A Preliminary Investigation of Radiation-Sensitive Ultrasound Contrast Agents for Photon Dosimetry.

Radiotherapy treatment plans have become highly conformal, posing additional constraints on the accuracy of treatment delivery. Here, we explore the use of radiation-sensitive ultrasound contrast agents (superheated phase-change nanodroplets) as dosimetric radiation sensors. In a series of experiments, we irradiated perfluorobutane nanodroplets dispersed in gel phantoms at various temperatures and assessed the radiation-induced nanodroplet vaporization events using offline or online ultrasound imaging. At 25 °C and 37 °C, the nanodroplet response was only present at higher photon energies (≥10 MV) and limited to <2 vaporization events per cm2 per Gy. A strong response (~2000 vaporizations per cm2 per Gy) was observed at 65 °C, suggesting radiation-induced nucleation of the droplet core at a sufficiently high degree of superheat. These results emphasize the need for alternative nanodroplet formulations, with a more volatile perfluorocarbon core, to enable in vivo photon dosimetry. The current nanodroplet formulation carries potential as an innovative gel dosimeter if an appropriate gel matrix can be found to ensure reproducibility. Eventually, the proposed technology might unlock unprecedented temporal and spatial resolution in image-based dosimetry, thanks to the combination of high-frame-rate ultrasound imaging and the detection of individual vaporization events, thereby addressing some of the burning challenges of new radiotherapy innovations.

New optically stimulated luminescence dosimetry film optimized for energy dependence guided by Monte Carlo simulations.

Optically stimulated luminescence (OSL) film dosimeters, based on BaFBr:Eu2+phosphor material, have major dosimetric advantages such as dose linearity, high spatial resolution, film re-usability, and immediate film readout. However, they exhibit an energy-dependent over-response at low photon energies because they are not made of tissue-equivalent materials. In this work, the OSL energy-dependent response was optimized by lowering the phosphor grain size and seeking an optimal choice of phosphor concentration and film thickness to achieve sufficient signal sensitivity. This optimization process combines measurement-based assessments of energy response in narrow x-ray beams with various energy response calculation methods applied to different film metrics. Theoretical approaches and MC dose simulations were used for homogeneous phosphor distributions and for isolated phosphor grains of different dimensions, where the dose in the phosphor grain was calculated. In total 8 OSL films were manufactured with different BaFBr:Eu2+median particle diameters (D50): 3.2µm, 1.5µm and 230 nm and different phosphor concentrations (1.6%, 5.3% and 21.3 %) and thicknesses (from 5.2 to 49µm). Films were irradiated in narrow x-ray spectra (N60, N80, N-150 and N-300) and the signal intensity relative to the nominal dose-to-water value was normalized to Co-60. Finally, we experimentally tested the response of several films in Varian 6MV TrueBeam STx linear accelerator using the following settings: 10 × 10 cm2field, 0deggantry angle, 90 cm SSD, 10 cm depth. The x-ray irradiation experiment reported a reduced energy response for the smallest grain size with an inverse correlation between response and grain size. The N-60 irradiation showed a 43% reduction in the energy over-response when going from 3µm to 230 nm grain size for the 5% phosphor concentration. Energy response calculation using a homogeneous dispersion of the phosphor underestimated the experimental response and was not able to obtain the experimental correlation between grain size and energy response. Isolated grain size modeling combined with MC dose simulations allowed to establish a good agreement with experimental data, and enabled steering the production of optimized OSL-films. The clinical 6 MV beam test confirmed a reduction in energy dependence, which is visible in small-grain films where a decrease in out-of-field over-response was observed.

A patient- and acquisition-tailored injection approach for improving consistency of CT enhancement towards a target CT value in coronary CT angiography.

BACKGROUND: Unoptimized coronary CT angiography (CTA) exams typically result in a highly variable arterial enhancement (HUa ) across patients. This study aimed at harmonizing arterial enhancement by implementing a patient-, contrast- and kV-tailored injection protocol. METHODS: First, the optimal body size metric to predict HUa was identified by retrospectively analysing images of 76 patients, acquired with 70 ml contrast media (G1). Second, using phantom experiments, correction factors for the effect of kV and contrast concentration on HUa were determined. Third, a model was developed, prescribing the optimal contrast dose to be injected to obtain a diagnostically appropriate arterial target enhancement HUtarget . The model was then validated on 278 prospectively collected patients, in two groups with two different HUtarget : 525 HU (207 patients, G2A) and 425 HU (71 patients, G2B). The HUa histograms were compared among groups and to the target enhancement through their mean and standard deviation (SD) at 100 kVp reference level. Also, signal-to-noise ratio was obtained and compared among the groups. RESULTS: Fat free mass (FFM) showed the highest correlation with HUa (r = 0.69). KVp correction factors ranged from 0.65 at 70 kVp to 1.22 at 140 kVp. The obtained model reduced the group heterogeneity (SD) from 101HU for reference G1 to 75HU (p < 0.001) for G2A and 68HU (p < 0.001) for G2B. The mean HUa of 506HU in G2A was slightly below HUtarget  = 525HU (p = 0.01) whereas in G2B, the mean HUa of 414HU was not significantly different from HUtarget  = 425HU (p = 0.54). The total iodine dose was lowered from 19.5 g-I to 17.6 g-I and 14.2 g-I from G1 to G2A and G2B, on average. CONCLUSION: A contrast injection model, based on patient's fat free mass and accounting for the contrast agent concentration and the planned CT-scan tube voltage, harmonized arterial enhancement among patients towards a predefined target enhancement in coronary CTA scanning, without affecting the bolus timing.

Calibration and time fading characterization of a new optically stimulated luminescence film dosimeter.

BACKGROUND: Optically stimulated luminescence (OSL) dosimeters produce a signal linear to the dose, which fades with time due to the spontaneous recombination of energetically unstable electron/hole traps. When used for radiotherapy (RT) applications, fading affects the signal-to-dose conversion and causes an error in the final dose measurement. Moreover, the signal fading depends to some extent on treatment-specific irradiation conditions such as irradiation times. PURPOSE: In this work, a dose calibration function for a novel OSL film dosimeter was derived accounting for signal fading. The proposed calibration allows to perform dosimetry evaluation for different RT treatment regimes. METHODS: A novel BaFBr:Eu2+ -based OSL film (Zeff , 6 MV  = 4.7) was irradiated on a TrueBeam STx using a 6 MV beam with setup: 0° gantry angle, 90 cm SSD, 10 cm depth, 10 × 10 cm2 field. A total of 86 measurements were acquired for dose-rates ( D ̇ $\dot{D}$ ) of 600, 300, and 200 MU/min for irradiation times (tir ) of 0.2, 1, 2, 4.5, 12, and 23 min and various readout times (tscan ) between 4 and 1440 min from the start of the exposure (beam-on time). The OSL signal, S ( D ̇ , t i r , t s c a n ) $S(\dot{D},{t}_{ir},{t}_{scan})$ , was modeled via robust nonlinear regression, and two different power-law fading models were tested, respectively, independent (linear model) and dependent on the specific t i r ${t}_{ir}$ (delivery-dependent model). RESULTS: After 1 day from the exposure, the error on the dose measurement can be as high as 48% if a fading correction is not considered. The fading contribution was characterized by two accurate models with adjusted-R2 of 0.99. The difference between the two models is <4.75% for all t i r ${t}_{ir}$ and t s c a n ${t}_{scan}$ . For different beam-on times, 3, 10.5, and 20 min, the optimum t s c a n ${t}_{scan}$ was calculated in order to achieve a signal-to-dose conversion with a model-related error <1%. In the case of a 3 min irradiation, this condition is already met when the OSL-film is scanned immediately after the end of the irradiation. For an irradiation of 10.5 and 20 min, the minimum scanning time to achieve this model-related error increases, respectively, to 30 and 90 min. Under these conditions, the linear model can be used for the signal-to-dose conversion as an approximation of the delivery-dependent model. The signal-to-dose function, D(Mi , j , t s c a n $\ {t}_{scan}$ ), has a residual mean error of 0.016, which gives a residual dose uncertainty of 0.5 mGy in the region of steep signal fading (i.e., t s c a n ${t}_{scan}\ $ = 4 min). The function of two variables is representable as a dose surface depending on the signal (Mi , j ) measured for each i,j-pixel and the time of scan ( t s c a n ${t}_{scan}$ ). CONCLUSIONS: The calibration of a novel OSL-film usable for dosimetry in different RT treatments was corrected for its signal fading with two different models. A linear calibration model independent from the treatment-specific irradiation condition results in a model-related error <1% if a proper scanning time is used for each irradiation length. This model is more practical than the delivery-dependent model because it does not need a pixel-to-pixel fading correction for different t i r ${t}_{ir}$ .

Intra-fraction motion monitoring during fast modulated radiotherapy delivery in a closed-bore gantry linac.

BACKGROUND AND PURPOSE: New closed-bore linacs allow for highly streamlined workflows and fast treatment delivery resulting in brief treatment sessions. Motion management technology has only recently been integrated inside the bore, yet is required in future online adaptive workflows. We measured patient motion during every step of the workflow: image acquisition, evaluation and treatment delivery using surface scanning. MATERIALS AND METHODS: Nineteen patients treated for breast, lung or esophageal cancer were prospectively monitored from the end of setup to the end of treatment delivery in the Halcyon linac (Varian Medical Systems). Motion of the chest was tracked by way of 6 degrees-of-freedom surface tracking. Baseline drift and rate of drift were determined. The influence of fraction number, patient and fraction duration were analyzed with multi-way ANOVA. RESULTS: Median fraction duration was 4 min 48 s including the IGRT procedure (kV-CBCT acquisition and evaluation) (N = 221). Baseline drift at the end of the fraction was -1.8 ± 1.5 mm in the anterior-posterior, -0.0 ± 1.7 mm in the cranio-caudal direction and 0.1 ± 1.8 mm in the medio-lateral direction of which 75% occurred during the IGRT procedure. The highest rate of baseline drift was observed between 1 and 2 min after the end of patient setup (-0.62 mm/min). Baseline drift was patient and fraction duration dependent (p < 0.001), but fraction number was not significant (p = 0.33). CONCLUSION: Even during short treatment sessions, patient baseline drift is not negligible. Drift is largest during the initial minutes after completion of patient setup, during verification imaging and evaluation. Patients will need to be monitored during extended contouring and re-planning procedures in online adaptive workflows.

Spirometer-guided breath-hold breast VMAT verified with portal images and surface tracking.

BACKGROUND AND PURPOSE: Fast rotating closed-bore gantry linacs are ideally suited for breath-hold treatments due to reduced imaging and delivery times. We evaluated the reproducibility and stability of spirometer-guided breath-hold breast treatments, using intra-bore surface monitoring and portal imaging on Halcyon (Varian Medical Systems). MATERIALS AND METHODS: Seven left-sided breast cancer patients were treated in breath-hold using the SDX spirometer (Dyn'R) with an integrated boost volumetric arc protocol on Halcyon. A dual depth-camera surface scanning system monitored the left breast. The interfraction, intrafraction and intrabreath-hold motion was determined in the anterior-posterior (AP) and superior-inferior (SI) direction. Portal images (PI), acquired at a tangential gantry angle were manually registered to the planning-CT to determine inter- and intrafraction breath-hold errors for the SI and tangential-anterior-posterior ("AP") axis. Correlations between PI and surface imaging deviations were investigated. To evaluate workflow efficiency, the total time and the number of breath-holds were recorded. RESULTS: Systematic and random variability of breath-hold amplitude was below 0.7 mm for the AP and below 1.2 mm for the SI component as detected by surface monitoring (N = 130). Systematic and random errors retrieved from portal images (N = 140) were below 1.2 mm for the "AP" and 2.1 mm for SI axis. A limited correlation was found between PI and surface monitoring deviations for both the SI and "AP" axes (R2 = 0.27/0.38, p < 0.01). 75% of fractions were completed using four breath-holds and 82% within 10 min. CONCLUSION: Surface imaging indicated spirometer-guided breath-hold VMAT breast radiotherapy can be accurately and quickly performed on a closed-bore gantry linac. Intra-bore surface scanning proved a valuable technique for monitoring breathing motion in closed-bore systems.

Development and accuracy evaluation of a single-camera intra-bore surface scanning system for radiotherapy in an O-ring linac.

BACKGROUND AND PURPOSE: Current commercial surface scanning systems are not able to monitor patients during radiotherapy fractions in closed-bore linacs during adaptive workflows. In this work a surface scanning system for monitoring in an O-ring linac is proposed. METHODS AND MATERIALS: A depth camera was mounted at the backend of the bore. The acquired surface point cloud was transformed to the linac coordinate system after a cube detection calibration step. The real-time surface was registered using an Iterative Closest Point algorithm to a reference region-of-interest of the body contour from the planning CT and of a depth camera surface acquisition from the first fraction. The positioning accuracy was investigated using anthropomorphic 3D-printed phantoms with embedded markers: a head, hand and breast. To simulate clinically observed positioning errors, each phantom was placed 24 times with 0-10 mm and 0-8° offsets from the planned position. At every position a cone-beam CT (CBCT) was acquired and a surface registration performed. The surface registration error was determined as the difference between the surface registration and the CBCT-to-CT fiducial marker registration. RESULTS: The registration errors were (mean ±â€¯SD): lat: 0.4 ±â€¯0.8 mm, vert: -0.2 ±â€¯0.2 mm, long: 0.3 ±â€¯0.5 mm and Yaw: -0.2 ±â€¯0.6°, Pitch: 0.4 ±â€¯0.2°, Roll: 0.5 ±â€¯0.8° for the body contour reference, and lat: -0.7 ±â€¯0.7 mm, vert: 0.3 ±â€¯0.2 mm, long: 0.2 ±â€¯0.5 mm and Yaw: -0.5 ±â€¯0.5°, Pitch: 0.1 ±â€¯0.3°, Roll: -0.7 ±â€¯0.7° for the captured surface reference. CONCLUSION: The proposed single camera intra-bore surface system was capable of accurately detecting phantom displacements and allows intrafraction motion monitoring for surface guided radiotherapy inside the bore of O-ring gantries.

Volumetric modulated arc therapy of head-and-neck cancer on a fast-rotating O-ring linac: Plan quality and delivery time comparison with a C-arm linac.

BACKGROUND AND PURPOSE: Linac improvements in gantry speed, leaf speed and dose rate may increase the time-efficiency of volumetric modulated arc therapy (VMAT) delivery. The plan quality achievable with faster VMAT however remains to be investigated. In this study, a fast-rotating O-ring linac with fast-moving leaves is compared with a C-arm linac in terms of plan quality and delivery time for VMAT of head-and-neck cancer (HNC). MATERIAL AND METHODS: For 30 patients with HNC, treatment planning was performed using dual-arc (HA2) and triple-arc (HA3) VMAT on a Halcyon fast-rotating O-ring linac and using dual-arc VMAT on a TrueBeam C-arm linac (TB2). Target coverage metrics and complication probabilities were compared. Plan delivery was verified using 3%/3 mm gamma-index analysis of helical diode array measurements. Volumetric image acquisition and plan delivery times were compared. RESULTS: All studied VMAT-techniques fulfilled the target coverage objectives. D2% to the boost volume was higher for HA2 (median 103.7%, 1st-3rd quartile [103.5%;104.0%]) and HA3 (103.2% [103.0%;103.7%)] than for TB2 (102.6% [102.3%;103.0%)], resulting in an increased boost target dose heterogeneity for HA2 and HA3. Complication probabilities were comparable between HA2 and TB2, while HA3 showed a xerostomia probability reduction (0.8% [0.2%;1.8%]) and dysphagia probability reduction (1.0% [0.2%;1.8%]) compared with TB2. Gamma-index agreement scores were never below 93.0% for HA2, HA3 and TB2. Volumetric imaging and plan delivery time was shorter for HA2 (1 m 24 s ±â€¯1 s) and HA3 (1 m 54 s ±â€¯1 s) than for TB2 (2 m 47 s ±â€¯1 s). CONCLUSION: For VMAT of HNC, the fast-rotating O-ring linac at least maintains the plan quality of two arcs on a C-arm linac while reducing the image acquisition and plan delivery time.