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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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