A simple calibration routine for small inorganic scintillation detectors for in vivo dosimetry during brachytherapy.

BACKGROUND: In vivo dosimetry (IVD) is rarely performed in brachytherapy (BT), allowing potential dose misadministration to go unnoticed. This study presents a clinical routine-calibration method of detectors for IVD in high (HDR) and pulsed dose rate (PDR) Ir-192 BT. PURPOSE: To evaluate the dosimetric precision and feasibility of an in-clinic calibration routine of detectors for IVD in afterloading BT. METHODS: Calibrations were performed in a PMMA phantom with two needles inserted 20 mm apart. The source was loaded in one of the needles at 15 dwells for 10 s. The detector was placed in the other needle, and its signal was recorded. The mean signal at each dwell position was fitted to the expected dose rate with the calibration factor and the detector's longitudinal position being free parameters. The method was tested with an inorganic scintillation detector using one Ir-192 FlexiSource HDR and two Ir-192 GammaMedPlus PDR sources and followed by validation measurements in water. RESULTS: The standard measurement uncertainty (k = 1) of the calibration factor in absolute terms (Gy/s) was 3.2/3.4% for the HDR/PDR source. The uncertainty was dominated by source strength uncertainty, and the precision of the method was <1%. The mean ± 1SD of the difference in measured and expected dose rate during validation was 1.5 ± 4.7% (HDR) and 0.0 ± 4.1% (PDR) with a positional uncertainty in the setup of 0.33/0.23 mm (HDR/PDR) (k = 1). CONCLUSION: A precise and feasible in-clinic calibration method for IVD and source strength consistency tests in BT was presented.

Establishing a fingerprinting method for fast catheter identification in HDR brachytherapy in vivo dosimetry.

PURPOSE: To use quantities measurable during in vivo dosimetry to build unique channel identifiers, that enable detection of brachytherapy errors. MATERIALS AND METHODS: Treatment plan of 360 patients with prostate cancer who underwent high-dose-rate brachytherapy (range, 16-25 catheters; mean, 17) were used. A single point virtual dosimeter was placed at multiple positions within the treatment geometry, and the source-dosimeter distance and dwell time were determined for each dwell position in each catheter. These values were compared across all catheters, dwell position by dwell position, simulating a treatment delivery. A catheter was considered uniquely identified if, for a given dwell position, no other catheters had the same measured values. The minimum number of dwell positions needed to identify a specific catheter and the optimal dosimeter location uniquely were determined. The radial (r) and vertical (z) dimensions of the source-dosimeter distance were also examined for their utility in discriminating catheters. RESULTS: Using a virtual dosimeter with no uncertainties, all catheters were identified in 359 of the 360 cases with 9 dwell position measurements. When only the dwell time were measured, all catheters were uniquely identified after 1 dwell position. With a 2-mm spatial accuracy (r,z), all catheters were identified in 94% of the plans. Simultaneous measurement of source-dosimeter distance and dwell time ensured full catheter identification in all plans ranging from 2 to 6 dwell positions. The number of dwell positions needed to uniquely identify all catheters was lower when the distance from the implant center was higher. CONCLUSIONS: The most efficient fingerprinting approach involved combining source-dosimeter distance (i.e., source tracking) and dwell time. The further the dosimeter is placed from the center of the implant the better it can uniquely identify catheters.

Time-resolved dose rate measurements in pencil beam scanning proton FLASH therapy with a fiber-coupled scintillator detector system.

BACKGROUND: The spatial and temporal dose rate distribution of pencil beam scanning (PBS) proton therapy is important in ultra-high dose rate (UHDR) or FLASH irradiations. Validation of the temporal structure of the dose rate is crucial for quality assurance and may be performed using detectors with high temporal resolution and large dynamic range. PURPOSE: To provide time-resolved in vivo dose rate measurements using a scintillator-based detector during proton PBS pre-clinical mouse experiments with dose rates ranging from conventional to UHDR. METHODS: All irradiations were performed at the entrance plateau of a 250 MeV PBS proton beam. A detector system with four fiber-coupled ZnSe:O inorganic scintillators and 20 µs temporal resolution was used for dose rate measurements. The system was first characterized in terms of precision and stem signal. The detector precision was determined through repeated irradiations with the same field. The stem signal contribution was quantified by irradiating two of the detector probes alongside a bare fiber (fiber without a coupled scintillator). Next, the detector system was calibrated against an ionization chamber (IC) with all four detector probes and the IC placed in a water bath at 2 cm depth. A scan pattern covering 9.6 × 9.6 cm was used. Multiple irradiations with different requested nozzle currents provided instantaneous dose rates at the detector positions in the range of 7-1270 Gy/s. The correspondence of the detector signal (in Volts) to the instantaneous dose rate (in Gy/s) was found. The instantaneous dose rate was calculated from the beam current and the spot-to-detector distance assuming a Gaussian beam profile at distances up to 8 mm from the spot. Afterwards, the calibrated system was used in vivo, in mouse experiments, where mouse legs were irradiated with a constant dose and varying field dose rates of 0.7-87.5 Gy/s. The instantaneous dose rate was measured for each delivered spot and the delivered dose was determined as the integrated instantaneous dose rate. The spot dose profile and PBS dose rate map were calculated. The dose contamination to neighbouring mice were measured together with the upper limit of the dose to the mouse body. RESULTS: The detectors showed high precision with ≤0.4% fluctuations in the measured dose. The stem signal exceeded 10% for spots <5 mm from the optical fiber and >18 mm from the scintillator. It contributed up to 0.2% to the total dose, which was considered negligible. All four detectors showed a non-linear relation between signal and instantaneous dose rate, which was modelled with a polynomial response function. In the mouse experiments, the measured scintillator dose showed 1.8% fluctuations, independent of the field dose rate. The in vivo measured spot dose profile had tails that deviated from a Gaussian profile with measurable dose contributions from spots up to 85 mm from the detector. Neighbour mouse irradiation contributed ∼1% of the total mouse dose. The upper limit of the mouse body dose was 6% of the mouse leg dose. CONCLUSIONS: A fiber-coupled inorganic scintillator-based detector system can provide high precision in vivo measurements of the instantaneous dose rate if correction for the non-linear dose rate dependency is applied.

Monte Carlo characterization of high atomic number inorganic scintillators for in vivo dosimetry in 192 Ir brachytherapy.

BACKGROUND: There is increased interest in in vivo dosimetry for 192 Ir brachytherapy (BT) treatments using high atomic number (Z) inorganic scintillators. Their high light output enables construction of small detectors with negligible stem effect and simple readout electronics. Experimental determination of absorbed-dose energy dependence of detectors relative to water is prevalent, but it can be prone to high detector positioning uncertainties and does not allow for decoupling of absorbed-dose energy dependence from other factors affecting detector response . PURPOSE: To investigate which measurement conditions and detector properties could affect their absorbed-dose energy dependence in BT in vivo dosimetry. METHODS: We used a general-purpose Monte Carlo (MC) code PENELOPE for the characterization of high-Z inorganic scintillators with the focus on ZnSe ( Z ¯ = 32 $\bar{Z}=32$ ) Z. Two other promising media CsI ( Z ¯ = 54 $\bar{Z}=54$ ) and Al2 O3 ( Z ¯ = 11 $\bar{Z}=11$ ) were included for comparison in selected scenarios. We determined absorbed-dose energy dependence of crystals relative to water under different scatter conditions (calibration phantom 12 × 12 × 30 cm3 , characterization phantoms 20 × 20 × 20 cm3 , 30 × 30 × 30 cm3 , 40 × 40 × 40 cm3 , and patient-like elliptic phantom 40 × 30 × 25 cm3 ). To mimic irradiation conditions during prostate treatments, we evaluated whether the presence of pelvic bones and calcifications affect ZnSe response. ZnSe detector design influence was also investigated. RESULTS: In contrast to low-Z organic and medium-Z inorganic scintillators, ZnSe and CsI media have substantially greater absorbed-dose energy dependence relative to water. The response was phantom-size dependent and changed by 11% between limited- and full-scatter conditions for ZnSe, but not for Al2 O3 . For a given phantom size, a part of the absorbed-dose energy dependence of ZnSe is caused not due to in-phantom scatter but due to source anisotropy. Thus, the absorbed-dose energy dependence of high-Z scintillators is a function of not only the radial distance but also the polar angle. Pelvic bones did not affect ZnSe response, whereas large and intermediate size calcifications reduced it by 9% and 5%, respectively, when placed midway between the source and the detector. CONCLUSIONS: Unlike currently prevalent low- and medium-Z scintillators, high-Z crystals are sensitive to characterization and in vivo measurement conditions. However, good agreement between MC data for ZnSe in the present study and experimental data for ZnSe:O by Jørgensen et al. (2021) suggests that detector signal is proportional to the average absorbed dose to the detector cavity. This enables an easy correction for non-TG43-like scenarios (e.g., patient sizes and calcifications) through MC simulations. Such information should be provided to the clinic by the detector vendors.

Toward 3D dose verification of an electronic brachytherapy source with a plastic scintillation detector.

BACKGROUND: Electronic brachytherapy (eBT) is considered a safe treatment with good outcomes. However, eBT lacks standardized and independent dose verification, which could impede future use. PURPOSE: To validate the 3D dose-to-water distribution of an electronic brachytherapy (eBT) source using a small-volume plastic scintillation detector (PSD). METHODS: The relative dose distribution of a Papillon 50 (P50) (Ariane Medical Systems, UK) eBT source was measured in water with a PSD consisting of a cylindrical scintillating BCF-12 fiber (length: 0.5 mm, Ø: 1 mm) coupled to a photodetector via an optical fiber. The measurements were performed with the PSD mounted on a motorized stage in a water phantom (MP3) (PTW, Germany). This allowed the sensitive volume of the PSD to be moved to predetermined positions relative to the P50 applicator, which pointed vertically downward while just breaching the water surface. The percentage depth-dose (PDD) was measured from 0 to 50 mm source-to-detector distance (SDD) in 1-3 mm steps. Dose profiles were measured along two perpendicular axes at five different SDDs with step sizes down to 0.5 mm. Characterization of the PSD consisted of determining the energy correction through Monte Carlo (MC) simulation and by measuring the stability and dose rate linearity using a well-type ionization chamber as a reference. The measured PDD and profiles were validated with corresponding MC simulations. RESULTS: The measured and simulated PDD curves agreed within 2% (except at 0 mm and 43 mm depth) after the PSD measurements were corrected for energy dependency. The absorbed dose decreased by a factor of 2 at 7 mm depth and by a factor of 10 at 26 mm depth. The measured dose profiles showed dose gradients at the profile edges of more than 50%/mm at 5 mm depth and 15%/mm at 50 mm depth. The measured profile widths increased 0.66 mm per 1 mm depth, while the simulated profile widths increased 0.74 mm per 1 mm depth. An azimuthal dependency of > 10% was observed in the dose at 10 mm distance from the beam center. The total uncertainty of the measured relative dose is < 2.5% with a positional uncertainty of 0.4 mm. The measurements for a full 3D dose characterization (PDD and profiles) can be carried out within 8 h, the limiting factor being cooling of the P50. CONCLUSION: The PSD and MP3 water phantoms provided a method to independently verify the relative 3D dose distribution in water of an eBT source.

3D dose reconstruction based on in vivo dosimetry for determining the dosimetric impact of geometric variations in high-dose-rate prostate brachytherapy.

INTRODUCTION: In vivo dosimetry (IVD) can be used for source tracking (ST), i.e., estimating source positions, during brachytherapy. The aim of this study was to exploit IVD-based ST to perform 3D dose reconstruction for high-dose-rate prostate brachytherapy and to evaluate the robustness of the treatments against observed geometric variations. MATERIALS AND METHODS: Twenty-three fractions of high-dose-rate prostate brachytherapy were analysed. The treatment planning was based on MRI. Time-resolved IVD was performed using a fibre-coupled scintillator. ST was retrospectively performed using the IVD measurements. The ST identified 2D positional shifts of each treatment catheter and thereby inferred updated source positions. For each fraction, the dose was recalculated based on the source-tracked catheter positions and compared with the original plan dose using differences in dose volume histogram indices. RESULTS: Of 352 treatment catheters, 344 had shifts of less than 5 mm. Shifts between 5 and 10 mm were observed for 3 catheters, and shifts greater than 10 mm for 2 catheters. The ST failed for 3 catheters. The maximum relative difference in clinical target volume (prostate + 3 mm isotropic margin) D90% was 5%. In one fraction, the bladder D2cm3 dose increased by 18% (1.4 Gy) due to a single source position being inside the bladder rather than nearby as planned. The max increase in urethra dose was 1.5 Gy (15%). CONCLUSION: IVD-based 3D dose reconstruction for high-dose-rate prostate brachytherapy is feasible. The dosimetric impact of the observed catheter shifts was limited. Dose reconstruction can therefore aid in determining the dosimetric impact of geometric variations and errors in brachytherapy.

Time structure of pencil beam scanning proton FLASH beams measured with scintillator detectors and compared with log files.

PURPOSE: Key factors in FLASH treatments are the ultra-high dose rate (UHDR) and the time structure of the beam delivery. Measurement of the time structure in pencil beam scanning (PBS) proton FLASH treatments is challenging for many types of detectors since high temporal resolution is needed. In this study, a fast scintillator detector system was developed and used to measure the individual spot durations as well as the time when the beam moves between two positions (transition duration) during PBS proton FLASH and UHDR treatments. The spot durations were compared with machine log-file recordings. METHODS: A detector system based on inorganic scintillating crystals was developed. The system consisted of four detector probes made of a sub-millimeter ZnSe:O crystal that was coupled via an optical fiber to an optical reader with 50 kHz sampling rate. The detector system was used in two experiments, both performed with a PBS proton beam with 250 MeV beam energy and 215 nA requested nozzle beam current. The sampling rate enabled multiple measurements during each spot delivery and during the beam transition between spots. First, the detector was tested in a phantom experiment, where a total of 305 scan sequences were delivered to the four detectors. The number of spots delivered without beam interruption in a single scan sequence ranged from one to 35. The spot duration and transition duration were measured for each individual spot. Secondly, the detector system was used in vivo in preclinical experiments with FLASH irradiation of mouse legs placed in the entrance plateau of the beam. A single detector was placed 1 cm downstream of the irradiated mouse leg. The mouse dose ranged from 30.5 to 44.2 Gy and the field consisted of 35 spots. The spot durations as well as the mean dose rate (field dose divided by the measured field duration) for each mouse were determined using the detector and then compared with the corresponding log files. RESULTS: The phantom experiment showed that the logged total duration of an uninterrupted spot sequence was consistently shorter than the measured duration with a difference of -0.252 ms (95% confidence interval: [-0.255, -0.249 ms]). This corresponded to 0.05%-0.07% of the spot sequence duration in the mice experiments. For individual spots, the mean ± 1SD difference between logged and measured spot duration was -0.39 ± 0.05 ms for the first spot in a sequence, 0.13 ± 0.04 ms for the last spot in a sequence, and -0.0017 ± 0.09 ms for the intermediate spots in a sequence. The measured spot transition durations were 0.20 ± 0.04 ms (5.1 mm horizontal steps) and 0.50 ± 0.04 ms (5.0 mm vertical steps). For the mouse experiments, the mean dose rate calculated from the measured field duration was 84.1-92.5 Gy/s. It agreed with log files with a root mean square difference of 0.02 Gy/s. CONCLUSIONS: Fiber-coupled scintillator detectors were designed with sufficient temporal resolution to measure the spot and transition duration during PBS proton UHDR deliveries. Their small volume makes them feasible for in vivo use in preclinical FLASH studies. The logged spot durations were in excellent agreement with measurements but showed small systematic errors in the logged duration for the first and last spot in a sequence.

A high-Z inorganic scintillator-based detector for time-resolved in vivo dosimetry during brachytherapy.

PURPOSE: High-dose rate (HDR) and pulsed-dose rate (PDR) brachytherapy would benefit from an independent treatment verification system to monitor treatment delivery and to detect errors in real time. This paper characterizes and provides an uncertainty budget for a detector based on a fiber-coupled high-Z inorganic scintillator capable of performing time-resolved in vivo dosimetry during HDR and PDR brachytherapy. METHOD: The detector was composed of a detector probe and an optical reader. The detector probe consisted of either a 0.5 × 0.4 × 0.4 mm3 (HDR) or a 1.0 × 0.4 × 0.4 mm3 (PDR) cuboid ZnSe:O crystal glued onto an optical-fiber cable. The outer diameter of the detector probes was 1 mm, and fit inside standard brachytherapy catheters. The signal from the detector probe was read out at 20 Hz by a photodiode and a data acquisition device inside the optical reader. In order to construct an uncertainty budget for the detector, six characteristics were determined: (1) temperature dependence of the detector probe, (2) energy dependence as a function of the probe-to-source position in 2D (determined with 2 mm resolution using a robotic arm), (3) the signal-to-noise ratio (SNR), (4) short-term stability over 8 h, and (5) long-term stability of three optical readers and four probes used for in vivo monitoring in HDR and PDR treatments over 21 months (196 treatments and 189 detector calibrations, and (6) dose-rate dependence. RESULTS: The total uncertainty of the detector at a 20 mm probe-to-source distance was < 5.1% and < 5.8% for the HDR and PDR versions, respectively. Regarding the above characteristics, (1) the sensitivity of the detector decreased by an average of 1.4%/°C for detector probe temperatures varying from 22 to 37°C; (2) the energy dependence of the detector was nonlinear and depended on both probe-to-source distance and the angle between the probe and the brachytherapy source; (3) the median SNRs were 187 and 34 at a 20 mm probe-to-source distance for the HDR and PDR versions, respectively (corresponding median source activities of 4.8 and 0.56 Ci, respectively); (4) the detector response varied by 0.6% in 11 identical irradiations over 8 h; (5) the sensitivity of the four detector probes decreased systematically by 0-1.2%/100 Gy of dose delivered to the probes, and random fluctuations of 4.8% in the sensitivity were observed for the three probes used in PDR and 1.9% for the probe used in HDR; and (6) the detector response was linear with dose rate. CONCLUSION: ZnSe:O detectors can be used effectively for in vivo dosimetry and with high accuracy for HDR and PDR brachytherapy applications.

Accuracy of an in vivo dosimetry-based source tracking method for afterloading brachytherapy - A phantom study.

PURPOSE: To report on the accuracy of an in vivo dosimetry (IVD)-based source tracking (ST) method for high dose rate (HDR) prostate brachytherapy (BT). METHODS: The ST was performed on a needle-by-needle basis. A least square fit of the expected to the measured dose rate was performed using the active dwell positions in the given needle. Two fitting parameters were used to determine the position of each needle relative to the IVD detector: radial (away or toward the detector) and longitudinal (along the axis of the treatment needle). The accuracy of the ST was assessed in a phantom where the geometries of five HDR prostate BT treatments previously treated at our clinic were reproduced. For each of the five treatment geometries, one irradiation was performed with the detector placed in the middle of the implant. Furthermore, four additional irradiations were performed for one of the geometries where the detector was retracted caudally in four steps of 10-15 mm and up to 12 mm inferior of the most inferior active dwell position, which represented the prostate apex. The time resolved dose measurements were retrieved at a rate of 20 Hz using a detector based on an Al2 O3 :C radioluminescence crystal, which was placed inside a standard BT needle. Individual calibrations of the detector were performed prior to each of the nine irradiations. RESULTS: Source tracking could be applied in all needles across all nine irradiations. For irradiations with the detector located in the middle region of the implant (a total of 89 needles), the mean ± standard deviation (SD, k = 1) accuracy was -0.01 mm ± 0.38 mm and 0.30 mm ± 0.38 mm in the radial and longitudinal directions, respectively. Caudal retraction of the detector did not lead to reduced accuracy as long as the detector was located superior to the most inferior active dwell positions in all needles. However, reduced accuracy was observed for detector positions inferior to the most inferior active dwell positions which corresponded to detector positions in and inferior to the prostate apex region. Detector positions in the prostate apex and 12 mm inferior to the prostate resulted in mean ± SD (k = 1) ST accuracy of 0.7 mm ± 1 mm and 2.8 mm ± 1.6 mm, respectively, in radial direction, and -1.7 mm ± 1 mm and -2.1 mm ± 1.1 mm, respectively, in longitudinal direction. The largest deviations for the configurations with those detector positions were 2.6 and 5.4 mm, respectively, in the radial direction and -3.5 and -3.8 mm, respectively, in the longitudinal direction. CONCLUSION: This phantom study demonstrates that ST based on IVD during prostate BT is adequately accurate for clinical use. The ST yields submillimeter accuracy on needle positions as long as the IVD detector is positioned superior to at least one active dwell position in all needles. Locations of the detector inferior to the prostate apex result in decreased ST accuracy while detector locations in the apex region and above are advantageous for clinical applications.

3D source tracking and error detection in HDR using two independent scintillator dosimetry systems.

PURPOSE: The aim of this study is to perform three-dimensional (3D) source position reconstruction by combining in vivo dosimetry measurements from two independent detector systems. METHODS: Time-resolved dosimetry was performed in a water phantom during HDR brachytherapy irradiation with 192 Ir source using two detector systems. The first was based on three plastic scintillator detectors and the second on a single inorganic crystal (CsI:Tl). Brachytherapy treatments were simulated in water under TG-43U1 conditions, including a HDR prostate plan. Treatment needles were placed in distances covering a range of source movement of 120 mm around the detectors. The distance from each dwell position to each scintillator was determined based on the measured dose rates. The three distances given by the mPSD were recalculated to a position along the catheter (z) and a distance radially away from the mPSD (xy) for each dwell position (a circumference around the mPSD). The source x, y, and z coordinates were derived from the intersection of the mPSD's circumference with the sphere around the ISD based on the distance to this detector. We evaluated the accuracy of the source position reconstruction as a function of the distance to the source, the most likely location for detector positioning within a prostate volume, as well as the capacity to detect positioning errors. RESULTS: Approximately 4000 source dwell positions were tracked for eight different HDR plans. An intersection of the mPSD torus and the ISD sphere was observed in 77.2% of the dwell positions, assuming no uncertainty in the dose rate determined distance. This increased to 100% if 1σ search regions were added. However, only 73(96)% of the expected dwell positions were found within the intersection band for 1(2) σ uncertainties. The agreement between the source's reconstructed and expected positions was within 3 mm for a range of distances to the source up to 50 mm. The experiments on a HDR prostate plan, showed that by having at least one of the detectors located in the middle of the prostate volume, reduces the measurement deviations considerably compared to scenarios where the detectors were located outside of the prostate volume. The analysis showed a detection probability that, in most cases, is far from the random detection threshold. Errors of 1(2) mm can be detected in ranges of 5-25 (25-50) mm from the source, with a true detection probability rate higher than 80%, while the false probability rate is kept below 20%. CONCLUSIONS: By combining two detector responses, we enabled the determination of the absolute source coordinates. The combination of the mPSD and the ISD in vivo dosimetry constitutes a promising alternative for real-time 3D source tracking in HDR brachytherapy.

Cross-validation of a non-invasive positron detector to measure the arterial input function for pharmacokinetic modelling in dynamic positron emission tomography.

Kinetic modeling of positron emission tomography (PET) data can assess index rate of uptake, metabolism and predict disease progression more accurately than conventional static PET. However, it requires knowledge of the time-course of the arterial blood radioactivity concentration, called the arterial input function (AIF). The gold standard to acquire the AIF is by invasive means. The purpose of this study was to validate a previously developed dual readout scintillating fiber-based non-invasive positron detector, hereinafter called non-invasive detector (NID), developed to determine the AIF for dynamic PET measured from the human radial artery. The NID consisted of a 3 m long plastic scintillating fiber with each end coupled to a 5 m long transmission fiber followed by a silicon photomultiplier. The scintillating fiber was enclosed inside the grooves of a plastic cylindrical shell. Two sets of experiments were performed to test the NID against a previously validated microfluidic positron detector. A closed-loop microfluidic system combined with a wrist phantom was used. During the first experiment, the three PET radioisotopes 18F, 11C and 68Ga were tested. After optimizing the detector, a second series of tests were performed using only 18F and 11C. The maximum pulse amplitude to electronic noise ratio was 52 obtained with 11C. Linear regressions showed a linear relation between the two detectors. These preliminary results show that the NID can accurately detect positrons from a patient's wrist and has the potential to non-invasively measure the AIF during a dynamic PET scan. The accuracy of these measurements needs to be determined.

In vivo dosimetry in brachytherapy: Requirements and future directions for research, development, and clinical practice.

Brachytherapy can deliver high doses to the target while sparing healthy tissues due to its steep dose gradient leading to excellent clinical outcome. Treatment accuracy depends on several manual steps making brachytherapy susceptible to operational mistakes. Currently, treatment delivery verification is not routinely available and has led, in some cases, to systematic errors going unnoticed for years. The brachytherapy community promoted developments in in vivo dosimetry (IVD) through research groups and small companies. Although very few of the systems have been used clinically, it was demonstrated that the likelihood of detecting deviations from the treatment plan increases significantly with time-resolved methods. Time-resolved methods could interrupt a treatment avoiding gross errors which is not possible with time-integrated dosimetry. In addition, lower experimental uncertainties can be achieved by using source-tracking instead of direct dose measurements. However, the detector position in relation to the patient anatomy remains a main source of uncertainty. The next steps towards clinical implementation will require clinical trials and systematic reporting of errors and near-misses. It is of utmost importance for each IVD system that its sensitivity to different types of errors is well understood, so that end-users can select the most suitable method for their needs. This report aims to formulate requirements for the stakeholders (clinics, vendors, and researchers) to facilitate increased clinical use of IVD in brachytherapy. The report focuses on high dose-rate IVD in brachytherapy providing an overview and outlining the need for further development and research.

Inorganic scintillation detectors for 192Ir brachytherapy.

Many brachytherapy (BT) errors could be detected with real-time in vivo dosimetry technology. Inorganic scintillation detectors (ISDs) have demonstrated promising capabilities for BT, because some ISD materials can generate scintillation signals large enough that (a) the background signal emitted in the fiber-optic cable (stem signal) is insignificant, and (b) small detector volumes can be used to avoid volume averaging effects in steep dose gradients near BT sources. We investigated the characteristics of five ISD materials to identify one that is appropriate for BT. ISDs consisting of a 0.26 to 1.0 mm3 volume of ruby (Al2O3:Cr), a mixture of Y2O3:Eu and YVO4:Eu, ZnSe:O, or CsI:Tl coupled to a fiber-optic cable were irradiated in a water-equivalent phantom using a high-dose-rate 192Ir BT source. Detectors based on plastic scintillators BCF-12 and BCF-60 (0.8 mm3 volume) were used as a reference. Measurements demonstrated that the ruby, Y2O3:Eu+YVO4:Eu, ZnSe:O, and CsI:Tl ISDs emitted scintillation signals that were up to 19, 19, 250, and 880 times greater, respectively, than that of the BCF-12 detector. While the total signals of the plastic scintillation detectors were dominated by the stem signal for source positions 0.5 cm from the fiber-optic cable and >3.5 cm from the scintillator volume, the stem signal for the ruby and Y2O3:Eu+YVO4:Eu ISDs were <1% of the total signal for source positions <3.4 and <4.4 cm from the scintillator, respectively, and <0.7% and <0.5% for the ZnSe:O and CsI:Tl ISDs, respectively, for positions ⩽8.0 cm. In contrast to the other ISDs, the Y2O3:Eu+YVO4:Eu ISD exhibited unstable scintillation and significant afterglow. All ISDs exhibited significant energy dependence, i.e. their dose response to distance-dependent 192Ir energy spectra differed significantly from the absorbed dose in water. Provided that energy dependence is accounted for, ZnSe:O ISDs are promising for use in error detection and patient safety monitoring during BT.

Characterization of scintillating fibers for use as positron detector in positron emission tomography.

PURPOSE: Manual and automatic blood sampling at different time intervals is considered the gold standard to determine the arterial input function (AIF) in dynamic positron emission tomography (PET). However, blood sampling is characterized by poor time resolution and is an invasive procedure. The aim of this study was to characterize the scintillating fibers used to develop a non-invasive positron detector. METHODS: The detector consists of a scintillating fiber coupled at each end to transmission fiber-optic cables that are connected to photo multiplier tubes in a dual readout setup. The detector is designed to be wrapped around the wrist of the patient undergoing dynamic PET. The attenuation length and bending losses were measured with excitation from gamma radiation (137Cs) and ultraviolet (UV) light. The response to positron-emitting radio-tracers was evaluated with 18F and 11C. RESULTS: The attenuation length for a 3.0 m and 1.5 m long scintillating fiber both coincides with the attenuation length given by the manufacturer when excited with the 137Cs source, but not with the UV source due to the differences in scintillation mechanisms. The bending losses are smaller than the measurement uncertainty for the 137Cs source irradiation, and increase when the bending radius decrease for the UV source irradiation. The signal-to-noise ratio for 18F and 11C solutions are 1.98 and 22.54 respectively. The measured decay constant of 11C agrees with its characteristic value. CONCLUSION: The performed measurements in the dual readout configuration suggest that scintillating fibers may be suitable to determine the AIF non-invasively.

Time-resolved in vivo dosimetry for source tracking in brachytherapy.

PURPOSE: The purpose of this article is to demonstrate that brachytherapy source tracking can be realized with in vivo dosimetry. This concept could enable real-time treatment monitoring. METHODS: In vivo dosimetry was incorporated in the clinical routine during high-dose-rate prostate brachytherapy at Aarhus University Hospital. The dosimetry was performed with a radioluminescent crystal positioned in a dedicated brachytherapy needle in the prostate. The dose rate was recorded every 50-100 ms during treatment and analyzed retrospectively. The measured total delivered dose and dose rates for each dwell position with dwell times >0.7 s were compared with expected values. Furthermore, the distance between the source and dosimeter, which was derived from the measured dose rates, was compared with expected values. The measured dose rate pattern in each needle was used to determine the most likely position of the needle relative to the dosimeter. RESULTS: In total, 305 needles and 3239 dwell positions were analyzed based on 20 treatments. The measured total doses differed from the expected values by -4.7 ± 8.4% (1SD) with range (-17% to 12%). It was possible to determine needle shifts for 304 out of 305 needles. The mean radial needle shift between imaging and treatment was 0.2 ± 1.1 mm (1SD), and the mean longitudinal shift was 0.3 ± 2.0 mm (1SD). CONCLUSION: Time-resolved in vivo dosimetry can be used to provide geometric information about the treatment progression of afterloading brachytherapy. This information may provide a clear indication of errors and uncertainties during a treatment and, therefore, enables real-time treatment monitoring.

Inorganic scintillation detectors based on Eu-activated phosphors for 192Ir brachytherapy.

The availability of real-time treatment verification during high-dose-rate (HDR) brachytherapy is currently limited. Therefore, we studied the luminescence properties of the widely commercially available scintillators using the inorganic materials Eu-activated phosphors Y2O3:Eu, YVO4:Eu, Y2O2S:Eu, and Gd2O2S:Eu to determine whether they could be used to accurately and precisely verify HDR brachytherapy doses in real time. The suitability for HDR brachytherapy of inorganic scintillation detectors (ISDs) based on the 4 Eu-activated phosphors in powder form was determined based on experiments with a 192Ir HDR brachytherapy source. The scintillation intensities of the phosphors were 16-134 times greater than that of the commonly used organic plastic scintillator BCF-12. High signal intensities were achieved with an optimized packing density of the phosphor mixture and with a shortened fiber-optic cable. The influence of contaminating Cerenkov and fluorescence light induced in the fiber-optic cable (stem signal) was adequately suppressed by inserting between the fiber-optic cable and the photodetector a 25 nm band-pass filter centered at the emission peak. The spurious photoluminescence signal induced by the stem signal was suppressed by placing a long-pass filter between the scintillation detector volume and the fiber-optic cable. The time-dependent luminescence properties of the phosphors were quantified by measuring the non-constant scintillation during irradiation and the afterglow after the brachytherapy source had retracted. We demonstrated that a mixture of Y2O3:Eu and YVO4:Eu suppressed the time-dependence of the ISDs and that the time-dependence of Y2O2S:Eu and Gd2O2S:Eu introduced large measurement inaccuracies. We conclude that ISDs based on a mixture of Y2O3:Eu and YVO4:Eu are promising candidates for accurate and precise real-time verification technology for HDR BT that is cost effective and straightforward to manufacture. Widespread dissemination of this technology could lead to an improved understanding of error types and frequencies during BT and to improved patient safety during treatment.

Ruby-based inorganic scintillation detectors for 192Ir brachytherapy.

We tested the potential of ruby inorganic scintillation detectors (ISDs) for use in brachytherapy and investigated various unwanted luminescence properties that may compromise their accuracy. The ISDs were composed of a ruby crystal coupled to a poly(methyl methacrylate) fiber-optic cable and a charge-coupled device camera. The ISD also included a long-pass filter that was sandwiched between the ruby crystal and the fiber-optic cable. The long-pass filter prevented the Cerenkov and fluorescence background light (stem signal) induced in the fiber-optic cable from striking the ruby crystal, which generates unwanted photoluminescence rather than the desired radioluminescence. The relative contributions of the radioluminescence signal and the stem signal were quantified by exposing the ruby detectors to a high-dose-rate brachytherapy source. The photoluminescence signal was quantified by irradiating the fiber-optic cable with the detector volume shielded. Other experiments addressed time-dependent luminescence properties and compared the ISDs to commonly used organic scintillator detectors (BCF-12, BCF-60). When the brachytherapy source dwelled 0.5 cm away from the fiber-optic cable, the unwanted photoluminescence was reduced from >5% to <1% of the total signal as long as the ISD incorporated the long-pass filter. The stem signal was suppressed with a band-pass filter and was <3% as long as the source distance from the scintillator was <7 cm. Some ruby crystals exhibited time-dependent luminescence properties that altered the ruby signal by >5% within 10 s from the onset of irradiation and after the source had retracted. The ruby-based ISDs generated signals of up to 20 times that of BCF-12-based detectors. The study presents solutions to unwanted luminescence properties of ruby-based ISDs for high-dose-rate brachytherapy. An optic filter should be sandwiched between the ruby crystal and the fiber-optic cable to suppress the photoluminescence. Furthermore, we recommend avoiding ruby crystals that exhibit significant time-dependent luminescence.

Adaptive error detection for HDR/PDR brachytherapy: guidance for decision making during real-time in vivo point dosimetry.

PURPOSE: This study presents an adaptive error detection algorithm (AEDA) for real-time in vivo point dosimetry during high dose rate (HDR) or pulsed dose rate (PDR) brachytherapy (BT) where the error identification, in contrast to existing approaches, does not depend on an a priori reconstruction of the dosimeter position. Instead, the treatment is judged based on dose rate comparisons between measurements and calculations of the most viable dosimeter position provided by the AEDA in a data driven approach. As a result, the AEDA compensates for false error cases related to systematic effects of the dosimeter position reconstruction. Given its nearly exclusive dependence on stable dosimeter positioning, the AEDA allows for a substantially simplified and time efficient real-time in vivo BT dosimetry implementation. METHODS: In the event of a measured potential treatment error, the AEDA proposes the most viable dosimeter position out of alternatives to the original reconstruction by means of a data driven matching procedure between dose rate distributions. If measured dose rates do not differ significantly from the most viable alternative, the initial error indication may be attributed to a mispositioned or misreconstructed dosimeter (false error). However, if the error declaration persists, no viable dosimeter position can be found to explain the error, hence the discrepancy is more likely to originate from a misplaced or misreconstructed source applicator or from erroneously connected source guide tubes (true error). RESULTS: The AEDA applied on two in vivo dosimetry implementations for pulsed dose rate BT demonstrated that the AEDA correctly described effects responsible for initial error indications. The AEDA was able to correctly identify the major part of all permutations of simulated guide tube swap errors and simulated shifts of individual needles from the original reconstruction. Unidentified errors corresponded to scenarios where the dosimeter position was sufficiently symmetric with respect to error and no-error source position constellations. The AEDA was able to correctly identify all false errors represented by mispositioned dosimeters contrary to an error detection algorithm relying on the original reconstruction. CONCLUSIONS: The study demonstrates that the AEDA error identification during HDR/PDR BT relies on a stable dosimeter position rather than on an accurate dosimeter reconstruction, and the AEDA's capacity to distinguish between true and false error scenarios. The study further shows that the AEDA can offer guidance in decision making in the event of potential errors detected with real-time in vivo point dosimetry.

In vivo dosimetry in brachytherapy.

In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification.