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Genetic analysis of Physcomitrella patens identifies ABSCISIC ACID NON-RESPONSIVE , a regulator of ABA responses unique to basal land plants and required for desiccation tolerance

The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain. anr mutants fail to accumulate dehydration tolerance-associated gene products in response to drought, ABA, or osmotic stress and do not acquire ABA-dependent desiccation tolerance. The crystal structure of the PAS domain, determined to 1.7-Å resolution, shows a conserved PAS-fold that dimerizes through a weak dimerization interface. Targeted mutagenesis of a conserved tryptophan residue within the PAS domain generates plants with ABA nonresponsive growth and strongly attenuated ABA-responsive gene expression, whereas deleting this domain retains a fully ABA-responsive phenotype. ANR orthologs are found in early-diverging land plant lineages and aquatic algae but are absent from more recently diverged vascular plants. Lastly, we propose that ANR genes represent an ancestral adaptation that enabled drought stress survival of the first terrestrial colonizers but were lost during land plant evolution.

59 BASIC BIOLOGICAL SCIENCES↗

Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model

Purpose: Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors’ framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. Methods: The authors’ image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. Results: The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology—MRI fusion, in the context of an initial use case involving characterization of chronic inflammation in a mouse model. The authors’ evaluation considered three mice, two with an inflammation phenotype and one control. The authors’ iterative 3D histology reconstruction yielded a 70.1% ± 2.7% overlap with the ex vivo MRI volume. Across a total of 17 anatomic landmarks manually delineated at the division of airways, the target registration error between the ex vivo MRI and 3D histology reconstruction was 0.85 ± 0.44 mm, suggesting that a good alignment of the ex vivo 3D histology and ex vivo MRI had been achieved. The 3D histology-in vivo MRI coregistered volumes resulted in an overlap of 73.7% ± 0.9%. Preliminary computerized feature analysis was performed on an additional four control mice, for a total of seven mice considered in this study. Gabor texture filters appeared to best capture differences between the inflamed and noninflamed regions on MRI. Conclusions: The authors’ 3D histology reconstruction and multimodal registration framework were successfully employed to reconstruct the histology volume of the lung and fuse it with in vivo MRI to create a ground truth map for inflammation on in vivo MRI. The analytic platform presented here lays the framework for a rigorous validation of the identified imaging features for chronic lung inflammation on MRI in a large prospective cohort.

60 APPLIED LIFE SCIENCES↗

SU-E-J-251: Incorporation of Pre-Therapy 18F-FDG Uptake with CT Texture Features in a Predictive Model for Radiation Pneumonitis Development

Purpose: To determine whether the addition of standardized uptake value (SUV) statistical variables to CT lung texture features can improve a predictive model of radiation pneumonitis (RP) development in patients undergoing radiation therapy. Methods: Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were retrospectively collected including pre-therapy PET/CT scans, pre-/posttherapy diagnostic CT scans and RP status. Twenty texture features (firstorder, fractal, Laws’ filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. The mean, maximum, standard deviation, and 50th–95th percentiles of the SUV values for all lung voxels in the corresponding PET scans were acquired. For each texture feature, a logistic regression-based classifier consisting of (1) the average change in that texture feature value between the pre- and post-therapy CT scans and (2) the pre-therapy SUV standard deviation (SUV{sub SD}) was created. The RP-classification performance of each logistic regression model was compared to the performance of its texture feature alone by computing areas under the receiver operating characteristic curves (AUCs). T-tests were performed to determine whether the mean AUC across texture features changed significantly when SUV{sub SD} was added to the classifier. Results: The AUC for single-texturefeature classifiers ranged from 0.58–0.81 in high-dose (≥ 30 Gy) regions of the lungs and from 0.53–0.71 in low-dose (< 10 Gy) regions. Adding SUVSD in a logistic regression model using a 50/50 data partition for training and testing significantly increased the mean AUC by 0.08, 0.06 and 0.04 in the low-, medium- and high-dose regions, respectively. Conclusion: Addition of SUVSD from a pre-therapy PET scan to a single CT-based texture feature improves RP-classification performance on average. These findings demonstrate the potential for more accurate prediction of RP using information from multiple imaging modalities. Supported, in part, by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under grant number T32 EB002103; SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology. HA receives royalties through the University of Chicago for computer-aided diagnosis technology.

60 APPLIED LIFE SCIENCES↗

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

NASA Discipline Neuroscience↗

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter

Purpose: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Methods and Materials: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. Results: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of Δ{sub D} of 0 ± 5 cGy or %Δ{sub D} of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (−2 ± 5 cGy) or summed field percentage dose difference (−6% ± 7%). Conclusions: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Exploration Clinical Decision Support System: Medical Data Architecture

The Exploration Clinical Decision Support (ECDS) System project is intended to enhance the Exploration Medical Capability (ExMC) Element for extended duration, deep-space mission planning in HRP. A major development guideline is the Risk of "Adverse Health Outcomes & Decrements in Performance due to Limitations of In-flight Medical Conditions". ECDS attempts to mitigate that Risk by providing crew-specific health information, actionable insight, crew guidance and advice based on computational algorithmic analysis. The availability of inflight health diagnostic computational methods has been identified as an essential capability for human exploration missions. Inflight electronic health data sources are often heterogeneous, and thus may be isolated or not examined as an aggregate whole. The ECDS System objective provides both a data architecture that collects and manages disparate health data, and an active knowledge system that analyzes health evidence to deliver case-specific advice. A single, cohesive space-ready decision support capability that considers all exploration clinical measurements is not commercially available at present. Hence, this Task is a newly coordinated development effort by which ECDS and its supporting data infrastructure will demonstrate the feasibility of intelligent data mining and predictive modeling as a biomedical diagnostic support mechanism on manned exploration missions. The initial step towards ground and flight demonstrations has been the research and development of both image and clinical text-based computer-aided patient diagnosis. Human anatomical images displaying abnormal/pathological features have been annotated using controlled terminology templates, marked-up, and then stored in compliance with the AIM standard. These images have been filtered and disease characterized based on machine learning of semantic and quantitative feature vectors. The next phase will evaluate disease treatment response via quantitative linear dimension biomarkers that enable image content-based retrieval and criteria assessment. In addition, a data mining engine (DME) is applied to cross-sectional adult surveys for predicting occurrence of renal calculi, ranked by statistical significance of demographics and specific food ingestion. In addition to this precursor space flight algorithm training, the DME will utilize a feature-engineering capability for unstructured clinical text classification health discovery. The ECDS backbone is a proposed multi-tier modular architecture providing data messaging protocols, storage, management and real-time patient data access. Technology demonstrations and success metrics will be finalized in FY16.

Biomedical support↗

SU-E-I-33: Establishment of CT Diagnostic Reference Levels in Province Nova Scotia

Purpose: To evaluate patient radiation dose from the most frequently performed CT examinations and to establish provincial diagnostic reference levels (DRLs) as a tool for protocol optimization. Methods: The study investigated the following CT examinations: head, chest, abdomen/pelvis, and chest/abdomen/pelvis (CAP). Dose data, volume CT dose index (CTDIvol) and dose-length product (DLP), were collected from 15 CT scanners installed during 2004–2014 in 11 hospital sites of Nova Scotia. All scanners had dose modulation options and multislice capability (16–128 detector rows). The sample for each protocol included 15 average size patients (70±20 kg). Provincial DRLs were calculated as the 75th percentile of patient dose distributions. The differences in dose between hospitals were evaluated with a single factor ANOVA statistical test. Generalized linear modeling was used to determine the factors associated with higher radiation dose. A sample of 36 abdominal studies performed on three different scanners was blinded and randomized for an assessment by an experienced radiologist who graded the imaging quality of anatomic structures. Results: Data for 900 patients were collected. The DRLs were proposed using CTDIvol (mGy) and DLP (mGy*cm) values for CT head (67 and 1049, respectively), chest (12 and 393), abdomen/pelvis (16 and 717), and CAP (14 and 1034). These DRLs were lower than the published national data except for the head CTDIvol. The differences between the means of the dose distributions from each scanner were statistically significant (p<0.05) for all examinations. A very weak correlation was found between the dose and the scanner age or the number of slices with Pearson’s correlation coefficients of 0.011–0.315. The blinded analysis of image quality demonstrated no clinically significant difference except for the noise category. Conclusion: Provincial DRLs were established for typical CT examinations. The variations in dose between the hospitals suggested a large potential for optimization of examinations. Radiology Research Foundation grant.

60 APPLIED LIFE SCIENCES↗

Spectrotemporal CT data acquisition and reconstruction at low dose

Purpose: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D + dual energy + time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. Methods: The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction problem using the split Bregman method and GPU-based implementations of backprojection, reprojection, and kernel regression. Using a preclinical mouse model, the authors apply the proposed algorithm to study myocardial injury following radiation treatment of breast cancer. Results: Quantitative 5D simulations are performed using the MOBY mouse phantom. Twenty data sets (ten cardiac phases, two energies) are reconstructed with 88 μm, isotropic voxels from 450 total projections acquired over a single 360° rotation. In vivo 5D myocardial injury data sets acquired in two mice injected with gold and iodine nanoparticles are also reconstructed with 20 data sets per mouse using the same acquisition parameters (dose: ∼60 mGy). For both the simulations and the in vivo data, the reconstruction quality is sufficient to perform material decomposition into gold and iodine maps to localize the extent of myocardial injury (gold accumulation) and to measure cardiac functional metrics (vascular iodine). Their 5D CT imaging protocol represents a 95% reduction in radiation dose per cardiac phase and energy and a 40-fold decrease in projection sampling time relative to their standard imaging protocol. Conclusions: Their 5D CT data acquisition and reconstruction protocol efficiently exploits the rank-sparse nature of spectral and temporal CT data to provide high-fidelity reconstruction results without increased radiation dose or sampling time.

60 APPLIED LIFE SCIENCES↗

Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. Results: The mean TRE (and standard deviation) was 0.6 ± 0.7 mm (smaller than the voxel dimension) for DIR between pre contrast and postcontrast end-inspiratory CT image data sets. No singularities were observed in the displacement vector fields. The mean HU enhancement (and standard deviation) was 37.3 ± 10.5 HU for normal lung subjects and 30.7 ± 13.5 HU for diseased lung subjects. Spatial heterogeneity of regional perfusion was found to be higher for diseased lung subjects than for normal lung subjects, i.e., a mean coefficient of variation of 2.06 vs 1.59 (p = 0.07). The average gravitationally directed gradient was strong and significant (R{sup 2} = 0.99, p < 0.01) for normal lung dogs, whereas it was moderate and nonsignificant (R{sup 2} = 0.61, p = 0.12) for diseased lung dogs. Conclusions: This canine study demonstrated the accuracy of DIR with subvoxel TREs on average, higher spatial heterogeneity of regional perfusion for diseased lung subjects than for normal lung subjects, and a strong gravitationally directed gradient for normal lung subjects, providing proof-of-principle for single-energy CT pulmonary perfusion imaging. Further studies such as comparison with other perfusion imaging modalities will be necessary to validate the physiological significance.

60 APPLIED LIFE SCIENCES↗

Computational Hemodynamic Simulation of Human Circulatory System under Altered Gravity

A computational hemodynamics approach is presented to simulate the blood flow through the human circulatory system under altered gravity conditions. Numerical techniques relevant to hemodynamics issues are introduced to non-Newtonian modeling for flow characteristics governed by red blood cells, distensible wall motion due to the heart pulse, and capillary bed modeling for outflow boundary conditions. Gravitational body force terms are added to the Navier-Stokes equations to study the effects of gravity on internal flows. Six-type gravity benchmark problems are originally presented to provide the fundamental understanding of gravitational effects on the human circulatory system. For code validation, computed results are compared with steady and unsteady experimental data for non-Newtonian flows in a carotid bifurcation model and a curved circular tube, respectively. This computational approach is then applied to the blood circulation in the human brain as a target problem. A three-dimensional, idealized Circle of Willis configuration is developed with minor arteries truncated based on anatomical data. Demonstrated is not only the mechanism of the collateral circulation but also the effects of gravity on the distensible wall motion and resultant flow patterns.

Kim. Chang Sung↗

Clinical Implementation of a Model-Based In Vivo Dose Verification System for Stereotactic Body Radiation Therapy–Volumetric Modulated Arc Therapy Treatments Using the Electronic Portal Imaging Device

Purpose: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically. Methods and Materials: From December 2013 to July 2016, 117 stereotactic body radiation therapy–volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB–predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors. Results: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively. Conclusions: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Personalized and uncertainty-aware coronary hemodynamics simulations: From Bayesian estimation to improved multi-fidelity uncertainty quantification

Non-invasive simulations of coronary hemodynamics have improved clinical risk stratification and treatment outcomes for coronary artery disease, compared to relying on anatomical imaging alone. However, simulations typically use empirical approaches to distribute total coronary flow amongst the arteries in the coronary tree, which ignores patient variability, the presence of disease, and other clinical factors. Further, uncertainty in the clinical data often remains unaccounted for in the modeling pipeline. We present an end-to-end uncertainty-aware pipeline to (1) personalize coronary flow simulations by incorporating vessel-specific coronary flows as well as cardiac function; and (2) predict clinical and biomechanical quantities of interest with improved precision, while accounting for uncertainty in the clinical data. We assimilate patient-specific measurements of myocardial blood flow from clinical CT myocardial perfusion imaging to estimate branch-specific coronary artery flows. Simulated noise in the clinical data is used to estimate the joint posterior distributions of the model parameters using adaptive Markov Chain Monte Carlo sampling. Additionally, the posterior predictive distribution for the relevant quantities of interest is determined using a new approach combining multi-fidelity Monte Carlo estimation with non-linear, data-driven dimensionality reduction. This leads to improved correlations between high- and low-fidelity model outputs. Our framework accurately recapitulates clinically measured cardiac function as well as branch-specific coronary flows under measurement noise uncertainty. We observe substantial reductions in confidence intervals for estimated quantities of interest compared to single-fidelity Monte Carlo estimation and state-of-the-art multi-fidelity Monte Carlo methods. This holds especially true for quantities of interest that showed limited correlation between the low- and high-fidelity model predictions. In addition, the proposed multi-fidelity Monte Carlo estimators are significantly cheaper to compute than traditional estimators, under a specified confidence level or variance. The proposed pipeline for personalized and uncertainty-aware predictions of coronary hemodynamics is based on routine clinical measurements and recently developed techniques for CT myocardial perfusion imaging. The proposed pipeline offers significant improvements in precision and reduction in computational cost.

Bayesian parameter estimation↗

Phonetic acquisition in cortical dynamics, a computational approach

Many computational theories have been developed to improve artificial phonetic classification performance from linguistic auditory streams. However, less attention has been given to psycholinguistic data and neurophysiological features recently found in cortical tissue. We focus on a context in which basic linguistic units-such as phonemes-are extracted and robustly classified by humans and other animals from complex acoustic streams in speech data. We are especially motivated by the fact that 8-month-old human infants can accomplish segmentation of words from fluent audio streams based exclusively on the statistical relationships between neighboring speech sounds without any kind of supervision. In this paper, we introduce a biologically inspired and fully unsupervised neurocomputational approach that incorporates key neurophysiological and anatomical cortical properties, including columnar organization, spontaneous micro-columnar formation, adaptation to contextual activations and Sparse Distributed Representations (SDRs) produced by means of partial N-Methyl-D-aspartic acid (NMDA) depolarization. Its feature abstraction capabilities show promising phonetic invariance and generalization attributes. Our model improves the performance of a Support Vector Machine (SVM) classifier for monosyllabic, disyllabic and trisyllabic word classification tasks in the presence of environmental disturbances such as white noise, reverberation, and pitch and voice variations. Furthermore, our approach emphasizes potential self-organizing cortical principles achieving improvement without any kind of optimization guidance which could minimize hypothetical loss functions by means of-for example-backpropagation. Thus, our computational model outperforms multiresolution spectro-temporal auditory feature representations using only the statistical sequential structure immerse in the phonotactic rules of the input stream.

60 APPLIED LIFE SCIENCES↗

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections

Purpose: Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Methods: Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the “gold-standard” on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔD{sub min}), maximum dose (ΔD{sub max}), and mean dose (ΔD{sub mean}), and the absolute deviations of prescription dose coverage (ΔV{sub 100%}) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Results: Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). Conclusions: MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.

60 APPLIED LIFE SCIENCES↗

A Data-Driven Framework for Predicting the Sorting and Screening Performance of an Integrated Biomass Feedstock Preprocessing System

The characteristics of mechanically sorted and screened lignocellulosic biomass, such as the mass contents of corn stover anatomical fractions (leaves, husks, stalks, cobs, etc.), can be used to calculate the intermediate feedstock quality attributes “yield” and “purity” that indicate the conversion efficiency of biocrude. No prior study has investigated the correlations from the characteristics of raw biomass and preprocessing unit operation parameters to those intermediate feedstock quality attributes. This work presents a data-driven framework for assessing and predicting the intermediate feedstock quality attributes in an integrated biomass feedstock preprocessing system. Our study used corn stover as a typical type of herbaceous biomass because of its abundance in the U.S. It began with data acquisition of moisture content, particle size distribution, and anatomical fractions of the materials after each unit operation in the system. The objective of this preprocessing system is to minimize husks and leaves and maximizing cobs and stalks by mechanically separating the materials into three streams via disc screen and air separator. Prototype neural network models were then developed to evaluate the feasibility of predicting process outcomes based on measurable parameters. It is found that incorporating physical constraints into these prediction models significantly enhances the accuracy of the predicted yield and purity against the ground truth data. The experimental data and model predictions indicate that decreasing throughput increases purity, while higher throughput results in lower purity. Finally, an optimization problem was introduced to search optimal combinations of feed material properties and preprocessing unit operation parameters, as the intermediate feedstock quality attributes – yield and purity, appeared to be competing factors. The study also suggests the continual need to improve the data-driven framework’s predictability by incorporating more accurate physical models to describe the dynamics in the preprocessing units such as the air separator.

09 - BIOMASS FUELS↗

In vivo nuclear magnetic resonance imaging

A number of physiological changes have been demonstrated in bone, muscle and blood after exposure of humans and animals to microgravity. Determining mechanisms and the development of effective countermeasures for long duration space missions is an important NASA goal. The advent of tomographic nuclear magnetic resonance imaging (NMR or MRI) gives NASA a way to greatly extend early studies of this phenomena in ways not previously possible; NMR is also noninvasive and safe. NMR provides both superb anatomical images for volume assessments of individual organs and quantification of chemical/physical changes induced in the examined tissues. The feasibility of NMR as a tool for human physiological research as it is affected by microgravity is demonstrated. The animal studies employed the rear limb suspended rat as a model of mucle atrophy that results from microgravity. And bedrest of normal male subjects was used to simulate the effects of microgravity on bone and muscle.

Leblanc, A.↗

Optimized 3D co-registration of ultra-low-field and high-field magnetic resonance images

The prototypes of ultra-low-field (ULF) MRI scanners developed in recent years represent new, innovative, cost-effective and safer systems, which are suitable to be integrated in multi-modal (Magnetoencephalography and MRI) devices. Integrated ULF-MRI and MEG scanners could represent an ideal solution to obtain functional (MEG) and anatomical (ULF MRI) information in the same environment, without errors that may limit source reconstruction accuracy. However, the low resolution and signal-to-noise ratio (SNR) of ULF images, as well as their limited coverage, do not generally allow for the construction of an accurate individual volume conductor model suitable for MEG localization. Thus, for practical usage, a high-field (HF) MRI image is also acquired, and the HF-MRI images are co-registered to the ULF-MRI ones. We address here this issue through an optimized pipeline (SWIM—Sliding WIndow grouping supporting Mutual information). The co-registration is performed by an affine transformation, the parameters of which are estimated using Normalized Mutual Information as the cost function, and Adaptive Simulated Annealing as the minimization algorithm. The sub-voxel resolution of the ULF images is handled by a sliding-window approach applying multiple grouping strategies to down-sample HF MRI to the ULF-MRI resolution. The pipeline has been tested on phantom and real data from different ULF-MRI devices, and comparison with well-known toolboxes for fMRI analysis has been performed. Our pipeline always outperformed the fMRI toolboxes (FSL and SPM). The HF–ULF MRI co-registration obtained by means of our pipeline could lead to an effective integration of ULF MRI with MEG, with the aim of improving localization accuracy, but also to help exploit ULF MRI in tumor imaging.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

TU-AB-303-11: Predict Parotids Deformation Applying SIS Epidemiological Model in H&N Adaptive RT

Purpose: The aim is to investigate the use of epidemiological models to predict morphological variations in patients undergoing radiation therapy (RT). The susceptible-infected-susceptible (SIS) deterministic model was applied to simulate warping within a focused region of interest (ROI). Hypothesis is to consider each voxel like a single subject of the whole sample and to treat displacement vector fields like an infection. Methods: Using Raystation hybrid deformation algorithms and automatic re-contouring based on mesh grid, we post-processed 360 MVCT images of 12 H&N patients treated with Tomotherapy. Study focused on parotid glands, identified by literature and previous analysis, as ROI more susceptible to warping in H&N region. Susceptible (S) and infectious (I) cases were identified in voxels with inter-fraction movement respectively under and over a set threshold. IronPython scripting allowed to export positions and displacement data of surface voxels for every fraction. A MATLAB homemade toolbox was developed to model the SIS. Results: SIS model was validated simulating organ motion on QUASAR phantom. Applying model in patients, within a [0–1cm] range, a single voxel movement of 0.4cm was selected as displacement threshold. SIS indexes were evaluated by MATLAB simulations. Dynamic time warping algorithm was used to assess matching between model and parotids behavior days of treatments. The best fit of the model was obtained with contact rate of 7.89±0.94 and recovery rate of 2.36±0.21. Conclusion: SIS model can follow daily structures evolutions, making possible to compare warping conditions and highlighting challenges due to abnormal variation and set-up errors. By epidemiology approach, organ motion could be assessed and predicted not in terms of average of the whole ROI, but in a voxel-by-voxel deterministic trend. Identifying anatomical region subjected to variations, would be possible to focus clinic controls within a cohort of pre-selected patients eligible for adaptive RT. The research is partially co-funded by the Italian Research Grant: Dose warping methods for IGRT and Adaptive RT: dose accumulation based on organ motion and anatomical variations of the patients during radiation therapy treatments,MoH (GR-2010-2318757) and Tecnologie Avanzate S.r.l.(Italy)

60 APPLIED LIFE SCIENCES↗