Peritumoral radiomics features predict distant metastasis in locally advanced NSCLC.

PURPOSE: Radiomics provides quantitative tissue heterogeneity profiling and is an exciting approach to developing imaging biomarkers in the context of precision medicine. Normal-appearing parenchymal tissues surrounding primary tumors can harbor microscopic disease that leads to increased risk of distant metastasis (DM). This study assesses whether computed-tomography (CT) imaging features of such peritumoral tissues can predict DM in locally advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: 200 NSCLC patients of histological adenocarcinoma were included in this study. The investigated lung tissues were tumor rim, defined to be 3mm of tumor and parenchymal tissue on either side of the tumor border and the exterior region extended from 3 to 9mm outside of the tumor. Fifteen stable radiomic features were extracted and evaluated from each of these regions on pre-treatment CT images. For comparison, features from expert-delineated tumor contours were similarly prepared. The patient cohort was separated into training and validation datasets for prognostic power evaluation. Both univariable and multivariable analyses were performed for each region using concordance index (CI). RESULTS: Univariable analysis reveals that six out of fifteen tumor rim features were significantly prognostic of DM (p-value < 0.05), as were ten features from the visible tumor, and only one of the exterior features was. Multivariablely, a rim radiomic signature achieved the highest prognostic performance in the independent validation sub-cohort (CI = 0.64, p-value = 2.4×10-5) significantly over a multivariable clinical model (CI = 0.53), a visible tumor radiomics model (CI = 0.59), or an exterior tissue model (CI = 0.55). Furthermore, patient stratification by the combined rim signature and clinical predictor led to a significant improvement on the clinical predictor alone and also outperformed stratification using the combined tumor signature and clinical predictor. CONCLUSIONS: We identified peritumoral rim radiomic features significantly associated with DM. This study demonstrated that peritumoral imaging characteristics may provide additional valuable information over the visible tumor features for patient risk stratification due to cancer metastasis.

Comparison of lung tumor motion measured using a model-based 4DCT technique and a commercial protocol.

PURPOSE: To compare lung tumor motion measured with a model-based technique to commercial 4-dimensional computed tomography (4DCT) scans and describe a workflow for using model-based 4DCT as a clinical simulation protocol. METHODS AND MATERIALS: Twenty patients were imaged using a model-based technique and commercial 4DCT. Tumor motion was measured on each commercial 4DCT dataset and was calculated on model-based datasets for 3 breathing amplitude percentile intervals: 5th to 85th, 5th to 95th, and 0th to 100th. Internal target volumes (ITVs) were defined on the 4DCT and 5th to 85th interval datasets and compared using Dice similarity. Images were evaluated for noise and rated by 2 radiation oncologists for artifacts. RESULTS: Mean differences in tumor motion magnitude between commercial and model-based images were 0.47 ± 3.0, 1.63 ± 3.17, and 5.16 ± 4.90 mm for the 5th to 85th, 5th to 95th, and 0th to 100th amplitude intervals, respectively. Dice coefficients between ITVs defined on commercial and 5th to 85th model-based images had a mean value of 0.77 ± 0.09. Single standard deviation image noise was 11.6 ± 9.6 HU in the liver and 6.8 ± 4.7 HU in the aorta for the model-based images compared with 57.7 ± 30 and 33.7 ± 15.4 for commercial 4DCT. Mean model error within the ITV regions was 1.71 ± 0.81 mm. Model-based images exhibited reduced presence of artifacts at the tumor compared with commercial images. CONCLUSION: Tumor motion measured with the model-based technique using the 5th to 85th percentile breathing amplitude interval corresponded more closely to commercial 4DCT than the 5th to 95th or 0th to 100th intervals, which showed greater motion on average. The model-based technique tended to display increased tumor motion when breathing amplitude intervals wider than 5th to 85th were used because of the influence of unusually deep inhalations. These results suggest that care must be taken in selecting the appropriate interval during image generation when using model-based 4DCT methods.

A Method for Assessing Ground-Truth Accuracy of the 5DCT Technique.

PURPOSE: To develop a technique that assesses the accuracy of the breathing phase-specific volume image generation process by patient-specific breathing motion model using the original free-breathing computed tomographic (CT) scans as ground truths. METHODS: Sixteen lung cancer patients underwent a previously published protocol in which 25 free-breathing fast helical CT scans were acquired with a simultaneous breathing surrogate. A patient-specific motion model was constructed based on the tissue displacements determined by a state-of-the-art deformable image registration. The first image was arbitrarily selected as the reference image. The motion model was used, along with the free-breathing phase information of the original 25 image datasets, to generate a set of deformation vector fields that mapped the reference image to the 24 nonreference images. The high-pitch helically acquired original scans served as ground truths because they captured the instantaneous tissue positions during free breathing. Image similarity between the simulated and the original scans was assessed using deformable registration that evaluated the pointwise discordance throughout the lungs. RESULTS: Qualitative comparisons using image overlays showed excellent agreement between the simulated images and the original images. Even large 2-cm diaphragm displacements were very well modeled, as was sliding motion across the lung-chest wall boundary. The mean error across the patient cohort was 1.15 ± 0.37 mm, and the mean 95th percentile error was 2.47 ± 0.78 mm. CONCLUSION: The proposed ground truth-based technique provided voxel-by-voxel accuracy analysis that could identify organ-specific or tumor-specific motion modeling errors for treatment planning. Despite a large variety of breathing patterns and lung deformations during the free-breathing scanning session, the 5-dimensionl CT technique was able to accurately reproduce the original helical CT scans, suggesting its applicability to a wide range of patients.

Technical Note: Simulation of 4DCT tumor motion measurement errors.

PURPOSE: To determine if and by how much the commercial 4DCT protocols under- and overestimate tumor breathing motion. METHODS: 1D simulations were conducted that modeled a 16-slice CT scanner and tumors moving proportionally to breathing amplitude. External breathing surrogate traces of at least 5-min duration for 50 patients were used. Breathing trace amplitudes were converted to motion by relating the nominal tumor motion to the 90th percentile breathing amplitude, reflecting motion defined by the more recent 5DCT approach. Based on clinical low-pitch helical CT acquisition, the CT detector moved according to its velocity while the tumor moved according to the breathing trace. When the CT scanner overlapped the tumor, the overlapping slices were identified as having imaged the tumor. This process was repeated starting at successive 0.1 s time bin in the breathing trace until there was insufficient breathing trace to complete the simulation. The tumor size was subtracted from the distance between the most superior and inferior tumor positions to determine the measured tumor motion for that specific simulation. The effect of the scanning parameter variation was evaluated using two commercial 4DCT protocols with different pitch values. Because clinical 4DCT scan sessions would yield a single tumor motion displacement measurement for each patient, errors in the tumor motion measurement were considered systematic. The mean of largest 5% and smallest 5% of the measured motions was selected to identify over- and underdetermined motion amplitudes, respectively. The process was repeated for tumor motions of 1-4 cm in 1 cm increments and for tumor sizes of 1-4 cm in 1 cm increments. RESULTS: In the examined patient cohort, simulation using pitch of 0.06 showed that 30% of the patients exhibited a 5% chance of mean breathing amplitude overestimations of 47%, while 30% showed a 5% chance of mean breathing amplitude underestimations of 36%; with a separate simulation using pitch of 0.1 showing, respectively, 37% overestimation and 61% underestimation. CONCLUSIONS: The simulation indicates that commercial low-pitch helical 4DCT processes potentially yield large tumor motion measurement errors, both over- and underestimating the tumor motion.

Comparison of breathing gated CT images generated using a 5DCT technique and a commercial clinical protocol in a porcine model.

PURPOSE: To demonstrate that a "5DCT" technique which utilizes fast helical acquisition yields the same respiratory-gated images as a commercial technique for regular, mechanically produced breathing cycles. METHODS: Respiratory-gated images of an anesthetized, mechanically ventilated pig were generated using a Siemens low-pitch helical protocol and 5DCT for a range of breathing rates and amplitudes and with standard and low dose imaging protocols. 5DCT reconstructions were independently evaluated by measuring the distances between tissue positions predicted by a 5D motion model and those measured using deformable registration, as well by reconstructing the originally acquired scans. Discrepancies between the 5DCT and commercial reconstructions were measured using landmark correspondences. RESULTS: The mean distance between model predicted tissue positions and deformably registered tissue positions over the nine datasets was 0.65 ± 0.28 mm. Reconstructions of the original scans were on average accurate to 0.78 ± 0.57 mm. Mean landmark displacement between the commercial and 5DCT images was 1.76 ± 1.25 mm while the maximum lung tissue motion over the breathing cycle had a mean value of 27.2 ± 4.6 mm. An image composed of the average of 30 deformably registered images acquired with a low dose protocol had 6 HU image noise (single standard deviation) in the heart versus 31 HU for the commercial images. CONCLUSIONS: An end to end evaluation of the 5DCT technique was conducted through landmark based comparison to breathing gated images acquired with a commercial protocol under highly regular ventilation. The techniques were found to agree to within 2 mm for most respiratory phases and most points in the lung.

Does the γ dose distribution comparison technique default to the distance to agreement test in clinical dose distributions?

PURPOSE: To determine the validity of the assumption that the γ dose distribution comparison tool defaults to the distance to agreement test under conditions of clinically relevant steep dose gradients and γ test criteria. METHODS: The assumption was tested by computing the angle θ between the dose axis and γ vector for clinical treatment plans. θ was a function of the evaluated dose distribution dose gradient and the ratio (α) of the dose difference to distance to agreement (DTA) criteria. Dose distributions from prostate, head and neck, and lung clinical treatment plans were examined: 50 treatment plans were selected for each of the prostate and head neck sites and 27 treatment plans were selected for lung. Dose-gradient histograms were prepared for each of the treatment plans using α = 1%/mm (e.g., 3%, 3 mm dose difference and DTA criteria, respectively). To determine how frequently different values of α were used in publications, papers that referenced the original γ paper were examined to identify the dose difference and DTA criteria used in those publications. In order to compare θ calculated using α = 1%/mm to θ for other values of α, the relationship between θ and α was determined. RESULTS: For most of the targets and critical structures, the maximum value of θ approached 90°, so the assumption that the γ tool defaulted to the DTA test in steep dose gradients was correct. Most of the published papers using the γ tool employed the 3%, 3 mm dose difference and DTA criteria, respectively. Most of the other evaluations used criteria such that α ≥ 1%/mm, so the conclusions relating to the examined dose distributions applied. There were a few papers employing very small values of α (including one where α = 0.17%/mm), breaking the assumption that the γ dose comparison tool defaulted to the DTA tool in steep dose gradients. CONCLUSIONS: Most published cases utilized values of α ≥ 1%/mm, and for those the implicit assumption that the γ dose comparison tool defaults to the DTA test in steep dose gradient regions was true. There were a few cases for which α was small enough to potentially invalidate this assumption. Care should be taken by investigators when selecting the γ test criteria to assure that the γ test will appropriately default to the DTA test in the steepest dose gradients being evaluated.

A client-server framework for 3D remote visualization of radiotherapy treatment space.

Radiotherapy is safely employed for treating wide variety of cancers. The radiotherapy workflow includes a precise positioning of the patient in the intended treatment position. While trained radiation therapists conduct patient positioning, consultation is occasionally required from other experts, including the radiation oncologist, dosimetrist, or medical physicist. In many circumstances, including rural clinics and developing countries, this expertise is not immediately available, so the patient positioning concerns of the treating therapists may not get addressed. In this paper, we present a framework to enable remotely located experts to virtually collaborate and be present inside the 3D treatment room when necessary. A multi-3D camera framework was used for acquiring the 3D treatment space. A client-server framework enabled the acquired 3D treatment room to be visualized in real-time. The computational tasks that would normally occur on the client side were offloaded to the server side to enable hardware flexibility on the client side. On the server side, a client specific real-time stereo rendering of the 3D treatment room was employed using a scalable multi graphics processing units (GPU) system. The rendered 3D images were then encoded using a GPU-based H.264 encoding for streaming. Results showed that for a stereo image size of 1280 × 960 pixels, experts with high-speed gigabit Ethernet connectivity were able to visualize the treatment space at approximately 81 frames per second. For experts remotely located and using a 100 Mbps network, the treatment space visualization occurred at 8-40 frames per second depending upon the network bandwidth. This work demonstrated the feasibility of remote real-time stereoscopic patient setup visualization, enabling expansion of high quality radiation therapy into challenging environments.

Dispersion control with reflection grisms of an ultra-broadband spectrum approaching a full octave.

We report the design, implementation, and characterization of a grism-pair stretcher in a near-infrared noncollinear optical parametric chirped-pulse amplifier (OPCPA) that is capable of controlling a bandwidth of 440 nm. Our dynamic dispersion control scheme relies on the grism stretcher working in conjunction with an acousto-optic programmable dispersive filter (Dazzler) to jointly compensate large amount of material dispersion. A spectral interference technique is used to characterize the spectral phase of the grism stretcher. This ultra-broadband device opens up the way to generate sub-2-cycle laser pulses.