Robustness analysis of dynamic trajectory radiotherapy and volumetric modulated arc therapy plans for head and neck cancer.

Background and purpose: Dynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare the robustness of DTRT and VMAT treatment-plans for head and neck (H&N) cancer to patient-setup (PS) and machine-positioning uncertainties. Materials and methods: The robustness of DTRT and VMAT plans previously created for 46 H&N cases, prescribed 50-70 Gy to 95 % of the planning-target-volume, was assessed. For this purpose, dose distributions were recalculated using Monte Carlo, including uncertainties in PS (translation and rotation) and machine-positioning (gantry-, table-, collimator-rotation and multi-leaf collimator (MLC)). Plan robustness was evaluated by the uncertainties' impact on normal tissue complication probabilities (NTCP) for xerostomia and dysphagia and on dose-volume endpoints. Differences between DTRT and VMAT plan robustness were compared using Wilcoxon matched-pair signed-rank test (α = 5 %). Results: Average NTCP for moderate-to-severe xerostomia and grade ≥ II dysphagia was lower for DTRT than VMAT in the nominal scenario (0.5 %, p = 0.01; 2.1 %, p < 0.01) and for all investigated uncertainties, except MLC positioning, where the difference was not significant. Average differences compared to the nominal scenario were ≤ 3.5 Gy for rotational PS (≤ 3°) and machine-positioning (≤ 2°) uncertainties, <7 Gy for translational PS uncertainties (≤ 5 mm) and < 20 Gy for MLC-positioning uncertainties (≤ 5 mm). Conclusions: DTRT and VMAT plan robustness to the investigated uncertainties depended on uncertainty direction and location of the structure-of-interest to the target. NTCP remained on average lower for DTRT than VMAT even when considering uncertainties.

Data-Driven Gradient Regularization for Quasi-Newton Optimization in Iterative Grating Interferometry CT Reconstruction.

Grating interferometry CT (GI-CT) is a promising technology that could play an important role in future breast cancer imaging. Thanks to its sensitivity to refraction and small-angle scattering, GI-CT could augment the diagnostic content of conventional absorption-based CT. However, reconstructing GI-CT tomographies is a complex task because of ill problem conditioning and high noise amplitudes. It has previously been shown that combining data-driven regularization with iterative reconstruction is promising for tackling challenging inverse problems in medical imaging. In this work, we present an algorithm that allows seamless combination of data-driven regularization with quasi-Newton solvers, which can better deal with ill-conditioned problems compared to gradient descent-based optimization algorithms. Contrary to most available algorithms, our method applies regularization in the gradient domain rather than in the image domain. This comes with a crucial advantage when applied in conjunction with quasi-Newton solvers: the Hessian is approximated solely based on denoised data. We apply the proposed method, which we call GradReg, to both conventional breast CT and GI-CT and show that both significantly benefit from our approach in terms of dose efficiency. Moreover, our results suggest that thanks to its sharper gradients that carry more high spatial-frequency content, GI-CT can benefit more from GradReg compared to conventional breast CT. Crucially, GradReg can be applied to any image reconstruction task which relies on gradient-based updates.

Dosimetrically motivated beam-angle optimization for non-coplanar arc radiotherapy with and without dynamic collimator rotation.

BACKGROUND: Non-coplanar techniques have shown to improve the achievable dose distribution compared to standard coplanar techniques for multiple treatment sites but finding optimal beam directions is challenging. Dynamic collimator trajectory radiotherapy (colli-DTRT) is a new intensity modulated radiotherapy technique that uses non-coplanar partial arcs and dynamic collimator rotation. PURPOSE: To solve the beam angle optimization (BAO) problem for colli-DTRT and non-coplanar VMAT (NC-VMAT) by determining the table-angle and the gantry-angle ranges of the partial arcs through iterative 4π fluence map optimization (FMO) and beam direction elimination. METHODS: BAO considers all available beam directions sampled on a gantry-table map with the collimator angle aligned to the superior-inferior axis (colli-DTRT) or static (NC-VMAT). First, FMO is performed, and beam directions are scored based on their contributions to the objective function. The map is thresholded to remove the least contributing beam directions, and arc candidates are formed by adjacent beam directions with the same table angle. Next, FMO and arc candidate trimming, based on objective function penalty score, is performed iteratively until a desired total gantry angle range is reached. Direct aperture optimization on the final set of colli-DTRT or NC-VMAT arcs generates deliverable plans. colli-DTRT and NC-VMAT plans were created for seven clinically-motivated cases with targets in the head and neck (two cases), brain, esophagus, lung, breast, and prostate. colli-DTRT and NC-VMAT were compared to coplanar VMAT plans as well as to class-solution non-coplanar VMAT plans for the brain and head and neck cases. Dosimetric validation was performed for one colli-DTRT (head and neck) and one NC-VMAT (breast) plan using film measurements. RESULTS: Target coverage and conformity was similar for all techniques. colli-DTRT and NC-VMAT plans had improved dosimetric performance compared to coplanar VMAT for all treatment sites except prostate where all techniques were equivalent. For the head and neck and brain cases, mean dose reduction-in percentage of the prescription dose-to parallel organs was on average 0.7% (colli-DTRT), 0.8% (NC-VMAT) and 0.4% (class-solution) compared to VMAT. The reduction in D2% for the serial organs was on average 1.7% (colli-DTRT), 2.0% (NC-VMAT) and 0.9% (class-solution). For the esophagus, lung, and breast cases, mean dose reduction to parallel organs was on average 0.2% (colli-DTRT) and 0.3% (NC-VMAT) compared to VMAT. The reduction in D2% for the serial organs was on average 1.3% (colli-DTRT) and 0.9% (NC-VMAT). Estimated delivery times for colli-DTRT and NC-VMAT were below 4 min for a full gantry angle range of 720°, including transitions between arcs, except for the brain case where multiple arcs covered the whole table angle range. These times are in the same order as the class-solution for the head and neck and brain cases. Total optimization times were 25%-107% longer for colli-DTRT, including BAO, compared to VMAT. CONCLUSIONS: We successfully developed dosimetrically motivated BAO for colli-DTRT and NC-VMAT treatment planning. colli-DTRT and NC-VMAT are applicable to multiple treatment sites, including body sites, with beneficial or equivalent dosimetric performances compared to coplanar VMAT and reasonable delivery times.

Technical note: A collision prediction tool using Blender.

Non-coplanar radiotherapy treatment techniques on C-arm linear accelerators have the potential to reduce dose to organs-at-risk in comparison with coplanar treatment techniques. Accurately predicting possible collisions between gantry, table and patient during treatment planning is needed to ensure patient safety. We offer a freely available collision prediction tool using Blender, a free and open-source 3D computer graphics software toolset. A geometric model of a C-arm linear accelerator including a library of patient models is created inside Blender. Based on the model, collision predictions can be used both to calculate collision-free zones and to check treatment plans for collisions. The tool is validated for two setups, once with and once without a full body phantom with the same table position. For this, each gantry-table angle combination with a 2° resolution is manually checked for collision interlocks at a TrueBeam system and compared to simulated collision predictions. For the collision check of a treatment plan, the tool outputs the minimal distance between the gantry, table and patient model and a video of the movement of the gantry and table, which is demonstrated for one use case. A graphical user interface allows user-friendly input of the table and patient specification for the collision prediction tool. The validation resulted in a true positive rate of 100%, which is the rate between the number of correctly predicted collision gantry-table combinations and the number of all measured collision gantry-table combinations, and a true negative rate of 89%, which is the ratio between the number of correctly predicted collision-free combinations and the number of all measured collision-free combinations. A collision prediction tool is successfully created and able to produce maps of collision-free zones and to test treatment plans for collisions including visualisation of the gantry and table movement.

Airspace Diameter Map-A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases.

(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (ßENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with µCT, sugges-ting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.

Impact of the gradient in gantry-table rotation on dynamic trajectory radiotherapy plan quality.

BACKGROUND: To improve organ at risk (OAR) sparing, dynamic trajectory radiotherapy (DTRT) extends VMAT by dynamic table and collimator rotation during beam-on. However, comprehensive investigations regarding the impact of the gantry-table (GT) rotation gradient on the DTRT plan quality have not been conducted. PURPOSE: To investigate the impact of a user-defined GT rotation gradient on plan quality of DTRT plans in terms of dosimetric plan quality, dosimetric robustness, deliverability, and delivery time. METHODS: The dynamic trajectories of DTRT are described by GT and gantry-collimator paths. The GT path is determined by minimizing the overlap of OARs with planning target volume (PTV). This approach is extended to consider a GT rotation gradient by means of a maximum gradient of the path ( G m a x ${G}_{max}$ ) between two adjacent control points ( G = | Δ table angle / Δ gantry angle | $G = | \Delta {{\mathrm{table\ angle}}/\Delta {\mathrm{gantry\ angle}}} |$ ) and maximum absolute change of G ( Δ G m a x ${{\Delta}}{G}_{max}$ ). Four DTRT plans are created with different maximum G&∆G: G m a x ${G}_{max}$ & Δ G m a x ${{\Delta}}{G}_{max}$  = 0.5&0.125 (DTRT-1), 1&0.125 (DTRT-2), 3&0.125 (DTRT-3) and 3&1|(DTRT-4), including 3-4 dynamic trajectories, for three clinically motivated cases in the head and neck and brain region (A, B, and C). A reference VMAT plan for each case is created. For all plans, plan quality is assessed and compared. Dosimetric plan quality is evaluated by target coverage, conformity, and OAR sparing. Dosimetric robustness is evaluated against systematic and random patient-setup uncertainties between ± 3 mm $ \pm 3\ {\mathrm{mm}}$ in the lateral, longitudinal, and vertical directions, and machine uncertainties between ± 4 ∘ $ \pm 4^\circ \ $ in the dynamically rotating machine components (gantry, table, collimator rotation). Delivery time is recorded. Deliverability and delivery accuracy on a TrueBeam are assessed by logfile analysis for all plans and additionally verified by film measurements for one case. All dose calculations are Monte Carlo based. RESULTS: The extension of the DTRT planning process with user-defined G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ to investigate the impact of the GT rotation gradient on plan quality is successfully demonstrated. With increasing G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ , slight (case C, D m e a n , p a r o t i d l . ${D}_{mean,\ parotid\ l.}$ : up to|-1|Gy) and substantial (case A, D 0.03 c m 3 , o p t i c n e r v e r . ${D}_{0.03c{m}^3,\ optic\ nerve\ r.}$ : up to -9.3 Gy, case|B, D m e a n , b r a i n $\ {D}_{mean,\ brain}$ : up to -4.7|Gy) improvements in OAR sparing are observed compared to VMAT, while maintaining similar target coverage. All plans are delivered on the TrueBeam. Expected and actual machine position values recorded in the logfiles deviated by <0.2° for gantry, table and collimator rotation. The film measurements agreed by >96% (2%|global/2 mm Gamma passing rate) with the dose calculation. With increasing G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ , delivery time is prolonged by <2 min/trajectory (DTRT-4) compared to VMAT and DTRT-1. The DTRT plans for case A and B and the VMAT plan for case C plan reveal the best dosimetric robustness for the considered uncertainties. CONCLUSION: The impact of the GT rotation gradient on DTRT plan quality is comprehensively investigated for three cases in the head and neck and brain region. Increasing freedom in this gradient improves dosimetric plan quality at the cost of increased delivery time for the investigated cases. No clear dependency of GT rotation gradient on dosimetric robustness is observed.

Technical note: Feasibility of gating for dynamic trajectory radiotherapy - Mechanical accuracy and dosimetric performance.

BACKGROUND: Dynamic trajectory radiotherapy (DTRT) extends state-of-the-art volumetric modulated arc therapy (VMAT) by dynamic table and collimator rotations during beam-on. The effects of intrafraction motion during DTRT delivery are unknown, especially regarding the possible interplay between patient and machine motion with additional dynamic axes. PURPOSE: To experimentally assess the technical feasibility and quantify the mechanical and dosimetric accuracy of respiratory gating during DTRT delivery. METHODS: A DTRT and VMAT plan are created for a clinically motivated lung cancer case and delivered to a dosimetric motion phantom (MP) placed on the table of a TrueBeam system using Developer Mode. The MP reproduces four different 3D motion traces. Gating is triggered using an external marker block, placed on the MP. Mechanical accuracy and delivery time of the VMAT and DTRT deliveries with and without gating are extracted from the logfiles. Dosimetric performance is assessed by means of gamma evaluation (3% global/2 mm, 10% threshold). RESULTS: The DTRT and VMAT plans are successfully delivered with and without gating for all motion traces. Mechanical accuracy is similar for all experiments with deviations <0.14° (gantry angle), <0.15° (table angle), <0.09° (collimator angle) and <0.08 mm (MLC leaf positions). For DTRT (VMAT), delivery times are 1.6-2.3 (1.6- 2.5) times longer with than without gating for all motion traces except one, where DTRT (VMAT) delivery is 5.0 (3.6) times longer due to a substantial uncorrected baseline drift affecting only DTRT delivery. Gamma passing rates with (without) gating for DTRT/VMAT were ≥96.7%/98.5% (≤88.3%/84.8%). For one VMAT arc without gating it was 99.6%. CONCLUSION: Gating is successfully applied during DTRT delivery on a TrueBeam system for the first time. Mechanical accuracy is similar for VMAT and DTRT deliveries with and without gating. Gating substantially improved dosimetric performance for DTRT and VMAT.

A Novel Three-Dimensional Approach Towards Evaluating Endomyocardial Biopsies for Follow-Up After Heart Transplantation: X-Ray Phase Contrast Imaging and Its Agreement With Classical Histopathology.

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 µm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection.

Iterative phase contrast CT reconstruction with novel tomographic operator and data-driven prior.

Breast cancer remains the most prevalent malignancy in women in many countries around the world, thus calling for better imaging technologies to improve screening and diagnosis. Grating interferometry (GI)-based phase contrast X-ray CT is a promising technique which could make the transition to clinical practice and improve breast cancer diagnosis by combining the high three-dimensional resolution of conventional CT with higher soft-tissue contrast. Unfortunately though, obtaining high-quality images is challenging. Grating fabrication defects and photon starvation lead to high noise amplitudes in the measured data. Moreover, the highly ill-conditioned differential nature of the GI-CT forward operator renders the inversion from corrupted data even more cumbersome. In this paper, we propose a novel regularized iterative reconstruction algorithm with an improved tomographic operator and a powerful data-driven regularizer to tackle this challenging inverse problem. Our algorithm combines the L-BFGS optimization scheme with a data-driven prior parameterized by a deep neural network. Importantly, we propose a novel regularization strategy to ensure that the trained network is non-expansive, which is critical for the convergence and stability analysis we provide. We empirically show that the proposed method achieves high quality images, both on simulated data as well as on real measurements.

Intensity-based iterative reconstruction for helical grating interferometry breast CT with static grating configuration.

Grating interferometry breast computed tomography (GI-BCT) has the potential to provide enhanced soft tissue contrast and to improve visualization of cancerous lesions for breast imaging. However, with a conventional scanning protocol, a GI-BCT scan requires longer scanning time and higher operation complexity compared to conventional attenuation-based CT. This is mainly due to multiple grating movements at every projection angle, so-called phase stepping, which is used to retrieve attenuation, phase, and scattering (dark-field) signals. To reduce the measurement time and complexity and extend the field of view, we have adopted a helical GI-CT setup and present here the corresponding tomographic reconstruction algorithm. This method allows simultaneous reconstruction of attenuation, phase contrast, and scattering images while avoiding grating movements. Experiments on simulated phantom and real initial intensity, visibility and phase maps are provided to validate our method.

Development of a Monte Carlo based robustness calculation and evaluation tool.

BACKGROUND: Evaluating plan robustness is a key step in radiotherapy. PURPOSE: To develop a flexible Monte Carlo (MC)-based robustness calculation and evaluation tool to assess and quantify dosimetric robustness of intensity-modulated radiotherapy (IMRT) treatment plans by exploring the impact of systematic and random uncertainties resulting from patient setup, patient anatomy changes, and mechanical limitations of machine components. METHODS: The robustness tool consists of two parts: the first part includes automated MC dose calculation of multiple user-defined uncertainty scenarios to populate a robustness space. An uncertainty scenario is defined by a certain combination of uncertainties in patient setup, rigid intrafraction motion and in mechanical steering of the following machine components: angles of gantry, collimator, table-yaw, table-pitch, table-roll, translational positions of jaws, multileaf-collimator (MLC) banks, and single MLC leaves. The Swiss Monte Carlo Plan (SMCP) is integrated in this tool to serve as the backbone for the MC dose calculations incorporating the uncertainties. The calculated dose distributions serve as input for the second part of the tool, handling the quantitative evaluation of the dosimetric impact of the uncertainties. A graphical user interface (GUI) is developed to simultaneously evaluate the uncertainty scenarios according to user-specified conditions based on dose-volume histogram (DVH) parameters, fast and exact gamma analysis, and dose differences. Additionally, a robustness index (RI) is introduced with the aim to simultaneously evaluate and condense dosimetric robustness against multiple uncertainties into one number. The RI is defined as the ratio of scenarios passing the conditions on the dose distributions. Weighting of the scenarios in the robustness space is possible to consider their likelihood of occurrence. The robustness tool is applied on IMRT, a volumetric modulated arc therapy (VMAT), a dynamic trajectory radiotherapy (DTRT), and a dynamic mixed beam radiotherapy (DYMBER) plan for a brain case to evaluate the robustness to uncertainties of gantry-, table-, collimator angle, MLC, and intrafraction motion. Additionally, the robustness of the IMRT, VMAT, and DTRT plan against patient setup uncertainties are compared. The robustness tool is validated by Delta4 measurements for scenarios including all uncertainty types available. RESULTS: The robustness tool performs simultaneous calculation of uncertainty scenarios, and the GUI enables their fast evaluation. For all evaluated plans and uncertainties, the planning target volume (PTV) margin prevented major clinical target volume (CTV) coverage deterioration (maximum observed standard deviation of D 98 % CTV $D98{\% _{{\rm{CTV}}}}$ was 1.3 Gy). OARs close to the PTV experienced larger dosimetric deviations (maximum observed standard deviation of D 2 % chiasma $D2{\% _{{\rm{chiasma}}}}$ was 14.5 Gy). Robustness comparison by RI evaluation against patient setup uncertainties revealed better dosimetric robustness of the VMAT and DTRT plans as compared to the IMRT plan. Delta4 validation measurements agreed with calculations by >96% gamma-passing rate (3% global/2 mm). CONCLUSIONS: The robustness tool was successfully implemented. Calculation and evaluation of uncertainty scenarios with the robustness tool were demonstrated on a brain case. Effects of patient and machine-specific uncertainties and the combination thereof on the dose distribution are evaluated in a user-friendly GUI to quantitatively assess and compare treatment plans and their robustness.

INSIDEnet: Interpretable NonexpanSIve Data-Efficient network for denoising in grating interferometry breast CT.

PURPOSE: Breast cancer is the most common malignancy in women. Unfortunately, current breast imaging techniques all suffer from certain limitations: they are either not fully three dimensional, have an insufficient resolution or low soft-tissue contrast. Grating interferometry breast computed tomography (GI-BCT) is a promising X-ray phase contrast modality that could overcome these limitations by offering high soft-tissue contrast and excellent three-dimensional resolution. To enable the transition of this technology to clinical practice, dedicated data-processing algorithms must be developed in order to effectively retrieve the signals of interest from the measured raw data. METHODS: This article proposes a novel denoising algorithm that can cope with the high-noise amplitudes and heteroscedasticity which arise in GI-BCT when operated in a low-dose regime to effectively regularize the ill-conditioned GI-BCT inverse problem. We present a data-driven algorithm called INSIDEnet, which combines different ideas such as multiscale image processing, transform-domain filtering, transform learning, and explicit orthogonality to build an Interpretable NonexpanSIve Data-Efficient network (INSIDEnet). RESULTS: We apply the method to simulated breast phantom datasets and to real data acquired on a GI-BCT prototype and show that the proposed algorithm outperforms traditional state-of-the-art filters and is competitive with deep neural networks. The strong inductive bias given by the proposed model's architecture allows to reliably train the algorithm with very limited data while providing high model interpretability, thus offering a great advantage over classical convolutional neural networks (CNNs). CONCLUSIONS: The proposed INSIDEnet is highly data-efficient, interpretable, and outperforms state-of-the-art CNNs when trained on very limited training data. We expect the proposed method to become an important tool as part of a dedicated plug-and-play GI-BCT reconstruction framework, needed to translate this promising technology to the clinics.

Can grating interferometry-based mammography discriminate benign from malignant microcalcifications in fresh biopsy samples?

PURPOSE: In addition to absorption imaging, grating interferometry-based mammography (GIM) is capable of detecting differential-phase and scattering signals. In particular, the scattering signal can enable a quantifiable characterization of breast lesions. The purpose of this study was to determine if suspicious microcalcifications associated with benign or malignant lesions can be discriminated based on their absorption and scattering properties. MATERIALS AND METHODS: In this prospective, ethically approved study, 62 patients (mean age 60 y, range 39-89) with suspicious microcalcifications, who underwent stereotactic biopsies, were included. Biopsies were measured with an experimental GIM device and the ratios of the scattering and absorption signal (R-value) for microcalcifications were calculated. The mean R-values for benign and malignant lesions associated with microcalcifications were compared with the final histopathological diagnosis using a t-test. RESULTS: Twenty of the 62 participants had microcalcifications associated with malignancy. Comparing the two largest histopathological sub-groups of fibrosis (n = 23) vs. ductal carcinoma in situ (n = 15) resulted in an average R-value of 4.08 for benign and 2.80 for malignant lesions; p = 0.07. All microcalcifications associated with malignancy had an R-value below 4.71. Excluding microcalcifications with an R-value above this threshold would result in an 11 % reduction of false positives. CONCLUSION: The novel GIM modality has the potential to non-invasively characterize microcalcifications and might aid in the discrimination of benign from malignant lesions in fresh biopsy samples.

Metal assisted chemical etching of silicon in the gas phase: a nanofabrication platform for X-ray optics.

High aspect ratio nanostructuring requires high precision pattern transfer with highly directional etching. In this work, we demonstrate the fabrication of structures with ultra-high aspect ratios (up to 10 000 : 1) in the nanoscale regime (down to 10 nm) by platinum assisted chemical etching of silicon in the gas phase. The etching gas is created by a vapour of water diluted hydrofluoric acid and a continuous air flow, which works both as an oxidizer and as a gas carrier for reactive species. The high reactivity of platinum as a catalyst and the formation of platinum silicide to improve the stability of the catalyst pattern allow a controlled etching. The method has been successfully applied to produce straight nanowires with section size in the range of 10-100 nm and length of hundreds of micrometres, and X-ray optical elements with feature sizes down to 10 nm and etching depth in the range of tens of micrometres. This work opens the possibility of a low cost etching method for stiction-sensitive nanostructures and a large range of applications where silicon high aspect ratio nanostructures and high precision of pattern transfer are required.

Correction to: Towards clinical grating-interferometry mammography.

The article Towards clinical grating-interferometry mammography, written by Carolina Arboleda, Zhentian Wang, Konstantins Jefimovs, Thomas Koehler, Udo Van Stevendaal, Norbert Kuhn, Bernd David, Sven Prevrhal, Kristina Lång, Serafino Forte, Rahel Antonia Kubik-Huch, Cornelia Leo.

Towards clinical grating-interferometry mammography.

OBJECTIVES: Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. METHODS: We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. RESULTS AND CONCLUSION: Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. KEY POINTS: • Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

Adaptive step size algorithm to increase efficiency of proton macro Monte Carlo dose calculation.

PURPOSE: To provide fast and accurate dose calculation in voxelized geometries for proton radiation therapy by implementing an adaptive step size algorithm in the proton macro Monte Carlo (pMMC) method. METHODS: The in-house developed local-to-global MMC method for proton dose calculation is extended with an adaptive step size algorithm for efficient proton transport through a voxelized geometry by sampling transport parameters from a pre-simulated database. Adaptive choice of an adequate slab size in dependence of material interfaces in the proton's longitudinal and lateral vicinity is investigated. The dose calculation algorithm is validated against the non-adaptive pMMC and full MC simulation for pencil and broad beams with various energies impinging on academic phantoms as well as a head and neck patient CT. RESULTS: For material interfaces perpendicular to a proton's direction, choice of nearest neighbor slab thickness shows best trade-off between dosimetric accuracy and calculation efficiency. Adaptive reduction of chosen slab size is shown to be required for material interfaces closer than 0.5 mm in lateral direction. For the academic phantoms, dose differences of within 1% or 1 mm compared to full Geant4 MC simulation are found, while achieving an efficiency gain of up to a factor of 5.6 compared to the non-adaptive algorithm and 284 compared to Geant4. For the head and neck patient CT, dose differences are within 1% or 1 mm with an efficiency gain factor of up to 3.4 compared to the non-adaptive algorithm and 145 compared to Geant4. CONCLUSION: An adaptive step size algorithm for proton macro Monte Carlo was implemented and evaluated. The dose calculation provides the accuracy of full MC simulations, while achieving an efficiency gain factor of three compared to the non-adaptive algorithm and two orders of magnitude compared to full MC for a complex patient CT.

Microbubbles as a contrast agent in grating interferometry mammography: an ex vivo proof-of-mechanism study.

Grating interferometry mammography (GIM) is an experimental breast imaging method at the edge of being clinically implemented. Besides attenuation, GIM can measure the refraction and scattering of x-rays resulting in differential phase contrast (DPC) and dark-field (DF) images. In this exploratory study, we assessed the feasibility of using microbubbles as a contrast agent in GIM. Two millilitres of microbubbles and iodine were respectively injected into ex vivo breast phantoms, consisting of fresh chicken breasts. Native and postcontrast images were acquired with a clinically compatible GIM setup, operated at 38 kVp, 14-s acquisition time, and with a dose of 1.3 mGy. The visibility of the contrast agents was analysed in a side-by-side comparison by three radiologists. The contrast-to-noise-ratio (CNR) was calculated for each contrast agent. We found that both contrast agents were judged to be visible by the readers. The mean CNR was 3.1 ± 1.9 for microbubbles in DF and 24.2 ± 6.5 for iodine in attenuation. In conclusion, this is a first proof-of-mechanism study that microbubbles could be used as a contrast agent in clinically compatible GIM, due to their scattering properties, which implies the potential use of a contrast agent with a high safety profile in x-ray-based breast imaging.

Complex Congenital Heart Disease Associated With Disordered Myocardial Architecture in a Midtrimester Human Fetus.

BACKGROUND: In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, result in altered myocardial function both before and after surgery. To gain a better understanding and develop appropriate and individualized treatment strategies, the microscopic organization of cardiomyocytes, and their integration at a macroscopic level, needs to be completely understood. The aim of this study is to describe, for the first time, in 3 dimensions and nondestructively the detailed remodeling of cardiac microstructure present in a human fetal heart with complex CHD. METHODS AND RESULTS: Synchrotron X-ray phase-contrast imaging was used to image an archival midgestation formalin-fixed fetal heart with right isomerism and complex CHD and compare with a control fetal heart. Analysis of myocyte aggregates, at detail not accessible with other techniques, was performed. Macroanatomic and conduction system changes specific to the disease were clearly observable, together with disordered myocyte organization in the morphologically right ventricle myocardium. Electrical activation simulations suggested altered synchronicity of the morphologically right ventricle. CONCLUSIONS: We have shown the potential of X-ray phase-contrast imaging for studying cardiac microstructure in the developing human fetal heart at high resolution providing novel insight while preserving valuable archival material for future study. This is the first study to show myocardial alterations occur in complex CHD as early as midgestation.

TLD measurements and Monte Carlo calculations of head and neck organ and effective doses for cone beam computed tomography using 3D Accuitomo 170.

OBJECTIVES: In dentistry, the use of cone beam CT has steadily increased over the last few years. The aim of this study was to measure organ doses and to perform dose calculations based on Monte Carlo (MC) simulations to work out a basis for full three-dimensional (3D) dose calculations for any patient examination performed with the machine used in this study. METHODS: TLD-100 LiF detectors were placed at 71 measurement positions on the surface and within a RT-Humanoid phantom to cover all relevant radiosensitive organs and tissues. Three examinations with different protocols were performed with the 3D Accuitomo® and dose calculations with MC simulations were carried out for the same three protocols using the EGSnrc MC transport code system. RESULTS: Field of views of 140 × 100, 80 × 50 and 40 × 40 mm2 were selected, the mean organ doses were measured as 5.2, 2.75 and 1.5 mGy and the effective doses were determined as 250, 97 and 48 µSv. For the MC simulation of organ doses and the thermoluminescent dosemeter measurements, an overall agreement within ±10.1% (two standard deviations) was achieved. The measured dose values for 3D Accuitomo® were about a factor 2 lower when compared with conventional CT examinations. CONCLUSIONS: Reliable results for the organ doses as well as effective dose values were achieved with thermoluminescent dosemeter measurements in the RT-Humanoid phantom. This study provides the basis for the application of MC simulations for further dose determinations of cone beam CT machines. The MC calculation may therefore be a valuable tool to support the dentists in the evaluation of the trade-off between additional information that may be relevant to the choice of therapy and the additional dose given to the patient.