Results for “Models, Anatomic” — Page 16

DOE OSTI2016

SU-F-R-47: Quantitative Shape Relationship Analysis of PTV Modification for Critical Anatomy Sparing and Its Impact On Pathologic Response for Neoadjuvant Stereotactic Radiotherapy for Pancreatic Cancer

Purpose: Stereotactic body radiation therapy (SBRT) may be used to increase surgery candidacy in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. However, the planning target volume (PTV) may need to be limited to avoid toxicity when the gross tumor volume (GTV) is anatomically involved with surrounding critical structures. Our study aims to characterize the coverage of GTV and investigate the association between modified PTV and pathologic (pCR) or near pathologic (npCR) complete response rates determined from the surgical specimen. Methods: Patients treated with neoadjuvant pancreas SBRT followed by surgery from 2010–2015 were selected from Oncospace. Overlap volume histogram (OVH) analysis was performed to determine the extent of compromise of the PTV from both the GTV and a standard target (GTV+3mm). Subsequently, normalized overlap volume (%) was calculated for: (1) GTV-PTV, and (2) GTV+3mm expansion-PTV. A logistic regression model was used to identify the association between the overlap ratios and ≥ npCR(pCR/npCR) stratified by active breathing control (ABC) versus free-breathing status. Results: Eighty-one (BRPC: n=42, LAPC: n=39) patients were available for analysis. Nearly 40% (31/81) had ≥npCR and 75% (61/81) were able to complete ABC. Mean coverage of the GTV-PTV was 92.6% (range, 59.9%–100%, SD = 8.68) and coverage of the GTV+3mm expansion-PTV was 85. 2% (range, 59.9% −100.0%, SD= 8.67). Among the patients with ABC, every 10% increase in GTV coverage doubled the odds to have ≥npCR (OR = 1.82, p=0.06). Coverage of GTV+3mm expansion was not associated with ≥npCR regardless of ABC status. Conclusion: Preferential sparing of critical anatomy over GTV-PTV coverage with ABC management suggests worse ≥npCR rates for neoadjuvant SBRT in BRPC and LAPC. Limiting the GTV and GTV+3mm expansion in free-breathing patients was not associated with pathologic response perhaps due to larger GTV definitions as a result of motion artifacts in free-breathing CT scans. Collaboration with Toshiba, Elekta, and Phillips.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-H-206-00: Advances in Preclinical Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-H-206-01: Photoacoustic Tomography: Multiscale Imaging From Organelles to Patients by Ultrasonically Beating the Optical Diffusion Limit

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-H-206-03: Promises and Challenges of Benchtop X-Ray Fluorescence CT (XFCT) for Quantitative in Vivo Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2002

Understanding How Astronauts Adapt to Space and to Earth: Anatomical Studies of Central Vestibular Adaptation

Significant changes take place in the nervous systems of astronauts during and following exposure to microgravity. These changes, particularly in the part of the brain that controls balance, the vestibular system, can cause sensations of rotation, dizziness, and vertigo, as well as space adaptation syndrome. Adaptation to the microgravity environment usually occurs within one week, and a subsequent re-adaptation period of several days is often required upon return to Earth. In order to realize long-term spaceflight, effective countermeasures for these symptoms must be developed. The structural changes that take place in one of the vestibular regions of the brain (the cerebellar cortex) during the process of adaptation to Earth's gravity remain unclear and are the subject of an experiment being conducted on STS-107 by Dr. Gay Holstein of the Mount Sinai School of Medicine in New York. Using the rat as a model, Dr. Holstein and her team will seek to identify the cellular changes underlying the vestibular changes experienced by astronauts.

Holstein, Gay↗

DOE OSTI2015

SU-E-T-761: TOMOMC, A Monte Carlo-Based Planning VerificationTool for Helical Tomotherapy

Purpose: Present a new Monte Carlo code (TOMOMC) to calculate 3D dose distributions for patients undergoing helical tomotherapy treatments. TOMOMC performs CT-based dose calculations using the actual dynamic variables of the machine (couch motion, gantry rotation, and MLC sequences). Methods: TOMOMC is based on the GEPTS (Gama Electron and Positron Transport System) general-purpose Monte Carlo system (Chibani and Li, Med. Phys. 29, 2002, 835). First, beam models for the Hi-Art Tomotherpy machine were developed for the different beam widths (1, 2.5 and 5 cm). The beam model accounts for the exact geometry and composition of the different components of the linac head (target, primary collimator, jaws and MLCs). The beams models were benchmarked by comparing calculated Pdds and lateral/transversal dose profiles with ionization chamber measurements in water. See figures 1–3. The MLC model was tuned in such a way that tongue and groove effect, inter-leaf and intra-leaf transmission are modeled correctly. See figure 4. Results: By simulating the exact patient anatomy and the actual treatment delivery conditions (couch motion, gantry rotation and MLC sinogram), TOMOMC is able to calculate the 3D patient dose distribution which is in principal more accurate than the one from the treatment planning system (TPS) since it relies on the Monte Carlo method (gold standard). Dose volume parameters based on the Monte Carlo dose distribution can also be compared to those produced by the TPS. Attached figures show isodose lines for a H&N patient calculated by TOMOMC (transverse and sagittal views). Analysis of differences between TOMOMC and TPS is an ongoing work for different anatomic sites. Conclusion: A new Monte Carlo code (TOMOMC) was developed for Tomotherapy patient-specific QA. The next step in this project is implementing GPU computing to speed up Monte Carlo simulation and make Monte Carlo-based treatment verification a practical solution.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy

Purpose: Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis. Methods: The method is based on the computation of a normalized structural description of the rectum using a Laplacian-based model. This description takes advantage of the tubular structure of the rectum and its centerline to be embedded in a nonrigid registration-based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave-one-out cross validation. Results: Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose-organ overlap). Considering these scores, the proposed method outperforms intensity-based and distance maps-based registration methods. Conclusions: The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors

As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958–2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (–66% per decade, 95% CI: –88% to –32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (–1.93 power of attained age, 95% CI: –2.94 to –0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Diffusion processes in tumors: A nuclear medicine approach

The number of counts used in nuclear medicine imaging techniques, only provides physical information about the desintegration of the nucleus present in the the radiotracer molecules that were uptaken in a particular anatomical region, but that information is not a real metabolic information. For this reason a mathematical method was used to find a correlation between number of counts and {sup 18}F-FDG mass concentration. This correlation allows a better interpretation of the results obtained in the study of diffusive processes in an agar phantom, and based on it, an image from the PETCETIX DICOM sample image set from OsiriX-viewer software was processed. PET-CT gradient magnitude and Laplacian images could show direct information on diffusive processes for radiopharmaceuticals that enter into the cells by simple diffusion. In the case of the radiopharmaceutical {sup 18}F-FDG is necessary to include pharmacokinetic models, to make a correct interpretation of the gradient magnitude and Laplacian of counts images.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2020

Modelling kidney disease using ontology: insights from the Kidney Precision Medicine Project

An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them. Ontologies are critical to support the types of big data analysis necessary for kidney precision medicine, where heterogeneous clinical, imaging and biopsy data from diverse sources must be combined to define a patient’s phenotype. Here, the development of two new ontologies — the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation — will support the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney. These ontologies will improve the annotation of kidney-relevant data, and eventually lead to new definitions of kidney disease in support of precision medicine.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

A novel approach to assess the treatment response using Gaussian random field in PET

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. Results: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with ∼1 correlation coefficient. Conclusions: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2023

Clinical effects of 3D printing-assisted posterolateral incision in the treatment of ankle fractures involving the posterior malleolus

Objective To explore the clinical outcomes of a 3D printing-assisted posterolateral approach for the treatment of ankle fractures involving the posterior malleolus. Methods A total of 51 patients with ankle fractures involving the posterior malleolus admitted to our hospital from January 2018 to December 2019 were selected. The patients were divided into 3D printing group (28 cases) and control group (23 cases). 3D printing was performed for ankle fractures, followed by printing of a solid model and simulation of the operation on the 3D model. The operation was then performed according to the preoperative plan, including open reduction and internal fixation via the posterolateral approach with the patient in the prone position. Routine x-ray and CT examinations of the ankle joint were performed, and ankle function was evaluated using the American Foot and Ankle Surgery Association (AOFAS) ankle-hindfoot score. Results All patients underwent x-ray and CT examinations. All fractures healed clinically, without loss of reduction or failure of internal fixation. Good clinical effects were achieved in both groups of patients. The operation time, intraoperative blood loss and intraoperative fluoroscopy frequency in the 3D printing group were significantly less than those in the control group ( p < 0.05). There was no significant difference between the two groups in the anatomical reduction rate of fractures or the incidence of surgical complications ( p > 0.05). Conclusion The 3D printing-assisted posterolateral approach is effective in the treatment of ankle fractures involving the posterior malleolus. The approach can be well planned before the operation, is simple to perform, yields good fracture reduction and fixation, and has good prospects for clinical application.

Zheng, Hongming↗

DOE OSTI2015

TU-CD-BRB-09: Prediction of Chemo-Radiation Outcome for Rectal Cancer Based On Radiomics of Tumor Clinical Characteristics and Multi-Parametric MRI

Purpose: To evaluate the tumor clinical characteristics and quantitative multi-parametric MR imaging features for prediction of response to chemo-radiation treatment (CRT) in locally advanced rectal cancer (LARC). Methods: Forty-three consecutive patients (59.7±6.9 years, from 09/2013 – 06/2014) receiving neoadjuvant CRT followed by surgery were enrolled. All underwent MRI including anatomical T1/T2, Dynamic Contrast Enhanced (DCE)-MRI and Diffusion-Weighted MRI (DWI) prior to the treatment. A total of 151 quantitative features, including morphology/Gray Level Co-occurrence Matrix (GLCM) texture from T1/T2, enhancement kinetics and the voxelized distribution from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, along with clinical information (carcinoembryonic antigen CEA level, TNM staging etc.), were extracted for each patient. Response groups were separated based on down-staging, good response and pathological complete response (pCR) status. Logistic regression analysis (LRA) was used to select the best predictors to classify different groups and the predictive performance were calculated using receiver operating characteristic (ROC) analysis. Results: Individual imaging category or clinical charateristics might yield certain level of power in assessing the response. However, the combined model outperformed than any category alone in prediction. With selected features as Volume, GLCM AutoCorrelation (T2), MaxEnhancementProbability (DCE-MRI), and MeanADC (DWI), the down-staging prediciton accuracy (area under the ROC curve, AUC) could be 0.95, better than individual tumor metrics with AUC from 0.53–0.85. While for the pCR prediction, the best set included CEA (clinical charateristics), Homogeneity (DCE-MRI) and MeanADC (DWI) with an AUC of 0.89, more favorable compared to conventional tumor metrics with an AUC ranging from 0.511–0.79. Conclusion: Through a systematic analysis of multi-parametric MR imaging features, we are able to build models with improved predictive value over conventional imaging or clinical metrics. This is encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailor the treatment into the era of personalized medicine. This work is supported by the National Science Foundation of China (NSFC Grant No. 81201091), National High Technology Research and Development Program of China (863 program, Grant No. 2015AA020917), and Fund Project for Excellent Abroad Scholar Personnel in Science and Technology.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Core States of Neutron Stars from Anatomizing Their Scaled Structure Equations

Given an Equation of State (EOS) for neutron star (NS) matter, there is a unique mass–radius sequence characterized by a maximum mass ${M}_{\mathrm{NS}}^{\max}$ at radius $R$ max . We first show analytically that the ${M}_{\mathrm{NS}}^{\max}$ and $R$ max scale linearly with two different combinations of the NS central pressure $P$ $c$ and energy density $ε$ $c$ , by dissecting perturbatively the dimensionless Tolman–Oppenheimer–Volkoff (TOV) equations governing NS internal variables. The scaling relations are then verified via 87 widely used and rather diverse phenomenological as well as 17 microscopic NS EOSs with/without considering hadron–quark phase transitions and hyperons, by solving numerically the original TOV equations. The EOS of the densest NS matter allowed before it collapses into a black hole is then obtained. Using the universal ${M}_{\mathrm{NS}}^{\max}$ and $R$ max scalings and Neutron Star Interior Composition Explorer and XMM-Newton mass–radius observational data for PSR J0740+6620, a very narrow constraining band on the NS central EOS is extracted directly from the data for the first time, without using any specific input EOS model.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2022

DEEPER: An Intergrated Platform for Deeper Roots

Crops with deeper roots would have multiple benefits, including better drought tolerance, reduced requirement for nitrogen fertilizer, and better sequestration of atmospheric CO 2 . DEEPER is an integrated platform of phenomic, genomic, and in silico technologies to generate maize lines with deeper roots. DEEPER is: LEADER (Leaf Elemental Accumulation from Deep Roots) is a breakthrough technology to nondestructively measure rooting depth by using the plant itself as a sensor. LEADER uses handheld X-ray Fluorescence spectrometry to quantify foliar accumulation of elements that are differentially distributed in the soil profile. LEADER is nondestructive and is orders of magnitude cheaper, faster, and more precise than any competing assay of rooting depth in the field. LEADER is able to distinguish deep-rooted from shallow-rooted maize lines in the field without the need for costly and noisy soil coring. RootRobot/DIRT3D, to automatically phenotype root architecture in any field, combining RootRobot, a mechatronics platform to excavate, clean, section, and image mature root crowns, with DIRT3D, software to quantify architectural traits in 3D. Anatomics, a high-throughput platform to phenotype root anatomy, combining LAT 2.0, a technology for 3D imaging of root anatomy and composition, with RootScan3D, software to automatically extract 3D anatomical and cell wall composition metrics from LAT 2.0 output. Using this platform we discovered two novel root traits, parenchyma cell wall thickness and multiseriate cortical sclerenchyma, that improve rooting depth and drought tolerance in maize and wheat. OpenSimRoot/Deep, software to simulate root interaction with hard subsoils. Using this platform we discovered novel concepts regarding how to increase crop rooting depth by modulating how individual root axes respond to hard soil. DeepGenes, a toolkit of genes, parent lines, and genomic selection strategies to enable breeding hybrids with deeper roots. We discovered 3 novel root genes that increase rooting depth in maize and wheat. DEEPER discovered novel root phenotypes for deeper rooting, and delivered validated ideotypes for deeper-rooted maize; novel technologies to rapidly assess root depth, root architecture and anatomy in field-grown plants; novel software tools for root modeling and 3D image analysis of root architecture and anatomy; and validated genes and genomic selection models to deploy traits for deeper rooting in maize breeding. Each DEEPER technology is transformative in its own right, and exceeds existing technologies. They are mutually synergistic, deployable for field-grown plants, and are ready for application. The phenotyping and modeling technologies are readily applicable to many crops, and genetic leads in maize may have utility in other grasses. Taken as a whole they represent a transformative platform to develop deeper-rooted crops, with greater drought tolerance, reduced fertilizer requirement, and greater carbon sequestration.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

SU-F-E-03: PET/CT Guided Dose Boost to Hypoxic Sub-Volume in Nasopharyngeal Carcinomas Using Self-Optimizing Non-Uniform VMAT

Purpose: This study is to evaluate the feasibility of simultaneously integrated boost (SIB) to hypoxic subvolume (HTV) in nasopharyngeal carcinomas under the guidance of 18F-Fluoromisonidazole (FMISO) PET/CT using a novel non-uniform volumetric modulated arc therapy (VMAT)technique. Methods: Eight nasopharyngeal carcinoma patients treated with conventional uniform VMAT were retrospectively analyzed. For each treatment, actual conventional uniform VMAT plan with two or more arcs (2–2.5 arcs, totally rotating angle < 1000o) was designed with dose boost to hopxic subvolume (total dose, 84Gy) in the gross tumor volme (GTV) under the guidance of 18F- FMISO PET/CT. Based on the same dataset, experimental single arc non-uniform VAMT plans were generated with the same dose prescription using customized software tools. Dosimetric parameters, quality assurance and the efficiency of the treatment delivery were compared between the uniform and non-uniform VMAT plans. Results: To develop the non-uniform VMAT technique, a specific optimization model was successfully established. Both techniques generate high-quality plans with pass rate (>98%) with the 3mm, 3% criterion. HTV received dose of 84.1±0.75Gy and 84.1±1.2Gy from uniform and non-uniform VMAT plans, respectively. In terms of target coverage and dose homogeneity, there was no significant statistical difference between actual and experimental plans for each case. However, for critical organs at risk (OAR), including the parotids, oral cavity and larynx, dosimetric difference was significant with better dose sparing form experimental plans. Regarding plan implementation efficiency, the average machine time was 3.5 minutes for the actual VMAT plans and 3.7 minutes for the experimental nonuniform VMAT plans (p>0.050). Conclusion: Compared to conventional VMAT technique, the proposed non-uniform VMAT technique has the potential to produce efficient and safe treatment plans, especially in cases with complicated anatomical structures and demanding dose boost to subvolumes.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Population of 224 realistic human subject-based computational breast phantoms

Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was then applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range of breast types, volumes, densities, and parenchymal patterns.

61 RADIATION PROTECTION AND DOSIMETRY↗