Identifying and Responding to Lead in Drinking Water in a University Setting.

Lead is an established neurotoxicant, and it has known associations with adverse neurodevelopmental and reproductive outcomes. Exposure to lead at any level is unsafe, and the United States (US) has enacted various federal and state legislations to regulate lead levels in drinking water in K-12 schools and childcare facilities; however, no regulations exist for higher education settings. Upon the discovery of lead in drinking water fixtures in the University of North Carolina at Chapel Hill (UNC-CH) campus, a cross-campus water testing network and sampling plan was developed and deployed. The campaign was based on the US Environmental Protection Agency's (EPA) 3Ts (Training, Testing, and Taking Action) guidance. The seven-month campaign involved 5954 tests on 3825 drinking water fixtures across 265 buildings. A total of 502 (8.43%) tests showed lead above the limit of detection (1 part per billion, ppb), which represented 422 (11.03%) fixtures. Fewer than 1.5% of the tests were above the EPA action level for public water systems (15 ppb). In conclusion, systematic testing of all the fixtures across campus was required to identify localized contamination, and each entity in the cross-campus network undertook necessary roles to generate a successful testing campaign. UNC-CH established preventative measures to test drinking water fixtures every three years, which provide a framework for other higher education institutions in responding to lead contamination.

Validation of single reference variable flip angle (SR-VFA) dynamic T1 mapping with T2 * correction using a novel rotating phantom.

PURPOSE: To validate single reference variable flip angle (SR-VFA) dynamic T1 mapping with and without T2 * correction against inversion recovery (IR) T1 measurements. METHODS: A custom cylindrical phantom with three concentric compartments was filled with variably doped agar to produce a smooth spatial gradient of the T1 relaxation rate as a function of angle across each compartment. IR T1 , VFA T1 , and B1 + measurements were made on the phantom before rotation, and multi-echo stack-of-radial dynamic images were acquired during rotation via an MRI-compatible motor. B1 + -corrected SR-VFA and SR-VFA-T2 * T1 maps were computed from the sliding window reconstructed images and compared against rotationally registered IR and VFA T1 maps to determine the percentage error. RESULTS: Both VFA and SR-VFA-T2 * T1 maps fell within 10% of IR T1 measurements for a low rotational speed, with a mean accuracy of 2.3% ± 2.6% and 2.8% ± 2.6%, respectively. Increasing rotational speed was found to decrease the accuracy due to increasing temporal smoothing over ranges where the T1 change had a nonconstant slope. SR-VFA T1 mapping was found to have similar accuracy as the SR-VFA-T2 * and VFA methods at low TEs (˜<2 ms), whereas accuracy degraded strongly with later TEs. T2 * correction of the SR-VFA T1 maps was found to consistently improve accuracy and precision, especially at later TEs. CONCLUSION: SR-VFA-T2 * dynamic T1 mapping was found to be accurate against reference IR T1 measurements within 10% in an agar phantom. Further validation is needed in mixed fat-water phantoms and in vivo.

Heterogeneous Oxidation Products of Fine Particulate Isoprene Epoxydiol-Derived Methyltetrol Sulfates Increase Oxidative Stress and Inflammatory Gene Responses in Human Lung Cells.

Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous ·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by ·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2, and CAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by ·OH exposure was associated with an increased expression of glutathione pathway-related genes (GCLM and GCLC) and an anti-inflammatory gene (IL-10).

Extracellular Vesicles altered by a Per- and Polyfluoroalkyl Substance Mixture: In Vitro Dose-Dependent Release, Chemical Content, and MicroRNA Signatures involved in Liver Health.

Per- and polyfluoroalkyl substances (PFAS) have emerged as high priority contaminants due to their ubiquity and pervasiveness in the environment. Numerous PFAS co-occur across sources of drinking water, including areas of North Carolina (NC) with some detected concentrations above the Environmental Protection Agency's health advisory levels. While evidence demonstrates PFAS exposure induces harmful effects in the liver, the involvement of extracellular vesicles (EVs) as potential mediators of these effects has yet to be evaluated. This study set out to evaluate the hypothesis that PFAS mixtures induce dose-dependent release of EVs from liver cells, with exposures causing differential loading of microRNAs (miRNAs) and PFAS chemical signatures. To test this hypothesis, a defined PFAS mixture was prioritized utilizing data collected by the NC PFAS Testing Network. This mixture contained three substances, PFOS, PFOA, and PFHxA, selected based upon co-occurrence patterns and the inclusion of both short-chain (PFHxA) and long-chain (PFOA and PFOS) substances. HepG2 liver cells were exposed to equimolar PFAS, and secreted EVs were isolated from conditioned media and characterized for count and molecular content. Exposures induced a dose-dependent release of EVs carrying miRNAs that were differentially loaded upon exposure. These altered miRNA signatures were predicted to target mRNA pathways involved in hepatic fibrosis and cancer. Chemical concentrations of PFOS, PFOA, and PFHxA were also detected in both parent HepG2 cells and their released EVs, specifically within a 15-fold range after normalizing for protein content. This study therefore established EVs as novel biological responders and measurable endpoints for evaluating PFAS-induced toxicity.

Effect of Delayed Oncoplastic Reduction Mammoplasty on Radiation Treatment Delay Following Breast-Conserving Surgery for Breast Cancer.

BACKGROUND: The purpose of this study was to evaluate the delay in initiating adjuvant radiation therapy (RT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer who underwent oncoplastic reduction mammoplasty (ORM) following BCS compared with a matched cohort of patients who did not undergo ORM between BCS and RT. METHODS: Medical records of 112 women (56 ORMs and 56 matched non-ORMs) with carcinoma in situ or early-stage breast cancer treated with BCS were reviewed. ORM was performed in a delayed manner following BCS, allowing confirmation of negative surgical margins. Time to RT was defined as time from last oncologic surgery to start of RT. RESULTS: The median follow-up time was 6.8 years for the ORM cohort and 6.7 years for the control non-ORM cohort. Patients who underwent ORM following BCS experienced a significant delay in initiating RT (>8 weeks) than matched patients not undergoing ORM (66% vs. 34%; p < 0.001). Wound complications occurred in 44.6% (n = 25) of patients in the ORM cohort, which were mostly minor, including delayed wound healing and/or infection (39%). There was no significant difference in local recurrence between patients in the non-ORM and ORM cohorts (p = 0.32). CONCLUSIONS: This study demonstrates that ORM following BCS has the potential to delay RT >8 weeks, largely as a result of increased risk of wound complications; however, this delay did not impact local control. ORM can be safely considered for appropriately selected patients with breast cancer.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.

The American Society for Radiation Oncology Workforce Taskforce Review of the United States Radiation Oncology Workforce Analysis.

Over the past decade, concerns have arisen in radiation oncology regarding potential workforce supply and demand imbalance. The American Society for Radiation Oncology commissioned an independent analysis in 2022, looking at supply and demand in the United States radiation oncology workforce and projecting future trends for 2025 and 2030. The final report, titled Projected Supply and Demand for Radiation Oncologists in the U.S. in 2025 and 2030, is now available. The analysis included evaluating radiation oncologist (RO) supply (new graduates, exits from the specialty), potential changes in demand (growth of Medicare beneficiaries, hypofractionation, loss of indications, new indications) as well as RO productivity (growth of work relative value units [wRVUs] produced), and demand per beneficiary. The results demonstrated a relative balance between radiation oncology supply and demand for radiation services; the growth in ROs was balanced by the rapid growth of Medicare beneficiaries over the same period. The primary factors driving the model were found to be growth of Medicare beneficiaries and change in wRVU productivity, with hypofractionation and loss of indication having only a moderate effect; although the most likely scenario was a balance of workforce supply and demand, scenarios did demonstrate the possibility of over- and undersupply. Oversupply may become a concern if RO wRVU productivity reaches the highest region; beyond 2030, this is also possible if growth in RO supply does not parallel Medicare beneficiary growth, which is projected to decline and will require corresponding supply adjustment. Limitations of the analysis included uncertainty regarding the true number of ROs, the lack of inclusion of most technical reimbursement and its effect as well as failing to account for stereotactic body radiation therapy. A modeling tool is available to allow individuals to evaluate different scenarios. Moving forward, continued study will be needed to evaluate trends (particularly wRVU productivity and Medicare beneficiary growth) to allow for continued assessment of workforce supply and demand in radiation oncology.

Comparison of Prospective and Retrospective Gated 4D Flow Cardiac MR Image Acquisitions in the Carotid Bifurcation.

PURPOSE: To evaluate the agreement of 4D flow cMRI-derived bulk flow features and fluid (blood) velocities in the carotid bifurcation using prospective and retrospective gating techniques. METHODS: Prospective and retrospective ECG-gated three-dimensional (3D) cine phase-contrast cardiac MRI with three-direction velocity encoding (i.e., 4D flow cMRI) data were acquired in ten carotid bifurcations from men (n = 3) and women (n = 2) that were cardiovascular disease-free. MRI sequence parameters were held constant across all scans except temporal resolution values differed. Velocity data were extracted from the fluid domain and evaluated across the entire volume or at defined anatomic planes (common, internal, external carotid arteries). Qualitative agreement between gating techniques was performed by visualizing flow streamlines and topographical images, and statistical comparisons between gating techniques were performed across the fluid volume and defined anatomic regions. RESULTS: Agreement in the kinematic data (e.g., bulk flow features and velocity data) were observed in the prospectively and retrospectively gated acquisitions. Voxel differences in time-averaged, peak systolic, and diastolic-averaged velocity magnitudes between gating techniques across all volunteers were 2.7%, 1.2%, and 6.4%, respectively. No significant differences in velocity magnitudes or components ([Formula: see text], [Formula: see text], [Formula: see text]) were observed. Importantly, retrospective acquisitions captured increased retrograde flow in the internal carotid artery (i.e., carotid sinus) compared to prospective acquisitions (10.4 ± 6.3% vs. 4.6 ± 5.3%; [Formula: see text] < 0.05). CONCLUSION: Prospective and retrospective ECG-gated 4D flow cMRI acquisitions provide comparable evaluations of fluid velocities, including velocity vector components, in the carotid bifurcation. However, the increased temporal coverage of retrospective acquisitions depicts increased retrograde flow patterns (i.e., disturbed flow) not captured by the prospective gating technique.

Association between high-risk extracranial carotid plaque and covert brain infarctions and cerebral microbleeds.

PURPOSE: Covert brain infarctions (CBIs) and cerebral microbleeds (CMBs) represent subclinical sequelae of ischemic and hemorrhagic cerebral small vessel disease, respectively. In addition to thromboembolic stroke, carotid atherosclerosis has been associated with downstream vascular brain injury, including inflammation and small vessel disease. The specific plaque features responsible for this are unknown. We aimed to determine the association of specific vulnerable carotid plaque features to CBIs and CMBs to better understand the relation of large and small vessel disease in a single-center retrospective observational study. METHODS: Intraplaque hemorrhage (IPH) and plaque ulceration were recorded on carotid MRA and total, cortical, and lacunar CBIs and CMBs were recorded on brain MR in 349 patients (698 carotid arteries). Multivariable Poisson regression was performed to relate plaque features to CBIs and CMBs. Within-subject analysis in those with unilateral IPH and ulceration was performed with Poisson regression. RESULTS: Both IPH and plaque ulceration were associated with total CBI (prevalence ratios (PR) 3.33, 95% CI: 2.16-5.15 and 1.91, 95% CI: 1.21-3.00, respectively), after adjusting for stenosis, demographic, and vascular risk factors. In subjects with unilateral IPH, PR was 2.83, 95% CI: 1.76-4.55, for CBI in the ipsilateral hemisphere after adjusting for stenosis. Among those with unilateral ulceration, PR was 1.82, 95% CI: 1.18-2.81, for total CBI ipsilateral to ulceration after adjusting for stenosis. No statistically significant association was seen with CMBs. CONCLUSION: Both IPH and plaque ulceration are associated with total, cortical, and lacunar type CBIs but not CMBs suggesting that advanced atherosclerosis contributes predominantly to ischemic markers of subclinical vascular injury.

Dapsone-induced methemoglobinemia and hemolysis in a woman without G6PD deficiency presenting with idiopathic urticaria.

BACKGROUND: The appearance of bite cells associated with methemoglobinemia can be caused by oxidizing drugs such as dapsone in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or high drug serum levels. Bite cells are often pathognomonic for oxidant injury in patients with G6PD deficiency and suggest active hemolysis. CASE PRESENTATION: We report a case of a woman with no prior history of G6PD deficiency who presented with anemia, methemoglobinemia and bite cells on peripheral blood smear after dapsone therapy for new onset idiopathic urticaria. Laboratory tests for G6PD, blood count and liver function were within normal limits prior to initiation of therapy. During the patient's hospital course, moderate methemoglobinemia and anemia were identified despite mildly increased serum G6PD level. These pathologies were reversed upon stopping dapsone therapy. CONCLUSION: This case highlights the potential for therapeutic levels of dapsone to induce side effects in patients without G6PD deficiency and highlights the importance of routine blood monitoring for anemia and hemolysis during the course of drug therapy.

Placental genomics mediates genetic associations with complex health traits and disease.

As the master regulator in utero, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we perform distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 traits, integrating placental multi-omics from the Extremely Low Gestational Age Newborn Study. At [Formula: see text], we detect 248 GTAs, mostly for neonatal and metabolic traits, across 176 genes, enriched for cell growth and immunological pathways. In aggregate, genetic effects mediated by placental expression significantly explain 4 early-life traits but no later-in-life traits. 89 GTAs show significant mediation through distal genetic variants, identifying hypotheses for distal regulation of GTAs. Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS, and multiple genes involved in metabolic pathways. These results suggest profound health impacts of placental genomic regulation in developmental programming across the life course.

Differential placental CpG methylation is associated with chronic lung disease of prematurity.

BACKGROUND: Chronic lung disease (CLD) is the most common pulmonary morbidity in extremely preterm infants. It is unclear to what extent prenatal exposures influence the risk of CLD. Epigenetic variation in placenta DNA methylation may be associated with differential risk of CLD, and these associations may be dependent upon sex. METHODS: Data were obtained from a multi-center cohort of infants born extremely preterm (<28 weeks' gestation) and an epigenome-wide approach was used to identify associations between placental DNA methylation and CLD (n = 423). Associations were evaluated using robust linear regression adjusting for covariates, with a false discovery rate of 0.05. Analyses stratified by sex were used to assess differences in methylation-CLD associations. RESULTS: CLD was associated with differential methylation at 49 CpG sites representing 46 genes in the placenta. CLD was associated with differential methylation of probes within genes related to pathways involved in fetal lung development, such as p53 signaling and myo-inositol biosynthesis. Associations between CpG methylation and CLD differed by sex. CONCLUSIONS: Differential placental methylation within genes with key roles in fetal lung development may reflect complex cell signaling between the placenta and fetus which mediate CLD risk. These pathways appear to be distinct based on fetal sex. IMPACT: In extremely preterm infants, differential methylation of CpG sites within placental genes involved in pathways related to cell signaling, oxidative stress, and trophoblast invasion is associated with chronic lung disease of prematurity. DNA methylation patterns associated with chronic lung disease were distinctly based on fetal sex, suggesting a potential mechanism underlying dimorphic phenotypes. Mechanisms related to fetal hypoxia and placental myo-inositol signaling may play a role in fetal lung programming and the developmental origins of chronic lung disease. Continued research of the relationship between the placental epigenome and chronic lung disease could inform efforts to ameliorate or prevent this condition.

Quasistatic Solutions versus Full-Wave Solutions of Single-Channel Circular RF Receive Coils on Phantoms of Varying Conductivities at 3 Tesla.

PURPOSE: Although full-wave simulations could be used to aid in RF coil design, the algorithms may be too slow for an iterative optimization algorithm. If quasistatic simulations are accurate within the design tolerance, then their use could reduce simulation time by orders of magnitude compared to full-wave simulations. This paper examines the accuracy of quasistatic and full-wave simulations at 3 Tesla. METHODS: Three sets of eight coils ranging from 3-10 cm (24 total) were used to measure SNR on three phantoms with conductivities of 0.3, 0.6, and 0.9 S/m. The phantom conductivities were chosen to represent those typically found in human tissues. The range of coil element sizes represents the sizes of coil elements seen in typical coil designs. SNR was determined using the magnetic and electric fields calculated by quasistatic and full-wave simulations. Each simulated SNR dataset was scaled to minimize the root mean squared error (RMSE) when compared against measured SNR data. In addition, the noise values calculated by each simulation were compared against benchtop measured noise values. RESULTS: The RMSE was 0.285 and 0.087 for the quasistatic and full-wave simulations, respectively. The maximum and minimum quotient values, when taking the ratio of simulated to measured SNR values, were 1.69 and 0.20 for the quasistatic simulations and 1.29 and 0.75 for the full-wave simulations, respectively. The ratio ranges, for the calculated quasistatic and full-wave total noise values compared to benchtop measured noise values, were 0.83-1.06 and 0.27-3.02, respectively. CONCLUSIONS: Full-wave simulations were on average 3x more accurate than the quasistatic simulations. Full-wave simulations were more accurate in characterizing the wave effects within the sample, though they were not able to fully account for the skin effect when calculating coil noise.

ReIMAGINE: a prostate cancer research consortium with added value through its patient and public involvement and engagement.

BACKGROUND: ReIMAGINE aims to improve the current prostate specific antigen (PSA)/biopsy risk stratification for prostate cancer (PCa) and develop a new image-based method (with biomarkers) for diagnosing high/low risk PCa in men. ReIMAGINE's varied patient and public involvement (PPI) and engagement (PE) strategy maximises the impact of its scientific output by informing and shaping the different stages of research. AIMS: Through including the voice of patients and the public, the ReIMAGINE Consortium aims to translate these different perspectives into the design and implementation process. This will improve the overall quality of the research by: reflecting the needs and priorities of patients and the public, ensuring methods and procedures are feasible and appropriate ensuring information is relevant and accessible to those being recruited to the study identifying dissemination channels relevant to patients/the public and developing outputs that are accessible to a lay audience With support from our patient/user groups, the ReIMAGINE Consortium aims to improve our ability to derive prognostic information and allocate men to the most appropriate and effective therapies, using a novel image-based risk stratification with investigation of non-imaging biomarkers. FINDINGS: We have been working with patients and the public from initiation of the project to ensure that the research is relevant to men and their families. Our PPI Sub-Committee, led by a PCa patient, has been involved in our dissemination strategy, outreach activities, and study design recommendations. For example, the sub-committee have developed a variety of informative videos relevant and accessible to those being recruited, and organised multiple online research engagement events that are accessible to a lay audience. As quoted by one of the study participants, "the more we present the benefits and opportunities to patients and the public, the more research commitment we obtain, and the sooner critical clinical questions such as PCa diagnostics will be addressed".

One in eight men will be diagnosed with prostate cancer (PCa). Most will not die of it, but our ability to identify those men whose cancer poses the greatest threat to life has, thus far, been poor. Some men are diagnosed with small cancers which will never cause them a problem, some will have treatment which is unnecessary, others will have their cancers missed, and others will be misclassified as either having low risk cancer and will therefore miss out on the appropriate treatment, or told their cancer is high risk and have unnecessary treatment. Nowhere else in modern medicine are these errors of over-diagnosis, over-treatment, missed-diagnoses, and poor risk-stratification more common. The ReIMAGINE Consortium has been developed to undertake discoveries that will correct these four key errors in the PCa diagnostic pathway. We will investigate how to best identify which men have, or will develop, aggressive prostate cancer using imaging combined with advanced biomarker analyses of blood and urine (i.e., OMICs technologies such as whole genome sequencing, targeted sequencing (e.g.: = , methylation). We will achieve this by building on established partnerships between patients, advocacy organisations, clinicians, imaging experts, molecular biologists, methodologists, and a broad range of industrial partners.The Patient and Public Involvement (PPI) sub-committee is an integral part of the study workflow, contributing to study design and recruitment, results analysis, and dissemination. The committee, led by a funded PPI co-ordinator and a patient chair, have given invaluable insight into the study modifications due to COVID-19 restrictions.

Improving image quality in transcranial magnetic resonance guided focused ultrasound using a conductive screen.

Transcranial Magnetic Resonance guided Focused Ultrasound (TcMRgFUS) has been proven to be an effective treatment for some neurological disorders such as essential and Parkinson's tremor. However, magnetic resonance guidance at 3 Tesla (3T) frequencies and using the large hemispherical transducers required for TcMRgFUS results in artifactual low-signal bands that pass through key regions of the brain. The purpose of this work was to investigate the use of a circular conductive Radio Frequency (RF) screen, that is bent to have a 12 cm radius in one direction and positioned near the top or back of the head, to reduce or remove these artifactual low-signal bands in TcMRgFUS. The impact of using an RF screen to remove these low signal bands was studied in both imaging experiments and electromagnetic simulations. Hydrophone measurements of the acoustic transparency of the bronze 2 mm diameter square mesh screen used in the imaging studies were compared with temperature measurements with and without the screen in heating studies in the TcMRgFUS system. The imaging and simulation studies both show that for the different screen configurations studied in this work, RF screen removes the low-signal bands and increases both homogeneity and signal-to-noise ratio (SNR) throughout the region of the brain. Hydrophone and heating studies indicate that even a 2 mm wire mesh provides minimal attenuation to the ultrasound beam. Simulation results also suggest that a 1 cm mesh will provide adequate artifact suppression with even less ultrasound attenuation. An RF screen that disrupts the natural waveguide nature of the transducer in the 3T MR environment can change the electromagnetic field profile to reduce unwanted artifacts and provide an imaging region which has more homogeneity and higher SNR throughout the brain.

Youth and parent report of sleep-based interventions and utilization of technology resources in the treatment of pediatric mood disorders.

OBJECTIVES: Mood disorders in youth are associated with social and academic impairment, and difficulties within the family system. Engagement in sleep hygiene, and family- and technology-based treatment models can address these impairments. The current study evaluates changes in functioning for youth who participated in a family-based partial hospitalization program (PHP) for mood disorders. Child and parent views of the importance and application of sleep hygiene and utilization of technology-based interventions were also evaluated. METHODS: 474 youth diagnosed with a primary mood disorder and their caregivers participated in a family-based PHP that addressed the role of sleep hygiene, technology use for symptom management, and components of evidence-based treatments in ameliorating mood disorders. Participants were evaluated 1-, 3-, and 6-month following treatment. RESULTS: Participants demonstrated improved functioning in social, home, and school domains. The majority of participants and parents found the sleep hygiene content and application important or very important as a component of treatment. Parents were significantly more likely than youth to be interested in using technology to access after care resources. CONCLUSIONS: Findings revealed significantly less impairment in functioning at follow-up. Parents and youth reported interest in sleep hygiene strategies as part of a comprehensive treatment for mood disorders as well as the use of technology-based resources to assist with treatment. Limitations include sample demographics and follow-up sample size.

A Breast-Specific MR Guided Focused Ultrasound Platform and Treatment Protocol: First-in-Human Technical Evaluation.

OBJECTIVE: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. METHODS: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). RESULTS: Successful technical treatments were achieved in 80 % of the patients. All patients underwent the treatment with no sedation and 60 % of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 ±1.8 mm while 6.2 ±1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 % and 70 % of patients, respectively. CONCLUSION: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts.

Phase 1 study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery in the primary management of patients with inoperable, previously irradiated metastatic epidural spinal cord compression.

BACKGROUND: Patients with previously irradiated metastatic epidural spinal cord compression (MESCC) who are not surgical candidates are at high risk of neurologic deterioration due to disease in the setting of limited treatment options. We seek to establish the feasibility of using salvage spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of MESCC in inoperable patients monitoring for radiation related toxicity and radiographic local control (LC). METHODS: Inoperable patients with previously irradiated MESCC were enrolled on this prospective Phase 1 single institution protocol. Single fraction SSRS was delivered to a prescription dose of 18 Gy. Spinal cord constraint relaxation was performed incrementally from an initial allowable Dmax cohort of 8 Gy to 14 Gy in the final planned cohort. Patients were monitored every 3 months with follow-up visits and MRI scans. RESULTS: The trial was closed early due to slow accrual. From 2011 to 2014, 11 patients were enrolled of which 9 patients received SSRS. Five patients were in the 8 Gy cord Dmax cohort and 4 in the 10 Gy cord Dmax cohort.The median overall survival (OS) was 11.9 months (95% CI 7.1, 22 months). Of the 9 patients treated with SSRS, 1 died prior to post-SSRS evaluation. Of the remaining 8 patients, 5 experienced a local failure. Three of the five were treated with surgery while two received systemic therapy. Two of the five failures ultimately resulted in loss of neurologic function. The median LC was 9.1 months (95%CI 4.8, 20.1 months). With a median clinical follow-up of 6.8 months, there were no cases of RM. CONCLUSIONS: Despite the limited life expectancy in this high-risk cohort of patients, strategies to optimize LC are necessary to prevent neurologic deterioration. Larger prospective trials exploring optimal dose/fractionation and cord constraints are required.

Placental microRNAs: Responders to environmental chemicals and mediators of pathophysiology of the human placenta.

MicroRNAs (miRNAs) are epigenetic modifiers that play an important role in the regulation of the expression of genes across the genome. miRNAs are expressed in the placenta as well as other organs, and are involved in several biological processes including the regulation of trophoblast differentiation, migration, invasion, proliferation, apoptosis, angiogenesis and cellular metabolism. Related to their role in disease process, miRNAs have been shown to be differentially expressed between normal placentas and placentas obtained from women with pregnancy/health complications such as preeclampsia, gestational diabetes mellitus, and obesity. This dysregulation indicates that miRNAs in the placenta likely play important roles in the pathogenesis of diseases during pregnancy. Furthermore, miRNAs in the placenta are susceptible to altered expression in relation to exposure to environmental toxicants. With relevance to the placenta, the dysregulation of miRNAs in both placenta and blood has been associated with maternal exposures to several toxicants. In this review, we provide a summary of miRNAs that have been assessed in the context of human pregnancy-related diseases and in relation to exposure to environmental toxicants in the placenta. Where data are available, miRNAs are discussed in their context as biomarkers of exposure and/or disease, with comparisons made across-tissue types, and conservation across studies detailed.

Technical Note: Effect of transducer position and ground plane configuration on image quality in MR-guided focused ultrasound therapies.

PURPOSE: To evaluate the effect of a focused ultrasound transducer position and ground plane configuration on magnetic resonance image quality. METHODS: The effect of transducer position with respect to the MRI B0 field and the radiofrequency receive coils was evaluated in a breast-specific MRgFUS system with an integrated RF phased-array coil. Image signal-to-noise ratio was evaluated at different transducer locations. The effect of ultrasound transducer ground plane configuration was evaluated using a replica transducer with 12 ground plane configurations. All evaluations were performed at 3 Tesla. RESULTS: Both transducer position and ground plane configuration were found to have a considerable effect on overall image SNR. A 67% increase in SNR was achieved by positioning the transducer face perpendicular to the B0 field. A 25% increase in SNR was achieved by segmenting the replica transducer ground plane from one continuous plane to nine individual segments. CONCLUSIONS: Advances in focused ultrasound hardware allow for integrated radiofrequency MRI coils as well as adjustable transducer positioning. The placement of the ultrasound transducer with respect to both the magnetic field and RF coils can have a considerable effect on image SNR and the resulting MR images that are used for MR-guided focused ultrasound treatment planning, monitoring and assessment.