Graeff, Christian

Abstract Background Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single‐event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is crucial to evaluate the image quality of integrated mode iRad systems. Purpose We report extensive image quality metrics of integrated mode carbon ion radiographs (cRads) and compare them with proton radiographs (pRads). Methods iRads were obtained at the Marburg Ion Beam Therapy Center using a plastic volumetric scintillator equipped with CCD cameras. The detector captures orthogonal views of the 3D energy deposition in the scintillator from individual pencil beams. Four phantoms were scanned using a field of view and a beam spacing of 1 mm. First, 9 tissue‐substitute inserts were used to evaluate water equivalent thickness (WET) accuracy. Radiographs of those inserts were reconstructed for beam spacings ranging from 1 to 7 mm to evaluate the impact of spacing on quantitative accuracy. For spatial resolution, custom 3D printed line pair (lp) modules ranging from 0.5 to 10 lp/cm were scanned. To evaluate low contrast detectability, a custom 3D printed low contrast module consisting of 20 holes with depths ranging from 1 to 8 mm and diameters from 1 to 10 mm was scanned. iRads of an anthropomorphic head phantom were also obtained. Results Spatial resolution and low contrast detection are systematically improved for cRads compared to pRads. Image resolution was 3.7 lp/cm for cRads and 1.7 lp/cm for pRads in the center of the field of view. Spatial resolution was found to vary with the object's location in the field of view. While pRads could mostly resolve low contrast holes of 10 mm in diameter, cRads could resolve holes of up in 4 mm diameter. WET accuracy is similar for both ion species, with a root mean squared error of approximately 1 mm. WET accuracy was stable (maximum of 0.1 mm increase) across beam spacings, although important under‐sampling artifacts were observed for iRads reconstructed using large beam spacings, especially for cRads. iRads of the anthropomorphic head phantom showed improved apparent contrast using cRads, especially to identify bony structures. Conclusions This work is the first investigation of image quality metrics such as spatial resolution and low contrast detectability for integrated mode cRads, with a full comparison with pRads. Enhanced image quality is obtained with cRads compared to pRads, although pRads still maintain high WET accuracy and deliver image quality within acceptable bounds.

AbstractBackgroundMotion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.PurposeProton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated‐mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring tumor motion.MethodsProton radiographs of an anthropomorphic lung phantom, with a motor‐driven tumor insert, were acquired approximately every 1 s, using tumor inserts of 10, 20, and 30 mm undergoing a known periodic motion. The proton radiography system used a monolithic scintillator block and digital cameras to capture the residual range of each pencil beam passing through the phantom. These ranges were then used to produce a water equivalent thickness map of the phantom. The centroid of the tumor insert in the radiographs was used to determine its position. This measured position was then compared to the known motion of the phantom to determine the accuracy.ResultsSubmillimeter accuracy on the measurement of the tumor insert was achieved when using a 30 mm tumor insert with a period of 24 s and was found to be improved for decreasing motion amplitudes with a mean absolute error (MAE) of 1.0, 0.9, and 0.7 mm for 20, 15, and 10 mm respectively. Using smaller tumor inserts reduced the accuracy with a MAE of 1.8 and 1.9 mm for a 20 and 10 mm insert respectively undergoing a periodic motion with an amplitude of 20 mm and a period of 24 s. Using a shorter period resulted in significant motion artifacts reducing the accuracy to a MAE of 2.2 mm for a 12 s period and 3.1 mm for a 6 s period for the 30 mm insert with an amplitude of 20 mm.ConclusionsThis work demonstrates that the position of a lung tumor insert in a realistic anthropomorphic phantom can be measured with high accuracy using proton radiographs. Results show that the accuracy of the position measurement is the highest for slower tumor motions due to a reduction in motion artifacts. This indicates that the primary obstacle to accurate measurement is the speed of the radiograph acquisition. Although the slower tumor motions used in this study are not clinically realistic, this work demonstrates the potential for using proton radiography for measuring tumor motion with an increased scanning speed that results in a decreased acquisition time.

Abstract Noninvasive ablation of cardiac arrhythmia by scanned particle radiotherapy is highly promising, but especially challenging due to cardiac and respiratory motion. Irradiations for catheter-free ablation in intact pigs were carried out at the GSI Helmholtz Center in Darmstadt using scanned carbon ions. Here, we present real-time electrocardiogram (ECG) data to estimate time-resolved (4D) delivered dose. For 11 animals, surface ECGs and temporal structure of beam delivery were acquired during irradiation. R waves were automatically detected from surface ECGs. Pre-treatment ECG-triggered 4D-CT phases were synchronized to the R – R interval. 4D-dose calculation was performed using GSI’s in-house 4D treatment planning system. Resulting dose distributions were assessed with respect to coverage ( D 95 and V 95), heterogeneity (HI = D 5– D 95) and normal tissue exposure. Final results shown here were performed offline, but first calculations were started shortly after irradiation The D 95 for TV and PTV was above 95% for 10 and 8 out of 11 animals, respectively. HI was reduced for PTV versus TV volumes, especially for some of the animals targeted at the atrioventricular junction, indicating residual interplay effects due to cardiac motion. Risk structure exposure was comparable to static and 4D treatment planning simulations. ECG-based 4D-dose reconstruction is technically feasible in a patient treatment-like setting. Further development of the presented approach, such as real-time dose calculation, may contribute to safe, successful treatments using scanned ion beams for cardiac arrhythmia ablation.

Noninvasive AF Ablation With Carbon IonsIntroductionCatheter ablation with isolation of the pulmonary veins is a common treatment option for atrial fibrillation but still has insufficient success rates and carries several interventional risks. These treatment planning studies assessed if high‐dose single fraction treatment with scanned carbon ions (12C) can be reliably delivered for AF ablation, while sparing risk structures and considering respiratory and contractile target motion.Methods and ResultsTime resolved CT scans of complete respiratory and cardiac cycles of 9 and 5 patients, respectively, were obtained. Ablation lesions and organs at risk for beam delivery were contoured. Single fraction intensity‐modulated particle therapy with target doses of 25 and 40 Gy were studied and motion influences on these deliveries mitigated. Respiration had a large influence on lesion displacement (≤ 2 cm). End expiration could be exploited as a stable gating window. Smaller, but less predictable, heartbeat displacements (< 6 mm) remained to be mitigated because cardiac contraction resulted in insufficient dose coverage (V95 < 90 %) if uncompensated. Repeated irradiation (12C beam rescanning) during breath hold was used to accommodate contractile motion, resulting in good dose coverage. Dose depositions to all organs at risk were carefully examined and did not exceed values for X‐ray cancer treatment.ConclusionTreatment planning of 12C with delivery of physical ionizing radiation doses that have been described to induce complete block is feasible for AF ablation, considering human anatomy, dose constraints, and encasing underlying motion patterns from respiration and cardiac contraction at the LA–PV junction into treatment planning.

Background— Particle therapy, with heavy ions such as carbon-12 ( 12 C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam. Methods and Results— Intact hearts were explanted from 4 (30–40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomgraphic scans (1 mm voxel and slice spacing) were acquired and 12 C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomgraphic scans for detection of β + ( 11 C) activity were obtained. A 12 C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomgraphy demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong γH2AX signals in the target region, whereas no γH2AX signals were detected in the unirradiated control heart. Conclusions— This is the first report of the application of a 12 C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.