Results for “Models, Anatomic” — Page 19

NASA NTRS1998

Vestibular influences on autonomic cardiovascular control in humans

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

Review↗

DOE OSTI2016

Volume of interest CBCT and tube current modulation for image guidance using dynamic kV collimation

Purpose: The focus of this work is the development of a novel blade collimation system enabling volume of interest (VOI) CBCT with tube current modulation using the kV image guidance source on a linear accelerator. Advantages of the system are assessed, particularly with regard to reduction and localization of dose and improvement of image quality. Methods: A four blade dynamic kV collimator was developed to track a VOI during a CBCT acquisition. The current prototype is capable of tracking an arbitrary volume defined by the treatment planner for subsequent CBCT guidance. During gantry rotation, the collimator tracks the VOI with adjustment of position and dimension. CBCT image quality was investigated as a function of collimator dimension, while maintaining the same dose to the VOI, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert centered on isocenter. Dose distributions were modeled using a dynamic BEAMnrc library and DOSXYZnrc. The resulting VOI dose distributions were compared to full-field CBCT distributions to quantify dose reduction and localization to the target volume. A novel method of optimizing x-ray tube current during CBCT acquisition was developed and assessed with regard to contrast-to-noise ratio (CNR) and imaging dose. Results: Measurements show that the VOI CBCT method using the dynamic blade system yields an increase in contrast-to-noise ratio by a factor of approximately 2.2. Depending upon the anatomical site, dose was reduced to 15%–80% of the full-field CBCT value along the central axis plane and down to less than 1% out of plane. The use of tube current modulation allowed for specification of a desired SNR within projection data. For approximately the same dose to the VOI, CNR was further increased by a factor of 1.2 for modulated VOI CBCT, giving a combined improvement of 2.6 compared to full-field CBCT. Conclusions: The present dynamic blade system provides significant improvements in CNR for the same imaging dose and localization of imaging dose to a predefined volume of interest. The approach is compatible with tube current modulation, allowing optimization of the imaging protocol.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Impact of anatomical fractionation of corn stover on hammer mill throughput and energy consumption

The goal of this Case Study was to quantify the impacts of variable moisture and ash on hammer mill throughput and energy consumption and on loss of very wet stover that causes failures in the first stage grinder and that are not able to be fed to conversion, as compared to a status quo Base Case system. Also considered was convertible carbohydrate content (minimum total carbohydrate specification) and maximum ash content and the delivered feedstock cost impacts of not being able to feed stover not meeting the total carbohydrate specification to the conversion reactor. Laboratory data on the impacts of moisture content and tissue fraction on throughput and energy consumption in a stage 2 hammer mill were received from FCIC Subtask 5.1. Additional air classifier throughput, energy consumption and separation efficiency data were obtained from FCIC Subtask 5.1 for the new air classifier, which has three exit streams (lights, middle and heavies). These data were utilized to develop the necessary response surface equations to perform throughput analysis using discrete event simulation. Because the ash contents and particle sizes had not been analyzed in the laboratory at the time of the model runs, we assumed that the ash distributed proportionally with total mass into the lights and heavies in an air classifier having two exit streams (lights and heavies) and that the lights fraction from the air classifier was not removed. Key takeaways from this Case Study are that due to lower energy consumption, it is more cost effective to hammer mill fractionated corn stover tissues than whole stover. Reduction of grinding energy was significant and may possibly be connected to particle-particle interactions in the grinder that lead to increased residence time of leaves and husks, resulting in decreased throughput and higher generation of fines when milling whole stover. While we did not see significant impacts to throughput, this was due to moisture failures of the first stage grinder in each system dominating failures and downtime. The operating cost savings of reduced grinding energy savings in the second stage hammer mills alone was high enough to offset the added capital cost of the air classifier and extra grinding line.

09 BIOMASS FUELS↗

DOE OSTI2020

The maximum carboxylation rate of Rubisco affects CO2 refixation in temperate broadleaved forest trees

Mesophyll resistance to CO 2 diffusion (rm) and the maximum carboxylation rate of Rubisco (Vcmax) affect photosynthetic rates, and can potentially also influence the percentage of respiratory and photorespiratory CO 2 being refixated (Pr) by mesophyll cells. Here we investigated how various leaf anatomical traits (e.g. leaf mass per area [LMA] and leaf dry matter content [LDMC]) influenced rm in leaves of mature forest trees. We further explored how rm and Vcmax in turn affected Pr, and if these traits varied among species and leaves along a light gradient. Photosynthetic CO 2 response of leaves grown in high-, medium-, and low-light environments was measured, from Pinus sylvestris [Scots pine], Picea abies [Norway spruce], Quercus robur [English oak], and Betula pendula [Silver birch] in southern Sweden. A modified version of the Farquhar-von Caemmerer-Berry model was fitted to the leaf gas exchange data to estimate Vcmax, rm and Pr. We found that of all leaf traits measured, only LMA for Q. robur was significantly higher in leaves from high-light environments. When comparing species, both rm and LMA were significantly higher in the conifers, and rm had a negative correlation with Vcmax. We found that Pr was similar between different species and functional groups, with an average of 73.2% (and SD of ±10.4) across all species. There was a strong, positive correlation between Pr and Vcmax in broadleaves, and we hypothesise that this effect might derive from a higher CO 2 drawdown near Rubisco in leaves with high Vcmax.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2018

Xylem embolism refilling and resilience against drought-induced mortality in woody plants: processes and trade-offs

Understanding which species are able to recover from drought, under what conditions, and the mechanistic processes involved, will facilitate predictions of plant mortality in response to global change. In response to drought, some species die because of embolism-induced hydraulic failure, whilst others are able to avoid mortality and recover, following rehydration. Several tree species have evolved strategies to avoid embolism, whereas others tolerate high embolism rates but can recover their hydraulic functioning upon drought relief. Here, we focus on structures and processes that might allow some plants to recover from drought stress via embolism reversal. We provide insights into how embolism repair may have evolved, anatomical and physiological features that facilitate this process, and describe possible trade-offs and related costs. Recent controversies on methods used for estimating embolism formation/repair are also discussed, providing some methodological suggestions. Although controversial, embolism repair processes are apparently based on the activity of phloem and ray/axial parenchyma. The mechanism is energetically demanding, and the costs to plants include metabolism and transport of soluble sugars, water and inorganic ions. We propose that embolism repair should be considered as a possible component of a ‘hydraulic efficiency-safety’ spectrum. We also advance a framework for vegetation models, describing how vulnerability curves may change in hydrodynamic model formulations for plants that recover from embolism.

54 ENVIRONMENTAL SCIENCES↗

NASA NTRS1993

Skeletal muscle metabolism in hypokinetic rats

This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

Tischler, Marc E.↗

DOE OSTI2017

A Method to Recognize Anatomical Site and Image Acquisition View in X-ray Images

A method was developed to recognize anatomical site and image acquisition view automatically in 2D X-ray images that are used in image-guided radiation therapy. The purpose is to enable site and view dependent automation and optimization in the image processing tasks including 2D-2D image registration, 2D image contrast enhancement, and independent treatment site confirmation. The X-ray images for 180 patients of six disease sites (the brain, head-neck, breast, lung, abdomen, and pelvis) were included in this study with 30 patients each site and two images of orthogonal views each patient. A hierarchical multiclass recognition model was developed to recognize general site first and then specific site. Each node of the hierarchical model recognized the images using a feature extraction step based on principal component analysis followed by a binary classification step based on support vector machine. Given two images in known orthogonal views, the site recognition model achieved a 99% average F1 score across the six sites. If the views were unknown in the images, the average F1 score was 97%. If only one image was taken either with or without view information, the average F1 score was 94%. The accuracy of the site-specific view recognition models was 100%.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2015

Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations

Purpose: To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment. Methods: Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma pass rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose–volume histogram. Results: Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 − 0.94, changes in patient body habitus, AUC = 0.67 − 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 − 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D{sub 99} change <7%]. Larger variations have even higher detectability. Displacements in the patient’s position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D{sub 99} of the PTV changed by up to 57% for the patient position shifts considered here. Conclusions: In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC’s, and changes in the patient habitus. Shifts in the patient’s position which can introduce large changes in the target dose coverage were not readily detected.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

A beam hardening and dispersion correction for x-ray dark-field radiography

Purpose: X-ray dark-field imaging promises information on the small angle scattering properties even of large samples. However, the dark-field image is correlated with the object’s attenuation and phase-shift if a polychromatic x-ray spectrum is used. A method to remove part of these correlations is proposed. Methods: The experimental setup for image acquisition was modeled in a wave-field simulation to quantify the dark-field signals originating solely from a material’s attenuation and phase-shift. A calibration matrix was simulated for ICRU46 breast tissue. Using the simulated data, a dark-field image of a human mastectomy sample was corrected for the finger print of attenuation- and phase-image. Results: Comparing the simulated, attenuation-based dark-field values to a phantom measurement, a good agreement was found. Applying the proposed method to mammographic dark-field data, a reduction of the dark-field background and anatomical noise was achieved. The contrast between microcalcifications and their surrounding background was increased. Conclusions: The authors show that the influence of and dispersion can be quantified by simulation and, thus, measured image data can be corrected. The simulation allows to determine the corresponding dark-field artifacts for a wide range of setup parameters, like tube-voltage and filtration. The application of the proposed method to mammographic dark-field data shows an increase in contrast compared to the original image, which might simplify a further image-based diagnosis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

WE-D-303-00: Computational Phantoms

Modern medical physics deals with complex problems such as 4D radiation therapy and imaging quality optimization. Such problems involve a large number of radiological parameters, and anatomical and physiological breathing patterns. A major challenge is how to develop, test, evaluate and compare various new imaging and treatment techniques, which often involves testing over a large range of radiological parameters as well as varying patient anatomies and motions. It would be extremely challenging, if not impossible, both ethically and practically, to test every combination of parameters and every task on every type of patient under clinical conditions. Computer-based simulation using computational phantoms offers a practical technique with which to evaluate, optimize, and compare imaging technologies and methods. Within simulation, the computerized phantom provides a virtual model of the patient’s anatomy and physiology. Imaging data can be generated from it as if it was a live patient using accurate models of the physics of the imaging and treatment process. With sophisticated simulation algorithms, it is possible to perform virtual experiments entirely on the computer. By serving as virtual patients, computational phantoms hold great promise in solving some of the most complex problems in modern medical physics. In this proposed symposium, we will present the history and recent developments of computational phantom models, share experiences in their application to advanced imaging and radiation applications, and discuss their promises and limitations. Learning Objectives: Understand the need and requirements of computational phantoms in medical physics research Discuss the developments and applications of computational phantoms Know the promises and limitations of computational phantoms in solving complex problems.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

WE-D-303-01: Development and Application of Digital Human Phantoms

Modern medical physics deals with complex problems such as 4D radiation therapy and imaging quality optimization. Such problems involve a large number of radiological parameters, and anatomical and physiological breathing patterns. A major challenge is how to develop, test, evaluate and compare various new imaging and treatment techniques, which often involves testing over a large range of radiological parameters as well as varying patient anatomies and motions. It would be extremely challenging, if not impossible, both ethically and practically, to test every combination of parameters and every task on every type of patient under clinical conditions. Computer-based simulation using computational phantoms offers a practical technique with which to evaluate, optimize, and compare imaging technologies and methods. Within simulation, the computerized phantom provides a virtual model of the patient’s anatomy and physiology. Imaging data can be generated from it as if it was a live patient using accurate models of the physics of the imaging and treatment process. With sophisticated simulation algorithms, it is possible to perform virtual experiments entirely on the computer. By serving as virtual patients, computational phantoms hold great promise in solving some of the most complex problems in modern medical physics. In this proposed symposium, we will present the history and recent developments of computational phantom models, share experiences in their application to advanced imaging and radiation applications, and discuss their promises and limitations. Learning Objectives: Understand the need and requirements of computational phantoms in medical physics research Discuss the developments and applications of computational phantoms Know the promises and limitations of computational phantoms in solving complex problems.

60 APPLIED LIFE SCIENCES↗

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↗