X-ray Fluorescence Microscopy to Develop Elemental Classifiers and Investigate Elemental Signatures in BALB/c Mouse Intestine a Week after Exposure to 8 Gy of Gamma Rays.

Iron redistribution in the intestine after total body irradiation is an established phenomenon. However, in the literature, there are no reports about the use of X-ray fluorescence microscopy or equivalent techniques to generate semi-quantitative 2D maps of iron in sectioned intestine samples from irradiated mice. In this work, we used X-ray fluorescence microscopy (XFM) to map the elemental content of iron as well as phosphorus, sulfur, calcium, copper and zinc in tissue sections of the small intestine from eight-week-old BALB/c male mice that developed gastrointestinal acute radiation syndrome (GI-ARS) in response to exposure to 8 Gray of gamma rays.

Revisiting the Historic Strontium-90 Ingestion Beagle Study Conducted at the University of California Davis: Opportunity in Archival Materials.

Strontium-90 is a radionuclide found in high concentrations in nuclear reactor waste and nuclear fallout from reactor accidents and atomic bomb explosions. In the 1950s, little was known regarding the health consequences of strontium-90 internalization. To assess the health effects of strontium-90 ingestion in infancy through adolescence, the Atomic Energy Commission and Department of Energy funded large-scale beagle studies at the University of California Davis.

Gene Expression and Early Radiation Response of Two Distinct Neuroblastoma Cell Lines.

Introduction: Neuroblastoma is one of the most common childhood cancers with one of the lowest survival rates, accounting for 15% of childhood cancer mortality. Approximately half of children treated for high-risk neuroblastoma will relapse following remission, while another 15% of patients do not respond to initial treatment. External beam radiation is infrequently used for treatment of pediatric cancer such as neuroblastoma, typically reserved for palliative care in patients with aggressive metastatic disease who fail to respond to alternative treatments.

Proof of principle study: synchrotron X-ray fluorescence microscopy for identification of previously radioactive microparticles and elemental mapping of FFPE tissues.

Biobanks containing formalin-fixed, paraffin-embedded (FFPE) tissues from animals and human atomic-bomb survivors exposed to radioactive particulates remain a vital resource for understanding the molecular effects of radiation exposure. These samples are often decades old and prepared using harsh fixation processes which limit sample imaging options. Optical imaging of hematoxylin and eosin (H&E) stained tissues may be the only feasible processing option, however, H&E images provide no information about radioactive microparticles or radioactive history.

Lessons learned in the practice of community-based participatory research with community partner collaboration in study design and implementation: the community scientist model.

Engagement of community participation is an innovative driver of modern research. However, to benefit the communities being studied, it is imperative to continuously evaluate ethical considerations, the relationship dynamic between researchers and community members, and the responsiveness of research teams to the needs and preferences of communities. Northwestern University's Center for Health Equity Transformation founded a community scientist program in 2018 that implemented a study using the Community-Based Participatory Research (CBPR) model.

Findings from international archived data: Fractionation reduces mortality risk of ionizing radiation for total doses below 4 Gray in rodents.

Ionizing radiation is omnipresent and unavoidable on Earth; nevertheless, the range of doses and modes of radiation delivery that represent health risks remain controversial. Radiation protection policy for civilians in US is set at 1 mSv per year. Average persons from contemporary populations are exposed to several hundred milliSieverts (mSv) over their lifetimes from both natural and human made sources such as radon, cosmic rays, CT-scans (20-50 mSv partial body exposure per scan), etc.

A reliable workflow for improving nanoscale X-ray fluorescence tomographic analysis on nanoparticle-treated HeLa cells.

Scanning X-ray fluorescence (XRF) tomography provides powerful characterization capabilities in evaluating elemental distribution and differentiating their inter- and intra-cellular interactions in a three-dimensional (3D) space. Scanning XRF tomography encounters practical challenges from the sample itself, where the range of rotation angles is limited by geometric constraints, involving sample substrates or nearby features either blocking or converging into the field of view. This study aims to develop a reliable and efficient workflow that can (1) expand the experimental window for nanoscale tomographic analysis of local areas of interest within a laterally extended specimen, and (2) bridge 3D analysis at micrometer and nanoscales on the same specimen.

The enduring legacy of Marie Curie: impacts of radium in 21st century radiological and medical sciences.

Purpose: This review is focused on radium and radionuclides in its decay chain in honor of Marie Curie, who discovered this element.

Materials And Methods: We conglomerated current knowledge regarding radium and its history predating our present understanding of this radionuclide.

Results: An overview of the properties of radium and its dose assessment is shown followed by discussions about both the negative detrimental and positive therapeutic applications of radium with this history and its evolution reflecting current innovations in medical science.

Development of FeO core-TiO shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization.

Background: Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of FeO core-TiO shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using FeO core-TiO shell nanocomposites could be used to enhance radiation effects in neuroblastoma.

Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples.

Research in cancer nanotechnology is entering its third decade, and the need to study interactions between nanomaterials and cells remains urgent. Heterogeneity of nanoparticle uptake by different cells and subcellular compartments represent the greatest obstacles to a full understanding of the entire spectrum of nanomaterials' effects. In this work, we used flow cytometry to evaluate changes in cell cycle associated with non-targeted nanocomposite uptake by individual cells and cell populations.

Use of X-Ray Fluorescence Microscopy for Studies on Research Models of Hepatocellular Carcinoma.

TheraSphere microspheres containing yttrium Y are among many radioembolization agents used clinically to reduce liver tumor burden, and their effects on cancer volume reduction are well-established. At the same time, concerns about off target tissue injury often limit their use. Deeper investigation into tissue distribution and long-term impact of these microspheres could inform us about additional ways to use them in practice.

Paramagnetic MnFe--Polystyrene Nanobeads as a Potential T-T Multimodal Magnetic Resonance Imaging Contrast Agent with Studies.

In developing a cluster-nanocarrier design, as a magnetic resonance imaging contrast agent, we have investigated the enhanced relaxivity of a manganese and iron-oxo cluster grafted within a porous polystyrene nanobead with increased relaxivity due to a higher surface area. The synthesis of the cluster-nanocarrier for the cluster MnFeO(OCCHCH═CH)(HO), cross-linked with polystyrene (the nanocarrier), under miniemulsion conditions is described. By including a branched hydrophobe, -octane, the resulting nanobeads are porous and ∼70 nm in diameter.

Analyses of cancer incidence and other morbidities in neutron irradiated B6CF1 mice.

The Department of Energy conduced ten large-scale neutron irradiation experiments at Argonne National Laboratory between 1972 and 1989. Using a new approach to utilize experimental controls to determine whether a cross comparison between experiments was appropriate, we amalgamated data on neutron exposures to discover that fractionation significantly improved overall survival. A more detailed investigation showed that fractionation only had a significant impact on the death hazard for animals that died from solid tumors, but did not significantly impact any other causes of death.

Effects of low dose and low dose rate low linear energy transfer radiation on animals - review of recent studies relevant for carcinogenesis.

Carcinogenic effects of radiation are often assumed to be universally understood, more often than, for example, carcinogenic effects of many different chemicals. This in turn leads to an assumption that any dose of radiation, delivered at any dose rate, poses a serious health challenge. This remains an issue of dispute and low dose radiation research is focused on understanding whether these exposures contribute to cancer incidence.

Analyses of cancer incidence and other morbidities in gamma irradiated B6CF1 mice.

With increasing medical radiation exposures, it is important to understand how different modes of delivery of ionizing radiation as well as total doses of exposure impact health outcomes. Our lab studied the risks associated with ionizing radiation by analyzing the Northwestern University Radiation Archive for animals (NURA). NURA contains detailed data from a series of 10 individual neutron and gamma irradiation experiments conducted on over 50,000 mice.

Overcoming challenges in human saliva gene expression measurements.

Saliva, as a non-invasive and easily accessible biofluid, has been shown to contain RNA biomarkers for prediction and diagnosis of several diseases. However, systematic analysis done by our group identified two problematic issues not coherently described before: (1) most of the isolated RNA originates from the oral microbiome and (2) the amount of isolated human RNA is comparatively low. The degree of bacterial contamination showed ratios up to 1:900,000, so that only about one out of 900,000 RNA copies was of human origin, but the RNA quality (average RIN 6.

Activation of DNA damage repair factors in HPV positive oropharyngeal cancers.

The mechanisms regulating viral pathogenesis of human papillomavirus (HPV) associated oropharyngeal squamous cell cancers (OPSCC) are not well understood. In the cervix, activation of DNA damage repair pathways is critical for viral replication but little is known about their role in OPSCC. APOBEC factors have been shown to be increased in OPSCC but the significance of this is unclear.

Insights into platinum-induced peripheral neuropathy-current perspective.

Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors.

Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma.

Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of exploratory analysis into the trace elemental composition of oropharyngeal squamous cell carcinoma (OPSCC), we performed elemental quanitification by X-ray fluorescence microscopy (XFM) on a small cohort (n = 32) of patients with HPV-positive and -negative OPSCC and identified in HPV-positive cases increased zinc (Zn) concentrations in tumor tissue relative to normal tissue.

Optimization-based simultaneous alignment and reconstruction in multi-element tomography.

As x-ray microscopy is pushed into the nanoscale with the advent of more bright and coherent x-ray sources, associated improvement in spatial resolution becomes highly vulnerable to geometrical errors and uncertainties during data collection. We address a form of error in tomography experiments, namely, the drift between projections during the tomographic scan. Our proposed method can simultaneously recover the drift, while tomographically reconstructing the specimen based on a joint iterative optimization scheme.

The Transition from Metal-Based to Metal-Free Contrast Agents for Magnetic Resonance Imaging Enhancement.

Magnetic resonance imaging (MRI) has received significant attention as the noninvasive diagnostic technique for complex diseases. Image-guided therapeutic strategy for diseases such as cancer has also been at the front line of biomedical research, thanks to the innovative MRI, enhanced by the prior delivery of contrast agents (CAs) into patients' bodies through injection. These CAs have contributed a great deal to the clinical utility of MRI but have been based on metal-containing compounds such as gadolinium, manganese, and iron oxide.

Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin.

Radiation databases and archives - examples and comparisons.

Studies of ionizing radiation effects through the archiving of data began with standardizing medical treatments in the early 1900s shortly after the discovery of X-rays. Once the breadth of the delayed effects of ionizing radiation was recognized, the need for long-term follow up became apparent. There are now many human archives of data from nuclear disasters and accidents, occupational exposures, and medical procedures.

Funding for radiation research: past, present and future.

For more than a century, ionizing radiation has been indispensable mainly in medicine and industry. Radiation research is a multidisciplinary field that investigates radiation effects. Radiation research was very active in the mid- to late 20th century, but has then faced challenges, during which time funding has fluctuated widely.