Magnetic resonance imaging for pathobiological assessment and interventional treatment of the coronary arteries.

X-ray-based fluoroscopy is the standard tool for diagnostics and intervention in coronary artery disease. In recent years, computed tomography has emerged as a non-invasive alternative to coronary angiography offering detection of coronary calcification and imaging of the vessel lumen by the use of iodinated contrast agents. Even though currently available invasive or non-invasive techniques can show the degree of vessel stenosis, they are unable to provide information about biofunctional plaque properties, e.g. plaque inflammation. Furthermore, the use of radiation and the necessity of iodinated contrast agents remain unfavourable prerequisites. Magnetic resonance imaging (MRI) is a radiation-free alternative to X-ray which offers anatomical and functional imaging contrasts fostering the idea of non-invasive biofunctional assessment of the coronary vessel wall. In combination with molecular contrast agents that target-specific epitopes of the vessel wall, MRI might reveal unique plaque properties rendering it, for example, 'vulnerable and prone to rupture'. Early detection of these lesions may allow for early or prophylactic treatment even before an adverse coronary event occurs. Besides diagnostic imaging, advances in real-time image acquisition and motion compensation now provide grounds for MRI-guided coronary interventions. In this article, we summarize our research on MRI-based molecular imaging in cardiovascular disease and feature our advances towards real-time MRI-based coronary interventions in a porcine model.

La fluoroscopia con rayos X es la herramienta estándar para el diagnóstico y la intervención de coronariopatías. En los últimos años, la tomografía computarizada se ha convertido en una alternativa atraumática a la coronariografía, ya que se puede detectar la calcificación coronaria y ver a través de imágenes las luces de los vasos sanguíneos mediante el uso de medios de contraste yodados. Si bien las técnicas traumáticas o atraumáticas disponibles actualmente pueden mostrar el grado de la estenosis vascular, no pueden proporcionar información sobre las propiedades biofuncionales de la placa de ateroma, por ejemplo, inflamación de la placa de ateroma. Por otra parte, el uso de radiación y la necesidad de agentes de contraste yodados siguen siendo requisitos desfavorables. La resonancia magnética (RM) es una alternativa sin radiación a los rayos X que proporciona contrates de imagen con información anatómica y funcional, lo cual refuerza la idea del diagnóstico biofuncional atraumático de las paredes de los vasos coronarios. En combinación con medios de contraste molecular que actúan sobre epítopos específicos de las paredes de los vasos, la RM puede poner de manifiesto propiedades particulares de la placa de ateroma mediante su representación, por ejemplo, «vulnerabilidad y predisposición a rotura¼. La detección precoz de este tipo de lesiones puede facilitar un tratamiento a tiempo o preventivo antes de que tenga lugar una complicación coronaria grave.Además del diagnóstico por imagen, los avances en la adquisición de imágenes en tiempo real y la compensación del movimiento sirven de base para las intervenciones coronarias guiadas por RM. En este artículo, ofrecemos un resumen de nuestra investigación sobre imagen molecular con resonancia magnética en enfermedades cardiovasculares y presentamos nuestros avances hacia las intervenciones coronarias con RM en tiempo real en un modelo porcino.

Current practices and knowledge supporting oil spill risk assessment in the Arctic.

Oil spill response (OSR) in the Arctic marine environment conducted as part of operational planning and preparedness supporting exploration and development is most successful when knowledge of the ecosystem is readily available and applicable in an oil spill risk assessment framework. OSR strategies supporting decision-making during the critical period after a spill event should be explicit about the environmental resources potentially at risk and the efficacy of OSR countermeasures that best protect sensitive and valued resources. At present, there are 6 prominent methods for spill impact mitigation assessment (SIMA) in the Arctic aimed at supporting OSR and operational planning and preparedness; each method examines spill scenarios and identifies response strategies best suited to overcome the unique challenges posed by polar ecosystems and to minimize potential long-term environmental consequences. The different methods are grounded in classical environmental risk assessment and the net environmental benefit analysis (NEBA) approach that emerged in the 1990s after the Exxon Valdez oil spill. The different approaches share 5 primary assessment elements (oil physical and chemical properties, fate and transport, exposure, effects and consequence analysis). This paper highlights how the different Arctic methods reflect this common risk assessment framework and share a common need for oil spill science relevant to Arctic ecosystems. An online literature navigation portal, developed as part of the 5-year Arctic Oil Spill Response Technologies Joint Industry Programme, complements the different approaches currently used in the Arctic by capturing the rapidly expanding body of scientific knowledge useful to evaluating exposure, vulnerability and recovery of the Arctic ecosystem after an oil spill.

Comparative risk assessment of oil spill response options for a deepwater oil well blowout: Part II. Relative risk methodology.

Subsea dispersant injection (SSDI) was a new oil spill response (OSR) technology deployed during the Deepwater Horizon accident. To integrate SSDI into future OSR decisions, a hypothetical deepwater oil spill to the Gulf of Mexico was simulated and a comparative risk assessment (CRA) tool applied to contrast three response strategies: (1) no intervention; (2) mechanical recovery, in-situ burning, and surface dispersants; and, (3) SSDI in addition to responses in (2). A comparative ecological risk assessment (CRA) was applied to multiple valued ecosystem components (VECs) inhabiting different environmental compartments (ECs) using EC-specific exposure and relative VEC population density and recovery time indices. Results demonstrated the added benefit of SSDI since relative risks to shoreline, surface wildlife and most aquatic life VECs were reduced. Sensitivity of results to different assumptions was also tested to illustrate flexibility of the CRA tool in addressing different stakeholder priorities for mitigating the impacts of a deepwater blowout.

Comparative Risk Assessment of spill response options for a deepwater oil well blowout: Part 1. Oil spill modeling.

Oil spill model simulations of a deepwater blowout in the Gulf of Mexico De Soto Canyon, assuming no intervention and various response options (i.e., subsea dispersant injection SSDI, in addition to mechanical recovery, in-situ burning, and surface dispersant application) were compared. Predicted oil fate, amount and area of surfaced oil, and exposure concentrations in the water column above potential effects thresholds were used as inputs to a Comparative Risk Assessment to identify response strategies that minimize long-term impacts. SSDI reduced human and wildlife exposure to volatile organic compounds; dispersed oil into a large water volume at depth; enhanced biodegradation; and reduced surface water, nearshore and shoreline exposure to floating oil and entrained/dissolved oil in the upper water column. Tradeoffs included increased oil exposures at depth. However, since organisms are less abundant below 200 m, results indicate that overall exposure of valued ecosystem components was minimized by use of SSDI.

Comparative risk assessment of spill response options for a deepwater oil well blowout: Part III. Stakeholder engagement.

This paper describes oil spill stakeholder engagement in a recent comparative risk assessment (CRA) project that examined the tradeoffs associated with a hypothetical offshore well blowout in the Gulf of Mexico, with a specific focus on subsea dispersant injection (SSDI) at the wellhead. SSDI is a new technology deployed during the Deepwater Horizon (DWH) oil spill response. Oil spill stakeholders include decision makers, who will consider whether to integrate SSDI into future tradeoff decisions. This CRA considered the tradeoffs associated with three sets of response strategies: (1) no intervention; (2) mechanical recovery, in-situ burning, and surface dispersants; and, (3) SSDI in addition to responses in (2). For context, the paper begins with a historical review of U.S. policy and engagement with oil spill stakeholders regarding dispersants. Stakeholder activities throughout the project involved decision-maker representatives and their advisors to inform the approach and consider CRA utility in future oil spill preparedness.

Evaluation of triclosan in Minnesota lakes and rivers: Part I - ecological risk assessment.

Triclosan, an antimicrobial compound found in consumer products, may be introduced into the aquatic environment via residual concentrations in municipal wastewater treatment effluent. We conducted an aquatic risk assessment that incorporated the available measured triclosan data from Minnesota lakes and rivers. Although only data reported from Minnesota were considered in the risk assessment, the developed toxicity benchmarks can be applied to other environments. The data were evaluated using a series of environmental fate models to ensure the data were internally consistent and to fill any data gaps. Triclosan was not detected in over 75% of the 567 surface water and sediment samples. Measured environmental data were used to model the predicted environmental exposures to triclosan in surface water, surface sediment, and biota tissues. Toxicity benchmarks based on fatty acid synthesis inhibition and narcosis were determined for aquatic organisms based, in part, on a species sensitivity distribution of chronic toxicity thresholds from the available literature. Predicted and measured environmental concentrations for surface water, sediment, and tissue were below the effects benchmarks, indicating that exposure to triclosan in Minnesota lakes and rivers would not pose an unacceptable risk to aquatic organisms.

Evaluation of triclosan in Minnesota lakes and rivers: Part II - human health risk assessment.

Triclosan, an antimicrobial compound found in consumer products, has been detected in low concentrations in Minnesota municipal wastewater treatment plant (WWTP) effluent. This assessment evaluates potential health risks for exposure of adults and children to triclosan in Minnesota surface water, sediments, and fish. Potential exposures via fish consumption are considered for recreational or subsistence-level consumers. This assessment uses two chronic oral toxicity benchmarks, which bracket other available toxicity values. The first benchmark is a lower bound on a benchmark dose associated with a 10% risk (BMDL10) of 47mg per kilogram per day (mg/kg-day) for kidney effects in hamsters. This value was identified as the most sensitive endpoint and species in a review by Rodricks et al. (2010) and is used herein to derive an estimated reference dose (RfD(Rodricks)) of 0.47mg/kg-day. The second benchmark is a reference dose (RfD) of 0.047mg/kg-day derived from a no observed adverse effect level (NOAEL) of 10mg/kg-day for hepatic and hematopoietic effects in mice (Minnesota Department of Health [MDH] 2014). Based on conservative assumptions regarding human exposures to triclosan, calculated risk estimates are far below levels of concern. These estimates are likely to overestimate risks for potential receptors, particularly because sample locations were generally biased towards known discharges (i.e., WWTP effluent).

Glioma vessel abnormality quantification using time-of-flight MR angiography.

OBJECTIVES: To differentiate between abnormal tumor vessels and regular brain vasculature using new quantitative measures in time-of-flight (TOF) MR angiography (MRA) data. MATERIALS AND METHODS: In this work time-of-flight (TOF) MR angiography data are acquired in 11 glioma patients to quantify vessel abnormality. Brain vessels are first segmented with a new algorithm, efficient monte-carlo image-analysis for the location of vascular entity (EMILOVE), and are then characterized in three brain regions: tumor, normal-appearing contralateral brain, and the total brain volume without the tumor. For characterization local vessel orientation angles and the dot product between local orientation vectors are calculated and averaged in the 3 regions. Additionally, correlation with histological and genetic markers is performed. RESULTS: Both the local vessel orientation angles and the dot product show a statistically significant difference (p < 0.005) between tumor vessels and normal brain vasculature. Furthermore, the connection to both histology and the gene expression of the tumor can be found-here, the measures were compared to the proliferation marker Ki-67 [MIB] and genome-wide expression analysis. The results in a subgroup indicate that the dot product measure may be correlated with activated genetic pathways. CONCLUSION: It is possible to define a measure of vessel abnormality based on local vessel orientation angles which can differentiate between normal brain vasculature and glioblastoma vessels.

Fifty Years of Technological Innovation: Potential and Limitations of Current Technologies in Abdominal Magnetic Resonance Imaging and Computed Tomography.

Magnetic resonance imaging (MRI) has become an important modality for the diagnosis of intra-abdominal pathology. Hardware and pulse sequence developments have made it possible to derive not only morphologic but also functional information related to organ perfusion (dynamic contrast-enhanced MRI), oxygen saturation (blood oxygen level dependent), tissue cellularity (diffusion-weighted imaging), and tissue composition (spectroscopy). These techniques enable a more specific assessment of pathologic lesions and organ functionality. Magnetic resonance imaging has thus transitioned from a purely morphologic examination to a modality from which image-based disease biomarkers can be derived. This fits well with several emerging trends in radiology, such as the need to accurately assess response to costly treatment strategies and the need to improve lesion characterization to potentially avoid biopsy. Meanwhile, the cost-effectiveness, availability, and robustness of computed tomography (CT) ensure its place as the current workhorse for clinical imaging. Although the lower soft tissue contrast of CT relative to MRI is a long-standing limitation, other disadvantages such as ionizing radiation exposure have become a matter of public concern. Nevertheless, recent technical developments such as dual-energy CT or dynamic volume perfusion CT also provide more functional imaging beyond morphology.The aim of this article was to review and discuss the most important recent technical developments in abdominal MRI and state-of-the-art CT, with an eye toward the future, providing examples of their clinical utility for the evaluation of hepatic and renal pathologies.

Changing boreal methane sources and constant biomass burning during the last termination.

Past atmospheric methane concentrations show strong fluctuations in parallel to rapid glacial climate changes in the Northern Hemisphere superimposed on a glacial-interglacial doubling of methane concentrations. The processes driving the observed fluctuations remain uncertain but can be constrained using methane isotopic information from ice cores. Here we present an ice core record of carbon isotopic ratios in methane over the entire last glacial-interglacial transition. Our data show that the carbon in atmospheric methane was isotopically much heavier in cold climate periods. With the help of a box model constrained by the present data and previously published results, we are able to estimate the magnitude of past individual methane emission sources and the atmospheric lifetime of methane. We find that methane emissions due to biomass burning were about 45 Tg methane per year, and that these remained roughly constant throughout the glacial termination. The atmospheric lifetime of methane is reduced during cold climate periods. We also show that boreal wetlands are an important source of methane during warm events, but their methane emissions are essentially shut down during cold climate conditions.

Impact of oxygen inhalation on the pulmonary circulation: assessment by magnetic resonance (MR)-perfusion and MR-flow measurements.

PURPOSE: Oxygen-enhanced magnetic resonance (MR)-ventilation imaging of the lung is based on the inhalation of a high concentration of oxygen (hyperoxia). However, the effect of hyperoxia on the pulmonary circulation is not yet fully understood. In this study the impact of hyperoxia on the pulmonary circulation was evaluated. MATERIALS AND METHODS: Ten healthy volunteers were examined in a 1.5 T MRI system with contrast-enhanced perfusion MRI (saturation recovery 2D turboFLASH) of the lung and phase-contrast flow measurements in the pulmonary trunk. Both measurements were performed breathing room air (RA) and, subsequently, 100% oxygen (15 L/min) (O(2)). RESULTS: The perfusion measurements showed a significant difference between RA and O(2) for the pulmonary blood flow (181 vs. 257 mL/min/100 mL, P = 0.04) and blood volume (14 vs. 21 mL/100 mL, P = 0.008). The mean transit time of the contrast bolus was not changed (P = 0.4) in the dorsal part of the lung, whereas it was significantly prolonged (P = 0.006) in the central part. The mean heart rate during flow measurements breathing RA (67 +/- 11 beats/min) and O(2) (61 +/- 12 beats/min) were not significantly different (P = 0.055). The average cardiac output (pulmonary trunk) was not significantly lower while breathing O(2) (RA: 5.9 vs. O(2): 5.5 L/min, P = 0.054). CONCLUSION: Hyperoxia causes a significant increase and redistribution of the pulmonary perfusion, whereas it leads to a not significant decrease in cardiac output. Thus, for MR-perfusion and MR-flow measurements oxygen inhalation should be avoided, if possible. In the context of oxygen-enhanced MR-ventilation imaging of the lung the contribution of this effect needs to be further evaluated.

Manganese-enhanced magnetic resonance imaging for in vivo assessment of damage and functional improvement following spinal cord injury in mice.

In past decades, much effort has been invested in developing therapies for spinal injuries. Lack of standardization of clinical read-out measures, however, makes direct comparison of experimental therapies difficult. Damage and therapeutic effects in vivo are routinely evaluated using rather subjective behavioral tests. Here we show that manganese-enhanced magnetic resonance imaging (MEMRI) can be used to examine the extent of damage following spinal cord injury (SCI) in mice in vivo. Injection of MnCl2 solution into the cerebrospinal fluid leads to manganese uptake into the spinal cord. Furthermore, after injury MEMRI-derived quantitative measures correlate closely with clinical locomotor scores. Improved locomotion due to treating the detrimental effects of SCI with an established therapy (neutralization of CD95Ligand) is reflected in an increase of manganese uptake into the injured spinal cord. Therefore, we demonstrate that MEMRI is a sensitive and objective tool for in vivo visualization and quantification of damage and functional improvement after SCI. Thus, MEMRI can serve as a reproducible surrogate measure of the clinical status of the spinal cord in mice, potentially becoming a standard approach for evaluating experimental therapies.

Regional lung perfusion: assessment with partially parallel three-dimensional MR imaging.

PURPOSE: To evaluate partially parallel three-dimensional (3D) magnetic resonance (MR) imaging for assessment of regional lung perfusion in healthy volunteers and patients suspected of having lung cancer or metastasis. MATERIALS AND METHODS: Seven healthy volunteers and 20 patients suspected of having lung cancer or metastasis were examined with 3D gradient-echo MR imaging with partially parallel image acquisitions (fast low-angle shot 3D imaging; repetition time msec/echo time msec, 1.9/0.8; flip angle, 40 degrees; acceleration factor, two; number of reference k-space lines for calibration, 24; field of view, 500 x 440 mm; matrix, 256 x 123; slab thickness, 160 mm; number of partitions, 32; voxel size, 3.6 x 2.0 x 5.0 mm(3); acquisition time, 1.5 seconds) after administration of 0.1 mmol/kg of gadobenate dimeglumine. In volunteers, 3D MR perfusion data sets were assessed for topographic and temporal distribution of regional lung perfusion. Sensitivity, specificity, accuracy, and positive and negative predictive values for perfusion MR imaging for detecting perfusion abnormalities in patients were calculated, with conventional radionuclide perfusion scintigraphy as the standard of reference. Interobserver and intermodality agreement was determined by using kappa statistics. RESULTS: Topographic analysis of lung perfusion in volunteers revealed a significantly higher signal-to-noise ratio (SNR) of up to 327% in gravity-dependent lung areas. Temporal analysis similarly revealed much shorter lag time to peak enhancement in gravity-dependent lung areas. In patients, perfusion MR imaging achieved high sensitivity (88%-94%), specificity (100%), and accuracy (90%-95%) for detection of perfusion abnormalities. Interobserver agreement (kappa = 0.86) was very good and intermodality agreement (kappa = 0.69-0.83) was good to very good for detection of perfusion defects. A significant difference (P <.0001) in SNR was observed between normally perfused lung (14 +/- 7 [SD]) and perfusion defects (7 +/- 4) in patients. CONCLUSION: Partially parallel MR imaging with high spatial and temporal resolution allows assessment of regional lung perfusion and has high diagnostic accuracy for detecting perfusion abnormalities.

Partially parallel three-dimensional magnetic resonance imaging for the assessment of lung perfusion--initial results.

RATIONALE: Contrast-enhanced magnetic resonance imaging (MRI) of lung perfusion requires a high spatial and temporal resolution. Partially parallel MRI offers an improved spatial and temporal resolution. OBJECTIVE: To assess the feasibility of partially parallel MRI for the assessment of lung perfusion. METHODS: Two healthy volunteers and 14 patients were examined with a contrast-enhanced 3D gradient-echo pulse sequence with partially parallel image acquisitions (TE/TR/alpha: 0.8/1.9 milliseconds/40 degrees; voxel size 3.6 x 2.0 x 5.0 mm3, TA: 1.5 seconds). The image analysis included an analysis of the signal-to-noise ratio in the lungs in areas with normal and impaired perfusion. 3D MR perfusion image data were analyzed for perfusion defects and compared with radionuclide perfusion scans, which were available for 10 of 14 patients. RESULTS: The analysis of the 3D perfusion-weighted data allowed a clear differentiation of perfusion abnormalities: MRI showed normal lung perfusion in 9 of 16 cases, whereas perfusion abnormalities were observed in 7 cases. When compared with the radionuclide perfusion scans, a good intermodality agreement was shown (kappa = 0.74). When compared with normally perfused lung a significantly lower signal to noise ratio was observed in hypoperfused lung (7 versus 17; P = 0.02). CONCLUSION: Partially parallel MRI might be used for the assessment of lung perfusion. Future studies are required to further evaluate the diagnostic impact of this technique.