A method of dose reconstruction for moving targets compatible with dynamic treatments.
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ABSTRACT: To develop a method that allows a commercial treatment planning system (TPS) to perform accurate dose reconstruction for rigidly moving targets and to validate the method in phantom measurements for a range of treatments including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and dynamic multileaf collimator (DMLC) tracking.An in-house computer program was developed to manipulate Dicom treatment plans exported from a TPS (Eclipse, Varian Medical Systems) such that target motion during treatment delivery was incorporated into the plans. For each treatment, a motion including plan was generated by dividing the intratreatment target motion into 1 mm position bins and construct sub-beams that represented the parts of the treatment that were delivered, while the target was located within each position bin. For each sub-beam, the target shift was modeled by a corresponding isocenter shift. The motion incorporating Dicom plans were reimported into the TPS, where dose calculation resulted in motion including target dose distributions. For experimental validation of the dose reconstruction a thorax phantom with a moveable lung equivalent rod with a tumor insert of solid water was first CT scanned. The tumor insert was delineated as a gross tumor volume (GTV), and a planning target volume (PTV) was formed by adding margins. A conformal plan, two IMRT plans (step-and-shoot and sliding windows), and a VMAT plan were generated giving minimum target doses of 95% (GTV) and 67% (PTV) of the prescription dose (3 Gy). Two conformal fields with MLC leaves perpendicular and parallel to the tumor motion, respectively, were generated for DMLC tracking. All treatment plans were delivered to the thorax phantom without tumor motion and with a sinusoidal tumor motion. The two conformal fields were delivered with and without portal image guided DMLC tracking based on an embedded gold marker. The target dose distribution was measured with a radiochromic film in the moving rod and compared with the reconstructed doses using gamma tests.Considerable interplay effects between machine motion and target motion were observed for the treatments without tracking. For nontracking experiments, the mean 2 mm∕2% gamma pass rate over all investigated scenarios was 99.6% between calculated and measured doses. For tracking experiments, the mean gamma pass rate was 99.4%.A method for accurate dose reconstruction for moving targets with dynamic treatments was developed and experimentally validated in a variety of delivery scenarios. The method is suitable for integration into TPSs, e.g., for reconstruction of the dose delivered to moving tumors or calculation of target doses delivered with DMLC tracking.
Project description:PurposeWhile four-dimensional computed tomography (4DCT) and deformable registration can be used to assess the dose delivered to regularly moving targets, there are few methods available for irregularly moving targets. 4DCT captures an idealized waveform, but human respiration during treatment is characterized by gradual baseline shifts and other deviations from a periodic signal. This paper describes a method for computing the dose delivered to irregularly moving targets based on 1D or 3D waveforms captured at the time of delivery.MethodsThe procedure uses CT or 4DCT images for dose calculation, and 1D or 3D respiratory waveforms of the target position at time of delivery. Dose volumes are converted from their Cartesian geometry into a beam-specific radiological depth space, parameterized in 2D by the beam aperture, and longitudinally by the radiological depth. In this new frame of reference, the proton doses are translated according to the motion found in the 1D or 3D trajectory. These translated dose volumes are weighted and summed, then transformed back into Cartesian space, yielding an estimate of the dose that includes the effect of the measured breathing motion. The method was validated using a synthetic lung phantom and a single representative patient CT. Simulated 4DCT was generated for the phantom with 2 cm peak-to-peak motion.ResultsA passively-scattered proton treatment plan was generated using 6 mm and 5 mm smearing for the phantom and patient plans, respectively. The method was tested without motion, and with two simulated breathing signals: a 2 cm amplitude sinusoid, and a 2 cm amplitude sinusoid with 3 cm linear drift in the phantom. The tumor positions were equally weighted for the patient calculation. Motion-corrected dose was computed based on the mid-ventilation CT image in the phantom and the peak exhale position in the patient. Gamma evaluation was 97.8% without motion, 95.7% for 2 cm sinusoidal motion, 95.7% with 3 cm drift in the phantom (2 mm, 2%), and 90.8% (3 mm, 3%)for the patient data.ConclusionsWe have demonstrated a method for accurately reproducing proton dose to an irregularly moving target from a single CT image. We believe this algorithm could prove a useful tool to study the dosimetric impact of baseline shifts either before or during treatment.
Project description:PurposeTo develop a 4D dose reconstruction method and to evaluate the delivered dose in respiratory-gated volumetric modulated arc therapy (VMAT).Materials and methodsA total 112 treatment sessions of gated VMAT for 30 stereotactic body radiotherapy (SBRT) patients (10 lung, 10 liver, and 10 pancreas) were evaluated. For respiratory-gated SBRT, 4DCT was acquired, and the CT data at the end-exhale phase was used for a VMAT plan. The delivered dose was reconstructed using a patient's respiratory motion and machine motion acquired during the beam delivery. The machine motion was obtained from the treatment log file, while the target position was estimated from an external respiratory marker position. The target position was divided into 1-mm position bins, and sub-beams with beam isocenters corresponding to each position bin were created in a motion mimicking plan, reflecting motion data including MLC leaf positions and gantry angle and target position data during beam treatment. The reconstructed 4D dose was compared with the dose of the original plan using these dosimetric parameters; the maximum dose (Dmax) and mean dose (Dmean) of gross target volume (GTV) or organs at risk (spinal cord, esophagus, heart, duodenum, kidney, spinal cord, and stomach). The minimum dose (Dmin) to GTV was also calculated to verify cold spots in tumors.ResultsThere was no significant difference of dose parameters regard to the GTV in all tumors. For the liver cases, there were significant differences in the Dmax of duodenum (-4.2 ± 1.4%), stomach (-3.5 ± 4.2%), left kidney (-4.1 ± 2.8%), and right kidney (-3.2 ± 1.3%), and in the Dmean of duodenum (-3.8 ± 1.4%), stomach (-3.9 ± 2.2%), left kidney (-3.1 ± 2.8%), and right kidney (-4.1 ± 2.6%). For the pancreas cases, there were significant differences in the Dmax of stomach (2.1 ± 3.0%), and in the Dmean of liver (1.5 ± 0.6%), duodenum (-1.0 ± 1.4%), stomach (2.1 ± 1.6%), and right kidney (-1.3 ± 0.9%). The average gamma pass rates were 97.6 ± 4.8% for lung cases, 99.6 ± 0.5% for liver cases, and 99.5 ± 0.5% for pancreas cases. Most cases showed insignificant dose variation, with gamma pass rates higher than 98%, except for two lung cases with gamma pass rates of 86.9% and 90.6%. The low gamma pass rates showed larger global motion ranges resulting from the baseline shift during beam delivery.ConclusionThe actual delivered dose in thoracic and abdominal VMAT under breathing motion was verified by 4D dose reconstruction using typical treatment equipment and software. The proposed method provides a verification method for the actual delivered dose and could be a dosimetric verification QA tool for radiation treatment under various respiratory management techniques.
Project description:Clinicians, basic researchers, representatives from pharma and families from around the world met in Cordoba, Argentina in October, 2014 to discuss recent research progress at the 14th International Congress on Neuronal Ceroid Lipofuscinoses (NCLs; Batten disease), a group of clinically overlapping fatal, inherited lysosomal disorders with primarily neurodegenerative symptoms. This brief review article will provide perspectives on the anticipated future directions of NCL basic and clinical research as we move towards improved diagnosis, care and treatment of NCL patients. This article is part of a Special Issue entitled: Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease).
Project description:Particle therapy of moving targets is still a great challenge. The motion of organs situated in the thorax and abdomen strongly affects the precision of proton and carbon ion radiotherapy. The motion is responsible for not only the dislocation of the tumour but also the alterations in the internal density along the beam path, which influence the range of particle beams. Furthermore, in case of pencil beam scanning, there is an interference between the target movement and dynamic beam delivery. This review presents the strategies for tumour motion monitoring and moving target irradiation in the context of hadron therapy. Methods enabling the direct determination of tumour position (fluoroscopic imaging of implanted radio-opaque fiducial markers, electromagnetic detection of inserted transponders and ultrasonic tumour localization systems) are presented. Attention is also drawn to the techniques which use external surrogate motion for an indirect estimation of target displacement during irradiation. The role of respiratory-correlated CT [four-dimensional CT (4DCT)] in the determination of motion pattern prior to the particle treatment is also considered. An essential part of the article is the review of the main approaches to moving target irradiation in hadron therapy: gating, rescanning (repainting), gated rescanning and tumour tracking. The advantages, drawbacks and development trends of these methods are discussed. The new accelerators, called "cyclinacs", are presented, because their application to particle therapy will allow making a breakthrough in the 4D spot scanning treatment of moving organs.
Project description:Drug Discovery is a lengthy and costly process and has faced a period of declining productivity within the last two decades resulting in increasing importance of integrative data-driven approaches. In this paper, data mining and integration is leveraged to inspect target innovation trends in drug discovery. The study highlights protein families and classes that have received more attention and those that have just emerged in the scientific literature, thus highlighting novel opportunities for drug intervention. In order to delineate the evolution of target-driven research interest from a biological perspective, trends in biological process annotations from Gene Ontology and disease annotations from DisGeNET are captured. The analysis reveals an increasing interest in targets related to immune system processes, and a recurrent trend for targets involved in circulatory system processes. At the level of diseases, targets associated with cancer-related pathologies, intellectual disability, and schizophrenia are increasingly investigated in recent years. The methodology enables researchers to capture trends in research attention in target space at an early stage during the drug discovery process. Workflows, scripts, and data used in this study are publicly available from https://github.com/BZdrazil/Moving_Targets . An interactive web application allows the customized exploration of target, biological process, and disease trends (available at https://rguha.shinyapps.io/MovingTargets/ ).
Project description:Measuring eye movement is a fundamental approach in cognitive science as it provides a variety of insightful parameters that reflect brain states such as visual attention and emotions. Combining eye-tracking with multimodal neural recordings or manipulation techniques is beneficial for understanding the neural substrates of cognitive function. Many commercially-available and custom-built systems have been widely applied to awake, head-fixed small animals. However, the existing eye-tracking systems used in freely-moving animals are still limited in terms of their compatibility with other devices and of the algorithm used to detect eye movements. Here, we report a novel system that integrates a general-purpose, easily compatible eye-tracking hardware with a robust eye feature-detection algorithm. With ultra-light hardware and a detachable design, the system allows for more implants to be added to the animal's exposed head and has a precise synchronization module to coordinate with other neural implants. Moreover, we systematically compared the performance of existing commonly-used pupil-detection approaches, and demonstrated that the proposed adaptive pupil feature-detection algorithm allows the analysis of more complex and dynamic eye-tracking data in free-moving animals. Synchronized eye-tracking and electroencephalogram recordings, as well as algorithm validation under five noise conditions, suggested that our system is flexibly adaptable and can be combined with a wide range of neural manipulation and recording technologies.
Project description:Optical coherence tomography allows for dynamic, three-dimensional (3D+T) imaging of the heart within animal embryos. However, direct 3D+T imaging frame rates remain insufficient for cardiodynamic analysis. Previously, this limitation has been addressed by reconstructing 3D+T representations of the beating heart based on sets of two-dimensional image sequences (2D+T) acquired sequentially at high frame rate and in fixed (and parallel) planes throughout the heart. These methods either require additional hardware to trigger the acquisition of each 2D+T series to the same phase of the cardiac cycle or accumulate registration errors as the slices are synchronized retrospectively by pairs, without a gating signal. Here, we present a sequential turning acquisition and reconstruction (STAR) method for 3D+T imaging of periodically moving structures, which does not require any additional gating signal and is not prone to registration error accumulation. Similarly to other sequential cardiac imaging methods, multiple fast image series are consecutively acquired for different sections but in between acquisitions, the imaging plane is rotated around the center line instead of shifted along the direction perpendicular to the slices. As the central lines of all image-sequences coincide and represent measurements of the same spatial position, they can be used to accurately synchronize all the slices to a single inherent reference signal. We characterized the accuracy of our method on a simulated dynamic phantom and successfully imaged a beating embryonic rat heart. Potentially, this method can be applied for structural or Doppler imaging approaches with any direct space imaging modality such as computed tomography, ultrasound, or light microscopy.
Project description:Structure-based drug design traditionally uses static protein models as inspirations for focusing on "active" site targets. Allosteric regulation of biological macromolecules, however, is affected by both conformational and dynamic properties of the protein or protein complex and can potentially lead to more avenues for therapeutic development. We discuss the advantages of searching for molecules that conformationally trap a macromolecule in its inactive state. Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process.
Project description:This study provides a proof of concept for real-time 4D dose reconstruction for lung stereotactic body radiation therapy (SBRT) with multileaf collimator (MLC) tracking and assesses the impact of tumor tracking on the size of target margins.The authors have implemented real-time 4D dose reconstruction by connecting their tracking and delivery software to an Agility MLC at an Elekta Synergy linac and to their in-house treatment planning software (TPS). Actual MLC apertures and (simulated) target positions are reported to the TPS every 40 ms. The dose is calculated in real-time from 4DCT data directly after each reported aperture by utilization of precalculated dose-influence data based on a Monte Carlo algorithm. The dose is accumulated onto the peak-exhale (reference) phase using energy-mass transfer mapping. To investigate the impact of a potentially reducible safety margin, the authors have created and delivered treatment plans designed for a conventional internal target volume (ITV) + 5 mm, a midventilation approach, and three tracking scenarios for four lung SBRT patients. For the tracking plans, a moving target volume (MTV) was established by delineating the gross target volume (GTV) on every 4DCT phase. These were rigidly aligned to the reference phase, resulting in a unified maximum GTV to which a 1, 3, or 5 mm isotropic margin was added. All scenarios were planned for 9-beam step-and-shoot IMRT to meet the criteria of RTOG 1021 (3 × 18 Gy). The GTV 3D center-of-volume shift varied from 6 to 14 mm.Real-time dose reconstruction at 25 Hz could be realized on a single workstation due to the highly efficient implementation of dose calculation and dose accumulation. Decreased PTV margins resulted in inadequate target coverage during untracked deliveries for patients with substantial tumor motion. MLC tracking could ensure the GTV target dose for these patients. Organ-at-risk (OAR) doses were consistently reduced by decreased PTV margins. The tracked MTV + 1 mm deliveries resulted in the following OAR dose reductions: lung V20 up to 3.5%, spinal cord D2 up to 0.9 Gy/Fx, and proximal airways D2 up to 1.4 Gy/Fx.The authors could show that for patient data at clinical resolution and realistic motion conditions, the delivered dose could be reconstructed in 4D for the whole lung volume in real-time. The dose distributions show that reduced margins yield lower doses to healthy tissue, whilst target dose can be maintained using dynamic MLC tracking.
Project description:For a bird, it is often vital to visually detect food items, predators, or individuals from the same flock, i.e. moving stimuli of various shapes. Yet, behavioural tests of visual spatial acuity traditionally use stationary gratings as stimuli. We have behaviourally tested the ability of budgerigars (Melopsittacus undulatus) to detect a black circular target, moving semi-randomly at 1.69 degrees s-1 against a brighter background. We found a detection threshold of 0.107±0.007 degrees of the visual field for a target size corresponding to a resolution of a grating with a spatial frequency of 4.68 cycles degree-1. This detection threshold is lower than the resolution limit for gratings but similar to the threshold for stationary single objects of the same shape. We conclude that the target acuity of budgerigars for moving single targets, just as for stationary single targets, is lower than their acuity for gratings.