Rat model of metastatic breast cancer monitored by MRI at 3 tesla and bioluminescence imaging with histological correlation

<p>Abstract</p> <p>Background</p> <p>Establishing a large rodent model of brain metastasis that can be monitored using clinically relevant magnetic resonance imaging (MRI) techniques is challenging. Non-invasive imaging of brain metastasis in mice usually requires high field strength MR units and long imaging acquisition times. Using the brain seeking MDA-MB-231BR transfected with luciferase gene, a metastatic breast cancer brain tumor model was investigated in the nude rat. Serial MRI and bioluminescence imaging (BLI) was performed and findings were correlated with histology. Results demonstrated the utility of multimodality imaging in identifying unexpected sights of metastasis and monitoring the progression of disease in the nude rat.</p> <p>Methods</p> <p>Brain seeking breast cancer cells MDA-MB-231BR transfected with firefly luciferase (231BRL) were labeled with ferumoxides-protamine sulfate (FEPro) and 1-3 × 10⁶cells were intracardiac (IC) injected. MRI and BLI were performed up to 4 weeks to monitor the early breast cancer cell infiltration into the brain and formation of metastases. Rats were euthanized at different time points and the imaging findings were correlated with histological analysis to validate the presence of metastases in tissues.</p> <p>Results</p> <p>Early metastasis of the FEPro labeled 231BRL were demonstrated onT2*-weighted MRI and BLI within 1 week post IC injection of cells. Micro-metastatic tumors were detected in the brain on T2-weighted MRI as early as 2 weeks post-injection in greater than 85% of rats. Unexpected skeletal metastases from the 231BRL cells were demonstrated and validated by multimodal imaging. Brain metastases were clearly visible on T2 weighted MRI by 3-4 weeks post infusion of 231BRL cells, however BLI did not demonstrate photon flux activity originating from the brain in all animals due to scattering of the photons from tumors.</p> <p>Conclusion</p> <p>A model of metastatic breast cancer in the nude rat was successfully developed and evaluated using multimodal imaging including MRI and BLI providing the ability to study the temporal and spatial distribution of metastases in the brain and skeleton.</p

Hemodynamic effects of short-term hyperoxia after coronary artery bypass grafting

Background: Although oxygen is generally administered in a liberal manner in the perioperative setting, the effects of oxygen administration on dynamic cardiovascular parameters, filling status and cerebral perfusion have not been fully unraveled. Our aim was to study the acute hemodynamic and microcirculatory changes before, during and after arterial hyperoxia in mechanically ventilated patients after coronary artery bypass grafting (CABG) surgery. Methods: This was a single-center physiological study in a tertiary care ICU in the Netherlands. Twenty-two patients scheduled for ICU admission after elective CABG were enrolled in the study between September 2014 and September 2015. In the ICU, patients were exposed to a fraction of inspired oxygen (FiO(2)) of 90% allowing a 15-min wash-in period. Various hemodynamic parameters were measured using direct pressure signals and continuous arterial waveform analysis at three sequential time points: before, during and after hyperoxia. Results: During a 15-min exposure to a fraction of inspired oxygen (FiO2) of 90%, the partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO(2)) were significantly higher. The systemic resistance increased (P <0.0001), without altering the heart rate. Stroke volume variation and pulse pressure variation decreased slightly. The cardiac output did not significantly decrease (P = 0.08). Mean systemic filling pressure and arterial critical closing pressure increased (P <0.01), whereas the percentage of perfused microcirculatory vessels decreased (P <0.01). Other microcirculatory parameters and cerebral blood flow velocity showed only slight changes. Conclusions: We found that short-term hyperoxia affects hemodynamics in ICU patients after CABG. This was translated in several changes in central circulatory variables, but had only slight effects on cardiac output, cerebral blood flow and the microcirculatio

COVID-19, systemic crisis, and possible implications for the wild meat trade in sub-Saharan Africa

Wild animals play an integral and complex role in the economies and ecologies of many countries across the globe, including those of West and Central Africa, the focus of this policy perspective. The trade in wild meat, and its role in diets, have been brought into focus as a consequence of discussions over the origins of COVID-19. As a result, there have been calls for the closure of China’s “wet markets”; greater scrutiny of the wildlife trade in general; and a spotlight has been placed on the potential risks posed by growing human populations and shrinking natural habitats for animal to human transmission of zoonotic diseases. However, to date there has been little attention given to what the consequences of the COVID-19 economic shock may be for the wildlife trade; the people who rely on it for their livelihoods; and the wildlife that is exploited. In this policy perspective, we argue that the links between the COVID-19 pandemic, rural livelihoods and wildlife are likely to be more complex, more nuanced, and more far-reaching, than is represented in the literature to date. We develop a causal model that tracks the likely implications for the wild meat trade of the systemic crisis triggered by COVID-19. We focus on the resulting economic shockwave, as manifested in the collapse in global demand for commodities such as oil, and international tourism services, and what this may mean for local African economies and livelihoods. We trace the shockwave through to the consequences for the use of, and demand for, wild meats as households respond to these changes. We suggest that understanding and predicting the complex dynamics of wild meat use requires increased collaboration between environmental and resource economics and the ecological and conservation sciences

The pursuit of hysteresis in polycrystalline ferromagnetic materials under stress

External stresses alter the magnetic properties of ferromagnetic materials such as iron and steel, a fact that has been the basis of substantial study in nondestructive testing. Existing theories and models have so far not proven reliable or accurate enough to develop a practical means of using the developed theory relating stress and magnetization to measure biaxial strains without prior knowledge of the strain or magnetic history of the sample. A deterministic model of ferromagnetic hysteresis and the effects of external stresses in materials such as iron and steel is introduced by this study. Changes in hysteresis loops due to stress are explained via changes in the magnetocrystalline anisotropy at the crystal-unit level, and are extended to the macroscopic effects that are seen in experiments. An original equation is presented which accurately describes experimentally acquired major hysteresis loops and directly relates two parameters to the two perpendicular principal strain axes thereby providing a technique able to determine the absolute stress/strain experienced by the sample. This model will potentially enable quantitative, nondestructive stress measuring devices to be developed. © 2009 IEEE

MRI measurement of oxygen extraction fraction, mean vessel size and cerebral blood volume using serial hyperoxia and hypercapnia.

Functional magnetic resonance imaging measures signal increases arising from a variety of interrelated effects and physiological sources. Recently there has been some success in disentangling this signal in order to quantify baseline physiological parameters, including the resting oxygen extraction fraction (OEF), cerebral blood volume (CBV) and mean vessel size. However, due to the complicated nature of the signal, each of these methods relies on certain physiological assumptions to derive a solution. In this work we present a framework for the simultaneous, voxelwise measurement of these three parameters. The proposed method removes the assumption of a fixed vessel size from the quantification of OEF and CBV, while simultaneously removing the need for an assumed OEF in the calculation of vessel size. The new framework is explored through simulations and validated with a pilot study in healthy volunteers. The MRI protocol uses a combined hyperoxia and hypercapnia paradigm with a modified spin labelling sequence collecting multi-slice gradient echo and spin echo data

MRI measurement of oxygen extraction fraction, mean vessel size and cerebral blood volume using serial hyperoxia and hypercapnia.

Functional magnetic resonance imaging measures signal increases arising from a variety of interrelated effects and physiological sources. Recently there has been some success in disentangling this signal in order to quantify baseline physiological parameters, including the resting oxygen extraction fraction (OEF), cerebral blood volume (CBV) and mean vessel size. However, due to the complicated nature of the signal, each of these methods relies on certain physiological assumptions to derive a solution. In this work we present a framework for the simultaneous, voxelwise measurement of these three parameters. The proposed method removes the assumption of a fixed vessel size from the quantification of OEF and CBV, while simultaneously removing the need for an assumed OEF in the calculation of vessel size. The new framework is explored through simulations and validated with a pilot study in healthy volunteers. The MRI protocol uses a combined hyperoxia and hypercapnia paradigm with a modified spin labelling sequence collecting multi-slice gradient echo and spin echo data

Origins of the magnetomechanical effect

A hypothesis is presented to explain the mechanism by which externally applied stresses can affect the magnetic properties of ferromagnetic materials. Experiments have revealed coincident points in the second and fourth quadrants on stressed hysteresis loops of mild steel. The results are presented along with an explanation of this effect. An atomic level theory of the origins of the magnetomechanical effect is introduced whereby spin-spin and spin-orbit coupling interact with magnetic moments to alter the magnetocrystalline anisotropy and exchange energies. © 2002 Elsevier Science B.V. All rights reserved