Results for “Commonality” — Page 98

DOE OSTI2013

Quality assurance of proton beams using a multilayer ionization chamber system

Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system.Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used to measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning.Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within −0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm. DDF values agreed within 0.3 ± 0.1 mm, with a maximum deviation of 0.6 mm. For the scanned proton pencil beams, Zebra and Bragg peak chamber range values demonstrated agreement of 0.0 ± 0.3 mm with a maximum deviation of 1.3 mm. The setup and measurement time for all Zebra measurements was 3 and 20 times less, respectively, compared to the water tank measurements.Conclusions: Our investigation shows that the Zebra can be useful not only for fast but also for accurate measurements of the depth-dose distributions of both scattered and scanned proton beams. The analysis of a large set of measurements shows that the commonly assessed beam quality parameters obtained with the Zebra are within the acceptable variations specified by the manufacturer for our delivery system.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2014

SU-E-T-602: Beryllium Seeds Implant for Photo-Neutron Yield Using External Beam Therapy

Purpose: To evaluate the Neutron yield obtained during prostate external beam irradiation. Methods: Neutrons, that are commonly a radiation safety concern for photon beams with energy above 10 MV, are induced inside a PTV from Beryllium implemented seeds. A high megavoltage photon beam delivered to a prostate will yield neutrons via the reaction Be-9(γ,n)2?. Beryllium was chosen for its low gamma,n reaction cross-section threshold (1.67 MeV) to be combined with a high feasible 25 MV photon beam. This beam spectra has a most probable photon energy of 2.5 to 3.0 MeV and an average photon energy of about 5.8 MeV. For this feasibility study we simulated a Beryllium-made common seed dimension (0.1 cm diameter and 0.5 cm height) without taking into account encapsulation. We created a 0.5 cm grid loading pattern excluding the Urethra, using Variseed (Varian inc.) A total of 156 seeds were exported to a 4cm diameter prostate sphere, created in Fluka, a particle transport Monte Carlo Code. Two opposed 25 MV beams were simulated. The evaluation of the neutron dose was done by adjusting the simulated photon dose to a common prostate delivery (e.g. 7560 cGy in 42 fractions) and finding the corresponding neutron dose yield from the simulation. A variance reduction technique was conducted for the neutrons yield and transported. Results: An effective dose of 3.65 cGy due to neutrons was found in the prostate volume. The dose to central areas of the prostate was found to be about 10 cGy. Conclusion: The neutron dose yielded does not justify a clinical implant of Beryllium seeds. Nevertheless, one should investigate the Neutron dose obtained when a larger Beryllium loading is combined with commercially available 40 MeV Linacs.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2014

Sci—Thur PM: Imaging — 06: Canada's National Computed Tomography (CT) Survey

The value of computed tomography (CT) in medical imaging is reflected in its' increased use and availability since the early 1990's; however, given CT's relatively larger exposures (vs. planar x-ray) greater care must be taken to ensure that CT procedures are optimised in terms of providing the smallest dose possible while maintaining sufficient diagnostic image quality. The development of CT Diagnostic Reference Levels (DRLs) supports this process. DRLs have been suggested/supported by international/national bodies since the early 1990's and widely adopted elsewhere, but not on a national basis in Canada. Essentially, CT DRLs provide guidance on what is considered good practice for common CT exams, but require a representative sample of CT examination data to make any recommendations. Canada's National CT Survey project, in collaboration with provincial/territorial authorities, has collected a large national sample of CT practice data for 7 common examinations (with associated clinical indications) of both adult and pediatric patients. Following completion of data entry into a common database, a survey summary report and recommendations will be made on CT DRLs from this data. It is hoped that these can then be used by local regions to promote CT practice optimisation and support any dose reduction initiatives.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems

Purpose: To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. Methods: A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom{sup TM}), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. Results: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the pinhole region-of-interest imaging. Conclusions: Onboard SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Toward optimizing patient-specific IMRT QA techniques in the accurate detection of dosimetrically acceptable and unacceptable patient plans

Purpose: The authors investigated the performance of several patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) dosimeters in terms of their ability to correctly identify dosimetrically acceptable and unacceptable IMRT patient plans, as determined by an in-house-designed multiple ion chamber phantom used as the gold standard. A further goal was to examine optimal threshold criteria that were consistent and based on the same criteria among the various dosimeters. Methods: The authors used receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of (1) a 2D diode array undergoing anterior irradiation with field-by-field evaluation, (2) a 2D diode array undergoing anterior irradiation with composite evaluation, (3) a 2D diode array using planned irradiation angles with composite evaluation, (4) a helical diode array, (5) radiographic film, and (6) an ion chamber. This was done with a variety of evaluation criteria for a set of 15 dosimetrically unacceptable and 9 acceptable clinical IMRT patient plans, where acceptability was defined on the basis of multiple ion chamber measurements using independent ion chambers and a phantom. The area under the curve (AUC) on the ROC curves was used to compare dosimeter performance across all thresholds. Optimal threshold values were obtained from the ROC curves while incorporating considerations for cost and prevalence of unacceptable plans. Results: Using common clinical acceptance thresholds, most devices performed very poorly in terms of identifying unacceptable plans. Grouping the detector performance based on AUC showed two significantly different groups. The ion chamber, radiographic film, helical diode array, and anterior-delivered composite 2D diode array were in the better-performing group, whereas the anterior-delivered field-by-field and planned gantry angle delivery using the 2D diode array performed less well. Additionally, based on the AUCs, there was no significant difference in the performance of any device between gamma criteria of 2%/2 mm, 3%/3 mm, and 5%/3 mm. Finally, optimal cutoffs (e.g., percent of pixels passing gamma) were determined for each device and while clinical practice commonly uses a threshold of 90% of pixels passing for most cases, these results showed variability in the optimal cutoff among devices. Conclusions: IMRT QA devices have differences in their ability to accurately detect dosimetrically acceptable and unacceptable plans. Field-by-field analysis with a MapCheck device and use of the MapCheck with a MapPhan phantom while delivering at planned rotational gantry angles resulted in a significantly poorer ability to accurately sort acceptable and unacceptable plans compared with the other techniques examined. Patient-specific IMRT QA techniques in general should be thoroughly evaluated for their ability to correctly differentiate acceptable and unacceptable plans. Additionally, optimal agreement thresholds should be identified and used as common clinical thresholds typically worked very poorly to identify unacceptable plans.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-D-BRA-06: Dual-Energy Chest CT: The Effects of Virtual Monochromatic Reconstructions On Texture Analysis Features

Purpose: To characterize the effect of virtual monochromatic reconstructions on several commonly used texture analysis features in DECT of the chest. Further, to assess the effect of monochromatic energy levels on the ability of these textural features to identify tissue types. Methods: 20 consecutive patients underwent chest CTs for evaluation of lung nodules using Siemens Somatom Definition Flash DECT. Virtual monochromatic images were constructed at 10keV intervals from 40–190keV. For each patient, an ROI delineated the lesion under investigation, and cylindrical ROI’s were placed within 5 different healthy tissues (blood, fat, muscle, lung, and liver). Several histogram- and Grey Level Cooccurrence Matrix (GLCM)-based texture features were then evaluated in each ROI at each energy level. As a means of validation, these feature values were then used in a random forest classifier to attempt to identify the tissue types present within each ROI. Their predictive accuracy at each energy level was recorded. Results: All textural features changed considerably with virtual monochromatic energy, particularly below 70keV. Most features exhibited a global minimum or maximum around 80keV, and while feature values changed with energy above this, patient ranking was generally unaffected. As expected, blood demonstrated the lowest inter-patient variability, for all features, while lung lesions (encompassing many different pathologies) exhibited the highest. The accuracy of these features in identifying tissues (76% accuracy) was highest at 80keV, but no clear relationship between energy and classification accuracy was found. Two common misclassifications (blood vs liver and muscle vs fat) accounted for the majority (24 of the 28) errors observed. Conclusion: All textural features were highly dependent on virtual monochromatic energy level, especially below 80keV, and were more stable above this energy. However, in a random forest model, these commonly used features were able to reliably differentiate between most tissues types regardless of energy level. Dr Godoy has received a dual-energy CT research grant from Siemens Healthcare. That grant did not directly fund this research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

WE-A-BRD-00: MR Basics II

Ever since its introduction as a diagnostic imaging modality over 30 years ago, the radiation therapy community has acknowledged the utility of MR imaging as a tool for not only improved visualization of the target volume but also for demarcation of adjacent organs at risk. However, the adaptation of MR imaging in radiation oncology has, until recently been slow due in large part to the inability to image radiation therapy patients in their treatment position. With the introduction of so-called wide bore high field MR scanners, multi element flexible receive only RF coils, high performance imaging gradients and a range of volumetric imaging sequences it is now possible to obtain both high resolution and high signal-to-noise ratio images of in-treatment radiation therapy patients within clinically feasible imaging times. As a Result, there is renewed interest in the use of MR imaging for radiation oncology treatment planning that is being translated into physical siting and integration of these systems into radiation oncology departments. As MR imaging expands into the radiation oncology domain there is a significant and unmet need for radiation therapy physicists to become educated regarding the strengths, limitations and technical challenges associated with MR imaging. The purpose of this presentation is to address this need by providing an educational overview of the techniques and challenges associated with MR imaging of patients for radiation therapy treatment planning. As such this presentation will: 1) describe the fundamental differences between imaging of patients for diagnostic and therapeutic purposes (i.e. radiation therapy planning), 2) describe most commonly used imaging sequences and contrasts for identification of disease for radiation planning, 3) identify the most common sources of image distortion and techniques to reduce their effect on spatial fidelity of the MR data, 4) describe the effects of motion and methods to quantify/correct it, and 5) identify emergent techniques for performing MR only treatment simulation. Upon completion attendees will have a working understanding of the basic methodologies associated with MR imaging in radiation oncology, the unique technical challenges imposed by MR imaging in the treatment position and techniques to address these. Learning Objectives: 1. Understand the differences between MR imaging for diagnostic imaging and for radiation therapy planning. 2. Identify the most common sources of distortion and artifacts and simple methods to correct them. 3. Understand the challenges with MR imaging in the therapy treatment position and appropriate techniques to address them.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

WE-A-BRD-01: MR Imaging for Treatment Planning: What Every Physicist Should Know

Ever since its introduction as a diagnostic imaging modality over 30 years ago, the radiation therapy community has acknowledged the utility of MR imaging as a tool for not only improved visualization of the target volume but also for demarcation of adjacent organs at risk. However, the adaptation of MR imaging in radiation oncology has, until recently been slow due in large part to the inability to image radiation therapy patients in their treatment position. With the introduction of so-called wide bore high field MR scanners, multi element flexible receive only RF coils, high performance imaging gradients and a range of volumetric imaging sequences it is now possible to obtain both high resolution and high signal-to-noise ratio images of in-treatment radiation therapy patients within clinically feasible imaging times. As a Result, there is renewed interest in the use of MR imaging for radiation oncology treatment planning that is being translated into physical siting and integration of these systems into radiation oncology departments. As MR imaging expands into the radiation oncology domain there is a significant and unmet need for radiation therapy physicists to become educated regarding the strengths, limitations and technical challenges associated with MR imaging. The purpose of this presentation is to address this need by providing an educational overview of the techniques and challenges associated with MR imaging of patients for radiation therapy treatment planning. As such this presentation will: 1) describe the fundamental differences between imaging of patients for diagnostic and therapeutic purposes (i.e. radiation therapy planning), 2) describe most commonly used imaging sequences and contrasts for identification of disease for radiation planning, 3) identify the most common sources of image distortion and techniques to reduce their effect on spatial fidelity of the MR data, 4) describe the effects of motion and methods to quantify/correct it, and 5) identify emergent techniques for performing MR only treatment simulation. Upon completion attendees will have a working understanding of the basic methodologies associated with MR imaging in radiation oncology, the unique technical challenges imposed by MR imaging in the treatment position and techniques to address these. Learning Objectives: 1. Understand the differences between MR imaging for diagnostic imaging and for radiation therapy planning. 2. Identify the most common sources of distortion and artifacts and simple methods to correct them. 3. Understand the challenges with MR imaging in the therapy treatment position and appropriate techniques to address them.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

IMRT QA: Selecting gamma criteria based on error detection sensitivity

Purpose: The gamma comparison is widely used to evaluate the agreement between measurements and treatment planning system calculations in patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA). However, recent publications have raised concerns about the lack of sensitivity when employing commonly used gamma criteria. Understanding the actual sensitivity of a wide range of different gamma criteria may allow the definition of more meaningful gamma criteria and tolerance limits in IMRT QA. We present a method that allows the quantitative determination of gamma criteria sensitivity to induced errors which can be applied to any unique combination of device, delivery technique, and software utilized in a specific clinic. Methods: A total of 21 DMLC IMRT QA measurements (ArcCHECK®, Sun Nuclear) were compared to QA plan calculations with induced errors. Three scenarios were studied: MU errors, multi-leaf collimator (MLC) errors, and the sensitivity of the gamma comparison to changes in penumbra width. Gamma comparisons were performed between measurements and error-induced calculations using a wide range of gamma criteria, resulting in a total of over 20 000 gamma comparisons. Gamma passing rates for each error class and case were graphed against error magnitude to create error curves in order to represent the range of missed errors in routine IMRT QA using 36 different gamma criteria. Results: This study demonstrates that systematic errors and case-specific errors can be detected by the error curve analysis. Depending on the location of the error curve peak (e.g., not centered about zero), 3%/3 mm threshold = 10% at 90% pixels passing may miss errors as large as 15% MU errors and ±1 cm random MLC errors for some cases. As the dose threshold parameter was increased for a given %Diff/distance-to-agreement (DTA) setting, error sensitivity was increased by up to a factor of two for select cases. This increased sensitivity with increasing dose threshold was consistent across all studied combinations of %Diff/DTA. Criteria such as 2%/3 mm and 3%/2 mm with a 50% threshold at 90% pixels passing are shown to be more appropriately sensitive without being overly strict. However, a broadening of the penumbra by as much as 5 mm in the beam configuration was difficult to detect with commonly used criteria, as well as with the previously mentioned criteria utilizing a threshold of 50%. Conclusions: We have introduced the error curve method, an analysis technique which allows the quantitative determination of gamma criteria sensitivity to induced errors. The application of the error curve method using DMLC IMRT plans measured on the ArcCHECK® device demonstrated that large errors can potentially be missed in IMRT QA with commonly used gamma criteria (e.g., 3%/3 mm, threshold = 10%, 90% pixels passing). Additionally, increasing the dose threshold value can offer dramatic increases in error sensitivity. This approach may allow the selection of more meaningful gamma criteria for IMRT QA and is straightforward to apply to other combinations of devices and treatment techniques.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TU-AB-207A-03: Image Quality, Dose, and Clinical Applications

Practicing medical physicists are often time charged with the tasks of evaluating and troubleshooting complex image quality issues related to CT scanners. This course will equip them with a solid and practical understanding of common CT imaging chain and its major components with emphasis on acquisition physics and hardware, reconstruction, artifacts, image quality, dose, and advanced clinical applications. The core objective is to explain the effects of these major system components on the image quality. This course will not focus on the rapid-changing advanced technologies given the two-hour time limit, but the fundamental principles discussed in this course may facilitate better understanding of those more complicated technologies. The course will begin with an overview of CT acquisition physics and geometry. X-ray tube and CT detector are important acquisition hardware critical to the overall image quality. Each of these two subsystems consists of several major components. An in-depth description of the function and failure modes of these components will be provided. Examples of artifacts related to these failure modes will be presented: off-focal radiation, tube arcing, heel effect, oil bubble, offset drift effect, cross-talk effect, and bad pixels. The fundamentals of CT image reconstruction will first be discussed on an intuitive level. Approaches that do not require rigorous derivation of mathematical formulations will be presented. This is followed by a detailed derivation of the Fourier slice theorem: the foundation of the FBP algorithm. FBP for parallel-beam, fan-beam, and cone-beam geometries will be discussed. To address the issue of radiation dose related to x-ray CT, recent advances in iterative reconstruction, their advantages, and clinical applications will also be described. Because of the nature of fundamental physics and mathematics, limitations in data acquisition, and non-ideal conditions of major system components, image artifact often arise in the reconstructed images. Because of the limited scope of this course, only major imaging artifacts, their appearance, and possible mitigation and corrections will be discussed. Assessment of the performance of a CT scanner is a complicated subject. Procedures to measure common image quality metrics such as high contrast spatial resolution, low contrast detectability, and slice profile will be described. The reason why these metrics used for FBP may not be sufficient for statistical iterative reconstruction will be explained. Optimizing radiation dose requires comprehension of CT dose metrics. This course will briefly describe various dose metrics, and interaction with acquisition parameters and patient habitus. CT is among the most frequently used imaging tools due to its superior image quality, easy to operate, and a broad range of applications. This course will present several interesting CT applications such as a mobile CT unit on an ambulance for stroke patients, low dose lung cancer screening, and single heartbeat cardiac CT. Learning Objectives: Understand the function and impact of major components of X-ray tube on the image quality. Understand the function and impact of major components of CT detector on the image quality. Be familiar with the basic procedure of CT image reconstruction. Understand the effect of image reconstruction on CT image quality and artifacts. Understand the root causes of common CT image artifacts. Be familiar with image quality metrics especially high and low contrast resolution, noise power spectrum, slice sensitivity profile, etc. Understand why basic image quality metrics used for FBP may not be sufficient to characterize the performance of advanced iterative reconstruction. Be familiar with various CT dose metrics and their interaction with acquisition parameters. New development in advanced CT clinical applications. JH: Employee of GE Healthcare. FD: No disclosure.; J. Hsieh, Jiang Hsieh is an employee of GE Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TU-D-209-01: Dosimetry of Diagnostic Work Up Mammography

Purpose: To investigate patient average glandular dose (AGD) characteristics of diagnostic mammography. Methods: The techniques used to image 14420 patients who received diagnostic work up mammography from October 2008 to December 2014 at one academic hospital were retrospectively collected. The most common diagnostic views and the techniques used for each according to compressed breast thickness were determined. For all techniques, 1st half value layer and air kerma output per tube current-exposure time product were measured; then the incident air kerma for each acquisition was calculated. The values for normalized glandular dose (DgN) were obtained with a validated Monte Carlo simulation of mammographic acquisition. The mono-energetic DgN results were combined according to relative fluence using the TASMICS model to obtain DgN coefficients for each spectrum. The spectral DgN and calculated incident air kerma were used to estimate AGD of patients with breast thickness ranging from 2 to 8 cm. Results: The most common views utilized during diagnostic mammography were magnification craniocaudal (24%), magnification mediolateral (19%), spot craniocaudal (28%), and spot mediolateral oblique (24%). The AGD increased with increasing breast thickness for both the magnification and spot views. The AGD for a 5.5 cm thick breast was approximately 6.8 mGy and 2.2 mGy for the magnification and spot views, respectively. The AGD ranged from 3.6 mGy to 6.8 mGy for the magnification views and from 1.0 mGy to 3.1 mGy for spot views. The difference in AGD between the two magnification views or the two spot views was not significant. Conclusion: These results provide information on breast dose to which screening recalled women are exposed to. In addition to understanding the dose used for common clinical imaging tests, this data could be used when comparing use of mammography for diagnostic workup to other potential modalities, such as breast tomosynthesis and breast CT.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-B-207B-00: Pediatric Image Quality Optimization

This imaging educational program will focus on solutions to common pediatric image quality optimization challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children’s hospitals. One of the most commonly encountered pediatric imaging requirements for the non-specialist hospital is pediatric CT in the emergency room setting. Thus, this educational program will begin with optimization of pediatric CT in the emergency department. Though pediatric cardiovascular MRI may be less common in the non-specialist hospitals, low pediatric volumes and unique cardiovascular anatomy make optimization of these techniques difficult. Therefore, our second speaker will review best practices in pediatric cardiovascular MRI based on experiences from a children’s hospital with a large volume of cardiac patients. Learning Objectives: To learn techniques for optimizing radiation dose and image quality for CT of children in the emergency room setting. To learn solutions for consistently high quality cardiovascular MRI of children.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-B-207B-01: Optimizing Pediatric CT in the Emergency Department

This imaging educational program will focus on solutions to common pediatric image quality optimization challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children’s hospitals. One of the most commonly encountered pediatric imaging requirements for the non-specialist hospital is pediatric CT in the emergency room setting. Thus, this educational program will begin with optimization of pediatric CT in the emergency department. Though pediatric cardiovascular MRI may be less common in the non-specialist hospitals, low pediatric volumes and unique cardiovascular anatomy make optimization of these techniques difficult. Therefore, our second speaker will review best practices in pediatric cardiovascular MRI based on experiences from a children’s hospital with a large volume of cardiac patients. Learning Objectives: To learn techniques for optimizing radiation dose and image quality for CT of children in the emergency room setting. To learn solutions for consistently high quality cardiovascular MRI of children.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-B-207B-02: Optimizing Pediatic Cardiovascular MRI

This imaging educational program will focus on solutions to common pediatric image quality optimization challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children’s hospitals. One of the most commonly encountered pediatric imaging requirements for the non-specialist hospital is pediatric CT in the emergency room setting. Thus, this educational program will begin with optimization of pediatric CT in the emergency department. Though pediatric cardiovascular MRI may be less common in the non-specialist hospitals, low pediatric volumes and unique cardiovascular anatomy make optimization of these techniques difficult. Therefore, our second speaker will review best practices in pediatric cardiovascular MRI based on experiences from a children’s hospital with a large volume of cardiac patients. Learning Objectives: To learn techniques for optimizing radiation dose and image quality for CT of children in the emergency room setting. To learn solutions for consistently high quality cardiovascular MRI of children.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

How Much Do rRNA Gene Surveys Underestimate Extant Bacterial Diversity?

The most common practice in studying and cataloguing prokaryotic diversity involves the grouping of sequences into operational taxonomic units (OTUs) at the 97% 16S rRNA gene sequence identity level, often using partial gene sequences, such as PCR-generated amplicons. Due to the high sequence conservation of rRNA genes, organisms belonging to closely related yet distinct species may be grouped under the same OTU. With this being said, it remains unclear how much diversity has been underestimated by this practice. To address this question, we compared the OTUs of genomes defined at the 97% or 98.5% 16S rRNA gene identity level against OTUs of the same genomes defined at the 95% whole-genome average nucleotide identity (ANI), which is a much more accurate proxy for species. Our results show that OTUs resulting from a 98.5% 16S rRNA gene identity cutoff are more accurate than 97% compared to 95% ANI (90.5% versus 89.9% accuracy) but indistinguishable from any other threshold in the 98.29 to 98.78% range. Even with the more stringent thresholds, the 16S rRNA gene-based approach commonly underestimates the number of OTUs by ~12%, on average, compared to the ANI-based approach (~14% underestimation when using the 97% identity threshold). Moreover, the degree of underestimation can become 50% or more for certain taxa, such as the genera Pseudomonas , Burkholderia , Escherichia , Campylobacter , and Citrobacter . These results provide a quantitative view of the degree of underestimation of extant prokaryotic diversity by 16S rRNA gene-defined OTUs and suggest that genomic resolution is often necessary. IMPORTANCE: Species diversity is one of the most fundamental pieces of information for community ecology and conservational biology. Thus, employing accurate proxies for what a species or the unit of diversity is are cornerstones for a large set of microbial ecology and diversity studies. The most common proxies currently used rely on the clustering of 16S rRNA gene sequences at some threshold of nucleotide identity, typically 97% or 98.5%. Here, we explore how well this strategy reflects the more accurate whole-genome-based proxies and determine the frequency with which the high conservation of 16S rRNA sequences masks substantial species-level diversity.

16S rRNA gene↗

DOE OSTI2014

Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing

Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five “standard” categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2017

Transport processes in plasma with an admixture of several heavy impurities

A two-temperature magnetohydrodynamic model of an ideal, fully ionized magnetized plasma consisting of electrons and several types of ions is developed for the case in which the mass of ions of the first type is much lower than that of jth-type ions, where j = 2,3,…, m{sub 1} ≪ m{sub j}, while the densities of heavy ions are so low that collisions between them can be neglected. The ion component is assigned a common velocity, common temperature, and common density, while its composition can vary in time and space.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2024

Novel mutation leading to splice donor loss in a conserved site of DMD gene causes Duchenne muscular dystrophy with cryptorchidism

Background As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. Methods In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype. Results In 30 of 115 patients (26.1%), we identified four novel genes ( ARSH , DMD , MAGEA4 and SHROOM2 ) affecting at least five unrelated patients and four known genes ( USP9Y , UBA1 , BCORL1 and KDM6A ) with the candidate rare pathogenic variants affecting at least two cases. Burden tests of rare variants revealed the genome-wide significances for newly identified genes (p<2.5×10 −6 ) under the Bonferroni correction. Surprisingly, novel and known genes were mainly found on X chromosome (seven on X and one on Y) and all rare X-chromosomal segregating variants exhibited a maternal inheritance rather than de novo origin. CRISPR-Cas9 mouse modelling of a splice donor loss variant in DMD (NC_000023.11:g.32454661C>G), which resides in a conserved site across vertebrates, replicated bilateral cryptorchidism phenotypes, confirmed by MRI at 4 and 10 weeks. The movement tests further revealed symptoms of Duchenne muscular dystrophy (DMD) in transgenic mice. Conclusion Our results revealed the role of the DMD gene mutation in causing cryptorchidism. The results also suggest that maternal-X inheritance of pathogenic defects could have a predominant role in the development of cryptorchidism.

Chen, Jianhai (ORCID:0000000300932003)↗