Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction.

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

Experimental validation of multi-fraction online adaptations in magnetic resonance guided radiotherapy.

Background and purpose: Radiotherapy plan verification is generally performed on the reference plan based on the pre-treatment anatomy. However, the introduction of online adaptive treatments demands a new approach, as plans are created daily on different anatomies. The aim of this study was to experimentally validate the accuracy of total doses of multi-fraction plan adaptations in magnetic resonance imaging guided radiotherapy in a phantom study, isolated from the uncertainty of deformable image registration. Materials and methods: We experimentally verified the total dose, measured on external beam therapy 3 (EBT3) film, using a treatment with five online adapted fractions. Three series of experiments were performed, each focusing on a category of inter-fractional variation; translations, rotations and body modifications. Variations were introduced during each fraction and adapted plans were generated and irradiated. Single fraction doses and total doses over five online adapted fractions were investigated. Results: The online adapted measurements and calculations showed a good agreement for single fractions and multi-fraction treatments for the dose profiles, gamma passing rates, dose deviations and distances to agreement. The gamma passing rate using a 2%/2 mm criterion ranged from 99.2% to 99.5% for a threshold dose of 10% of the maximum dose (Dmax) and from 96.2% to 100% for a threshold dose of 90% of Dmax, for the total translations, rotations and body modifications. Conclusions: The total doses of multi-fraction treatments showed similar accuracies compared to single fraction treatments, indicating an accurate dosimetric outcome of a multi-fraction treatment in adaptive magnetic resonance imaging guided radiotherapy.

Gating and intrafraction drift correction on a 1.5 T MR-Linac: Clinical dosimetric benefits for upper abdominal tumors.

This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.

On the feasibility of cardiac substructure sparing in magnetic resonance imaging guided stereotactic lung radiotherapy.

BACKGROUND: Lung stereotactic body radiotherapy (SBRT) has proven an effective treatment for medically inoperable lung tumors, even for (ultra-)central tumors. Recently, there has been growing interest in radiation-induced cardiac toxicity in lung radiotherapy. More specifically, dose to cardiac (sub-)structures (CS) was found to correlate with survival after radiotherapy. PURPOSE: Our goal is first, to investigate the percentage of patients who require CS sparing in an magnetic resonance imaging guided lung SBRT workflow, and second, to quantify how successful implementation of cardiac sparing would be. METHODS: The patient cohort consists of 34 patients with stage II-IV lung cancer who were treated with SBRT between 2017 and 2020. A mid-position computed tomography (CT) image was used to create treatment plans for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) following clinical templates. Under guidance of a cardio-thoracic radiologist, 11 CS were contoured manually for each patient. Dose constraints for five CS were extracted from the literature. Patients were stratified according to their need for cardiac sparing depending on the CS dose in their non-CS constrained MR-linac treatment plans. Cardiac sparing treatment plans (CSPs) were then created and dosimetrically compared with their non-CS constrained treatment plan counterparts. CSPs complied with the departmental constraints and were considered successful when fulfilling all CS constraints, and partially successful if some CS constraints could be fulfilled. Predictors for the need for and feasibility of cardiac sparing were explored, specifically planning target volume (PTV) size, cranio-caudal (CC) distance, 3D distance, and in-field overlap volume histograms (iOVH). RESULTS: 47% of the patients (16 out of 34) were in need of cardiac sparing. A successful CSP could be created for 62.5% (10 out of 16) of these patients. Partially successful CSPs still complied with two to four CS constraints. No significant difference in dose to organs at risk (OARs) or targets was identified between CSPs and the corresponding non-CS constrained MR-linac plans. The need for cardiac sparing was found to correlate with distance in the CC direction between target and all of the individual CS (Mann-Whitney U-test p-values <10-6 ). iOVHs revealed that complying with dose constraints for CS is primarily determined by in-plane distance and secondarily by PTV size. CONCLUSION: We demonstrated that CS can be successfully spared in lung SBRT on the MR-linac for most of this patient cohort, without compromising doses to the tumor or to other OARs. CC distance between the target and CS can be used to predict the need for cardiac sparing. iOVHs, in combination with PTV size, can be used to predict if cardiac sparing will be successful for all constrained CS except the left ventricle.

Towards mid-position based Stereotactic Body Radiation Therapy using online magnetic resonance imaging guidance for central lung tumours.

Background and purpose: Central lung tumours can be treated by magnetic resonance (MR)-guided radiotherapy. Complications might be reduced by decreasing the Planning Target Volume (PTV) using mid-position (midP)-based planning instead of Internal Target Volume (ITV)-based planning. In this study, we aimed to verify a method to automatically derive patient-specific PTV margins for midP-based planning, and show dosimetric robustness of midP-based planning for a 1.5T MR-linac. Materials and methods: Central(n = 12) and peripheral(n = 4) central lung tumour cases who received 8x7.5 Gy were included. A midP-image was reconstructed from ten phases of the 4D-Computed Tomography using deformable image registration. The Gross Tumor Volume (GTV) was delineated on the midP-image and the PTV margin was automatically calculated based on van Herk's margin recipe, treating the standard deviation of all Deformation Vector Fields, within the GTV, as random error component. Dosimetric robustness of midP-based planning for MR-linac using automatically derived margins was verified by 4D dose-accumulation. MidP-based plans were compared to ITV-based plans. Automatically derived margins were verified with manually derived margins. Results: The mean D95% target coverage in GTV + 2 mm was 59.9 Gy and 62.0 Gy for midP- and ITV-based central lung plans, respectively. The mean lung dose was significantly lower for midP-based treatment plans (difference:-0.3 Gy; p < 0.042 ). Automatically derived margins agreed within one millimeter with manually derived margins. Conclusions: This retrospective study indicates that mid-position-based treatment plans for central lung Stereotactic Body Radiation Therapy yield lower OAR doses compared to ITV-based treatment plans on the MR-linac. Patient-specific GTV-to-PTV margins can be derived automatically and result in clinically acceptable target coverage.

First experimental demonstration of VMAT combined with MLC tracking for single and multi fraction lung SBRT on an MR-linac.

BACKGROUND AND PURPOSE: VMAT is not currently available on MR-linacs but could maximize plan conformality. To mitigate respiration without compromising delivery efficiency, MRI-guided MLC tumour tracking was recently developed for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) in combination with IMRT. Here, we provide a first experimental demonstration of VMAT + MLC tracking for several lung SBRT indications. MATERIALS AND METHODS: We created central patient and phantom VMAT plans (8×7.5 Gy, 2 arcs) and we created peripheral phantom plans (3×18 & 1×34 Gy, 4 arcs). A motion phantom mimicked subject-recorded respiratory motion (A‾=11 mm, f‾=0.33 Hz, drift‾=0.3 mm/min). This was monitored using 2D-cine MRI at 4 Hz to continuously realign the beam with the target. VMAT + MLC tracking performance was evaluated using 2D film dosimetry and a novel motion-encoded and time-resolved pseudo-3D dosimetry approach. RESULTS: We found an MLC leaf and jaw end-to-end latency of 328.05(±3.78) ms and 317.33(±4.64) ms, which was mitigated by a predictor. The VMAT plans required maximum MLC speeds of 12.1 cm/s and MLC tracking superimposed an additional 1.48 cm/s. A local 2%/1 mm gamma analysis with a static measurement as reference, revealed pass-rates of 28-46% without MLC tracking and 88-100% with MLC tracking for the 2D film analysis. Similarly, the pseudo-3D gamma passing-rates increased from 22-77% to 92-100%. The dose area histograms showed that MLC tracking increased the GTV D98% by 5-20% and the PTV D95% by 7-24%, giving similar target coverage as their respective static reference. CONCLUSION: MRI-guided VMAT + MLC tracking is technically feasible on the MR-linac and results in highly conformal dose distribution.

Acceptance procedure for the linear accelerator component of the 1.5 T MRI-linac.

PURPOSE: To develop and implement an acceptance procedure for the new Elekta Unity 1.5 T MRI-linac. METHODS: Tests were adopted and, where necessary adapted, from AAPM TG106 and TG142, IEC 60976 and NCS 9 and NCS 22 guidelines. Adaptations were necessary because of the atypical maximum field size (57.4 × 22 cm), FFF beam, the non-rotating collimator, the absence of a light field, the presence of the 1.5 T magnetic field, restricted access to equipment within the bore, fixed vertical and lateral table position, and the need for MR image to MV treatment alignment. The performance specifications were set for stereotactic body radiotherapy (SBRT). RESULTS: The new procedure was performed similarly to that of a conventional kilovoltage x-ray (kV) image guided radiation therapy (IGRT) linac. Results were acquired for the first Unity system. CONCLUSIONS: A comprehensive set of tests was developed, described and implemented for the MRI-linac. The MRI-linac met safety requirements for patients and operators. The system delivered radiation very accurately with, for example a gantry rotation locus of isocenter of radius 0.38 mm and an average MLC absolute positional error of 0.29 mm, consistent with use for SBRT. Specifications for clinical introduction were met.

Initial Clinical Experience of MR-Guided Radiotherapy for Non-Small Cell Lung Cancer.

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and Elekta Unity. The challenges and potential solutions associated with MRgRT in lung cancer will also be highlighted.

Dosimetric evaluation of MRI-guided multi-leaf collimator tracking and trailing for lung stereotactic body radiation therapy.

PURPOSE: The treatment margins for lung stereotactic body radiotherapy (SBRT) are often large to cover the tumor excursions resulting from respiration, such that underdosage of the tumor can be avoided. Magnetic resonance imaging (MRI)-guided multi-leaf collimator (MLC) tracking can potentially reduce the influence of respiration to allow for smaller treatment margins. However, tracking is accompanied by system latency that may induce residual tracking errors. Alternatively, a simpler mid-position delivery combined with trailing can be used. Trailing reduces influences of respiration by compensating for baseline motion, to potentially improve target coverage. In this study, we aim to show the feasibility of MRI-guided tracking and trailing to reduce influences of respiration during lung SBRT. METHODS: We implemented MRI-guided tracking on the MR-linac using an Elekta research tracking interface to track tumor motion during intensity modulated radiotherapy (IMRT). A Quasar MRI 4 D phantom was used to generate Lujan motion ( cos 4 , 4 s period, 20 mm peak-to-peak amplitude) with and without 1.0 mm/min cranial drift. Phantom tumor positions were estimated from sagittal 2D cine-MRI (4 or 8 Hz) using cross-correlation-based template matching. To compensate the anticipated system latency, a linear ridge regression predictor was optimized for online MRI by comparing two predictor training approaches: training on multiple traces and training on a single trace. We created 15-beam clinical-grade lung SBRT plans for central targets (8 × 7.5 Gy) and peripheral targets (3 × 18 Gy) with different PTV margins for mid-position based motion management (3-5 mm) and for MLC tracking (3 mm). We used a film insert with a 3 cm spherical target to measure the spatial distribution and quantity of the delivered dose. A 1%/1 mm local gamma-analysis quantified dose differences between motion management strategies and reference cases. Additionally, a dose area histogram (DAH) revealed the target coverage relative to the reference scenario. RESULTS: The prediction filter gain was on average 25% when trained on multiple traces and 44% when trained on a single trace. The filter reduced system latency from 313 ± 2 ms to 0 ± 5 ms for 4 Hz imaging and from 215 ± 3 ms to 3 ± 3 ms for 8 Hz. The local gamma analysis for the central delivery showed that tracking improved the gamma pass-rate from 23% to 96% for periodic motion and from 14% to 93% when baseline drift was applied. For the peripheral delivery during periodic motion, delivery pass-rates improved from 22% to 93%. Comparing mid-position delivery to trailing for periodic+drift motion increased the local gamma pass rate from 15% to 98% for a central delivery and from 8% to 98% for a peripheral delivery. Furthermore, the DAHs revealed a relative D 98 % GTV coverage of 101% and 97% compared to the reference scenario for, respectively, central and peripheral tracking of periodic+drift motion. For trailing, a relative D 98 % of 99% for central and 98% for peripheral trailing was found. CONCLUSIONS: We provided a first experimental demonstration of the technical feasibility of MRI-guided MLC tracking and trailing for central and peripheral lung SBRT. Tracking maximizes the sparing of healthy tissue, while trailing is highly effective in mitigating baseline motion.

Improving the imaging performance of the 1.5 T MR-linac using a flexible, 32-channel, on-body receive array.

High impedance coils (HICs) are suitable as a building block of receive arrays for MRI-guided radiotherapy (MRIgRT) as HICs do not require radiation-attenuating capacitors and dense support materials. Recently, we proved the feasibility of using HICs to create a radiation transparent (i.e. radiolucent) window. In this work, we constructed a fully functional 32-channel array based on this design. The anterior element is flexible and follows the shape of the subject, while the posterior element is rigid to support the subject. Both elements feature a 2 × 8 channel layout. Here, we discuss the construction process and characterize the array's radiolucency and imaging performance. The dosimetric impact of the array was quantified by assessing the surface dose increase and attenuation of a single beam. The imaging performance of the prototype was compared to the clinical array in terms of visual appearance, signal-to-noise ratio (SNR), and acceleration performance, both in phantom and in-vivo measurements. Dosimetry measurements showed that on-body placement changed the anterior and posterior surface dose by +3% and -16% of the dose maximum. Attenuation under the anterior support materials and conductors was 0.3% and ≤1.5%, respectively. Phantom and in-vivo imaging with this array demonstrated an improvement of the SNR at the surface and the image quality in general. Simultaneous irradiation did not affect the SNR. G-factors were reduced considerably and clinically used sequences could be accelerated by up to 45%, which would greatly reduce pre-beam imaging times. Finally, the maximally achievable temporal resolution of abdominal 3D cine imaging was improved to 1.1 s, which was > 5 × faster than could be achieved with the clinical array. This constitutes a big step towards the ability to resolve respiratory motion in 3D. In conclusion, the proposed 32-channel array is compatible with MRIgRT and can significantly reduce scan times and/or improve the image quality of all on-line scans.

Design and feasibility of a flexible, on-body, high impedance coil receive array for a 1.5 T MR-linac.

The lack of radiation-attenuating tuning capacitors in high impedance coils (HICs) make HICs an interesting building block of receive arrays for MRI-guided radiotherapy (MRIgRT). Additionally, their flexibility and limited channel coupling allow for low-density support materials, which are likely to be more radiation transparent (radiolucent). In this work, we introduce the use of HICs in receive arrays for MRIgRT treatments. We discuss the design and show the dosimetric feasibility of a HIC receive array that has a high channel count and aims to improve the imaging performance of the 1.5 T MR-linac. Our on-body design comprises an anterior and posterior element, which each feature a [Formula: see text] channel layout (32 channels total). The anterior element is flexible, while the posterior element is rigid to support the patient. Mockups consisting of support materials and conductors were built, irradiated, and optimized to minimize impact on the surface dose (7% of the dose maximum) and dose at depth ([Formula: see text]0.8% under a single conductor and [Formula: see text]1.4% under a conductor crossing). Anatomical motion and the use of multiple beam angles will ensure that these slight dose changes at depth are clinically insignificant. Subsequently, several functional, single-channel HIC imaging prototypes and a 5-channel array were built to assess the performance in terms of signal-to-noise ratio (SNR). The performance was compared to the clinical MR-linac array and showed that the 5-channel imaging prototype outperformed the clinical array in terms of SNR and channel coupling. Imaging performance was not affected by the radiation beam. In conclusion, the use of HICs allowed for the design of our flexible, on-body receive array for MRIgRT. The design was shown to be dosimetrically feasible and improved the SNR. Future research with a full array will need to show the gain in parallel imaging performance and thus acceleration.

Adaptive radiotherapy: The Elekta Unity MR-linac concept.

BACKGROUND AND PURPOSE: The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods. MATERIALS AND METHODS: To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured. RESULTS: The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases. CONCLUSION: Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

Feasibility of stereotactic radiotherapy using a 1.5 T MR-linac: Multi-fraction treatment of pelvic lymph node oligometastases.

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.

Monte Carlo simulations of out-of-field surface doses due to the electron streaming effect in orthogonal magnetic fields.

The out-of-field surface dose contribution due to backscattered or ejected electrons, focused by the magnetic field, is evaluated in this work. This electron streaming effect (ESE) can contribute to out-of-field skin doses in orthogonal magnetic resonance guided radiation therapy machines. Using the EGSnrc Monte Carlo package, a phantom is set-up along the central axis of an incident 10 [Formula: see text] 10 cm2 7 MV FFF photon beam. The phantom exit or entry surface is inclined with respect to the magnetic field, and an out-of-field water panel is positioned 10 cm away from, and centered on, the isocenter. The doses from streaming backscattered or ejected electrons, for either a 0.35 T or 1.5 T magnetic field, are evaluated in the out-of-field water panel for surface inclines of 10, 30, and 45°. The magnetic field focuses electrons emitted from the inclined phantom. Dose distributions at the surface of the out-of-field water panel are sharper in the 1.5 T magnetic field as compared to 0.35 T. The maximum doses for the 0.35 T simulations are 23.2%, 37.8%, and 39.0% for the respective 10, 30, and 45° simulations. For 1.5 T, for the same angles, the maximum values are 17.1%, 29.8%, and 35.8%. Dose values drop to below 2% within the first 1 cm of the out-of-field water phantom. The phantom thickness is an important variable in the magnitude of the ESE dose. The ESE can produce large out-of-field skin doses and must be a consideration in treatment planning in the MRgRT work-flow. Treatments often include multiple beams which will serve to spread out the effect, and many beams, such as anterior-posterior, will reduce the skin dose due to the ESE. A 1 cm thick shielding of either a bolus placed on the patient or mounted on the present RF coils would greatly reduce the ESE dose contributions. Further exploration of the capabilities of treatment planning systems to screen for this effect is required.

Cardiac Structure Doses in Women Irradiated for Breast Cancer in the Past and Their Use in Epidemiological Studies.

PURPOSE: Incidental cardiac exposure during radiation therapy may cause heart disease. Dose-response relationships for cardiac structures (segments) may show which ones are most sensitive to radiation. Radiation-related cardiac injury can take years to develop; thus, studies need to involve women treated using 2-dimensional planning, with segment doses estimated using a typical computed tomography (CT) scan. We assessed whether such segment doses are accurate enough to use in dose-response relationships using the radiation therapy charts of women with known segment injury. We estimated interregimen and interpatient segment dose variability and segment dose correlations. METHODS AND MATERIALS: The radiation therapy charts of 470 women with cardiac segment injury after breast cancer radiation therapy were examined, and 41 regimens were identified. Regimens were reconstructed on a typical CT scan. Doses were estimated for 5 left ventricle (LV) and 10 coronary artery segments. Correlations between cardiac segments were estimated. Interpatient dose variation was assessed in 10 randomly selected CT scans for left regimens and in 5 for right regimens. RESULTS: For the typical CT scan, interregimen segment dose variation was substantial (range, LV segments <1-39 Gy; coronary artery segments <1-48 Gy). In 10 CT scans, interpatient segment dose variation was higher for segments near field borders (range, 3-47 Gy) than other segments (range, <2 Gy). Doses to different left-anterior descending coronary artery (LADCA) segments were highly correlated with each other, as were doses to different LV segments. Also, LADCA segment doses were highly correlated with doses to LV segments usually supplied by the LADCA. For individual regimens there was consistency in hotspot location and segment ranking of higher-versus-lower dose. CONCLUSIONS: The scope for developing quantitative cardiac segment dose-response relationships in patients who had 2-dimensional planning is limited because different segment doses are often highly correlated, and segment-specific dose uncertainties are not independent of each other. However, segment-specific doses may be reliably used to rank segments according to higher-versus-lower doses.

Dosimetric feasibility of the hybrid Magnetic Resonance Imaging (MRI)-linac System (MRL) for brain metastases: The impact of the magnetic field.

BACKGROUND AND PURPOSE: We aimed to investigate the suitability of treating patients with single brain metastases using stereotactic radiosurgery (SRS) with the MRL and to characterize the dosimetric impact at tissue-air interfaces resulting primarily from the electron return effect (ERE). MATERIAL AND METHODS: 24 patients treated for intact single brain metastases were analyzed. Three radiotherapy plans with the same prescribed dose were generated for each case: (1) noncoplanar volumetric modulated arc therapy (VMAT), (2) coplanar step-and-shoot intensity modulated radiotherapy (IMRT) on the MRL in the absence (MRLB=0), and (3) in the presence of the transverse magnetic field (MRLB=1.5). The plans were evaluated using cumulative dose-volume histograms and by calculation of Paddick conformity index (CI), V100%, V12Gy minus gross tumor volume (V12Gy - GTV), and V2Gy. At tissue-air boundaries, the dosimetric impact of the magnetic field was quantified using a 5 mm rim of tissue. RESULTS: All plans met the target coverage and organs-at-risk planning objectives. Differences between all investigated dosimetric parameters significantly favored the VMAT plans as compared to the MRLB=0 and MRLB=1.5 plans, except for V2Gy. The mean V12Gy - GTV and V2Gy marginally favored the MRLB=0 plans compared to the MRLB=1.5 plans (mean difference: 0.45 cm3, p = 0.0019 and 16.46 cm3, p < 0.0001, respectively). The presence of the magnetic field resulted in a statistically significant but small increase in mean dose and D2cc in the skin (0.08 Gy, p < 0.0001 and 0.6 Gy, p < 0.0001, respectively) and around air cavities (0.07 Gy, p = 0.0092 and 0.3 Gy, p = 0.0004, respectively). CONCLUSIONS: It is feasible to generate stereotactic radiation plans that satisfy clinical requirements using the MRL in the setting of single brain metastases. The dosimetric impact of the magnetic field including the ERE at tissue-air boundaries is minor and does not negatively impact target conformity or dose gradient.

18 F-fluoromisonidazole uptake in advanced stage non-small cell lung cancer: A voxel-by-voxel PET kinetics study.

PURPOSE: The aim of this study was to determine the relative abilities of compartment models to describe time-courses of 18 F-fluoromisonidazole (FMISO) uptake in tumor voxels of patients with non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography. Also to use fits of the best-performing model to investigate changes in fitted rate-constants with distance from the tumor edge. METHODS: Reversible and irreversible two- and three-tissue compartment models were fitted to 24 662 individual voxel time activity curves (TACs) obtained from tumors in nine patients, each imaged twice. Descriptions of the TACs provided by the models were compared using the Akaike and Bayesian information criteria (AIC and BIC). Two different models (two- and three-tissue) were fitted to 30 measured voxel TACs to provide ground-truth TACs for a statistical simulation study. Appropriately scaled noise was added to each of the resulting ground-truth TACs, generating 1000 simulated noisy TACs for each ground-truth TAC. The simulation study was carried out to provide estimates of the accuracy and precision with which parameter values are determined, the estimates being obtained for both assumptions about the ground-truth kinetics. A BIC clustering technique was used to group the fitted rate-constants, taking into consideration the underlying uncertainties on the fitted rate-constants. Voxels were also categorized according to their distance from the tumor edge. RESULTS: For uptake time-courses of individual voxels an irreversible two-tissue compartment model was found to be most precise. The simulation study indicated that this model had a one standard deviation precision of 39% for tumor fractional blood volumes and 37% for the FMISO binding rate-constant. Weighted means of fitted FMISO binding rate-constants of voxels in all tumors rose significantly with increasing distance from the tumor edge, whereas fitted fractional blood volumes fell significantly. When grouped using the BIC clustering, many centrally located voxels had high-fitted FMISO binding rate-constants and low rate-constants for tracer flow between the vasculature and tumor, both indicative of hypoxia. Nevertheless, many of these voxels had tumor-to-blood (TBR) values lower than the 1.4 level commonly expected for hypoxic tissues, possibly due to the low rate-constants for tracer flow between the vasculature and tumor cells in these voxels. CONCLUSIONS: Time-courses of FMISO uptake in NSCLC tumor voxels are best analyzed using an irreversible two-tissue compartment model, fits of which provide more precise parameter values than those of a three-tissue model. Changes in fitted model parameter values indicate that levels of hypoxia rise with increasing distance from tumor edges. The average FMISO binding rate-constant is higher for voxels in tumor centers than in the next tumor layer out, but the average value of the more simplistic TBR metric is lower in tumor centers. For both metrics, higher values might be considered indicative of hypoxia, and the mismatch in this case is likely to be due to poor perfusion at the tumor center. Kinetics analysis of dynamic PET images may therefore provide more accurate measures of the hypoxic status of such regions than the simpler TBR metric, a hypothesis we are presently exploring in a study of tumor imaging versus histopathology.

Constancy checks of well-type ionization chambers with external-beam radiation units.

Constancy checks of a well-type ionization chamber should be performed regularly as part of a quality assurance regime. The goal of this work was to test the feasibility of using a linear accelerator and an orthovoltage unit to check the constancy of a well-type chamber's response to an external radiation source. The reproducibility, linearity with dose, variation with dose-rate, and variation between energy-matched units of the well-type chamber response when exposed to 6 MV beams was examined. The robustness to errors in establishing the measurement conditions, including setting the source-to-surface distance and gantry angle, rotation of the chamber around the central axis of the beam, and the effect of changing the length of the chamber cable exposed to the field, were tested. The reproducibility and linearity with dose of the chamber response, and robustness to errors in establishing the measurement conditions for 100 kVp and 250 kVp beams from an orthovoltage unit, were also examined. The combined uncertainty, including contributions from errors in establishing the reference conditions, for well-type chamber measurements using a 6 MV beam from a linear accelerator is 1.0%. The combined uncertainties for measurements using 100 and 250 kVp beams were 1.8% and 1.5%, respectively. When focus-source distance errors were reduced to ≤ 1 mm, the combined uncertainties for the 100 and 250 kVp beams were 1.2% and 1.1%, respectively, when the dose to the chamber was confined to the linear region of the dose-response curve. The response of a well-type chamber should remain constant to within 1.2% when exposed to a constant dose from an external beam unit, if reference conditions can be reproducibly established. However, the uncertainty for establishing reference conditions for output measurements for an orthovoltage unit can be reduced, which would justify a reduction of the tolerance for constancy measurements.

Estimation of input functions from dynamic [18F]FLT PET studies of the head and neck with correction for partial volume effects.

BACKGROUND: We present a method for extracting arterial input functions from dynamic [18F]FLT PET images of the head and neck, directly accounting for the partial volume effect. The method uses two blood samples, for which the optimum collection times are assessed. METHODS: Six datasets comprising dynamic PET images, co-registered computed tomography (CT) scans and blood-sampled input functions were collected from four patients with head and neck tumours. In each PET image set, a region was identified that comprised the carotid artery (outlined on CT images) and surrounding tissue within the voxels containing the artery. The time course of activity in the region was modelled as the sum of the blood-sampled input function and a compartmental model of tracer uptake in the surrounding tissue.The time course of arterial activity was described by a mathematical function with seven parameters. The parameters of the function and the compartmental model were simultaneously estimated, aiming to achieve the best match between the modelled and imaged time course of regional activity and the best match of the estimated blood activity to between 0 and 3 samples. The normalised root-mean-square (RMSnorm) differences and errors in areas under the curves (AUCs) between the measured and estimated input functions were assessed. RESULTS: A one-compartment model of tracer movement to and from the artery best described uptake in the tissue surrounding the artery, so the final model of the input function and tissue kinetics has nine parameters to be estimated. The estimated and blood-sampled input functions agreed well when two blood samples, obtained at times between 2 and 8 min and between 8 and 60 min, were used in the estimation process (RMSnorm values of 1.1 ± 0.5 and AUC errors for the peak and tail region of the curves of 15% ± 9% and 10% ± 8%, respectively). A third blood sample did not significantly improve the accuracy of the estimated input functions. CONCLUSIONS: Input functions for FLT-PET studies of the head and neck can be estimated well using a one-compartment model of tracer movement and TWO blood samples obtained after the peak in arterial activity.

Comparison of low-dose, half-rotation, cone-beam CT with electronic portal imaging device for registration of fiducial markers during prostate radiotherapy.

This study evaluated the agreement of fiducial marker localization between two modalities--an electronic portal imaging device (EPID) and cone-beam computed tomography (CBCT)--using a low-dose, half-rotation scanning protocol. Twenty-five prostate cancer patients with implanted fiducial markers were enrolled. Before each daily treatment, EPID and half-rotation CBCT images were acquired. Translational shifts were computed for each modality and two marker-matching algorithms, seed-chamfer and grey-value, were performed for each set of CBCT images. The localization offsets, and systematic and random errors from both modalities were computed. Localization performances for both modalities were compared using Bland-Altman limits of agreement (LoA) analysis, Deming regression analysis, and Cohen's kappa inter-rater analysis. The differences in the systematic and random errors between the modalities were within 0.2 mm in all directions. The LoA analysis revealed a 95% agreement limit of the modalities of 2 to 3.5 mm in any given translational direction. Deming regression analysis demonstrated that constant biases existed in the shifts computed by the modalities in the superior-inferior (SI) direction, but no significant proportional biases were identified in any direction. Cohen's kappa analysis showed good agreement between the modalities in prescribing translational corrections of the couch at 3 and 5 mm action levels. Images obtained from EPID and half-rotation CBCT showed acceptable agreement for registration of fiducial markers. The seed-chamfer algorithm for tracking of fiducial markers in CBCT datasets yielded better agreement than the grey-value matching algorithm with EPID-based registration.