves to be a promising solution for real-time beam profile and dose monitoring for UHDR VHEE beams, with a linear response in the UHDR regime. Additionally it can perform pulse-by-pulse beam size measurements, a feature currently lacking in transmission ionisation monitor chambers, which may become crucial for implementing FLASH radiotherapy and its associated quality assurance requirements.

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Objective. Imaging of optical photons emitted from tissue during radiotherapy is a promising technique for real-time visualization of treatment delivery, offering applications in dose verification, treatment monitoring, and retrospective treatment plan comparison. This research aims to explore the feasibility of intensified imaging of tissue luminescence during proton therapy (PT), under both conventional and ultra-high dose rate (UHDR) conditions.Approach. Conventional and UHDR pencil beam scanning (PBS) PT irradiation of freshex vivoporcine tissue and tissue-mimicking plastic phantom was imaged using intensified complementary metal-oxide-semiconductor(CMOS) cameras. The optical emission from tissue was characterized during conventional irradiation using both blue and red-sensitive intensifiers to ensure adequate spectral coverage. Spectral characterization was performed using bandpass filters between the lens and sensor. Imaging of conventional proton fields (240 MeV, 10 nA) was performed at 100 Hz frame rate, while UHDR PBS proton delivery (250 MeV, 99 nA) was recorded at 1 kHz frame rate. Dependence of optical emission yield on proton energy was studied using an optical tissue-mimicking plastic phantom and a range shifter. Finally, we demonstrated fast beam tracking capability of fast camera towardsin vivomonitoring of FLASH PT.Main results. Under conventional treatment dose rates optical emission was imaged with single spot resolution. Spot profiles were found to agree with the treatment planning system calculation within >90% for all spectral bands and spot intensity was found to vary with spectral filtration. The resultant polychromatic emission presented a maximum intensity at 650 nm and decreasing signal at lower wavelengths, which is consistent with expected attenuation patterns of high fat and muscle tissue. For UHDR beam imaging, optical yield increased with higher proton energy. Imaging at 1 kHz allowed continuous monitoring of delivery during porcine tissue irradiation, with clear identification of individual dwell positions. The number of dwell positions matched the treatment plan in total and per row showing adequate temporal capability of iCMOS imaging.Significance. For the first time, this study characterizes optical emission from tissue during PT and demonstrates our capability of fast optical tracking of pencil proton beam on the tissue anatomy in both conventional and UHDR setting. Similar to the Cherenkov imaging in radiotherapy, this imaging modality could enable a seamless, independent validation of PT treatments.

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Objective.The goal of this work was to assess the potential use of non-contact scintillator imaging dosimetry for tracking delivery in total body irradiation (TBI).Approach. Studies were conducted to measure the time-gated light signals caused by radiation exposure to scintillators that were placed on tissue. The purpose was to assess efficacy in conditions common for TBI, such as the large source to surface distance (SSD) commonly used, the reduced dose rate, the inclusion of a plexiglass spoiler, angle of incidence and effects of peripheral patient support structures. Dose validation work was performed on phantoms that mimicked human tissue optical properties and body geometry. For this work, 1.5 cm diameter scintillating disks were developed and affixed to phantoms under various conditions. A time-gated camera synchronized to the linac pulses was used for imaging. Scintillation intensity was quantified in post processing and the values verified with simultaneous thermolumiescent dosimeter (TLD) measurements. Mean scintillation values in each region were compared to TLD measurements to produce dose response curves, and scatter effects from the spoiler and patient bed were quantified.Main results.The dose determined by scintillators placed in TBI conditions agreed with TLD dose determinations to within 2.7%, and did so repeatedly within 1.0% standard deviation variance. A linear fit between scintillator signal and TLD dose was achieved with anR2= 0.996 across several body sites. Scatter from the patient bed resulted in a maximum increase of 19% in dose.Significance.This work suggests that non-contact scintillator imaging dosimetry could be used to verify dose in real time to patients undergoing TBI at the prescribed long SSD and low dose rate. It also has shown that patient transport stretchers can significantly influence surface dose by increasing scatter.

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BACKGROUND: Cherenkov luminescence imaging has shown potential for relative dose distribution and field verification in radiation therapy. However, to date, limited research utilizing Cherenkov luminescence for absolute dose calibration has been conducted owing to uncertainties arising from camera positioning and tissue surface optical properties. PURPOSE: This paper introduces a novel approach to multispectral Cherenkov luminescence imaging combined with Fricke-xylenol orange gel (FXG) film, termed MCIFF, which can enable online full-field absolute dose measurement. By integrating these two approaches, MCIFF allows for calibration of the ratio between two spectral intensities with absorbed dose, thereby enabling absolute dose measurement. METHODS: All experiments are conducted on a Varian Clinac 23EX, utilizing an electron multiplying charge-coupled device (EMCCD) camera and a two-way image splitter for simultaneous capture of two-spectral Cherenkov imaging. In the first part of this study, the absorbance curves of the prepared FXG film, which receives different doses, are measured using a fluorescence spectrophotometer to verify the correlation between absorbance and dose. In the second part, the FXG film is positioned directly under the radiation beam to corroborate the dose measurement capacity of MCIFF across various beams. In the third part, the feasibility of MCIFF is tested in actual radiotherapy settings via a humanoid model, demonstrating its versatility with various radiotherapy materials. RESULTS: The results of this study indicate that the logarithmic ratios of spectral intensities at wavelengths of 550 ± 50 and 700 ± 100 nm accurately reflect variations in radiation dose (R2 > 0.96) across different radiation beams, particle energies, and dose rates. The slopes of the fitting lines remain consistent under varying beam conditions, with discrepancies of less than 8%. The optical profiles obtained using the MCIFF exhibit a satisfactory level of agreement with the measured results derived from the treatment planning system (TPS) and EBT3 films. Specifically, for photon beams, the lateral distances between the 80% and 20% isodose lines, referred to as the penumbra (P80-20) values, obtained through TPS, EBT3 films, and MCIFF, are determined as 0.537, 0.664, and 0.848 cm, respectively. Similarly, for electron beams, the P80-20 values obtained through TPS, EBT3 films, and MCIFF are found to be 0.432, 0.561, and 0.634 cm, respectively. Furthermore, imaging of the anthropomorphic phantom demonstrates the practical application of MCIFF in real radiotherapy environments. CONCLUSION: By combining an FXG film with Cherenkov luminescence imaging, MCIFF can calibrate Cherenkov luminescence to absorbed dose, filling the gap in online 2D absolute dose measurement methods in clinical practice, and providing a new direction for the clinical application of optical imaging to radiation therapy.

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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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Objective. The high production cost of commonly used lutetium-based fast scintillators and the development of silicon photomultipliers technology have made bismuth germanate (BGO) a promising candidate for time-of-flight positron emission tomography (TOF PET) detectors owing to its generation of prompt Cherenkov photons. However, using BGO as a hybrid scintillator is disadvantageous owing to its low photon statistics and distribution that does not conform well to a single Gaussian. To mitigate this, a proposal was made to increase the likelihood of detecting the first Cherenkov photons by positioning two photosensors in opposition at the entrance and exit faces of the scintillator and subsequently selectively picking an earlier timestamp. Nonetheless, the timing variation arising from the photon transit time remains affected by the entire length of the crystal, thereby presenting a possibility for further enhancement.Approach. In this study, we aimed to improve the timing performance of the dual-ended BGO Cherenkov TOF PET detector by capitalizing on the synergistic advantages of applying depth-of-interaction (DOI) information and crystal surface finishes or reflector properties. A dual-ended BGO detector was implemented using a 3 × 3 × 15 mm3BGO crystal. Coincidence events were acquired against a 3 × 3 × 3 mm3LYSO:Ce:Mg reference detector. The timing performance of the dual-ended BGO detectors was analyzed using conventionally proposed timestamp methods before and after DOI correction.Results. Through a DOI-based correction of photon transit time spread, we demonstrated a further improvement in the timing resolution of the BGO-based Cherenkov TOF PET detector utilizing a dual-ended detector configuration and adaptive arrival time pickoff. We achieved further improvements in timing resolution by correcting the offset spread induced by the fluctuation of timing signal rise time in the dual-ended detector.Significance. Although polishing the crystal surface was still favorable in terms of full-width-half-maximum value, incorporating DOI information from the unpolished crystal to compensate for photon travel time facilitated additional enhancement in the overall timing performance, thereby surpassing that achieved with the polished crystal.

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BACKGROUND: Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment. AIM: To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs. METHODS: The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence. RESULTS: The maximum absorbance of TCPP was at 390-430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP. CONCLUSION: This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.

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CONTEXT: Old-generation photosensitizers are minimally used in current photodynamic therapy (PDT) because they absorb in the UV/blue/green region of the spectrum where biological tissues are generally highly absorbing. The UV/blue light of Cherenkov Radiation (CR) from nuclear disintegration of beta-emitter radionuclides shows promise as an internal light source to activate these photosensitizers within tissue. Outline of the study: 1) radionuclide choice and Cherenkov Radiation, 2) Photosensitizer choice, synthesis and radiolabeling, 3) CR-induced fluorescence, 4) Verification of ROS formation, 5) CR-induced PDT with either free eosine and free CR emitter, or with radiolabelled eosin. RESULTS: Cherenkov Radiation Energy Transfer (CRET) from therapeutic radionuclides (90Y) and PET imaging radionuclides (18F, 68Ga) to eosin was shown by spectrofluorimetry and in vitro, and was shown to result in a PDT process. The feasibility of CR-induced PDT (CR-PDT) was demonstrated in vitro on B16F10 murine melanoma cells mixing free eosin (λabs = 524 nm, ΦΔ 0.67) with free CR-emitter [18F]-FDG under their respective intrinsic toxicity levels (0.5 mM/8 MBq) and by trapping singlet oxygen with diphenylisobenzofuran (DPBF). An eosin-DOTAGA-chelate conjugate 1 was synthesized and radiometallated with CR-emitter [68Ga] allowed to reach 25 % cell toxicity at 0.125 mM/2 MBq, i.e. below the toxicity threshold of each component measured on controls. Incubation time was carefully examined, especially for CR emitters, in light of its toxicity, and its CR-emitting yield expected to be 3 times as much for 68Ga than 18F (considering their ß particle energy) per radionuclide decay, while its half-life is about twice as small. PERSPECTIVE: This study showed that in complete darkness, as it is at depth in tissues, PDT could proceed relying on CR emission from radionuclides only. Interestingly, this study also repurposed PET imaging radionuclides, such as 68Ga, to trigger a therapeutic event (PDT), albeit in a modest extent. Moreover, although it remains modest, such a PDT approach may be used to achieve additional tumoricidal effect to RIT treatment, where radionuclides, such as 90Y, are strong CR emitters, i.e. very potent light source for photosensitizer activation.

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Cherenkov radiation occurs only when a charged particle moves with a velocity exceeding the phase velocity of light in that matter. This radiation mechanism creates directional light emission at a wide range of frequencies and could facilitate the development of on-chip light sources except for the hard-to-satisfy requirement for high-energy particles. Creating Cherenkov radiation from low-energy electrons that has no momentum mismatch with light in free space is still a long-standing challenge. Here, we report a mechanism to overcome this challenge by exploiting a combined effect of interfacial Cherenkov radiation and umklapp scattering, namely the constructive interference of light emission from sequential particle-interface interactions with specially designed (umklapp) momentum-shifts. We find that this combined effect is able to create the interfacial Cherenkov radiation from ultralow-energy electrons, with kinetic energies down to the electron-volt scale. Due to the umklapp scattering for the excited high-momentum Bloch modes, the resulting interfacial Cherenkov radiation is uniquely featured with spatially separated apexes for its wave cone and group cone.

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Objective. With the introduction of Cherenkov imaging technology on the Halcyon O-ring linear accelerator platform, we seek to demonstrate the imaging feasibility and optimize camera placement.Approach. Imaging parameters were probed by acquiring triggering data Cherenkov image frames for simplistic beams on the Halcyon and comparing the analyzed metrics with those from the TrueBeam platform. Camera position was analyzed by performing 3D rendering of patient treatment plans for various sites and iterating over camera positions to assess treatment area visibility.Main results. Commercial Cherenkov imaging systems are compatible with the pulse timing of the Halcyon, and this platform design favorably impacts signal to noise in Cherenkov image frames. Additionally, ideal camera placement is treatment site dependent and is always within a biconical zone of visibility centered on the isocenter. Visibility data is provided for four treatment sites, with suggestions for camera placement based on room dimensions. Median visibility values were highest for right breast plans, with values of 80.33% and 68.49% for the front and rear views respectively. Head and neck plans presented with the lowest values at 26.44% and 38.18% respectively.Significance. This work presents the first formal camera positional analysis for Cherenkov imaging on any platform and serves as a template for performing similar work for other irradiation platforms. Additionally, this study confirms the Cherenkov imaging parameters do not need to be changed for optimal imaging on the Halcyon. Lastly, the presented methodology provides a framework which could be further expanded to other optical imaging systems which rely on line of sight visibility to the patient.

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Time-of-flight (TOF) positron emission tomography (PET) detectors improve the signal-to-noise ratio of PET images by limiting the position of the generation of two 511 keV gamma-rays in space using the arrival time difference between the two photons. Unfortunately, bismuth germanate (BGO), widely used in conventional PET detectors, was limited as a TOF PET scintillator due to the relatively slow decay time of the scintillation photons. However, prompt Cerenkov light in BGO has been identified in addition to scintillation photons. Using Cerenkov photons for timing has significantly improved the coincidence timing resolution (CTR) of BGO. Based on this, further research on improving the CTR for a BGO-based TOF PET system is being actively conducted. Wrapping materials for BGO pixels have primarily employed white reflectors to most efficiently collect scintillation light. White reflectors have customarily been used as reflectors for BGO pixels even after Cerenkov light began to be utilized for timing calculations in pixel-level experiments. However, when the arrival-time differences of the two 511 keV annihilations photons were measured with pure Cerenkov radiators, painting the lateral sides of the radiators black can improve CTR by suppressing the reflection of Cerenkov photons. The use of BGO for TOF PET detectors requires simultaneously minimizing scintillation loss for good energy information and suppressing reflected Cerenkov photons for better timing performance. Thus, reflectors for BGO pixels should be optimized for better timing and energy performance. In this study, colored polytetrafluoroethylene (PTFE) tapes with discontinuous reflectance values at specific wavelengths were applied as a BGO reflector. We hypothesized that CTR could be enhanced by selectively suppressing reflected Cerenkov photons with an optimum colored reflector on the BGO pixel while minimizing scintillation photon loss. CTRs were investigated utilizing white and three colors (yellow, red, and green) PTFE tapes as a reflector. In addition, black-painted PTFE tape and enhanced specular reflector film were investigated as reference reflector materials. When 3 × 3 × 20 mm3BGO pixels were wrapped with the yellow PTFE reflector, the CTR was significantly improved to 365 ± 5 ps from 403 ± 14 ps measured with the conventional white PTFE reflector. Adequate energy information was still obtained with only 4.1% degradation in light collection compared to the white reflector. Colored reflectors show the possibility to further improve CTR for BGO pixels with optimum reflectance design.

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Noninvasive imaging techniques for the early detection of infections are in high demand. In this study, we present the development of an infection imaging agent consisting of the antimicrobial peptide fragment UBI (31-38) conjugated to the chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), which allows for labeling with the positron emitter Ga-68. The preclinical evaluation of [68 Ga]Ga-NODAGA-UBI (31-38) was conducted to investigate its potential for imaging bacterial infections caused by Staphylococcus aureus. The octapeptide derived from ubiquicidin, UBI (31-38), was synthesized and conjugated with the chelator NODAGA. The conjugate was then radiolabeled with Ga-68. The radiolabeling process and the stability of the radio formulation were confirmed through chromatography. The study included both in vitro evaluations using S. aureus and in vivo evaluations in an animal model of infection and inflammation. Positron emission tomography (PET) and Cherenkov luminescence imaging (CLI) were performed to visualize the targeted localization of the radio formulation at the site of infection. Ex vivo biodistribution studies were carried out to quantify the uptake of the radio formulation in different organs and tissues. Additionally, the uptake of [18 F]Fluorodeoxyglucose ([18 F] FDG) in the animal model was also studied for comparison. The [68 Ga]Ga-NODAGA-UBI (31-38) complex consistently exhibited high radiochemical purity (>90%) after formulation. The complex demonstrated stability in saline, phosphate-buffered saline, and human serum for up to 3 h. Notably, the complex displayed significantly higher uptake in S. aureus, which was inhibited in the presence of unconjugated UBI (29-41) peptide, confirming the specificity of the formulation for bacterial membranes. Bacterial imaging capability was also observed in PET and CLI images. Biodistribution results indicated a substantial target-to-nontarget ratio of approximately 4 at 1 h postinjection of the radio formulation. Conversely, the uptake of [18 F]FDG in the animal model did not allow for the discrimination of infected and inflamed sites. Our studies have demonstrated that [68 Ga]Ga-NODAGA-UBI (31-38) holds promise as a radiotracer for imaging bacterial infections caused by S. aureus.

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Objective.Recent SiPM developments and improved front-end electronics have opened new doors in TOF-PET with a focus on prompt photon detection. For instance, the relatively high Cherenkov yield of bismuth-germanate (BGO) upon 511 keV gamma interaction has triggered a lot of interest, especially for its use in total body positron emission tomography (PET) scanners due to the crystal's relatively low material and production costs. However, the electronic readout and timing optimization of the SiPMs still poses many questions. Lab experiments have shown the prospect of Cherenkov detection, with coincidence time resolutions (CTRs) of 200 ps FWHM achieved with small pixels, but lack system integration due to an unacceptable high power uptake of the used amplifiers.Approach.Following recent studies the most practical circuits with lower power uptake (<30 mW) have been implemented and the CTR performance with BGO of newly developed SiPMs from Fondazione Bruno Kessler tested. These novel SiPMs are optimized for highest single photon time resolution (SPTR).Main results.We achieved a best CTR FWHM of 123 ps for 2 × 2 × 3 mm3and 243 ps for 3 × 3 × 20 mm3BGO crystals. We further show that with these devices a CTR of 106 ps is possible using commercially available 3 × 3 × 20 mm3LYSO:Ce,Mg crystals. To give an insight in the timing properties of these SiPMs, we measured the SPTR with black coated PbF2of 2 × 2 × 3 mm3size. We confirmed an SPTR of 68 ps FWHM published in literature for standard devices and show that the optimized SiPMs can improve this value to 42 ps. Pushing the SiPM bias and using 1 × 1 mm2area devices we measured an SPTR of 28 ps FWHM.Significance.We have shown that advancements in readout electronics and SiPMs can lead to improved CTR with Cherenkov emitting crystals. Enabling time-of-flight with BGO will trigger a high interest for its use in low-cost and total-body PET scanners. Furthermore, owing to the prompt nature of Cherenkov emission, future CTR improvements are conceivable, for which a low-power electronic implementation is indispensable. In an extended discussion we will give a roadmap to best timing with prompt photons.

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