Biologically consistent dose accumulation using daily patient imaging.

BACKGROUND: This work addresses a basic inconsistency in the way dose is accumulated in radiotherapy when predicting the biological effect based on the linear quadratic model (LQM). To overcome this inconsistency, we introduce and evaluate the concept of the total biological dose, bEQDd. METHODS: Daily computed tomography imaging of nine patients treated for prostate carcinoma with intensity-modulated radiotherapy was used to compute the delivered deformed dose on the basis of deformable image registration (DIR). We compared conventional dose accumulation (DA) with the newly introduced bEQDd, a new method of accumulating biological dose that considers each fraction dose and tissue radiobiology. We investigated the impact of the applied fractionation scheme (conventional/hypofractionated), uncertainties induced by the DIR and by the assigned α/ß-value. RESULTS: bEQDd was systematically higher than the conventionally accumulated dose with difference hot spots of 3.3-4.9 Gy detected in six out of nine patients in regions of high dose gradient in the bladder and rectum. For hypofractionation, differences are up to 8.4 Gy. The difference amplitude was found to be in a similar range to worst-case uncertainties induced by DIR and was higher than that induced by α/ß. CONCLUSION: Using bEQDd for dose accumulation overcomes a potential systematic inaccuracy in biological effect prediction based on accumulated dose. Highest impact is found for serial-type late responding organs at risk in dose gradient regions and for hypofractionation. Although hot spot differences are in the order of several Gray, in dose-volume parameters there is little difference compared with using conventional or biological DA. However, when local dose information is used, e.g. dose surface maps, difference hot spots can potentially change outcomes of dose-response modelling and adaptive treatment strategies.

Technical Note: ADAM PETer - An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy.

OBJECTIVE: To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer). METHODS: The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three-dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K2 HPO4 and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient-specific activity concentrations of a Fluorine-18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner. RESULTS: The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2-weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured. CONCLUSION: The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T-MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI-based radiation treatment planning of prostate cancer patients.

Dosimetry in magnetic fields with dedicated MR-compatible ionization chambers.

MR-integrated radiotherapy requires suitable dosimetry detectors to be used in magnetic fields. This study investigates the feasibility of using dedicated MR-compatible ionization chambers at MR-integrated radiotherapy devices. MR-compatible ionization chambers (Exradin A19MR, A1SLMR, A26MR, A28MR) were precisely modeled and their relative response in a 6MV treatment beam in the presence of a magnetic field was simulated using EGSnrc. Monte Carlo simulations were carried out with the magnetic field in three orientations: the magnetic field aligned perpendicular to the chamber and beam axis (transverse orientation), the magnetic field parallel to the chamber as well as parallel to the beam axis. Monte Carlo simulation results were validated with measurements using an electromagnet with magnetic field strength upto 1.1 T with the chambers in transverse orientation. The measurements and simulation results were in good agreement, except for the A26MR ionization chamber in transverse orientation. The maximum increase in response of the ionization chambers observed was 8.6% for the transverse orientation. No appreciable change in chamber response due to the magnetic field was observed for the magnetic field parallel to the ionization chamber and parallel to the photon beam. Polarity and recombination correction factor were experimentally investigated in the transverse orientation. The polarity effect and recombination effect were not altered by a magnetic field. This study further investigates the response of the ionization chambers as a function of the chambers' rotation around their longitudinal axis. A variation in response was observed when the chamber was not rotationally symmetric, which was independent of the magnetic field.

An end-to-end test for MR-guided online adaptive radiotherapy.

In the evolving field of adaptive MR guided radiotherapy, the need for dedicated procedures for acceptance and quality assurance is increasing. Research has been devoted to MR compatible dosimeters and phantoms, but to date no end-to-end test has been presented that covers an MRgRT workflow. Such an end-to-end test should comprise each step of the workflow and include all associated uncertainties. The purpose of this study was to investigate the usability of an anthropomorphic deformable and multimodal pelvis (ADAM-pelvis) phantom in combination with film dosimetry for end-to-end testing of an MRgRT adaptive workflow. The ADAM-pelvis phantom included surrogates for muscle tissue, adipose and bone, as well as deformable silicone organs mimicking a prostate patient. At the interfaces of the critical structures (bladder and rectum), small pieces of GafChromic EBT3 films were placed to measure delivered dose. Pre-treatment MR imaging of the phantom was used to delineate the prostate, rectum and bladder and to generate a treatment plan to deliver 2 Gy to the prostate. Electron density (ED) map from CT imaging was used for dose calculation after deformable image registration (DIR) to the pre-treatment MR scan. At each fraction, bladder- and rectum filling was varied and a new adapted plan was generated. Dose calculation was performed using both a DIR-based ED map and a CT-based ED map after acquisition of a new CT scan of the phantom at each fraction. All dose calculations were performed taking into account the magnetic field. A good agreement between measured and calculated dose was found using both, the CT-derived and the DIR-based ED map (2.0% and 2.8% dose difference, respectively). The gamma index pass-rate (3%/2 mm) varied from 96.4% to 100%.The ADAM-pelvis phantom was suitable for end-to-end testing in MR-guided radiotherapy and a very good agreement with the calculated dose was achieved.

End-to-end empirical validation of dose accumulation in MRI-guided adaptive radiotherapy for prostate cancer using an anthropomorphic deformable pelvis phantom.

BACKGROUND AND PURPOSE: This work evaluates the accuracy of deformable dose accumulation for organs at risk (OAR) in MR-guided prostate SBRT using an anthropomorphic deformable phantom. MATERIALS AND METHODS: Six MR-guided prostate SBRT treatment courses were simulated using volumetric OAR (bladder and rectum) information derived from actual patient data. Deformed OAR contours, geometrical landmarks and GafChromic EBT3 film strips (1.25 × 2.0 cm2) placed at the surface of the OARs were used to validate DIR-based dose accumulation in MRgRT. Two DIR methods were applied: an intensity-based deformation (IB-D) applied to the whole image, and a contour-based deformation (CB-D), resulting in a separate deformation and dose accumulation for each OAR. Dosimetric accuracy was evaluated by quantifying the dose differences, and performing a gamma-index analysis between measured and DIR-derived accumulated dose for both OARs. Geometrical accuracy was assessed by measuring the Dice similarity coefficient (DSC), Hausdorff distance (HDD) and residual distance error (RDE) for all markers at each fraction. RESULTS: CB-D resulted in an average dose deviation from film measurements for rectum and bladder surfaces of 0.6% and 0.3%, respectively. IB-D led to worse results resulting in an overall average dose accumulation inaccuracy of 7.2% and 2.5% for rectum and bladder. CB-D also showed a higher geometrical accuracy than IB-D with significantly higher DSC values and lower RDE and HDD deviations. CONCLUSION: Empirical validation of dose accumulation in MR-guided SBRT for prostate cancer obtained a good agreement with reference film measurements when using a contour-based DIR approach.

Comparison of pancreatic respiratory motion management with three abdominal corsets for particle radiation therapy: Case study.

BACKGROUND AND PURPOSE: Abdominal organ motion seriously compromises the targeting accuracy for particle therapy in patients with pancreatic adenocarcinoma. This study compares three different abdominal corsets regarding their ability to reduce pancreatic motion and their potential usability in particle therapy. MATERIALS AND METHODS: A patient-individualized polyurethane (PU), a semi-individualized polyethylene (PE), and a patient-individualized three-dimensional-scan based polyethylene (3D-PE) corset were manufactured for one healthy volunteer. Time-resolved volumetric four-dimensional-magnetic resonance imaging (4D-MRI) and single-slice two-dimensional (2D) cine-MRI scans were acquired on two consecutive days to compare free-breathing motion patterns with and without corsets. The corset material properties, such as thickness variance, material homogeneity in Hounsfield units (HU) on computed tomography (CT) scans, and manufacturing features were compared. The water equivalent ratio (WER) of corset material samples was measured using a multi-layer ionization chamber for proton energies of 150 and 200 MeV. RESULTS: All corsets reduced the pancreatic motion on average by 9.6 mm in inferior-superior and by 3.2 mm in anterior-posterior direction. With corset, the breathing frequency was approximately doubled and the day-to-day motion variations were reduced. The WER measurements showed an average value of 0.993 and 0.956 for the PE and 3DPE corset, respectively, and of 0.298 for the PU corset. The PE and 3DPE corsets showed a constant thickness of 2.8 ± 0.2 and 3.8 ± 0.2 mm, respectively and a homogeneous material composition with a standard deviation (SD) of 31 and 32 HU, respectively. The PU corset showed a variable thickness of 4.2 - 25.6 mm and a heterogeneous structure with air inclusions with an SD of 113 HU. CONCLUSION: Abdominal corsets may be effective devices to reduce pancreatic motion. For particle therapy, PE-based corsets are preferred over PU-based corset due to their material homogeneity and constant thickness.

Comparing the effectiveness and efficiency of various gating approaches for PBS proton therapy of pancreatic cancer using 4D-MRI datasets.

Abdominal organ motion may lead to considerable uncertainties in pencil-beam scanning (PBS) proton therapy of pancreatic cancer. Beam gating, where irradiation only occurs in certain breathing phases in which the gating conditions are fulfilled, may be an option to reduce the interplay effect between tumor motion and the scanning beam. This study aims to, first, determine suitable gating windows with respect to effectiveness (low interplay effect) and efficiency (high duty cycles). Second, it investigates whether beam gating allows for a better mitigation of the interplay effect along the treatment course than free-breathing irradiations. Based on synthetic 4D-CTs, generated by warping 3D-CTs with vector fields extracted from time-resolved magnetic resonance imaging (4D-MRI) for 8 pancreatic cancer patients, 4D dose calculations (4DDC) were performed to analyze the duty cycle and homogeneity index HI = d5/d95 for four different gating scenarios. These were based on either fixed threshold values of CTV (clinical target volume) mean or maximum motion amplitudes (5 mm), relative CTV motion amplitudes (30%) or CTV overlap criteria (95%), respectively. 4DDC for 28-fractions treatment courses were performed with fixed and variable initial breathing phases to investigate the fractionation-induced mitigation of the interplay effect. Gating criteria, based on patient-specific relative 30% CTV motion amplitudes, showed the significantly best HI values with sufficient duty cycles, in contrast to inferior results by either fixed gating thresholds or overlap criteria. For gated treatments with 28 fractions, less fractionation-induced mitigation of the interplay effect was observed for gating criteria with gating windows ⩾30%, compared to free-breathing treatments. The gating effectiveness for multiple fractions was improved by allowing a variable initial breathing phase. Gating with relative amplitude thresholds are effective for proton therapy of pancreatic cancer. By combining beam gating with variable initial breathing phases, a pronounced mitigation of the interplay effect by fractionation can be achieved.

4DMRI-based investigation on the interplay effect for pencil beam scanning proton therapy of pancreatic cancer patients.

BACKGROUND: Time-resolved volumetric magnetic resonance imaging (4DMRI) offers the potential to analyze 3D motion with high soft-tissue contrast without additional imaging dose. We use 4DMRI to investigate the interplay effect for pencil beam scanning (PBS) proton therapy of pancreatic cancer and to quantify the dependency of residual interplay effects on the number of treatment fractions. METHODS: Based on repeated 4DMRI datasets for nine pancreatic cancer patients, synthetic 4DCTs were generated by warping static 3DCTs with 4DMRI deformation vector fields. 4D dose calculations for scanned proton therapy were performed to quantify the interplay effect by CTV coverage (v95) and dose homogeneity (d5/d95) for incrementally up to 28 fractions. The interplay effect was further correlated to CTV motion characteristics. For quality assurance, volume and mass conservation were evaluated by Jacobian determinants and volume-density comparisons. RESULTS: For the underlying patient cohort with CTV motion amplitudes < 15 mm, we observed significant correlations between CTV motion amplitudes and both the length of breathing cycles and the interplay effect. For individual fractions, tumor underdosage down to v95 = 70% was observed with pronounced dose heterogeneity (d5/d95 = 1.3). For full × 28 fractionated treatments, we observed a mitigation of the interplay effect with increasing fraction numbers. On average, after seven fractions, a CTV coverage with 95-107% of the prescribed dose was reached with sufficient dose homogeneity. For organs at risk, no significant differences were found between the static and accumulated dose plans for 28 fractions. CONCLUSION: Intrafractional organ motion exhibits a large interplay effect for PBS proton therapy of pancreatic cancer. The interplay effect correlates with CTV motion, but can be mitigated efficiently by fractionation, mainly due to different breathing starting phases in fractionated treatments. For hypofractionated treatments, a further restriction of motion may be required. Repeated 4DMRI measurements are a viable tool for pre- and post-treatment evaluations of the interplay effect.

Commissioning of a 4D MRI phantom for use in MR-guided radiotherapy.

PURPOSE: Systems for integrated magnetic resonance guided radiation therapy (MRgRT) provide real-time and online MRI guidance for unequaled targeting performance of moving tumors and organs at risk. The clinical introduction of such systems requires dedicated methods for commissioning and routine machine quality assurance (QA). The aim of the study was to develop a commissioning protocol and method for automatic quantification of target motion and geometric accuracy using a 4D MRI motion phantom. MATERIALS AND METHODS: The commissioning was performed on a clinically used 3 T MR scanner. The phantom was positioned on a flat tabletop overlay using an in-house constructed base plate for a quick and reproducible setup. The torso-shaped phantom body, which was filled with mineral oil as signal generating medium, included a 3D grid structure for image distortion analysis and a cylindrical thru-hole in which a software-controlled moving rod with a hypo-intense background gel and a decentralized hyper-intense target simulated 3D organ motion patterns. To allow for sequence optimization, MR relaxometry was performed to determine the longitudinal T1 and transverse T2 relaxation times of both target and background gel in the movable cylinder. The geometric image distortion was determined as the mean and maximum 3D Euclidean distance (Δmean , Δmax ) of grid points determined by nonrigid registration of a 3D spoiled gradient echo MRI scan and a CT scan. Sinusoidal 1D/2D/3D motion trajectories, varying in amplitude and frequency, as well as an exemplary 1D MR navigator diaphragm motion pattern extracted from a healthy volunteer scan, were scanned by means of 2D cine MRI and 4D MRI. Target positions were automatically extracted from 2D cine MRI using an in-house developed software tool. RESULTS: The base plate enabled a reproducible setup with a deviation of <1 mm in all directions. Relaxometry yielded T1 /T2 values for target and background gel of 208.1 ± 2.8/30.5 ± 4.7 ms and 871 ± 36/13.4  ±  1.3 ms, respectively. The 3D geometric image distortion increased with distance from the magnetic isocenter, with Δmean  = 0.58 ± 0.30 mm and Δmax  = 1.31 mm. The frequencies of the reconstructed motion patterns agreed with the preset values within 0.5%, whereas the reconstructed amplitudes showed a maximum deviation to the preset amplitudes of <0.5 mm in AP/LR direction and <0.3 mm in IS direction. CONCLUSION: A method and protocol for commissioning of a 4D MRI motion phantom on a 3 T MR scanner for MRgRT was developed. High-contrast and geometrically reliable 2D cine MR images of the phantom's moving target could be obtained. The preset motion parameters could be extracted with sufficient spatio-temporal accuracy from 2D cine MRI in all motion directions. The overall 3D geometric image distortion of <1.31 mm within the phantom grid confirms geometric accuracy of the clinically utilized 3D spoiled gradient echo sequence. The method developed can be used for routine QA tests of spatio-temporally resolved MRI data in MRgRT.

4D dose calculation for pencil beam scanning proton therapy of pancreatic cancer using repeated 4DMRI datasets.

4D magnetic resonance imaging (4DMRI) has a high potential for pancreatic cancer treatments using proton therapy, by providing time-resolved volumetric images with a high soft-tissue contrast without exposing the patient to any additional imaging dose. In this study, we aim to show the feasibility of 4D treatment planning for pencil beam scanning (PBS) proton therapy of pancreatic cancer, based on five repeated 4DMRI datasets and 4D dose calculations (4DDC) for one pancreatic cancer patient. To investigate the dosimetric impacts of organ motion, deformation vector fields were extracted from 4DMRI, which were then used to warp a static CT of the patient, so as to generate synthetic 4DCT (4DCT-MRI). CTV motion amplitudes <15 mm were observed for this patient. The results from 4DDC show pronounced interplay effects in the CTV with dose homogeneity d5/d95 and dose coverage v95 being 1.14 and 91%, respectively, after a single fraction of the treatment. An averaging effect was further observed when increasing the number of fractions. Motion effects can become less dominant and dose homogeneity d5/d95 = 1.03 and dose coverage v95 = [Formula: see text] within the CTV can be achieved after 28 fractions. The observed inter-fractional organ and tumor motion variations underline the importance of 4D imaging before and during PBS proton therapy.

Technical Note: On the size of susceptibility-induced MR image distortions in prostate and cervix in the context of MR-guided radiation therapy.

PURPOSE: To investigate the extent of MR image distortions in the pelvis caused by susceptibility-induced field inhomogeneities in MR images in the context of a study on MR-guided radiotherapy. METHODS: Using a high-bandwidth double-echo gradient echo sequence, field maps and distortion maps of the pelvis were calculated and evaluated for 219 exams (92 of female and 127 of male patients) to investigate patient-related image distortions caused by susceptibility differences in an ongoing study on MR-guided radiotherapy. The evaluation of distortions in the regions "rectum", "prostate", "cervix", and in a reference region in the gluteus maximus was based on masks drawn by two readers. RESULTS: Distortions in the prostate and cervix were smaller than 0.03 px (0.1 mm) for 99% of voxels, and reached a maximum value of 0.09 px (0.3 mm). In the reference region, maximum distortions were smaller than in the prostate and cervix. CONCLUSIONS: Using a geometric uncertainty of 0.2 px (0.6 mm) in margin definition for organs that are close to the rectum like the prostate and the cervix would be a cautious choice to account for susceptibility-induced distortions that can arise during MR-based treatment guidance for the imaging setting used in this study. Since distortions are inversely proportional to the readout bandwidth of the sequence, safety margins need to be adapted adequately. Additional sources of image distortions like gradient nonlinearities are not included in our margin recommendations and should be considered separately.

Prospective feasibility analysis of a novel off-line approach for MR-guided radiotherapy.

BACKGROUND: The present work aimed to analyze the feasibility of a shuttle-based MRI-guided radiation therapy (MRgRT) in the treatment of pelvic malignancies. PATIENTS AND METHODS: 20 patients with pelvic malignancies were included in this prospective feasibility analysis. Patients underwent daily MRI in treatment position prior to radiotherapy at the German Cancer Research Center. Positional inaccuracies, time and patient compliance were assessed for the application of off-line MRgRT. RESULTS: In 78% of applied radiation fractions, MR imaging for position verification could be performed without problems. Additionally, treatment-related side effects and reduced patient compliance were only responsible for omission of MRI in 9% of radiation fractions. The study workflow took a median time of 61 min (range 47-99 min); duration for radiotherapy alone was 13 min (range 7-26 min). Patient positioning, MR imaging and CT imaging including patient repositioning and the shuttle transfer required median times of 10 min (range 7-14 min), 26 min (range 15-60 min), 5 min (range 3-8 min) and 8 min (range 2-36 min), respectively. To assess feasibility of shuttle-based MRgRT, the reference point coordinates for the x, y and z axis were determined for the MR images and CT obtained prior to the first treatment fraction and correlated with the coordinates of the planning CT. In our dataset, the median positional difference between MR imaging and CT-based imaging based on fiducial matching between MR and CT imaging was equal to or less than 2 mm in all spatial directions. The limited space in the MR scanner influenced patient selection, as the bore of the scanner had to accommodate the immobilization device and the constructed stereotactic frame. Therefore, obese, extremely muscular or very tall patients could not be included in this trial in addition to patients for whom exposure to MRI was generally judged inappropriate. CONCLUSION: This trial demonstrated for the first time the feasibility and patient compliance of a shuttle-based off-line approach to MRgRT of pelvic malignancies.

The effect of density overrides on magnetic resonance-guided radiation therapy planning for lung cancer.

BACKGROUND AND PURPOSE: Inverse treatment planning for lung cancer can be challenging since density heterogeneities may appear inside the planning target volume (PTV). One method to improve the quality of intensity modulation is the override of low density tissues inside the PTV during plan optimization. For magnetic resonance-guided radiation therapy (MRgRT), where the influence of the magnetic field on secondary electrons is sensitive to the tissue density, the reliability of density overrides has not yet been proven. This work, therefore, gains a first insight into density override strategies for MRgRT. MATERIAL AND METHODS: Monte Carlo-based treatment plans for five lung cancer patients were generated based on free-breathing CTs and two density override strategies. Different magnetic field configurations were considered with their effect being accounted for during optimization. Optimized plans were forward calculated to 4D-CTs and accumulated for the comparison of planned and expected delivered dose. RESULTS: For MRgRT, density overrides led to a discrepancy between the delivered and planned dose. The tumor volume coverage deteriorated for perpendicular magnetic fields of 1.5 T to 93.6% (D98%). For inline fields a maximal increase of 2.2% was found for the mean dose. In terms of organs at risk, a maximal sparing of 0.6 Gy and 0.9 Gy was observed for lung and heart, respectively. CONCLUSIONS: In this work, first results on the effect of density overrides on treatment planning for MRgRT are presented. It was observed that the underestimation of magnetic field effects in overridden densities during treatment planning resulted in an altered delivered dose, depending on the field strength and orientation.

Effects of magnetic field orientation and strength on the treatment planning of nonsmall cell lung cancer.

PURPOSE: Magnetic resonance image-guided radiotherapy (MRgRT) has the potential to increase the accuracy of radiation treatment delivery. Several research groups have developed hybrid MRgRT devices differing by radiation source used and magnetic field orientation and strength. In this work, we investigate the impact of different magnetic field orientations and strengths on the treatment planning of nonsmall cell lung cancer patients (NSCLC). METHODS: A framework using the in-house developed treatment planning system matRad and the EGSnrc Monte Carlo code system was introduced to perform Monte Carlo-based treatment planning in the presence of a magnetic field. A specialized spectrum-based source model for the beam qualities of 6 MV and cobalt-60 was applied. Optimized plans for stereotactic body radiation therapy (SBRT) and intensity-modulated radiation therapy (IMRT) were generated for four NSCLC patients in the presence of different magnetic field orientations and strengths which are applied in hybrid MRgRT devices currently under development or in clinical use. RESULTS: SBRT and IMRT treatment planning could be performed with consistent plan quality for all magnetic field setups. Only minor effects on the treatment planning outcome were found in the case of magnetic fields orientated perpendicular to the beam direction. Compared to the perpendicular magnetic field orientation, the inline orientation showed the capability to reduce the dose to lung while maintaining equal target coverage. Particularly for tumors with a central position in lung, a distinct dose reduction was obtained which led to a maximum reduction of mean lung dose by 18.5% (0.5 Gy), when applying a 1 T inline magnetic field. CONCLUSION: All plans generated in this work obtained dose metrics within clinical constraints according to RTOG guidelines. When considering conventional dose metrics, no detrimental effects due to the magnetic fields were observed on the dose to the tumor or to organs at risk. An evaluation of the effects on skin dose was not ascertainable due to the simplified specification of the source model used. By accounting for the magnetic field during treatment planning, a dose reduction in lung could be achieved for inline-oriented magnetic fields. An inline orientation of the magnetic field therefore showed a potential benefit when treating NSCLC with MRgRT.

Generation of synthetic CT data using patient specific daily MR image data and image registration.

To fully exploit the advantages of magnetic resonance imaging (MRI) for radiotherapy (RT) treatment planning, a method is required to overcome the problem of lacking electron density information. We aim to establish and evaluate a new method for computed tomography (CT) data generation based on MRI and image registration. The thereby generated CT data is used for dose accumulation. We developed a process flow based on an initial pair of rigidly co-registered CT and T2-weighted MR image representing the same anatomical situation. Deformable image registration using anatomical landmarks is performed between the initial MRI data and daily MR images. The resulting transformation is applied to the initial CT, thus fractional CT data is generated. Furthermore, the dose for a photon intensity modulated RT (IMRT) or intensity modulated proton therapy (IMPT) plan is calculated on the generated fractional CT and accumulated on the initial CT via inverse transformation. The method is evaluated by the use of phantom CT and MRI data. Quantitative validation is performed by evaluation of the mean absolute error (MAE) between the measured and the generated CT. The effect on dose accumulation is examined by means of dose-volume parameters. One patient case is presented to demonstrate the applicability of the method introduced here. Overall, CT data derivation lead to MAEs with a median of 37.0 HU ranging from 29.9 to 66.6 HU for all investigated tissues. The accuracy of image registration showed to be limited in the case of unexpected air cavities and at tissue boundaries. The comparisons of dose distributions based on measured and generated CT data agree well with the published literature. Differences in dose volume parameters kept within 1.6% and 3.2% for photon and proton RT, respectively. The method presented here is particularly suited for application in adaptive RT in current clinical routine, since only minor additional technical equipment is required.

Evaluation of Dosimetric Robustness of Carbon Ion Boost Therapy for Anal Carcinoma.

PURPOSE: The radiation therapy treatment outcome of human papillomavirus-negative anal carcinoma may be improved by the biological effectiveness of carbon ions. However, abdominal tissue motion can compromise the precision of carbon ion therapy. This work aims to evaluate the dosimetric feasibility of carbon ion boost (CIB) therapy for anal carcinoma. MATERIALS AND METHODS: An algorithm to generate computed tomographies based on daily magnetic resonance imaging data and deformable image registration was developed. By means of this algorithm, fractional computed tomography data for 54 treatment fractions for 3 different patients with anal carcinoma were derived. The dose for a sequential CIB (CIBseq) treatment plan was recalculated on the fractional computed tomography data and accumulated over the number of fractions. The resulting dose distributions were compared to standard intensity-modulated radiation therapy treatment with an integrated photon boost. RESULTS: For the investigated patient cases, similar dosimetric results for CIBseq treatment and for intensity-modulated radiation therapy with an integrated photon boost were found. For CIBseq treatment, bladder-filling variation had the strongest influence on the dose distribution. However, the detrimental effects on the mean target dose remained below 1 Gy (RBE) as compared to photon therapy. CONCLUSION: This study shows the dosimetric feasibility of CIB therapy for anal carcinoma for the first time and gives reason for clinical exploitation of the enhanced biological effect of carbon ions for patients with human papillomavirus-negative anal cancer.

Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR-guided radiotherapy.

PURPOSE: Phantom surrogates were developed to allow multimodal [computed tomography (CT), magnetic resonance imaging (MRI), and teletherapy] and anthropomorphic tissue simulation as well as materials and methods to construct deformable organ shapes and anthropomorphic bone models. METHODS: Agarose gels of variable concentrations and loadings were investigated to simulate various soft tissue types. Oils, fats, and Vaseline were investigated as surrogates for adipose tissue and bone marrow. Anthropomorphic shapes of bone and organs were realized using 3D-printing techniques based on segmentations of patient CT-scans. All materials were characterized in dual energy CT and MRI to adapt CT numbers, electron density, effective atomic number, as well as T1- and T2-relaxation times to patient and literature values. RESULTS: Soft tissue simulation could be achieved with agarose gels in combination with a gadolinium-based contrast agent and NaF to simulate muscle, prostate, and tumor tissues. Vegetable oils were shown to be a good representation for adipose tissue in all modalities. Inner bone was realized using a mixture of Vaseline and K2HPO4, resulting in both a fatty bone marrow signal in MRI and inhomogeneous areas of low and high attenuation in CT. The high attenuation of outer bone was additionally adapted by applying gypsum bandages to the 3D-printed hollow bone case with values up to 1200 HU. Deformable hollow organs were manufactured using silicone. Signal loss in the MR images based on the conductivity of the gels needs to be further investigated. CONCLUSIONS: The presented surrogates and techniques allow the customized construction of multimodality, anthropomorphic, and deformable phantoms as exemplarily shown for a pelvic phantom, which is intended to study adaptive treatment scenarios in MR-guided radiation therapy.

Phenomenological modelling of second cancer incidence for radiation treatment planning.

It is still an unanswered question whether a relatively low dose of radiation to a large volume or a higher dose to a small volume produces the higher cancer incidence. This is of interest in view of modalities like IMRT or rotation therapy where high conformity to the target volume is achieved at the cost of a large volume of normal tissue exposed to radiation. Knowledge of the shape of the dose response for radiation-induced cancer is essential to answer the question of what risk of second cancer incidence is implied by which treatment modality. This study therefore models the dose response for radiation-induced second cancer after radiation therapy of which the exact mechanisms are still unknown. A second cancer risk estimation tool for treatment planning is presented which has the potential to be used for comparison of different treatment modalities, and risk is estimated on a voxel basis for different organs in two case studies. The presented phenomenological model summarises the impact of microscopic biological processes into effective parameters of mutation and cell sterilisation. In contrast to other models, the effective radiosensitivities of mutated and non-mutated cells are allowed to differ. Based on the number of mutated cells present after irradiation, the model is then linked to macroscopic incidence by summarising model parameters and modifying factors into natural cancer incidence and the dose response in the lower-dose region. It was found that all principal dose-response functions discussed in the literature can be derived from the model. However, from the investigation and due to scarcity of adequate data, rather vague statements about likelihood of dose-response functions can be made than a definite decision for one response. Based on the predicted model parameters, the linear response can probably be rejected using the dynamics described, but both a flattening response and a decrease appear likely, depending strongly on the effective cell sterilisation of the mutated cells. Thus insights could be gained into the impact of parameters describing the effective mutation or cell sterilisation of non-mutated as well as of mutated cells, which constitute precursors of cancer. The biggest drawbacks in the estimation of second cancer incidence remain the low statistical power of clinical studies on radiation induction of cancer and the inability to isolate the effect due to radiation alone - if the latter is possible at all. We conclude that at the present stage of knowledge, further investigations have to be carried out in order to really compare treatment modalities with respect to the second cancer risk they imply.