Anna Arns

Deep Inspiration Breath Hold-Based Radiation Therapy: A Clinical Review.

Several recent developments in linear accelerator-based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effects in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.

Breath-Hold Target Localization With Simultaneous Kilovoltage/Megavoltage Cone-Beam Computed Tomography and Fast Reconstruction

PURPOSE Hypofractionated high-dose radiotherapy for small lung tumors has typically been based on stereotaxy. Cone-beam computed tomography and breath-hold techniques have provided a noninvasive basis for precise cranial and extracranial patient positioning. The cone-beam computed tomography acquisition time of 60 s, however, is beyond the breath-hold capacity of patients, resulting in respiratory motion artifacts. By combining megavoltage (MV) and kilovoltage (kV) photon sources (mounted perpendicularly on the linear accelerator) and accelerating the gantry rotation to the allowed limit, the data acquisition time could be reduced to 15 s. METHODS AND MATERIALS An Elekta Synergy 6-MV linear accelerator, with iViewGT as the MV- and XVI as the kV-imaging device, was used with a Catphan phantom and an anthropomorphic thorax phantom. Both image sources performed continuous image acquisition, passing an angle interval of 90° within 15 s. For reconstruction, filtered back projection on a graphics processor unit was used. It reconstructed 100 projections acquired to a 512 × 512 × 512 volume within 6 s. RESULTS The resolution in the Catphan phantom (CTP528 high-resolution module) was 3 lines/cm. The spatial accuracy was within 2-3 mm. The diameters of different tumor shapes in the thorax phantom were determined within an accuracy of 1.6 mm. The signal-to-noise ratio was 68% less than that with a 180°-kV scan. The dose generated to acquire the MV frames accumulated to 82.5 mGy, and the kV contribution was <6 mGy. CONCLUSION The present results have shown that fast breath-hold, on-line volume imaging with a linear accelerator using simultaneous kV-MV cone-beam computed tomography is promising and can potentially be used for image-guided radiotherapy for lung cancer patients in the near future.

Evaluation of robustness of maximum likelihood cone-beam CT reconstruction with total variation regularization

The objective of this paper is to evaluate an iterative maximum likelihood (ML) cone-beam computed tomography (CBCT) reconstruction with total variation (TV) regularization with respect to the robustness of the algorithm due to data inconsistencies. Three different and (for clinical application) typical classes of errors are considered for simulated phantom and measured projection data: quantum noise, defect detector pixels and projection matrix errors. To quantify those errors we apply error measures like mean square error, signal-to-noise ratio, contrast-to-noise ratio and streak indicator. These measures are derived from linear signal theory and generalized and applied for nonlinear signal reconstruction. For quality check, we focus on resolution and CT-number linearity based on a Catphan phantom. All comparisons are made versus the clinical standard, the filtered backprojection algorithm (FBP). In our results, we confirm and substantially extend previous results on iterative reconstruction such as massive undersampling of the number of projections. Errors of projection matrix parameters of up to 1° projection angle deviations are still in the tolerance level. Single defect pixels exhibit ring artifacts for each method. However using defect pixel compensation, allows up to 40% of defect pixels for passing the standard clinical quality check. Further, the iterative algorithm is extraordinarily robust in the low photon regime (down to 0.05 mAs) when compared to FPB, allowing for extremely low-dose image acquisitions, a substantial issue when considering daily CBCT imaging for position correction in radiotherapy. We conclude that the ML method studied herein is robust under clinical quality assurance conditions. Consequently, low-dose regime imaging, especially for daily patient localization in radiation therapy is possible without change of the current hardware of the imaging system.

Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology.

Purpose There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. Materials and Methods 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 μm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18). Results Tumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively. Conclusion Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.

Phantom-based evaluation of dose exposure of ultrafast combined kV-MV-CBCT towards clinical implementation for IGRT of lung cancer

Purpose Combined ultrafast 90°+90° kV-MV-CBCT within single breath-hold of 15s has high clinical potential for accelerating imaging for lung cancer patients treated with deep inspiration breath-hold (DIBH). For clinical feasibility of kV-MV-CBCT, dose exposure has to be small compared to prescribed dose. In this study, kV-MV dose output is evaluated and compared to clinically-established kV-CBCT. Methods Accurate dose calibration was performed for kV and MV energy; beam quality was determined. For direct comparison of MV and kV dose output, relative biological effectiveness (RBE) was considered. CT dose index (CTDI) was determined and measurements in various representative locations of an inhomogeneous thorax phantom were performed to simulate the patient situation. Results A measured dose of 20.5mGE (Gray-equivalent) in the target region was comparable to kV-CBCT (31.2mGy for widely-used, and 9.1mGy for latest available preset), whereas kV-MV spared healthy tissue and reduced dose to 6.6mGE (30%) due to asymmetric dose distribution. The measured weighted CTDI of 12mGE for kV-MV lay in between both clinical presets. Conclusions Dosimetric properties were in agreement with established imaging techniques, whereas exposure to healthy tissue was reduced. By reducing the imaging time to a single breath-hold of 15s, ultrafast combined kV-MV CBCT shortens patient time at the treatment couch and thus improves patient comfort. It is therefore usable for imaging of hypofractionated lung DIBH patients.

Breath-Hold Target Localization with Simultaneous Kilovoltage/Megavoltage Cone-Beam CT and Fast Reconstruction

Hypofractionated high dose radiotherapy of small lung tumors is very effective and was based on stereotaxy until now. It has recently become possible to achieve a high patient positioning precision based on on-line imaging with cone-beam CT (CBCT) and breath-hold techniques. The CBCT acquisition time of roughly 60 seconds, however, is too long for one breath-hold, resulting in image degradation by respiratory motion artifacts. By using megavoltage (MV) an kilovoltage (kV) photon source (mounted perpendicularly on the Linac gantry) for volume reconstruction, we could reduce the acquisition time to 15 seconds.

Automated ultrafast kilovoltage–megavoltage cone-beam CT for image guided radiotherapy of lung cancer: System description and real-time results

PURPOSE To establish a fully automated kV-MV CBCT imaging method on a clinical linear accelerator that allows image acquisition of thoracic targets for patient positioning within one breath-hold (∼15s) under realistic clinical conditions. METHODS AND MATERIALS Our previously developed FPGA-based hardware unit which allows synchronized kV-MV CBCT projection acquisition is connected to a clinical linear accelerator system via a multi-pin switch; i.e. either kV-MV imaging or conventional clinical mode can be selected. An application program was developed to control the relevant linac parameters automatically and to manage the MV detector readout as well as the gantry angle capture for each MV projection. The kV projections are acquired with the conventional CBCT system. GPU-accelerated filtered backprojection is performed separately for both data sets. After appropriate grayscale normalization both modalities are combined and the final kV-MV volume is re-imported in the CBCT system to enable image matching. To demonstrate adequate geometrical accuracy of the novel imaging system the Penta-Guide phantom QA procedure is performed. Furthermore, a human plastinate and different tumor shapes in a thorax phantom are scanned. Diameters of the known tumor shapes are measured in the kV-MV reconstruction. RESULTS An automated kV-MV CBCT workflow was successfully established in a clinical environment. The overall procedure, from starting the data acquisition until the reconstructed volume is available for registration, requires ∼90s including 17s acquisition time for 100° rotation. It is very simple and allows target positioning in the same way as for conventional CBCT. Registration accuracy of the QA phantom is within ±1mm. The average deviation from the known tumor dimensions measured in the thorax phantom was 0.7mm which corresponds to an improvement of 36% compared to our previous kV-MV imaging system. CONCLUSIONS Due to automation the kV-MV CBCT workflow is speeded up by a factor of >10 compared to the manual approach. Thus, the system allows a simple, fast and reliable imaging procedure and fulfills all requirements to be successfully introduced into the clinical workflow now, enabling single-breath-hold volume imaging.