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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.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Predicting tumor cell line response to drug pairs with deep learning

The National Cancer Institute drug pair screening effort against 60 well-characterized human tumor cell lines (NCI-60) presents an unprecedented resource for modeling combinational drug activity. We present a computational model for predicting cell line response to a subset of drug pairs in the NCI-ALMANAC database. Based on residual neural networks for encoding features as well as predicting tumor growth, our model explains 94% of the response variance. While our best result is achieved with a combination of molecular feature types (gene expression, microRNA and proteome), we show that most of the predictive power comes from drug descriptors. To further demonstrate value in detecting anticancer therapy, we rank the drug pairs for each cell line based on model predicted combination effect and recover 80% of the top pairs with enhanced activity. We present promising results in applying deep learning to predicting combinational drug response. Our feature analysis indicates screening data involving more cell lines are needed for the models to make better use of molecular features.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening

Highlights: •A novel mechanism of MMP3 regulation by proton-sensing G-protein-coupled receptors was defined. •GPR65 was identified to induce the MMP3 expression. •GPR65 mediated MMP induction under acidic conditions. •AP-1 binding site in MMP3 promoter was crucial for MMP3 induction. •GPR65 overexpression can accelerate the invision of A549 cells. -- Abstract: Matrix metalloproteinases (MMPs) are over-expressed in nearly all cancers. To study novel regulatory factors of MMP expression in head and neck cancer (HNC), we screened a total of 636 candidate genes encoding putative human transmembrane proteins using MMP promoter reporter in a dual luciferase assay system. Three genes GPR65, AXL and TNFRSF10B dramatically activated the induction of MMP3 expression. The induction of MMP expression by GPR65 was further confirmed in A549 and/or FaDu cells. GPR65 mediated MMP induction under acidic conditions. The AP-1 binding site in MMP3 promoter was crucial for MMP3 induction. Moreover, the A549 cells infected by recombinant adenovirus of GPR65 showed accelerated cell invasion. In conclusion, we validate that GPR65 is vital regulatory genes upstream of MMP3, and define a novel mechanism of MMP3 regulation by proton-sensing G-protein-coupled receptors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

A review of breast tomosynthesis. Part I. The image acquisition process

Mammography is a very well-established imaging modality for the early detection and diagnosis of breast cancer. However, since the introduction of digital imaging to the realm of radiology, more advanced, and especially tomographic imaging methods have been made possible. One of these methods, breast tomosynthesis, has finally been introduced to the clinic for routine everyday use, with potential to in the future replace mammography for screening for breast cancer. In this two part paper, the extensive research performed during the development of breast tomosynthesis is reviewed, with a focus on the research addressing the medical physics aspects of this imaging modality. This first paper will review the research performed on the issues relevant to the image acquisition process, including system design, optimization of geometry and technique, x-ray scatter, and radiation dose. The companion to this paper will review all other aspects of breast tomosynthesis imaging, including the reconstruction process.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2010

An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy

Refractive index properties, especially at the nanoscale, have shown great potential in cancer diagnosis and screening. Due to the intrinsic complexity and weak refractive index fluctuation, the reconstruction of internal structures of a biological cell has been challenging. In this paper, we propose a simple and practical approach to derive the statistical properties of internal refractive index fluctuations within a biological cell with a new optical microscopy method – Low-coherence Statistical Amplitude Microscopy (SAM). We validated the capability of SAM to characterize the statistical properties of cell internal structures, which is described by numerical models of one-dimensional Gaussian random field. We demonstrated the potential of SAM in cancer detection with an animal model of intestinal carcinogenesis – multiple intestinal neoplasia mouse model. We showed that SAM-derived statistical properties of cell nuclear structures could detect the subtle changes that are otherwise undetectable by conventional cytopathology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

High-Dose-Rate Brachytherapy in the Management of Operable Rectal Cancer: A Systematic Review

Purpose: To evaluate the role of high-dose-rate endorectal brachytherapy (HDREBT) in the preoperative and definitive management of operable rectal cancer in terms of clinical outcomes and toxicities using a systematic review. Methods and Materials: A review of published articles from January 1990 to December 2016 was conducted using the PubMed, Embase, and Scopus databases using the search terms “rectal” or “rectum” in combination with “brachytherapy,” “high dose rate,” “HDR,” and “endorectal.” Additional publications were identified by scanning references. Only studies published in English reporting clinical outcomes with ≥30 patients treated with HDREBT were included. Results: The search identified 1688 articles, of which 22 met our inclusion criteria. Twelve studies were included in this systematic review. Following preoperative HDREBT with chemoradiation therapy (CRT), the pathologic complete response (pCR) rate ranged between 18% and 31% (weighted mean rate, 22.2%); R0 resection rate, between 80% and 99% (weighted mean rate, 95.5%); and sphincter-preservation rate, between 29% and 54% (weighted mean rate, 46.4%). The weighted mean 2-year progression-free survival and overall survival (OS) rates were 68.1% and 81.5%, respectively. After preoperative HDREBT alone, the pCR rate ranged between 10.4% and 27% (weighted mean rate, 23.8%), the R0 rate was 96.5% (1 study), and the sphincter-preservation rate ranged between 53.8% and 75.8% (weighted mean rate, 59.4%). The weighted mean 5-year progression-free survival and OS rates were 66.6% and 70.8%, respectively. There was only 1 study of HDREBT for nonsurgical management of rectal cancer, which reported a 2-year OS rate of 100%. Conclusions: Preoperative HDREBT either alone or in combination with CRT may result in a better pCR but may not necessarily translate into better survival, which is similar to outcomes seen following preoperative CRT alone. There were significant variations across studies in terms of patient selection, treatment approaches, and evaluation of clinical outcomes, suggesting the need for an international consensus on the dosimetric parameters and techniques of HDREBT, timing and methods of response assessment, definitions and assessment of toxicities, and optimal timing of surgery before further prospective studies. Future studies should include evaluation of the role of HDREBT in the nonsurgical curative treatment of screen-detected early cancers and organ preservation in lower rectal cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median, 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Laser-free RF-gun as a combined source of THz and ps-sub-ps X-rays

A coherent, mm-sub-mm-wave source driven by a RF electron gun is proposed for wide research applications as well as auxiliary inspection and screening, safe imaging, cancer diagnostics, surface defectoscopy, and enhanced time-domain spectroscopy. It allows generation of high peak and average THz-sub-THz radiation power provided by beam pre-bunching and chirping in the RF gun followed by microbunching in magnetic compressor, and resonant Cherenkov radiation of an essentially flat beam in a robust, ~inch-long, planar, mm-sub-mm gap structure. The proof-of-principle has been successfully demonstrated in Phase I on a 5 MeV beam of L-band thermionic injector of Idaho Accelerator Center. The system can also deliver an intense, ps-sub-ps bursts of low-to-moderate dose of relativistic electrons and X-ray radiation produced by the same beam required for pulsed radiolysis as well as to enhance screening efficiency, throughput and safety.

43 PARTICLE ACCELERATORS↗
DOE OSTI2011

Delineation of Gross Tumor Volume (GTV) for Radiation Treatment Planning of Locally Advanced Rectal Cancer Using Information From MRI or FDG-PET/CT: A Prospective Study

Purpose: Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV). Methods and Materials: From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at two university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered. Results: The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm{sup 3} vs. 87 cm{sup 3} (p < 0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5-72%). New lesions were seen in 15% of the patients for whom PET/CT was used. Conclusions: FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Cervical Precancers and Cancers Attributed to HPV Types by Race and Ethnicity: Implications for Vaccination, Screening, and Management

Abstract Background Racial and ethnic variations in attribution of cervical precancer and cancer to human papillomavirus (HPV) types may result in different HPV vaccine protection, screening test coverage, and clinical management. Methods Pooling data from 7 US studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided. Results For all racial and ethnic groups, most cases of cervical intraepithelial neoplasia grade 3 (CIN3) (84.2%-90.8% of 5526) and squamous cell carcinoma (SCC) (90.4%-93.8% of 1138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to nonvaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%; P = .002), non-Hispanic White (9.2%; P < .001), and Hispanic (11.3%; P = .004) women. The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (P = .80). A higher proportion of CIN3s were attributed to nonvaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic (3.0%; all P < .001) women. Compared with CIN3, the proportion of SCCs attributed to HPV35 among non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%; P = .70). Conclusion The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35- and other HPV16-related types.

Mix, Jacqueline (ORCID:0000000164187706)↗
DOE OSTI2018

Persistent organic pollutants in fish from Charleston Harbor and tributaries, South Carolina, United States: A risk assessment

Highlights: • Higher contaminant levels in fish from Cooper/Ashley Rivers than Charleston Harbor. • Mullet and spot were significantly higher in PCBs and pesticides than red drum. • PCBs were the predominant contaminant in whole fish and fillets from Charleston SC. • PCBs in all fillets exceed EPA human health values, consumption advisories warranted. • Whole fish PCBs, PBDEs exceed wildlife screening values, a concern for local dolphins. Fish consumption is an important route of exposure to persistent organic pollutants (POPs) in dolphins as well as humans. In order to assess the potential risks associated with these contaminants, 39 whole fish and 37 fillets from fish representing species consumed by dolphins and humans captured from Charleston Harbor and tributaries, South Carolina, USA, were measured for a suite of POPs. Polychlorinated biphenyls (PCBs) were the predominant contaminant with concentrations ranging from 5.02 to 232.20 ng/g in whole fish and 5.42–131.95 ng/g in fillets (weight weight ww) followed by total organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). Total POPs levels varied by location and species with general trends indicating significantly higher levels in fish from the Cooper (93.4 ng/g ww) and Ashley Rivers (56.2 ng/g ww) compared to Charleston Harbor (31.6 ng/g ww). Mullet and spot were found to have significantly higher PCBs, OCPs and total POPs, 2–3 times higher than red drum; mullet were also significantly higher in OCPs compared to seatrout. PCB concentrations in whole fish and fillets exceeded EPA human screening values for cancer risk in all fish sampled. For PCBs in fillets, all samples had values of maximum allowable meals per month that were less than the EPA, FDA guidelines for recommended fish meals per month, suggesting lower (more stringent) allowable fish meals per month. All fish exceeded PBDE wildlife values and all fish except two exceeded the level where 95% of the dolphin population would have tissue levels below the health effect threshold. Considering that POP concentrations in fish potentially consumed by humans exceed human health effect thresholds levels, consumption advisories should be considered as a prudent public health measure.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

The Impact of Radiation Therapy on the Risk of Lymphedema After Treatment for Breast Cancer: A Prospective Cohort Study

Purpose/Objective: Lymphedema after breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiation therapy-related risk factors for lymphedema. Methods and Materials: From 2005 to 2012, we prospectively performed arm volume measurements on 1476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099 of 1501 patients (73%) received radiation therapy. Arm measurements were performed preoperatively and postoperatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months postoperatively. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. Results: At a median follow-up time of 25.4 months (range, 3.4-82.6 months), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiation therapy type was as follows: 3.0% no radiation therapy, 3.1% breast or chest wall alone, 21.9% supraclavicular (SC), and 21.1% SC and posterior axillary boost (PAB). On multivariate analysis, the hazard ratio for regional lymph node radiation (RLNR) (SC ± PAB) was 1.7 (P=.025) compared with breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC + PAB (P=.96). Other independent risk factors included early postoperative swelling (P<.0001), higher body mass index (P<.0001), greater number of lymph nodes dissected (P=.018), and axillary lymph node dissection (P=.0001). Conclusions: In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased the risk of lymphedema compared with breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease against the increased risk of lymphedema.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

SU-E-T-317: The Development of a DIBH Technique for Left Sided Breast Patients Undergoing Radiation Therapy Utilizing Varians RPM System in a Community Hospital

Purpose: To develop and implement a Deep Inhalation Breath Hold program (DIBH) for treatment of patients with Left-sided breast cancer in a community hospital. Methods: All patients with left sided breast cancer underwent a screening free breathing CT. Evaluation of the conventional tangent treatment fields and the heart was conducted. If the heart would not be excluded using tangents, the patient then received DIBH breathe coaching. The patients returned for a 4D CT simulation. The patients breathing cycle was monitored using the Varian Real-Time position ManagementTM (RPM) system to assess duration of DIBH, amplitude, phase and recovery time to normal breathing. Then a DIBH CT was obtained at the desired amplitude. Duplicate plans were developed for both free breathing and DIBH on the Eclipse planning system and comparison DVH's were created. The plan that provided the prescribed treatment coverage and the least doses to the OAR (heart, Lt. Lung) was determined. Those patients selected to receive treatment with DIBH were set up for treatment, and breathing was monitored using the RPM system. Practice trials were used to confirm that the amplitude, phase and recovery were consistent with findings from simulation. Results: 10 patients have been treated using the DIBH procedure in our clinic. The DIBH patients had an average increase of 80% lung volume on DIBH, decreased lung volume receiving 50% of the dose, and decreases in the V20 dose. Significant reduction in the maximum and mean dose to the heart, as well as the dose to 1CC of the volume for the DIBH plans. Conclusion: Using the RPM system already available in the clinic, staff training, and patient coaching a simple DIBH program was setup. The use of DIBH has shown promise in reducing doses to the critical organs while maintaining PTV coverage for left sided breast treatments.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Radiation dosimetry in digital breast tomosynthesis: Report of AAPM Tomosynthesis Subcommittee Task Group 223

The radiation dose involved in any medical imaging modality that uses ionizing radiation needs to be well understood by the medical physics and clinical community. This is especially true of screening modalities. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Therefore, it is important that the medical physics community have the required information to be able to understand, estimate, and communicate the radiation dose levels involved in breast tomosynthesis imaging. For this purpose, the American Association of Physicists in Medicine Task Group 223 on Dosimetry in Tomosynthesis Imaging has prepared this report that discusses dosimetry in breast imaging in general, and describes a methodology and provides the data necessary to estimate mean breast glandular dose from a tomosynthesis acquisition. In an effort to maximize familiarity with the procedures and data provided in this Report, the methodology to perform the dose estimation in DBT is based as much as possible on that used in mammography dose estimation.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1984

High speed quantitative digital microscopy

Modern digital image processing hardware makes possible quantitative analysis of microscope images at high speed. This paper describes an application to automatic screening for cervical cancer. The system uses twelve MC6809 microprocessors arranged in a pipeline multiprocessor configuration. Each processor executes one part of the algorithm on each cell image as it passes through the pipeline. Each processor communicates with its upstream and downstream neighbors via shared two-port memory. Thus no time is devoted to input-output operations as such. This configuration is expected to be at least ten times faster than previous systems.

Castleman, K. R.↗
DOE OSTI2014

Computerized detection of breast cancer on automated breast ultrasound imaging of women with dense breasts

Purpose: Develop a computer-aided detection method and investigate its feasibility for detection of breast cancer in automated 3D ultrasound images of women with dense breasts. Methods: The HIPAA compliant study involved a dataset of volumetric ultrasound image data, “views,” acquired with an automated U-Systems Somo•V{sup ®} ABUS system for 185 asymptomatic women with dense breasts (BI-RADS Composition/Density 3 or 4). For each patient, three whole-breast views (3D image volumes) per breast were acquired. A total of 52 patients had breast cancer (61 cancers), diagnosed through any follow-up at most 365 days after the original screening mammogram. Thirty-one of these patients (32 cancers) had a screening-mammogram with a clinically assigned BI-RADS Assessment Category 1 or 2, i.e., were mammographically negative. All software used for analysis was developed in-house and involved 3 steps: (1) detection of initial tumor candidates, (2) characterization of candidates, and (3) elimination of false-positive candidates. Performance was assessed by calculating the cancer detection sensitivity as a function of the number of “marks” (detections) per view. Results: At a single mark per view, i.e., six marks per patient, the median detection sensitivity by cancer was 50.0% (16/32) ± 6% for patients with a screening mammogram-assigned BI-RADS category 1 or 2—similar to radiologists’ performance sensitivity (49.9%) for this dataset from a prior reader study—and 45.9% (28/61) ± 4% for all patients. Conclusions: Promising detection sensitivity was obtained for the computer on a 3D ultrasound dataset of women with dense breasts at a rate of false-positive detections that may be acceptable for clinical implementation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Vision 20/20: Mammographic breast density and its clinical applications

Breast density is a strong predictor of the failure of mammography screening to detect breast cancer and is a strong predictor of the risk of developing breast cancer. The many imaging options that are now available for imaging dense breasts show great promise, but there is still the question of determining which women are “dense” and what imaging modality is suitable for individual women. To date, mammographic breast density has been classified according to the Breast Imaging-Reporting and Data System (BI-RADS) categories from visual assessment, but this is known to be very subjective. Despite many research reports, the authors believe there has been a lack of physics-led and evidence-based arguments about what breast density actually is, how it should be measured, and how it should be used. In this paper, the authors attempt to start correcting this situation by reviewing the history of breast density research and the debates generated by the advocacy movement. The authors review the development of breast density estimation from pattern analysis to area-based analysis, and the current automated volumetric breast density (VBD) analysis. This is followed by a discussion on seeking the ground truth of VBD and mapping volumetric methods to BI-RADS density categories. The authors expect great improvement in VBD measurements that will satisfy the needs of radiologists, epidemiologists, surgeons, and physicists. The authors believe that they are now witnessing a paradigm shift toward personalized breast screening, which is going to see many more cancers being detected early, with the use of automated density measurement tools as an important component.

60 APPLIED LIFE SCIENCES↗