SEARCH · Engineering Papers

Results for “vesicles”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37

All sources NASA NTRS DOE OSTI

DOE OSTI2024

(2 + δ)-dimensional theory of the electromechanics of lipid membranes: Electrostatics

The coupling of electric fields to the mechanics of lipid membranes gives rise to intriguing electromechanical behavior, as, for example, evidenced by the deformation of lipid vesicles in external electric fields. Electromechanical effects are relevant for many biological processes, such as the propagation of action potentials in axons and the activation of mechanically gated ion channels. Currently, a theoretical framework describing the electromechanical behavior of arbitrarily curved and deforming lipid membranes does not exist. Purely mechanical models commonly treat lipid membranes as two-dimensional surfaces, ignoring their finite thickness. While holding analytical and numerical merit, this approach cannot describe the coupling of lipid membranes to electric fields and is thus unsuitable for electromechanical models. In a sequence of articles, we derive an effective surface theory of the electromechanics of lipid membranes, called the (2 + δ)-dimensional theory, which has the advantages of surface descriptions while accounting for finite thickness effects. The present article proposes a generic dimension reduction procedure relying on low-order spectral expansions. This procedure is applied to the electrostatics of lipid membranes to obtain the (2 + δ)-dimensional theory that captures potential differences across and electric fields within lipid membranes. Finally, this model is tested on different geometries relevant for lipid membranes, showing good agreement with the corresponding three-dimensional electrostatics theory.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2024

Patterning of multicomponent elastic shells by gaussian curvature

Recent findings suggest that shell protein distribution and the morphology of bacterial microcompartments regulate the chemical fluxes facilitating reactions which dictate their biological function. Here, we explore how the morphology and component patterning are coupled through the competition of mean and gaussian bending energies in multicomponent elastic shells that form three-component irregular polyhedra. We observe two softer components with lower bending rigidities allocated on the edges and vertices while the harder component occupies the faces. When subjected to a nonzero interfacial line tension, the two softer components further separate and pattern into subdomains that are mediated by the gaussian curvature. We find that this degree of fractionation is maximized when there is a weaker line tension and when the ratio of bending rigidities between the two softer domains ≈2. Our results reveal a patterning mechanism in multicomponent shells that can capture the observed morphologies of bacterial microcompartments, and moreover, can be realized in synthetic vesicles.

Monte Carlo methods↗

DOE OSTI2016

Population dynamics, information transfer, and spatial organization in a chemical reaction network under spatial confinement and crowding conditions

Here, we investigate, via Brownian dynamics simulations, the reaction dynamics of a generic, nonlinear chemical network under spatial confinement and crowding conditions. In detail, the Willamowski-Rossler chemical reaction system has been “extended” and considered as a prototype reaction-diffusion system. These results are potentially relevant to a number of open problems in biophysics and biochemistry, such as the synthesis of primitive cellular units (protocells) and the definition of their role in the chemical origin of life and the characterization of vesicle-mediated drug delivery processes. More generally, the computational approach presented in this work makes the case for the use of spatial stochastic simulation methods for the study of biochemical networks in vivo where the “well-mixed” approximation is invalid and both thermal and intrinsic fluctuations linked to the possible presence of molecular species in low number copies cannot be averaged out.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2022

Modeling the partitioning of amphiphilic molecules and co-solvents in biomembranes

We report amphiphilic co-solvents can have a significant impact on the structure, organization and physical properties of lipid bilayers. Describing the mutual impact of partitioning and induced structure changes is therefore a crucial consideration for a range of topics such as anesthesia and other pharmacokinetic effects, as well as microbial solvent tolerance in the production of biofuels and other fermentation products, where molecules such as ethanol, butanol or acetic acid might be generated. Small-angle neutron scattering (SANS) is a key method for studying lipid and polymer bilayer structures, with many models for extracting bilayer structure (thickness, area per lipid etc.) from scattering data in use today. However, the molecular details of co-solvent partitioning are conflated with induced changes to bilayer structure, making interpretation and modeling of the scattering curves a challenge with the existing set of models. To address this, a model of a bilayer structure is presented which invokes a two-term partition constant accounting for the localization of the co-solvent within the bilayer. This model was validated using a series of SANS measurements of lipid vesicles in the presence of the co-solvent tetrahydrofuran (THF), showing several strategies of how to deploy the two-parameter partition constant model to describe scattering data and extract both structure and partitioning information from the data. Molecular dynamics simulations are then used to evaluate assumptions of the model, provide additional molecular scale details and illustrate its complementary nature to the data fitting procedure. This approach results in estimates of the partition coefficient for THF in 1,2-dimyristoyl-sn-glycero-3-phosphocholine at 35°C, along with an estimate of the fraction of THF residing in the hydrophobic core of the membrane. The authors envision that this model will be applicable to a wide range of other bilayer/amphiphile interactions and provide the associated code needed to implement this model as a fitting algorithm for scattering data in the SasView suite.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Description of Freudenthalidium gen. nov. and Halluxium gen. nov. to Formally Recognize Clades Fr3 and H as Genera in the Family Symbiodiniaceae (Dinophyceae)

The Symbiodiniaceae are a family of marine dinoflagellates known mostly for their endosymbiotic interactions with invertebrates and protists, but facultatively and exclusively free‐living life histories in this family are also evident. A recent systematic revision of the Symbiodiniaceae replaced the clade‐based nomenclature of seven divergent lineages of “ Symbiodinium ” sensu lato with one based on formally described genera. The revised taxonomy was not extended to the whole group because type species to describe a new genus for each of the remaining clades and subclades were lacking. In an effort to characterize benthic habitats of symbiodiniaceans in sediments at Heron Island (Great Barrier Reef, Australia), we isolated >100 monoclonal Symbiodiniaceae cultures. Four of these belonged to Symbiodiniaceae ‘subclade’ Fr3, and three to Clade H, based on nucleotide sequence similarity (ITS2, LSU, cp23S, and mtCOB), representing the first cultures of these taxa. Based on these isolates, we propose two new genera: Freudenthalidium gen. nov. and Halluxium gen. nov., circumscribing Clades Fr3 and H, respectively. Three new species are described: Freudenthalidium heronense , F. endolithicum , and Halluxium pauxillum . Kofoidian tabulations of motile cells confirm previous observations that amphiesmal vesicle arrangements are generally conserved across the family. These descriptions are an important step toward completing the systematic revision of the Symbiodiniaceae. That this contribution was enabled by isolates from an endopsammic habitat highlights the potential of discovering new symbiodiniacean species in the environment, the study of which will lead to a deeper understanding of free‐living versus symbiotic life histories in this ecologically important family of dinoflagellates.

Nitschke, Matthew R.↗

DOE OSTI2026

Nanoscale elemental mapping reveals the effect of light and temperature on Gephyrocapsa huxleyi coccoliths

Coccolithophores produce vast quantities of stable calcium carbonate coccoliths, occupying the distinctive position as one of the most productive calcifying organisms on Earth. Gephyrocapsa huxleyi, the most abundant species of coccolithophores across modern oceans, plays an important role in the biological carbon pump and may serve as inspiration for nature-based carbon capture and sequestration technologies. Despite intensive study into G. huxleyi, the biological mechanisms of coccolith synthesis remain unclear. Here, we employ synchrotron X-ray fluorescence to quantitatively map elemental incorporation (calcium, Ca; strontium, Sr; sulfur, S; iron, Fe; and silicon, Si) into G. huxleyi coccoliths at 40-nanometer resolution. Trace elements play a role in determining the thermodynamic stability of coccolith carbonate sequestration and may provide insight into unknown mechanisms of coccolithogenesis. Although the coccolith Sr/Ca ratio has been widely applied as a paleoceanographic proxy, understanding of the Sr/Ca phenomena is limited. Our results confirm that Sr/Ca is temperature dependent but challenge the hypothesis that growth rate is a primary determinant. We find that increased light irradiance led to an ~30% decrease in calcium incorporated into the coccoliths. Surprisingly, X-ray fluorescence spectra and mapping revealed evidence of sulfur, at approximately three times the concentration of Sr, embedded in and around the calcite matrix, suggesting that G. huxleyi coccoliths may play an expanded role in the global sulfur cycle. Here, based on our elemental maps, we postulate that sulfur is active in the intracellular coccolith vesicle and plays a direct role in formation of G. huxleyi coccoliths.

36 MATERIALS SCIENCE↗

DOE OSTI2017

Mouse fat storage‐inducing transmembrane protein 2 ( FIT 2) promotes lipid droplet accumulation in plants

Summary Fat storage‐inducing transmembrane protein 2 ( FIT 2) is an endoplasmic reticulum ( ER )‐localized protein that plays an important role in lipid droplet ( LD ) formation in animal cells. However, no obvious homologue of FIT 2 is found in plants. Here, we tested the function of FIT 2 in plant cells by ectopically expressing mouse ( Mus musculus ) FIT 2 in Nicotiana tabacum suspension‐cultured cells, Nicotiana benthamiana leaves and Arabidopsis thaliana plants. Confocal microscopy indicated that the expression of FIT 2 dramatically increased the number and size of LD s in leaves of N. benthamiana and Arabidopsis, and lipidomics analysis and mass spectrometry imaging confirmed the accumulation of neutral lipids in leaves. FIT 2 also increased seed oil content by ~13% in some stable, overexpressing lines of Arabidopsis . When expressed transiently in leaves of N. benthamiana or suspension cells of N. tabacum , FIT 2 localized specifically to the ER and was often concentrated at certain regions of the ER that resembled ER ‐ LD junction sites. FIT 2 also colocalized at the ER with other proteins known to be involved in triacylglycerol biosynthesis or LD formation in plants, but not with ER resident proteins involved in electron transfer or ER ‐vesicle exit sites. Collectively, these results demonstrate that mouse FIT 2 promotes LD accumulation in plants, a surprising functional conservation in the context of a plant cell given the apparent lack of FIT 2 homologues in higher plants. These results suggest also that FIT 2 expression represents an effective synthetic biology strategy for elaborating neutral lipid compartments in plant tissues for potential biofuel or bioproduct purposes.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2018

A Vitis vinifera basic helix-loop-helix transcription factor enhances plant cell size, vegetative biomass and reproductive yield

Strategies for improving plant size are critical targets for plant biotechnology to increase vegetative biomass or reproductive yield. To improve biomass production, a codon-optimized helix–loop–helix transcription factor (VvCEB1 opt ) from wine grape was overexpressed in Arabidopsis thaliana resulting in significantly increased leaf number, leaf and rosette area, fresh weight and dry weight. Cell size, but typically not cell number, was increased in all tissues resulting in increased vegetative biomass and reproductive organ size, number and seed yield. Ionomic analysis of leaves revealed the VvCEB1 opt- overexpressing plants had significantly elevated, K, S and Mo contents relative to control lines. Increased K content likely drives increased osmotic potential within cells leading to greater cellular growth and expansion. To understand the mechanistic basis of VvCEB1 opt action, one transgenic line was genotyped using RNA-Seq mRNA expression profiling and revealed a novel transcriptional reprogramming network with significant changes in mRNA abundance for genes with functions in delayed flowering, pathogen–defence responses, iron homeostasis, vesicle-mediated cell wall formation and auxin-mediated signalling and responses. Direct testing of VvCEB1 opt- overexpressing plants showed that they had significantly elevated auxin content and a significantly increased number of lateral leaf primordia within meristems relative to controls, confirming that cell expansion and organ number proliferation were likely an auxin-mediated process. VvCEB1 opt overexpression in Nicotiana sylvestris also showed larger cells, organ size and biomass demonstrating the potential applicability of this innovative strategy for improving plant biomass and reproductive yield in crops.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

PpIX‐enabled fluorescence‐based detection and photodynamic priming of platinum‐resistant ovarian cancer cells under fluid shear stress

Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Design, characterization, and intracellular trafficking of biofunctionalized chitosan nanomicelles

The hydrophobically modified glycol chitosan (HGC) nanomicelle has received increasing attention as a promising platform for the delivery of chemotherapeutic drugs. To improve the tumor selectivity of HGC, here an avidin and biotin functionalization strategy was applied. The hydrodynamic diameter of the biotin-avidin-functionalized HGC (cy5.5-HGC-B4F) was observed to be 104.7 nm, and the surface charge was +3.1 mV. Confocal and structured illumination microscopy showed that at 0.1 mg/ml, cy5.5-HGC-B4F nanomicelles were distributed throughout the cytoplasm of MDA-MB-231 breast cancer cells after 2 h of exposure without significant cytotoxicity. To better understand the intracellular fate of the nanomicelles, entrapment studies were performed and demonstrated that some cy5.5-HGC-B4F nanomicelles were capable of escaping endocytic vesicles, likely via the proton sponge effect. Quantitative analysis of the movements of endosomes in living cells revealed that the addition of HGC greatly enhanced the motility of endosomal compartments, and the nanomicelles were transported by early and late endosomes from cell periphery to the perinuclear region. Our results validate the importance of using live-cell imaging to quantitatively assess the dynamics and mechanisms underlying the complex endocytic pathways of nanosized drug carriers.

Li, Weiyi↗

DOE OSTI2023

Insight into the assembly of lipid-hyaluronan complexes in osteoarthritic conditions

Interactions between molecules in the synovial fluid and the cartilage surface may play a vital role in the formation of adsorbed films that contribute to the low friction of cartilage boundary lubrication. Osteoarthritis (OA) is the most common degenerative joint disease. Previous studies have shown that in OA-diseased joints, hyaluronan (HA) not only breaks down resulting in a much lower molecular weight (MW), but also its concentration is reduced ten times. Here, we have investigated the structural changes of lipid-HA complexes as a function of HA concentration and MW to simulate the physiologically relevant conditions that exist in healthy and diseased joints. Small angle neutron scattering and dynamic light scattering were used to determine the structure of HA-lipid vesicles in bulk solution, while a combination of atomic force microscopy and quartz crystal microbalance was applied to study their assembly on a gold surface. We infer a significant influence of both MW and HA concentrations on the structure of HA-lipid complexes in bulk and assembled on a gold surface. Our results suggest that low MW HA cannot form an amorphous layer on the gold surface, which is expected to negatively impact the mechanical integrity and longevity of the boundary layer and could contribute to the increased wear of the cartilage that has been reported in joints diseased with OA.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2014

SU-D-16A-04: Accuracy of Treatment Plan TCP and NTCP Values as Determined Via Treatment Course Delivery Simulations

Purpose: To to determine if tumor control probability (TCP) and normal tissue control probability (NTCP) values computed on the treatment planning image are representative of TCP/NTCP distributions resulting from probable positioning variations encountered during external-beam radiotherapy. Methods: We compare TCP/NTCP as typically computed on the planning PTV/OARs with distributions of those parameters computed for CTV/OARs via treatment delivery simulations which include the effect of patient organ deformations for a group of 19 prostate IMRT pseudocases. Planning objectives specified 78 Gy to PTV1=prostate CTV+5 mm margin, 66 Gy to PTV2=seminal vesicles+8 mm margin, and multiple bladder/rectum OAR objectives to achieve typical clinical OAR sparing. TCP were computed using the Poisson Model while NTCPs used the Lyman-Kutcher-Bruman model. For each patient, 1000 30-fraction virtual treatment courses were simulated with each fractional pseudo- time-oftreatment anatomy sampled from a principle component analysis patient deformation model. Dose for each virtual treatment-course was determined via deformable summation of dose from the individual fractions. CTVTCP/ OAR-NTCP values were computed for each treatment course, statistically analyzed, and compared with the planning PTV-TCP/OARNTCP values. Results: Mean TCP from the simulations differed by <1% from planned TCP for 18/19 patients; 1/19 differed by 1.7%. Mean bladder NTCP differed from the planned NTCP by >5% for 12/19 patients and >10% for 4/19 patients. Similarly, mean rectum NTCP differed by >5% for 12/19 patients, >10% for 4/19 patients. Both mean bladder and mean rectum NTCP differed by >5% for 10/19 patients and by >10% for 2/19 patients. For several patients, planned NTCP was less than the minimum or more than the maximum from the treatment course simulations. Conclusion: Treatment course simulations yield TCP values that are similar to planned values, while OAR NTCPs differ significantly, indicating the need for probabilistic methods or PRVs for OAR risk assessment. Presenting author receives support from Philips Medical Systems.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-T-125: Dosimetric Comparison of Intensity Modulated Radiation Therapy Using Robotic Versus Traditional Linac Platform in Prostate Cancer

Purpose: Recent development of an MLC for robotic external beam radiotherapy has the potential of new clinical application in conventionally fractionated radiation therapy. This study offers a dosimetric comparison of IMRT plans using Cyberknife with MLC versus conventional linac plans. Methods: Ten prostate cancer patients treated on a traditional linac with IMRT to 7920cGy at 180cGy/fraction were randomly selected. GTVs were defined as prostate plus proximal seminal vesicles. PTVs were defined as GTV+8mm in all directions except 5mm posteriorly. Conventional IMRT planning was performed on Philips Pinnacle and delivered on a standard linac with CBCT and 10mm collimator leaf width. For each case a Cyberknife plan was created using Accuray Multiplan with same CT data set, contours, and dose constraints. All dosimetric data was transferred to third party software for independent computation of contour volumes and DVH. Delivery efficiency was evaluated using total MU, treatment time, number of beams, and number of segments. Results: Evaluation criteria including percent target coverage, homogeneity index, and conformity index were found to be comparable. All dose constraints from QUANTEC were found to be statistically similar except rectum V50Gy and bladder V65Gy. Average rectum V50Gy was lower for robotic IMRT (30.07%±6.57) versus traditional (34.73%±3.62, p=0.0130). Average bladder V65Gy was lower for robotic (17.87%±12.74) versus traditional (21.03%±11.93, p=0.0405). Linac plans utilized 9 coplanar beams, 48.9±3.8 segments, and 19381±2399MU. Robotic plans utilized 38.4±9.0 non-coplanar beams, 85.5±21.0 segments and 42554.71±16381.54 MU. The average treatment was 15.02±0.60 minutes for traditional versus 20.90±2.51 for robotic. Conclusion: The robotic IMRT plans were comparable to the traditional IMRT plans in meeting the target volume dose objectives. Critical structure dose constraints were largely comparable although statistically significant differences were found in favor of the robotic platform in terms of rectum V50Gy and bladder V65Gy at a cost of 25% longer treatment time.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-F-BRF-10: Deformable MRI to CT Validation Employing Same Day Planning MRI for Surrogate Analysis

Purpose: To compare rigid and deformable registrations of the prostate in the multi-modality setting (diagnostic-MRI to planning-CT) by utilizing a planning-MRI as a surrogate. The surrogate allows for the direct quantitative analysis which can be difficult in the multi-modality domain where intensity mapping differs. Methods: For ten subjects, T2 fast-spin-echo images were acquired at two different time points, the first several weeks prior to planning (diagnostic-MRI) and the second on the same day in which the planning CT was collected (planning-MRI). Significant effort in patient positioning and bowel/bladder preparation was undertaken to minimize distortion of the prostate in all datasets. The diagnostic-MRI was deformed to the planning-CT utilizing a commercially available deformable registration algorithm synthesized from local registrations. The deformed MRI was then rigidly aligned to the planning MRI which was used as the surrogate for the planning-CT. Agreement between the two MRI datasets was scored using intensity based metrics including Pearson correlation and normalized mutual information, NMI. A local analysis was performed by looking only within the prostate, proximal seminal vesicles, penile bulb and combined areas. A similar method was used to assess a rigid registration between the diagnostic-MRI and planning-CT. Results: Utilizing the NMI, the deformable registrations were superior to the rigid registrations in 9 of 10 cases demonstrating a 15.94% improvement (p-value < 0.001) within the combined area. The Pearson correlation showed similar results with the deformable registration superior in the same number of cases and demonstrating a 6.97% improvement (p-value <0.011). Conclusion: Validating deformable multi-modality registrations using spatial intensity based metrics is difficult due to the inherent differences in intensity mapping. This population provides an ideal testing ground for MRI to CT deformable registrations by obviating the need for multi-modality comparisons which are inherently more challenging. Deformable registrations generated in this work significantly outperformed rigid alignments. Research reported in this abstract was supported by the NIH National Cancer Institute R21CA153826 “MRI-Guided Radiotherapy and Biomarkers for Prostate Cancer” and Bankhead-Coley Cancer Research Program 10BT-03 “MRI-Guided Radiotherapy and Biomarkers for Prostate Cancer”.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-106: The Use of Deformable Image Registration with Cone-Beam CT for a Better Evaluation of Cumulative Dose to Organs

Purpose: The knowledge of dose accumulation in the patient tissues in radiotherapy helps in determining the treatment outcomes. This project aims at providing a workflow to map cumulative doses that takes into account interfraction organ motion without the need for manual re-contouring. Methods: Five prostate cancer patients were studied. Each patient had a planning CT (pCT) and 5 to 13 CBCT scans. On each series, a physician contoured the prostate, rectum, bladder, seminal vesicles and the intestine. First, a deformable image registration (DIR) of the pCTs onto the daily CBCTs yielded registered CTs (rCT) . This rCT combined the accurate CT numbers of the pCT with the daily anatomy of the CBCT. Second, the original plans (220 cGy per fraction for 25 fractions) were copied on the rCT for dose re-calculation. Third, the DIR software Elastix was used to find the inverse transform from the rCT to the pCT. This transformation was then applied to the rCT dose grid to map the dose voxels back to their pCT location. Finally, the sum of these deformed dose grids for each patient was applied on the pCT to calculate the actual dose delivered to organs. Results: The discrepancy between the planned D98 and D2 and these indices re-calculated on the rCT, are, on average, of −1 ± 1 cGy and 1 ± 2 cGy per fraction, respectively. For fractions with large anatomical motion, the D98 discrepancy on the re-calculated dose grid mapped onto the pCT can raise to −17 ± 4 cGy. The obtained cumulative dose distributions illustrate the same behavior. Conclusion: This approach allowed the evaluation of cumulative doses to organs with the help of uncontoured daily CBCT scans. With this workflow, the easy evaluation of doses delivered for EBRT treatments could ultimately lead to a better follow-up of prostate cancer patients.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients were set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-221: A Novel Expansion Method for MRI Based Target Delineation in Prostate Radiotherapy

Purpose: To compare a novel bladder/rectum carveout expansion method on MRI delineated prostate to standard CT and expansion based methods for maintaining prostate coverage while providing superior bladder and rectal sparing. Methods: Ten prostate cases were planned to include four trials: MRI vs CT delineated prostate/proximal seminal vesicles, and each image modality compared to both standard expansions (8mm 3D expansion and 5mm posterior, i.e. ∼8mm) and carveout method expansions (5mm 3D expansion, 4mm posterior for GTV-CTV excluding expansion into bladder/rectum followed by additional 5mm 3D expansion to PTV, i.e. ∼1cm). All trials were planned to total dose 7920 cGy via IMRT. Evaluation and comparison was made using the following criteria: QUANTEC constraints for bladder/rectum including analysis of low dose regions, changes in PTV volume, total control points, and maximum hot spot. Results: ∼8mm MRI expansion consistently produced the most optimal plan with lowest total control points and best bladder/rectum sparing. However, this scheme had the smallest prostate (average 22.9% reduction) and subsequent PTV volume, consistent with prior literature. ∼1cm MRI had an average PTV volume comparable to ∼8mm CT at 3.79% difference. Bladder QUANTEC constraints were on average less for the ∼1cm MRI as compared to the ∼8mm CT and observed as statistically significant with 2.64% reduction in V65. Rectal constraints appeared to follow the same trend. Case-by-case analysis showed variation in rectal V30 with MRI delineated prostate being most favorable regardless of expansion type. ∼1cm MRI and ∼8mm CT had comparable plan quality. Conclusion: MRI delineated prostate with standard expansions had the smallest PTV leading to margins that may be too tight. Bladder/rectum carveout expansion method on MRI delineated prostate was found to be superior to standard CT based methods in terms of bladder and rectal sparing while maintaining prostate coverage. Continued investigation is warranted for further validation.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-225: CEST Imaging in Head and Neck Cancer Patients

Purpose: Chemical Exchange Saturation Transfer (CEST) imaging is an MRI technique enables the detection and imaging of metabolically active compounds in vivo. It has been used to differentiate tumor types and metabolic characteristics. Unlike PET/CT,CEST imaging does not use isotopes so it can be used on patient repeatedly. This study is to report the preliminary results of CEST imaging in Head and Neck cancer (HNC) patients. Methods: A CEST imaging sequence and the post-processing software was developed on a 3T clinical MRI scanner. Ten patients with Human papilloma virus positive oropharyngeal cancer were imaged in their immobilized treatment position. A 5 mm slice CEST image was acquired (128×128, FOV=20∼24cm) to encompass the maximum dimension of tumor. Twenty-nine off-set frequencies (from −7.8ppm to +7.8 ppm) were acquired to obtain the Z-spectrum. Asymmetry analysis was used to extract the CEST contrasts. ROI at the tumor, node and surrounding tissues were measured. Results: CEST images were successfully acquired and Zspectrum asymmetry analysis demonstrated clear CEST contrasts in tumor as well as the surrounding tissues. 3∼5% CEST contrast in the range of 1 to 4 ppm was noted in tumor as well as grossly involved nodes. Injection of glucose produced a marked increase of CEST contrast in tumor region (∼10%). Motion and pulsation artifacts tend to smear the CEST contrast, making the interpretation of the image contrast difficult. Field nonuniformity, pulsation in blood vesicle and susceptibility artifacts caused by air cavities were also problematic for CEST imaging. Conclusion: We have demonstrated successful CEST acquisition and Z-spectrum reconstruction on HNC patients with a clinical scanner. MRI acquisition in immobilized treatment position is critical for image quality as well as the success of CEST image acquisition. CEST images provide novel contrast of metabolites in HNC and present great potential in the pre- and post-treatment assessment of patients undergoing radiation therapy.

60 APPLIED LIFE SCIENCES↗