Resolving microsatellite genotype ambiguity in populations of allopolyploid and diploidized autopolyploid organisms using negative correlations between allelic variables
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Biochemistry & Molecular Biology↗
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Media matters! Alterations in the loading and release of Histoplasma capsulatum extracellular vesicles in response to different nutritional milieus
Histoplasma capsulatum is a dimorphic fungus that most frequently causes pneumonia, but can also disseminate and proliferate in diverse tissues. H. capsulatum has a complex secretion system that mediates the release of macromolecule-degrading enzymes and virulence factors. The formation and release of extracellular vesicles (EVs) are an important mechanism for non-conventional secretion in both ascomycetes and basidiomycetes. H. capsulatum EVs contain diverse proteins associated with virulence and are immunologically active. Despite the growing knowledge of EVs from H. capsulatum and other pathogenic fungi, the extent that changes in the environment impact the sorting of organic molecules in EVs has not been investigated. In our research, we cultivated H. capsulatum with distinct culture media to investigate the potential plasticity in EV loading in response to differences in nutrition. Our findings reveal that nutrition plays an important role in EV loading and formation, which may translate into differences in biological activities of these fungi in various fluids and tissues.
59 BASIC BIOLOGICAL SCIENCES↗
An integrative framework reveals widespread gene flow during the early radiation of oaks and relatives in Quercoideae (Fagaceae)
ABSTRACT Although the frequency of ancient hybridization across the Tree of Life is greater than previously thought, little work has been devoted to uncovering the extent, timeline, and geographic and ecological context of ancient hybridization. Using an expansive new dataset of nuclear and chloroplast DNA sequences, we conducted a multifaceted phylogenomic investigation to identify ancient reticulation in the early evolution of oaks (Quercus). We document extensive nuclear gene tree and cytonuclear discordance among major lineages ofQuercusand relatives in Quercoideae. Our analyses recovered clear signatures of gene flow against a backdrop of rampant incomplete lineage sorting, with gene flow most prevalent among major lineages ofQuercusand relatives in Quercoideae during their initial radiation, dated to the Early‐Middle Eocene. Ancestral reconstructions including fossils suggest ancestors ofCastanea + Castanopsis,Lithocarpus, and the Old World oak clade probably co‐occurred in North America and Eurasia, while the ancestors ofChrysolepis, Notholithocarpus, and the New World oak clade co‐occurred in North America, offering ample opportunity for hybridization in each region. Our study shows that hybridization—perhaps in the form of ancient syngameons like those seen today—has been a common and important process throughout the evolutionary history of oaks and their relatives. Concomitantly, this study provides a methodological framework for detecting ancient hybridization in other groups.
Biochemistry & Molecular Biology↗
Phylogenomic analysis of the hemp family (Cannabaceae) reveals deep cyto‐nuclear discordance and provides new insights into generic relationships
Abstract Cannabaceae are a relatively small family of angiosperms, but they include several species of huge economic and cultural significance: marijuana or hemp ( Cannabis sativa ) and hops ( Humulus lupulus ). Previous phylogenetic studies have clarified the most deep relationships in Cannabaceae, but relationships remain ambiguous among several major lineages. Here, we sampled 82 species representing all genera of Cannabaceae and utilized a new dataset of 90 nuclear genes and 82 chloroplast loci from Hyb‐Seq to investigate the phylogenomics of Cannabaceae. Nuclear phylogenetic analyses revealed a robust and consistent backbone for Cannabaceae. We observed nuclear gene‐tree conflict at several deep nodes in inferred species trees, also cyto‐nuclear discordance concerning the relationship between Gironniera and Lozanella and the relationships among Trema s.l. (including Parasponia ), Cannabis + Humulus , and Chaetachme + Pteroceltis . Coalescent simulations and network analyses suggest that observed deep cyto‐nuclear discordances were most likely to stem from incomplete lineage sorting (ILS); nuclear gene‐tree conflict might be caused by both ILS and gene flow between species. All genera of Cannabaceae were recovered as monophyletic, except for Celtis , which consisted of two distinct clades: Celtis I (including most Celtis species) and Celtis II (including Celtis gomphophylla and Celtis schippii ). We suggest that Celtis II should be recognized as the independent genus Sparrea based on both molecular and morphological evidence. Our work provides the most comprehensive and reliable phylogeny to date for Cannabaceae, enabling further exploration of evolutionary patterns across this family and highlighting the necessity of comparing nuclear with chloroplast data to examine the evolutionary history of plant groups.
Plant Sciences↗
Hf‐W chronology of a macrochondrule from the L5/6 chondrite Northwest Africa 8192
Abstract A large, igneous‐textured, and 2 cm‐sized spherical object from the L5/6 chondrite NWA 8192 was investigated for its chemical composition, petrography, O isotopic composition, and Hf‐W chronology. The petrography and chemical data indicate that this object closely resembles commonly found chondrules in ordinary chondrites and is therefore classified as a “macrochondrule.* As a result of metal loss during its formation, the macrochondrule exhibits elevated Hf/W, which makes it possible to date this object using the short‐lived 182 Hf‐ 182 W system. The Hf‐W data provide a two‐stage model age for metal–silicate fractionation of 1.4 ± 0.6 Ma after Ca‐Al‐rich inclusion (CAI) formation, indicating that the macrochondrule formed coevally to normal‐sized chondrules from ordinary chondrites. By contrast, Hf‐W data for metal from the host chondrite yield a younger model age of ~11 Ma after CAIs. This younger age agrees with Hf‐W ages of other type 5–6 ordinary chondrites, and corresponds to the time of cooling below the Hf‐W closure temperature during thermal metamorphism on the parent body. The Hf‐W model age difference between the macrochondrule and the host metal demonstrates that the Hf‐W systematics of the bulk macrochondrule were not disturbed during thermal metamorphism, and therefore, that the formation age of such objects can still be determined even in strongly metamorphosed samples. Collectively, this study illustrates that chondrule formation was not limited to mm‐size objects, implying that the rarity of macrochondrules reflects either that this process was very inefficient, that subsequent nebular size‐sorting decimated large chondrules, or that large precursors were rare.
58 GEOSCIENCES↗
Building bridges between neuroscience, cognition and education with predictive modeling
As the field of Mind, Brain, and Education seeks new ways to credibly bridge the gap between neuroscience, the cognitive sciences, and education, various connections are being developed and tested. In this article, we present a framework and offers examples of one approach, predictive modeling within a virtual educational system that can include representations from the neural level to the policy level. Researchers could calibrate, test, and question the model, potentially providing quicker, more efficient, and more responsible ways of making advances in the developing educational field. Likewise, virtual investigations using models with this sort of capability can supplement the valuable information derived from carrying out policy and instructional experiments in real educational contexts.
60 APPLIED LIFE SCIENCES↗
Use of virus‐induced gene silencing to characterize genes involved in modulating hypersensitive cell death in maize
Abstract Plant disease resistance proteins (R‐proteins) detect specific pathogen‐derived molecules, triggering a defence response often including a rapid localized cell death at the point of pathogen penetration called the hypersensitive response (HR). The maize Rp1‐D21 gene encodes a protein that triggers a spontaneous HR causing spots on leaves in the absence of any pathogen. Previously, we used fine mapping and functional analysis in a Nicotiana benthamiana transient expression system to identify and characterize a number of genes associated with variation in Rp1‐D21 ‐induced HR. Here we describe a system for characterizing genes mediating HR, using virus‐induced gene silencing (VIGS) in a maize line carrying Rp1‐D21 . We assess the roles of 12 candidate genes. Three of these genes, SGT1 , RAR1 , and HSP90 , are required for HR induced by a number of R‐proteins across several plant–pathogen systems. We confirmed that maize HSP90 was required for full Rp1‐D21 ‐induced HR. However, suppression of SGT1 expression unexpectedly increased the severity of Rp1‐D21 ‐induced HR while suppression of RAR1 expression had no measurable effect. We confirmed the effects on HR of two genes we had previously validated in the N. benthamiana system, hydroxycinnamoyltransferase and caffeoyl CoA O‐methyltransferase . We further showed the suppression the expression of two previously uncharacterized, candidate genes, IQ calmodulin binding protein ( IQM3 ) and vacuolar protein sorting protein 37 , suppressed Rp1‐D21 ‐induced HR. This approach is an efficient way to characterize the roles of genes modulating the hypersensitive defence response and other dominant lesion phenotypes in maize.
59 BASIC BIOLOGICAL SCIENCES↗
Linking plant hydraulics and beta diversity in tropical forests
In tropical forests, studies of xylem traits governing water transport through plants, or ‘hydraulic architecture’ (Tyree et al., 1991), and changes in species composition across environmental gradients, or ‘beta diversity’ (Gentry, 1988; Ackerly & Cornwell, 2007), have progressedmostly in parallel until recently (Hao et al., 2008; Bartlett et al., 2016). In this issue of New Phytologist, Cosme et al. (pp. 000–5 000) present a timely contribution to the intersection of plant hydraulic architecture (HA) with trait-based community ecology. Building on previous biogeographical work that demonstrated shifts in species composition (beta diversity) across a gradient from valleys to plateaus in central Amazonia (Schietti et al., 2014), Cosme et al. explore how variation in HA might underpin this sorting, sampling pairs of congeneric species restrictedmostly to either plateau or valley habitats. Valley species had significantly lower wood density and higher hydraulically-weighted vessel diameter and vessel area. By contrast, trees with some of the largest hydraulically-weighted vessel diameters existed in tall, deciduous plateau species, while the leaf: sapwood area ratio decreased with height in valley but not plateau species. These intriguing results suggest that species differentiation in water transport traits mediate edaphic filtering along the valley-toplateau gradient, in contrast to previous work where wood mechanical support mediated valley-to-plateau environmental filtering (Fortunel et al., 2014).
Christoffersen, Bradley↗
Expression quantitative trait loci mapping identified PtrXB38 as a key hub gene in adventitious root development in Populus
Summary Plant establishment requires the formation and development of an extensive root system with architecture modulated by complex genetic networks. Here, we report the identification of the PtrXB38 gene as an expression quantitative trait loci (eQTL) hotspot, mapped using 390 leaf and 444 xylem Populus trichocarpa transcriptomes. Among predicted targets of this trans ‐eQTL were genes involved in plant hormone responses and root development. Overexpression of PtrXB38 in Populus led to significant increases in callusing and formation of both stem‐born roots and base‐born adventitious roots. Omics studies revealed that genes and proteins controlling auxin transport and signaling were involved in PtrXB38‐mediated adventitious root formation. Protein–protein interaction assays indicated that PtrXB38 interacts with components of endosomal sorting complexes required for transport machinery, implying that PtrXB38‐regulated root development may be mediated by regulating endocytosis pathway. Taken together, this work identified a crucial root development regulator and sheds light on the discovery of other plant developmental regulators through combining eQTL mapping and omics approaches.
54 ENVIRONMENTAL SCIENCES↗
Functionally discrete fine roots differ in microbial assembly, microbial functional potential, and produced metabolites
Traditionally, fine roots were grouped using arbitrary size categories, rarely capturing the heterogeneity in physiology, morphology and functionality among different fine root orders. Fine roots with different functional roles are rarely separated in microbiome-focused studies and may result in confounding microbial signals and host-filtering across different root microbiome compartments. Using a 26-year-old common garden, we sampled fine roots from four temperate tree species that varied in root morphology and sorted them into absorptive and transportive fine roots. The rhizoplane and rhizosphere were characterized using 16S rRNA gene and internal transcribed spacer region amplicon sequencing and shotgun metagenomics for the rhizoplane to identify potential microbial functions. Fine roots were subject to metabolomics to spatially characterize resource availability. Both fungi and bacteria differed according to root functional type. We observed additional differences between the bacterial rhizoplane and rhizosphere compartments for absorptive but not transportive fine roots. Rhizoplane bacteria, as well as the root metabolome and potential microbial functions, differed between absorptive and transportive fine roots, but not the rhizosphere bacteria. Functional differences were driven by sugar transport, peptidases and urea transport. Our data highlights the importance of root function when examining root-microbial relationships, emphasizing different host selective pressures imparted on different root microbiome compartments.
59 BASIC BIOLOGICAL SCIENCES↗
Incineration of European non-nuclear radioactive waste in the USA
Incineration of dry low level radioactive waste from nuclear stations is a well established process achieving high volume reduction factors to minimise disposal costs and to stabilise residues for disposal. Incineration has also been applied successfully in many European Union member countries to wastes arising from use of radionuclides in medicine, nonnuclear research and industry. However, some nations have preferred to accumulate wastes over many years in decay stores to reduce the radioactive burden at point of processing. After decay and sorting the waste, they then require a safe, industrial scale and affordable processing solution for the large volumes accumulated. This paper reports the regulatory, logistical and technical issues encountered in a programme delivered for Eckert and Ziegler Nuclitec to incinerate safely 100 te of waste collected originally from German research, hospital and industrial centres, applying for the first time a 'burn and return' process model for European waste in the US. The EnergySolutions incinerators at Bear Creek, Oak Ridge, Tennessee, USA routinely incinerate waste arising from the non-nuclear user community. To address the requirement from Germany, EnergySolutions had to run a dedicated campaign to reduce cross-contamination with non-German radionuclides to the practical minimum. The waste itself had to be sampled in a carefully controlled programme to ensure the exacting standards of Bear Creek's license and US emissions laws were maintained. Innovation was required in packaging of the waste to minimise transportation costs, including sea freight. The incineration was inspected on behalf of the German regulator (the BfS) to ensure suitability for return to Germany and disposal. This first 'burn and return' programme has safely completed the incineration phase in February and the arising ash will be returned to Germany presently. The paper reports the main findings and lessons learned on this first of its kind project. (authors)
12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
Data Analytics Applied to Coal Fired Boilers for Detecting Leaks
Data analytics were used to detect boiler leaks from five different coal-fired boilers including both subcritical and supercritical systems. Discriminant functions were developed that detected leaks up to two weeks prior to forced plant shutdowns for repairs. The leaks were identified to occur at different sections of the boiler for each plant, including waterwalls, economizer and superheater using conventional process measurement data. Leaking conditions were detected with a high degree of confidence (≪ 1% misclassified observations) and were able to distinguish normal operations from those time periods with steam leaks even while operating the power plants in power cycling mode.Multivariable statistical analyses, including Principal Component (PCA), cluster, and Fischer Discriminant Analysis (FDA) were used to characterize the leak occurrence. Normal and operational states with steam leaks were provided in the original process datasets. These datasets were split into two different groups for training and validation purposes. The data were sorted chronologically, and every third observation was assigned to training the Discriminant Function Model (DFM) while the rest were reserved for validation. PCA was used to reduce dimensionality of the original datasets. Canonical and FDA analyses were used to investigate the relationship between process variables. The outcome of the analyses revealed that nearly 35,000 observations were classified correctly; less than 0.05% of total observations were misclassified to be leaking, i.e. both false positives and false negatives.
Indrawan, Natarianto↗
Spatial and dose–response analysis of fibrotic lung changes after stereotactic body radiation therapy
Purpose: Stereotactic body radiation therapy (SBRT) is becoming the standard of care for early stage nonoperable lung cancers. Accurate dose–response modeling is challenging for SBRT because of the decreased number of clinical toxicity events. As a surrogate for a clinical toxicity endpoint, studies have proposed to use radiographic changes in follow up computed tomography (CT) scans to evaluate lung SBRT normal tissue effects. The purpose of the current study was to use local fibrotic lung regions to spatially and dosimetrically evaluate lung changes in patients that underwent SBRT.Methods: Forty seven SBRT patients treated at our institution from 2003 to 2009 were used for the current study. Our patient cohort had a total of 148 follow up CT scans ranging from 3 to 48 months post-therapy. Post-treatment scans were binned into intervals of 3, 6, 12, 18, 24, 30, and 36 months after the completion of treatment. Deformable image registration was used to align the follow up CT scans with the pretreatment CT and dose distribution. Areas of visible fibrotic changes were contoured. The centroid of each gross tumor volume (GTV) and contoured fibrosis volume was calculated and the fibrosis volume location and movement (magnitude and direction) relative to the GTV and 30 Gy isodose centroid were analyzed. To perform a dose–response analysis, each voxel in the fibrosis volume was sorted into 10 Gy dose bins and the average CT number value for each dose bin was calculated. Dose–response curves were generated by plotting the CT number as a function of dose bin and time posttherapy.Results: Both fibrosis and GTV centroids were concentrated in the upper third of the lung. The average radial movement of fibrosis centroids relative to the GTV centroids was 2.6 cm with movement greater than 5 cm occurring in 11% of patients. Evaluating dose–response curves revealed an overall trend of increasing CT number as a function of dose. The authors observed a CT number plateau at doses ranging from 30 to 50 Gy for the 3, 6, and 12 months posttherapy time points. There was no evident plateau for the dose–response curves generated using data from the 18, 24, 30, and 36 months posttherapy time points.Conclusions: Regions of local fibrotic lung changes in patients that underwent SBRT were evaluated spatially and dosimetrically. The authors found that the average fibrosis movement was 2.6 cm with movement greater than 5 cm possible. Evaluating dose–response curves revealed an overall trend of increasing CT number as a function of dose. Furthermore, our dose–response data also suggest that one of the possible explanations of the CT number plateau effect may be the time posttherapy of the acquired data. Understanding normal tissue dose–response is important for reducing toxicity after SBRT, especially in cases where larger tumors are treated. The methods presented in the current work build on prior quantitative studies and further enhance the understanding of normal lung dose–response after SBRT.
61 RADIATION PROTECTION AND DOSIMETRY↗
Motion-map constrained image reconstruction (MCIR): Application to four-dimensional cone-beam computed tomography
Purpose: Utilization of respiratory correlated four-dimensional cone-beam computed tomography (4DCBCT) has enabled verification of internal target motion and volume immediately prior to treatment. However, with current standard CBCT scan, 4DCBCT poses challenge for reconstruction due to the fact that multiple phase binning leads to insufficient number of projection data to reconstruct and thus cause streaking artifacts. The purpose of this study is to develop a novel 4DCBCT reconstruction algorithm framework called motion-map constrained image reconstruction (MCIR), that allows reconstruction of high quality and high phase resolution 4DCBCT images with no more than the imaging dose as well as projections used in a standard free breathing 3DCBCT (FB-3DCBCT) scan.Methods: The unknown 4DCBCT volume at each phase was mathematically modeled as a combination of FB-3DCBCT and phase-specific update vector which has an associated motion-map matrix. The motion-map matrix, which is the key innovation of the MCIR algorithm, was defined as the matrix that distinguishes voxels that are moving from stationary ones. This 4DCBCT model was then reconstructed with compressed sensing (CS) reconstruction framework such that the voxels with high motion would be aggressively updated by the phase-wise sorted projections and the voxels with less motion would be minimally updated to preserve the FB-3DCBCT. To evaluate the performance of our proposed MCIR algorithm, we evaluated both numerical phantoms and a lung cancer patient. The results were then compared with the (1) clinical FB-3DCBCT reconstructed using the FDK, (2) 4DCBCT reconstructed using the FDK, and (3) 4DCBCT reconstructed using the well-known prior image constrained compressed sensing (PICCS).Results: Examination of the MCIR algorithm showed that high phase-resolved 4DCBCT with sets of up to 20 phases using a typical FB-3DCBCT scan could be reconstructed without compromising the image quality. Moreover, in comparison with other published algorithms, the image quality of the MCIR algorithm is shown to be excellent.Conclusions: This work demonstrates the potential for providing high-quality 4DCBCT during on-line image-guided radiation therapy (IGRT), without increasing the imaging dose. The results showed that (at least) 20 phase images could be reconstructed using the same projections data, used to reconstruct a single FB-3DCBCT, without streak artifacts that are caused by insufficient projections.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Evaluation of a semiautomated lung mass calculation technique for internal dosimetry applications
Purpose: The authors sought to evaluate a simple, semiautomated lung mass estimation method using computed tomography (CT) scans obtained using a variety of acquisition techniques and reconstruction parameters for mass correction of medical internal radiation dose-based internal radionuclide radiation absorbed dose estimates.Methods: CT scans of 27 patients with lung cancer undergoing stereotactic body radiation therapy treatment planning with PET/CT were analyzed retrospectively. For each patient, free-breathing (FB) and respiratory-gated 4DCT scans were acquired. The 4DCT scans were sorted into ten respiratory phases, representing one complete respiratory cycle. An average CT reconstruction was derived from the ten-phase reconstructions. Mid expiration breath-hold CT scans were acquired in the same session for many patients. Deep inspiration breath-hold diagnostic CT scans of many of the patients were obtained from different scanning sessions at similar time points to evaluate the effect of contrast administration and maximum inspiration breath-hold. Lung mass estimates were obtained using all CT scan types, and intercomparisons made to assess lung mass variation according to scan type. Lung mass estimates using the FB CT scans from PET/CT examinations of another group of ten male and ten female patients who were 21–30 years old and did not have lung disease were calculated and compared with reference lung mass values. To evaluate the effect of varying CT acquisition and reconstruction parameters on lung mass estimation, an anthropomorphic chest phantom was scanned and reconstructed with different CT parameters. CT images of the lungs were segmented using the OsiriX MD software program with a seed point of about −850 HU and an interval of 1000. Lung volume, and mean lung, tissue, and air HUs were recorded for each scan. Lung mass was calculated by assuming each voxel was a linear combination of only air and tissue. The specific gravity of lung volume was calculated using the formula (lung HU − air HU)/(tissue HU − air HU), and mass = specific gravity × total volume × 1.04 g/cm{sup 3}.Results: The range of calculated lung masses was 0.51–1.29 kg. The average male and female lung masses during FB CT were 0.80 and 0.71 kg, respectively. The calculated lung mass varied across the respiratory cycle but changed to a lesser degree than did lung volume measurements (7.3% versus 15.4%). Lung masses calculated using deep inspiration breath-hold and average CT were significantly larger (p < 0.05) than were some masses calculated using respiratory-phase and FB CT. Increased voxel size and smooth reconstruction kernels led to high lung mass estimates owing to partial volume effects.Conclusions: Organ mass correction is an important component of patient-specific internal radionuclide dosimetry. Lung mass calculation necessitates scan-based density correction to account for volume changes owing to respiration. The range of lung masses in the authors’ patient population represents lung doses for the same absorbed energy differing from 25% below to 64% above the dose found using reference phantom organ masses. With proper management of acquisition parameters and selection of FB or midexpiration breath hold scans, lung mass estimates with about 10% population precision may be achieved.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Dynamic keyhole: A novel method to improve MR images in the presence of respiratory motion for real-time MRI
Purpose: In this work, the authors present a novel magnetic resonance imaging reconstruction method to improve the quality of MR images in the presence of respiratory motion for real-time thoracic image-guided radiotherapy. Methods: This new reconstruction method is called dynamic keyhole and utilizes a library of previously acquired, peripheral k-space datasets from the same (or similar) respiratory state in conjunction with central k-space datasets acquired in real-time. Internal or external respiratory signals are utilized to sort, match, and combine the two separate peripheral and central k-space datasets with respect to respiratory displacement, thereby reducing acquisition time and improving image quality without respiratory-related artifacts. In this study, the dynamic keyhole, conventional keyhole, and zero-filling methods were compared to full k-space acquisition (ground truth) for 60 coronal datasets acquired from 15 healthy human subjects. Results: For the same image-quality difference from the ground-truth image, the dynamic keyhole method reused 79% of the prior peripheral phase-encoding lines, while the conventional keyhole reused 73% and zero-filling 63% (p-value < 0.0001), corresponding to faster acquisition speed of dynamic keyhole for real-time imaging applications. Conclusions: This study demonstrates that the dynamic keyhole method is a promising technique for clinical applications such as image-guided radiotherapy requiring real-time MR monitoring of the thoracic region. Based on the results from this study, the dynamic keyhole method could increase the temporal resolution by a factor of five compared with full k-space methods.
60 APPLIED LIFE SCIENCES↗
SU-D-BRF-01: Applications of Photonuclear Activation of Biological Tissues in Clinical High-Energy X-Ray Beams
Purpose: The commercial availability of high-energy accelerators opens new therapeutic opportunities for X-rays with energies in excess of 15MV. Three clinical beams (Varian 18MV, Elekta SL25, and Top Grade LA45) were compared by the production of photo-activated positron emitters in five types of biological tissues. Methods: The activation studies were performed using FLUKA2011 Monte Carlo suite with beam models designed for the three accelerators. Absolute activity density (Bq/ml) distribution in space was obtained from this study. Additionally, the temporal evolution of all activated species was monitored for cooling times up to 30 minutes. Results: The relative activation contrast of tissue pairs was evaluated for 2Gy of dose at 10cm depth for five tissues (normal, hypoxic, adipose, bone, and lung). In bone the sort-lived isotopes O-15 and P-30 dominated the activity at the early cooling stages. In all tissues 15 minutes post-irradiation the C-11 activity became dominant. Tissues with higher carbon-to-oxygen ratio in their elemental composition became clearly visible in a PET scan at longer cooling times. Radiation treatment of a lung tumor with a hypoxic core was simulated in an anthropomorphic phantom using the LA45 beam model. Increase in the PET counts by more than 50% was measured in the hypoxic volume 15 minutes post-irradiation, demonstrating the benefits of the relative activation contrast concept. Conclusion: LA45 beam is found to produce measurable activation distribution for 2Gy of dose, suitable for tissue type discrimination studies. Maximum activation contrast of 1.7 between hypoxic and normal tissues was measured in a simulated treatment. The absolute activity density values obtained from these Monte Carlo studies suggest that the window of opportunity for a PET scan exists up to 60 minutes after 2Gy of dose is deposited by 45MV X-ray beam. Lung-to-tissue activation contrast can be explored for treatment QA purposes as well.
60 APPLIED LIFE SCIENCES↗
SU-E-J-89: Motion Effects On Organ Dose in Respiratory Gated Stereotactic Body Radiation Therapy
Purpose: Existing reports on gated radiation therapy focus mainly on optimizing dose delivery to the target structure. This work investigates the motion effects on radiation dose delivered to organs at risk (OAR) in respiratory gated stereotactic body radiation therapy (SBRT). A new algorithmic tool of dose analysis is developed to evaluate the optimality of gating phase for dose sparing on OARs while ensuring adequate target coverage. Methods: Eight patients with pancreatic cancer were treated on a phase I prospective study employing 4DCT-based SBRT. For each patient, 4DCT scans are acquired and sorted into 10 respiratory phases (inhale-exhale- inhale). Treatment planning is performed on the average CT image. The average CT is spatially registered to other phases. The resultant displacement field is then applied on the plan dose map to estimate the actual dose map for each phase. Dose values of each voxel are fitted to a sinusoidal function. Fitting parameters of dose variation, mean delivered dose and optimal gating phase for each voxel over respiration cycle are mapped on the dose volume. Results: The sinusoidal function accurately models the dose change during respiratory motion (mean fitting error 4.6%). In the eight patients, mean dose variation is 3.3 Gy on OARs with maximum of 13.7 Gy. Two patients have about 100cm{sup 3} volumes covered by more than 5 Gy deviation. The mean delivered dose maps are similar to plan dose with slight deformation. The optimal gating phase highly varies across the patient, with phase 5 or 6 on about 60% of the volume, and phase 0 on most of the rest. Conclusion: A new algorithmic tool is developed to conveniently quantify dose deviation on OARs from plan dose during the respiratory cycle. The proposed software facilitates the treatment planning process by providing the optimal respiratory gating phase for dose sparing on each OAR.
60 APPLIED LIFE SCIENCES↗