First experimental time-of-flight-based proton radiography using low gain avalanche diodes.

Objective.Ion computed tomography (iCT) is an imaging modality for the direct determination of the relative stopping power (RSP) distribution within a patient's body. Usually, this is done by estimating the path and energy loss of ions traversing the scanned volume utilising a tracking system and a separate residual energy detector. This study, on the other hand, introduces the first experimental study of a novel iCT approach based on time-of-flight (TOF) measurements, the so-called Sandwich TOF-iCT concept, which in contrast to any other iCT systems, does not require a residual energy detector for the RSP determination.Approach.A small Sandwich TOF-iCT demonstrator was built based on low gain avalanche diodes (LGADs), which are 4D-tracking detectors that allow to simultaneously measure the particle position and time-of-arrival with a precision better than 100µm and 100 ps, respectively. Using this demonstrator, the material and energy-dependent TOF was measured for several homogeneous PMMA slabs in order to calibrate the acquired TOF against the corresponding water equivalent thickness (WET). With this calibration, two proton radiographs (pRads) of a small aluminium stair phantom were recorded at MedAustron using 83 MeV and 100.4 MeV protons.Main results.Due to the simplified WET calibration models used in this very first experimental study of this novel approach, the difference between the measured and theoretical WET ranged between 37.09% and 51.12%. Nevertheless, the first TOF-based pRad was successfully recorded showing that LGADs are suitable detector candidates for Sandwich TOF-iCT.Significance.While the system parameters and WET estimation algorithms require further optimization, this work was an important first step to realize Sandwich TOF-iCT. Due to its compact and cost-efficient design, Sandwich TOF-iCT has the potential to make iCT more feasible and attractive for clinical application, which, eventually, could enhance the treatment planning quality.

Extension of the open-source TIGRE toolbox for proton imaging.

Proton irradiation is a well-established method to treat deep-seated tumors in radio oncology. Usually, an X-ray computed tomography (CT) scan is used for treatment planning. Since proton therapy is based on the precise knowledge of the stopping power describing the energy loss of protons in the patient tissues, the Hounsfield units of the planning CT have to be converted. This conversion introduces range errors in the treatment plan, which could be reduced, if the stopping power values were extracted directly from an image obtained using protons instead of X-rays. Since protons are affected by multiple Coulomb scattering, reconstruction of the 3D stopping power map results in limited image quality if the curved proton path is not considered. This work presents a substantial code extension of the open-source toolbox TIGRE for proton CT (pCT) image reconstruction based on proton radiographs including a curved proton path estimate. The code extension and the reconstruction algorithms are GPU-based, allowing to achieve reconstruction results within minutes. The performance of the pCT code extension was tested with Monte Carlo simulated data using three phantoms (Catphan® high resolution and sensitometry modules and a CIRS patient phantom). In the simulations, ideal and non-ideal conditions for a pCT setup were assumed. The obtained mean absolute percentage error was found to be below 1% and up to 8 lp/cm could be resolved using an idealized setup. These findings demonstrate that the presented code extension to the TIGRE toolbox offers the possibility for other research groups to use a fast and accurate open-source pCT reconstruction.

Feasibility study of a proton CT system based on 4D-tracking and residual energy determination via time-of-flight.

Objective.For dose calculations in ion beam therapy, it is vital to accurately determine the relative stopping power (RSP) distribution within the treatment volume. A suitable imaging modality to achieve the required RSP accuracy is proton computed tomography (pCT), which usually uses a tracking system and a separate residual energy (or range) detector to directly measure the RSP distribution. This work investigates the potential of a novel pCT system based on a single detector technology, namely low gain avalanche detectors (LGADs). LGADs are fast 4D-tracking detectors, which can be used to simultaneously measure the particle position and time with precise timing and spatial resolution. In contrast to standard pCT systems, the residual energy is determined via a time-of-flight (TOF) measurement between different 4D-tracking stations.Approach.To show the potential of using 4D-tracking for proton imaging, we studied and optimized the design parameters for a realistic TOF-pCT system using Monte Carlo simulations. We calculated the RSP accuracy and RSP resolution inside the inserts of the CTP404 phantom and compared the results to a simulation of an ideal pCT system.Main results.After introducing a dedicated calibration procedure for the TOF calorimeter, RSP accuracies less than 0.6% could be achieved. We also identified the design parameters with the strongest impact on the RSP resolution and proposed a strategy to further improve the image quality.Significance.This comprehensive study of the most important design aspects for a novel TOF-pCT system could help guide future hardware developments and, once implemented, improve the quality of treatment planning in ion beam therapy.

Calculating 1/ß2p2 for most likely path estimates for protons and helium ions using an analytical model.

In ion computed tomography, limited spatial resolution can be related to the non-straight path of ions resulting from multiple Coulomb scattering in the object to be imaged. By including sophisticated path estimates such as most likely path (MLP) or optimized cubic spline into the image reconstruction algorithm, the achieved spatial resolution can be substantially improved compared to assuming a simple straight line path only. The typically used implementation of the MLP is a matrix-based approach employing Bayesian statistics and modelling multiple Coulomb scattering as Gaussian distribution. For the elements of the scattering matrices, the term 1/ß(w)2p(w)2, depending on the momentum and velocity of an ion within a phantom depth w, has to be known and integrated along the depth w. Usually, this term is extracted from a Monte Carlo simulation and approximated by a polynomial fit to solve the integral. In the present study, an existing analytical model for ion ranges and stopping powers was used to calculate 1/ß(w)2p(w)2 and the scattering matrices for the MLP and was tested for protons and helium ions. The model was investigated for 10 cm to 40 cm water targets and initial energies ranging from 150 MeV to 300 MeV for protons and 150 MeV/u to 300 MeV/u for helium ions. In all cases, the calculated value obtained for 1/ß(w)2p(w)2 was compared to a GATE simulation. The difference between root-mean-square errors of MLP estimates using calculated and simulated 1/ß(w)2p(w)2 values were found to be smaller than 3 µm for all investigated water targets and energies.

First application of the GPU-based software framework TIGRE for proton CT image reconstruction.

In proton therapy, the knowledge of the proton stopping power, i.e. the energy deposition per unit length within human tissue, is essential for accurate treatment planning. One suitable method to directly measure the stopping power is proton computed tomography (pCT). Due to the proton interaction mechanisms in matter, pCT image reconstruction faces some challenges: the unique path of each proton has to be considered separately in the reconstruction process adding complexity to the reconstruction problem. This study shows that the GPU-based open-source software toolkit TIGRE, which was initially intended for X-ray CT reconstruction, can be applied to the pCT image reconstruction problem using a straight line approach for the proton path. This simplified approach allows for reconstructions within seconds. To validate the applicability of TIGRE to pCT, several Monte Carlo simulations modeling a pCT setup with two Catphan® modules as phantoms were performed. Ordered-Subset Simultaneous Algebraic Reconstruction Technique (OS-SART) and Adaptive-Steepest-Descent Projection Onto Convex Sets (ASD-POCS) were used for image reconstruction. Since the accuracy of the approach is limited by the straight line approximation of the proton path, requirements for further improvement of TIGRE for pCT are addressed.

Towards offline PET monitoring of proton therapy at MedAustron.

The characteristic depth-dose profile of protons traveling through material is the main advantage of proton therapy over conventional radiotherapy with photons or electrons. However, uncertainties regarding the range of the protons in human tissue prevent to exploit the full potential of proton therapy. Therefore, a non-invasive in-vivo dose monitoring is desired. At the ion beam center MedAustron in Wiener Neustadt/Austria, patient treatment with proton beams started in December 2016. A PET/CT is available in close vicinity of the treatment rooms, exclusively dedicated to offline PET monitoring directly after the therapeutic irradiation. Preparations for a patient study include workflow tests under realistic clinical conditions using two different phantoms, irradiated with protons prior to the scan in the PET/CT. GATE simulations of the C-11 production are used as basis for the prediction of the PET measurement. We present results from the workflow tests in comparison with simulation results, and by this, we demonstrate the applicability of the PET monitoring at the MedAustron facility.

Influence of PET reconstruction technique and matrix size on qualitative and quantitative assessment of lung lesions on [18F]-FDG-PET: A prospective study in 37 cancer patients.

PURPOSE: To evaluate the influence of point spread function (PSF)-based reconstruction and matrix size for PET on (1) lung lesion detection and (2) standardized uptake values (SUV). METHODS: This prospective study included oncological patients who underwent [18F]-FDG-PET/CT for staging. PET data were reconstructed with a 2D ordered subset expectation maximization (OSEM) algorithm, and a 2D PSF-based algorithm (TrueX), separately with two matrix sizes (168×168 and 336×336). The four PET reconstructions (TrueX-168; OSEM-168; TrueX-336; and OSEM-336) were read independently by two raters, and PET-positive lung lesions were recorded. Blinded to the PET findings, a third independent rater assessed lung lesions with diameters of >4mm on CT. Subsequently, PET and CT were reviewed side-by side in consensus. Multi-factorial logistic regression analyses and two-way repeated measures analyses of variance (ANOVA) were performed. RESULTS: Thirty-seven patients with 206 lung lesions were included. Lesion-based PET sensitivities differed significantly between reconstruction algorithms (P<0.001) and between reconstruction matrices (P=0.022). Sensitivities were 94.2% and 88.3% for TrueX-336; 88.3% and 85.9% for TrueX-168; 67.8% and 66.3% for OSEM-336; and 67.0% and 67.9% for OSEM-168; for rater 1 and rater 2, respectively. SUVmax and SUVmean were significantly higher for images reconstructed with 336×336 matrices than for those reconstructed with 168×168 matrices (P<0.001). CONCLUSION: Our results demonstrate that PSF-based PET reconstruction, and, to a lesser degree, higher matrix size, improve detection of metabolically active lung lesions. However, PSF-based PET reconstructions and larger matrix sizes lead to higher SUVs, which may be a concern when PET data from different institutions are compared.

Technical Note: Fully-automated analysis of Jaszczak phantom measurements as part of routine SPECT quality control.

PURPOSE: Inspection and quantitative validation of tomographic imaging properties of SPECT systems, i.e., spatial resolution, contrast, and inhomogeneity must be performed in regular intervals. Typically, the modular Jaszczak phantom is used for that purpose, as it offers the possibility to investigate all three system properties with a single measurement. The interpretation of the measurement is performed visually, thus, being insensitive to subtle changes in system performance. To overcome this limitation, a fully-automated software for the objective analysis of Jaszczak phantom measurements is proposed here. METHODS: The software was developed as an ImageJ plugin and offers a number of sequential evaluation steps: automatic determination of the type of Jaszczak phantom, calculation of sector and sphere contrast, detection of ring artifacts using either the Hough transform, followed by a threshold-based decision criterion, or Student's t-test. Monte Carlo simulations were used to estimate the detectability limits for ring artifacts. RESULTS: The software successfully calculated sector and sphere contrasts and reliably determined ring artifacts present in the homogeneity part of the Jaszczak phantom, based on automatic identification of the phantom type. CONCLUSION: Given the quantitative nature of the produced output, results from one imaging system can easily be compared to another in an objective way. The advantage of the software is clearly that the information provided is objective and does not rely on the experience level of the user.

Evaluating Treatment Response of Radioembolization in Intermediate-Stage Hepatocellular Carcinoma Patients Using 18F-Fluoroethylcholine PET/CT.

UNLABELLED: The aim of this study was to evaluate (18)F-fluoroethylcholine PET/CT as a metabolic imaging technique for the assessment of treatment response to (90)Y radioembolization in patients with locally advanced hepatocellular carcinoma (HCC). METHODS: Thirty-four HCC patients undergoing 78 (18)F-fluoroethylcholine PET/CT scans were identified for this study. Patients with initial or follow-up metastastic disease (n = 9) were excluded at the time point of the metastatic occurrence as well as patients with negative α-fetoprotein (AFP; n = 1), resulting in 24 patients and 57 scans that were eligible. All patients were scheduled for radioembolization and underwent 1 pretherapeutic and at least 1 posttherapeutic (18)F-fluoroethylcholine PET/CT scan. Volume-of-interest analysis and volume-of-interest subtractions were performed. Maximum, mean, and peak standardized uptake value (SUV) analysis was performed, and the total intrahepatic (18)F-fluoroethylcholine positive tumor volume (FEC-PTV) and tumor-to-background ratio were assessed. Statistical analysis was performed using a decreasing AFP of at least 20% as a standard of reference for therapy response including receiver-operating-characteristic analyses as well as descriptive and correlation analyses and multiple logistic regression. RESULTS: Fourteen follow-up examinations were categorized as responder and 19 follow-up examinations as nonresponder. Absolute AFP values did not correlate with SUV parameters (P = 0.055). In receiver-operating-characteristic analyses, the initial mean SUV, Δmaximum SUV, and Δtumor-to-background ratio demonstrated the highest area under the curve, 0.84 (P = 0.009), 0.83 (P = 0.011), and 0.83 (P = 0.012), respectively, resulting in a positive prediction of 82%, 83%, and 91% at the respective cutoff points. When multiple logistic regression analysis was applied, this resulted in an area under the curve of 0.90 (P = 0.001), with a positive prediction of 94% and a sensitivity of 94%. The FEC-PTV did not reach significance in the presented dataset. CONCLUSION: (18)F-fluoroethylcholine PET/CT demonstrates a high potential for follow-up assessment in the context of radioembolization in patients with locally advanced, but nonmetastatic, HCC and initially elevated AFP, possibly enabling early therapy monitoring independent of morphology.

A pencil beam algorithm for helium ion beam therapy.

PURPOSE: To develop a flexible pencil beam algorithm for helium ion beam therapy. Dose distributions were calculated using the newly developed pencil beam algorithm and validated using Monte Carlo (MC) methods. METHODS: The algorithm was based on the established theory of fluence weighted elemental pencil beam (PB) kernels. Using a new real-time splitting approach, a minimization routine selects the optimal shape for each sub-beam. Dose depositions along the beam path were determined using a look-up table (LUT). Data for LUT generation were derived from MC simulations in water using GATE 6.1. For materials other than water, dose depositions were calculated by the algorithm using water-equivalent depth scaling. Lateral beam spreading caused by multiple scattering has been accounted for by implementing a non-local scattering formula developed by Gottschalk. A new nuclear correction was modelled using a Voigt function and implemented by a LUT approach. Validation simulations have been performed using a phantom filled with homogeneous materials or heterogeneous slabs of up to 3 cm. The beams were incident perpendicular to the phantoms surface with initial particle energies ranging from 50 to 250 MeV/A with a total number of 10(7) ions per beam. For comparison a special evaluation software was developed calculating the gamma indices for dose distributions. RESULTS: In homogeneous phantoms, maximum range deviations between PB and MC of less than 1.1% and differences in the width of the distal energy fall off of the Bragg-Peak from 80% to 20% of less than 0.1 mm were found. Heterogeneous phantoms using layered slabs satisfied a γ-index criterion of 2%/2mm of the local value except for some single voxels. For more complex phantoms using laterally arranged bone-air slabs, the γ-index criterion was exceeded in some areas giving a maximum γ-index of 1.75 and 4.9% of the voxels showed γ-index values larger than one. The calculation precision of the presented algorithm was considered to be sufficient for clinical practice. Although only data for helium beams was presented, the performance of the pencil beam algorithm for proton beams was comparable. CONCLUSIONS: The pencil beam algorithm developed for helium ions presents a suitable tool for dose calculations. Its calculation speed was evaluated to be similar to other published pencil beam algorithms. The flexible design allows easy customization of measured depth-dose distributions and use of varying beam profiles, thus making it a promising candidate for integration into future treatment planning systems. Current work in progress deals with RBE effects of helium ions to complete the model.

PET based volume segmentation with emphasis on the iterative TrueX algorithm.

PURPOSE: To assess the influence of reconstruction algorithms for positron emission tomography (PET) based volume quantification. The specifically detected activity in the threshold defined volume was investigated for different reconstruction algorithms as a function of volume size and signal to background ratio (SBR), especially for volumes smaller than 1ml. Special attention was given to the Siemens specific iterative reconstruction algorithm TrueX. METHODS: Measurements were performed with a modified in-house produced IEC body phantom on a Siemens Biograph 64 True Point PET/CT scanner (Siemens, Medical Systems) for six different SBRs (2.1, 3.8, 4.9, 6.7, 8.9, 9.4 and without active background (BG)). The phantom consisted of a water-filled cavity with built-in plastic spheres (0.27, 0.52, 1.15, 2.57, 5.58 and 11.49ml). The following reconstruction algorithms available on the Siemens Syngo workstation were evaluated: Iterative OSEM (OSEM) (4 iterations, 21 subsets), iterative TrueX (TrueX) (4 iterations, 21 subsets) and filtered backprojection (FBP). For the threshold based volume segmentation the software Rover (ABX, Dresden) was used. RESULTS: For spheres larger than 2.5ml a constant threshold (standard deviation (SD) 10%) level was found for a given SBR and reconstruction algorithm and therefore a mean threshold for the largest three spheres was calculated. This threshold could be approximated by a function inversely proportional to the SBR. The threshold decreased with increasing SBR for all sphere sizes. For the OSEM algorithm the threshold for small spheres with 0.27, 0.52 and 1.15ml varied between 17% and 44% (depending on sphere size). The threshold for the TrueX algorithm was substantially lower (up to 17%) than for the OSEM algorithm for all sphere sizes. The maximum activity in a specific volume yielded the true activity for the OSEM algorithm when using a SBR independent correction factor C, which depended on sphere size. For the largest three volumes a constant factor C=1.10±0.03 was found. For smaller volumes, C increased exponentially due to the partial volume effect. For the TrueX algorithm the maximum activity overestimated the true activity. CONCLUSION: The threshold values for PET based target volume segmentation increased with increasing sphere size for all tested algorithms. True activity values of spheres in the phantom could be extracted using experimentally determined correction factors C. The TrueX algorithm has to be used carefully for quantitative comparison (e.g. follow-up) and multicenter studies.