In vivo assessment of tissue-specific radiological parameters with intra- and inter-patient variation using dual-energy computed tomography.

PURPOSE/OBJECTIVE: Experimental in vivo determination of radiological tissue parameters of organs in the head and pelvis within a large patient cohort, expanding on the current standard human tissue database summarized in ICRU46. MATERIAL/METHODS: Relative electron density (RED), effective atomic number (EAN) and stopping-power ratio (SPR) were obtained from clinical dual-energy CT scans using a clinically validated DirectSPR implementation and organ segmentations of 107 brain-tumor (brain, brainstem, spinal cord, chiasm, optical nerve, lens) and 120 pelvic cancer patients (prostate, kidney, liver, bladder). The impact of contamination by surrounding tissues on the tissue parameters was reduced with a dedicated contour adaption routine. Tissue parameters were characterized regarding the cohort mean value as well as the variation within each patient (2σintra) and between patients (2σinter). For the brain, age-dependent differences were determined. RESULTS: For 10 organs, including 4 structures not listed in ICRU46, the mean RED, EAN and SPR as well as their respective intra- and inter-patient variation were determined. SPR intra-patient variation was higher than 1.3% (1.3-4.6%) in all organs and always exceeded the inter-patient variation of the organ mean SPR (0.6-2.1%). For the brain, a significant SPR variation between pediatric and non-pediatric patients was determined. CONCLUSION: Radiological tissue parameters in the head and pelvis were characterized in vivo for a large patient cohort using dual-energy CT. This reassesses parts of the current standard database defined in ICRU46, furthermore complementing the data described in literature by smaller substructures in the brain as well as by the quantification of organ-specific inter- and intra-patient variation.

Experimental validation of 4D log file-based proton dose reconstruction for interplay assessment considering amplitude-sorted 4DCTs.

PURPOSE: The unpredictable interplay between dynamic proton therapy delivery and target motion in the thorax can lead to severe dose distortions. A fraction-wise four-dimensional (4D) dose reconstruction workflow allows for the assessment of the applied dose after patient treatment while considering the actual beam delivery sequence extracted from machine log files, the recorded breathing pattern and the geometric information from a 4D computed tomography scan (4DCT). Such an algorithm capable of accounting for amplitude-sorted 4DCTs was implemented and its accuracy as well as its sensitivity to input parameter variations was experimentally evaluated. METHODS: An anthropomorphic thorax phantom with a movable insert containing a target surrogate and a radiochromic film was irradiated with a monoenergetic field for various 1D target motion forms (sin, sin4 ) and peak-to-peak amplitudes (5/10/15/20/30 mm). The measured characteristic film dose distributions were compared to the respective sections in the 4D reconstructed doses using a 2D γ-analysis (3 mm, 3%); γ-pass rates were derived for different dose grid resolutions (1 mm/3 mm) and deformable image registrations (DIR, automatic/manual) applied during the 4D dose reconstruction process. In an additional analysis, the sensitivity of reconstructed dose distributions against potential asynchronous timing of the motion and machine log files was investigated for both a monoenergetic field and more realistic 4D robustly optimized fields by artificially introduced offsets of ±1/5/25/50/250 ms. The resulting dose distributions with asynchronized log files were compared to those with synchronized log files by means of a 3D γ-analysis (1 mm, 1%) and the evaluation of absolute dose differences. RESULTS: The induced characteristic interplay patterns on the films were well reproduced by the 4D dose reconstruction with 2D γ-pass rates ≥95% for almost all cases with motion magnitudes ≤15 mm. In general, the 2D γ-pass rates showed a significant decrease for larger motion amplitudes and increase when using a finer dose grid resolution but were not affected by the choice of motion form (sin, sin4 ). There was also a trend, though not statistically significant, toward the manually defined DIR for better quality of the reconstructed dose distributions in the area imaged by the film. The 4D dose reconstruction results for the monoenergetic as well as the 4D robustly optimized fields were robust against small asynchronies between motion and machine log files of up to 5 ms, which is in the order of potential network latencies. CONCLUSIONS: We have implemented a 4D log file-based proton dose reconstruction that accounts for amplitude-sorted 4DCTs. Its accuracy was proven to be clinically acceptable for target motion magnitudes of up to 15 mm. Particular attention should be paid to the synchronization of the log file generating systems as the reconstructed dose distribution may vary with log file asynchronies larger than those caused by realistic network delays.

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy.

PURPOSE: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. MATERIAL AND METHODS: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. RESULTS: An inter-centre variation in SPR prediction (2σ) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2σ) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung- and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. CONCLUSION: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion.

Material assignment for proton range prediction in Monte Carlo patient simulations using stopping-power datasets.

Motivation and objective. For each institute, the selection and calibration of the most suitable approach to assign material properties for Monte Carlo (MC) patient simulation in proton therapy is a major challenge. Current conventional approaches based on computed tomography (CT) depend on CT acquisition and reconstruction settings. This study proposes a material assignment approach, referred to as MATA (MATerial Assignment), which is independent of CT scanner properties and, therefore, universally applicable by any institute. MATERIALS AND METHODS: The MATA approach assigns material properties to the physical quantity stopping-power ratio (SPR) using a set of 40 material compositions specified for human tissues and linearly determined mass density. The application of clinically available CT-number-to-SPR conversion avoids the need for any further calibration. The MATA approach was validated with homogeneous and heterogeneous SPR datasets by assessing the SPR accuracy after material assignment obtained either based on dose scoring or determination of water-equivalent thickness. Finally, MATA was applied on patient datasets to evaluate dose differences induced by different approaches for material assignment and SPR prediction. RESULTS: The deviation between the SPR after material assignment and the input SPR was close to zero in homogeneous datasets and below 0.002 (0.2% relative to water) in heterogeneous datasets, which was within the systematic uncertainty in SPR estimation. The comparison of different material assignment approaches revealed relevant differences in dose distribution and SPR. The comparison between two SPR prediction approaches, a standard look-up table and direct SPR determination from dual-energy CT, resulted in patient-specific mean proton range shifts between 1.3 mm and 4.8 mm. CONCLUSION: MATA eliminates the need for institution-specific adaptations of the material assignment. It allows for using any SPR dataset and thus facilitates the implementation of more accurate SPR prediction approaches. Hence, MATA provides a universal solution for patient modeling in MC-based proton treatment planning.

Evaluation of Stopping-Power Prediction by Dual- and Single-Energy Computed Tomography in an Anthropomorphic Ground-Truth Phantom.

PURPOSE: To determine the accuracy of particle range prediction for proton and heavier ion radiation therapy based on dual-energy computed tomography (DECT) in a realistic inhomogeneous geometry and to compare it with the state-of-the-art clinical approach. METHODS AND MATERIALS: A 3-dimensional ground-truth map of stopping-power ratios (SPRs) was created for an anthropomorphic head phantom by assigning measured SPR values to segmented structures in a high-resolution CT scan. This reference map was validated independently comparing proton transmission measurements with Monte Carlo transport simulations. Two DECT-based methods for direct SPR prediction via the Bethe formula (DirectSPR) and 2 established approaches based on Hounsfield look-up tables (HLUTs) were chosen for evaluation. The SPR predictions from the 4 investigated methods were compared with the reference, using material-specific voxel statistics and 2-dimensional gamma analysis. Furthermore, range deviations were analyzed in an exemplary proton treatment plan. RESULTS: The established reference SPR map was successfully validated for the discrimination of SPR and range differences well below 0.3% and 1 mm, respectively, even in complex inhomogeneous settings. For the phantom materials of larger volume (mainly brain, soft tissue), the investigated methods were overall able to predict SPR within 1% median deviation. The DirectSPR methods generally performed better than the HLUT approaches. For smaller phantom parts (such as cortical bone, air cavities), all methods were affected by image smoothing, leading to considerable SPR under- or overestimation. This effect was superimposed on the general SPR prediction accuracy in the exemplary treatment plan. CONCLUSIONS: DirectSPR predictions proved to be more robust, with high accuracy in particular for larger volumes. In contrast, HLUT approaches exhibited a fortuitous component. The evaluation of accuracy in a realistic phantom with validated ground-truth SPR represents a crucial step toward possible clinical application of DECT-based SPR prediction methods.

Methodological accuracy of image-based electron density assessment using dual-energy computed tomography.

PURPOSE: Electron density is the most important tissue property influencing photon and ion dose distributions in radiotherapy patients. Dual-energy computed tomography (DECT) enables the determination of electron density by combining the information on photon attenuation obtained at two different effective x-ray energy spectra. Most algorithms suggested so far use the CT numbers provided after image reconstruction as input parameters, i.e., are imaged-based. To explore the accuracy that can be achieved with these approaches, we quantify the intrinsic methodological and calibration uncertainty of the seemingly simplest approach. METHODS: In the studied approach, electron density is calculated with a one-parametric linear superposition ('alpha blending') of the two DECT images, which is shown to be equivalent to an affine relation between the photon attenuation cross sections of the two x-ray energy spectra. We propose to use the latter relation for empirical calibration of the spectrum-dependent blending parameter. For a conclusive assessment of the electron density uncertainty, we chose to isolate the purely methodological uncertainty component from CT-related effects such as noise and beam hardening. RESULTS: Analyzing calculated spectrally weighted attenuation coefficients, we find universal applicability of the investigated approach to arbitrary mixtures of human tissue with an upper limit of the methodological uncertainty component of 0.2%, excluding high-Z elements such as iodine. The proposed calibration procedure is bias-free and straightforward to perform using standard equipment. Testing the calibration on five published data sets, we obtain very small differences in the calibration result in spite of different experimental setups and CT protocols used. Employing a general calibration per scanner type and voltage combination is thus conceivable. CONCLUSION: Given the high suitability for clinical application of the alpha-blending approach in combination with a very small methodological uncertainty, we conclude that further refinement of image-based DECT-algorithms for electron density assessment is not advisable.

Comparison study of in vivo dose response to laser-driven versus conventional electron beam.

The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.