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

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

Modeling the effect of hyperoxia on the spin–lattice relaxation rate R1 of tissues

Purpose Inducing hyperoxia in tissues is common practice in several areas of research, including oxygen-enhanced MRI (OE-MRI), which attempts to use the resulting signal changes to detect regions of tumor hypoxia or pulmonary disease. The linear relationship between PO2 and R1 has been reproduced in phantom solutions and body fluids such as vitreous fluid; however, in tissue and blood experiments, factors such as changes in deoxyhemoglobin levels can also affect the ΔR1. Theory and Methods This manuscript proposes a three-compartment model for estimating the hyperoxia-induced changes in R1 of tissues depending on B0, SO2, blood volume, hematocrit, oxygen extraction fraction, and changes in blood and tissue PO2. The model contains two blood compartments (arterial and venous) and a tissue compartment. This model has been designed to be easy for researchers to tailor to their tissue of interest by substituting their preferred model for tissue oxygen diffusion and consumption. A specific application of the model is demonstrated by calculating the resulting ΔR1 expected in healthy, hypoxic and necrotic tumor tissues. In addition, the effect of sex-based hematocrit differences on ΔR1 is assessed. Results The ΔR1 values predicted by the model are consistent with reported literature OE-MRI results: with larger positive changes in the vascular periphery than hypoxic and necrotic regions. The observed sex-based differences in ΔR1 agree with findings by Kindvall et al. suggesting that differences in hematocrit levels may sometimes be a confounding factor in ΔR1. Conclusion This model can be used to estimate the expected tissue ΔR1 in oxygen-enhanced MRI experiments

A simplified empirical model to estimate oxygen relaxivity at different magnetic fields

The change in longitudinal relaxation rate (R1) produced by oxygen has been used as a means of inferring oxygenation levels in magnetic resonance imaging in numerous applications. The relationship between oxygen partial pressure (pO2) and R1 is linear and reproducible, and the slope represents the relaxivity of oxygen (r1Ox) in that material. However, there is considerable variability in the values of r1Ox reported, and they have been shown to vary by field strength and temperature. Therefore, we have compiled 28 reported empirical values of the relaxivity of oxygen as a resource for researchers. Furthermore, we provide an empirical model for estimating the relaxivity of oxygen in water, saline, plasma, and vitreous fluids, accounting for magnetic field strength and temperature. The model agrees well (R2 = 0.93) with the data gathered from the literature for fields ranging from 0.011 to 8.45 T and temperatures of 21-40 °C. This provides a useful resource for researchers seeking to quantify pO2 in simple fluids in their studies, such as water and saline phantoms, or bodily fluids such as vitreous fluids, cerebrospinal fluids, and amniotic fluids