Dr. Danny Ragland Profile

Dr. Danny Ragland

at National Institute of Allergy and Infectious Diseases

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Proceedings Article | 28 February 2020 Paper

Evaluation of R2* as a noninvasive endogenous imaging biomarker for Ebola virus liver disease progression in nonhuman primates

Marcelo Castro, Ji Hyun Lee, Ian Crozier, Jeffrey Solomon, Joseph Laux, Danny Ragland, James Logue, Rebecca Shim, Laura Bollinger, David Thomasson, Lisa Hensley, Richard Bennett, Irwin Feuerstein

Proceedings Volume 11317, 1131726 (2020) https://doi.org/10.1117/12.2550405

KEYWORDS: Liver, Blood, Magnetic resonance imaging, Iron, Oxygen, Chemistry

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The main goal of this work is to evaluate R₂ * as an imaging biomarker of Ebola virus disease progression in the liver. Ebola virus (EBOV) disease targets the liver among other organs, resulting in hepatocellular necrosis and degeneration, hemorrhage, and edema. In the liver, EBOV destroys cells required to produce coagulation proteins and other important components of plasma and damage to blood vessels. Impairment of vascular integrity leads to disseminated intravascular coagulation and multiorgan failure, including lungs, kidneys, and liver. Noninvasive endogenous imaging biomarkers (e.g., R₂ * relaxivity from MRI) are attractive targets to monitor changes of paramagnetic substances that occur from hemorrhage and liver dysfunction during EBOV infection. R₂ maps exhibit a decreased relaxivity in edematous tissue due to higher T₂ relaxation time compared to that observed in nonedematous tissue. However, during later phases of infection, increased vascular congestion, hemorrhage, or thrombi may result in increased R₂ * because of local field inhomogeneities caused by paramagnetic molecules such as deoxyhemoglobin. In this study, R₂ * relaxivity was followed in rhesus monkeys at baseline and after exposure to a low lethality variant of EBOV through a prolonged disease course. Increases in R₂ * relaxivity measured after the acute phase of EBOV infection reached a peak about 3 weeks after exposure and then slowly returned to normal. After the acute phase, R₂ * curve roughly followed later changes in liver function tests. Lower variability of R₂ * in paravertebral muscles, hematocrit, and oxygen saturation, suggests that R₂ * changes may be liver-specific.

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