Evaluation of R-2* as a noninvasive endogenous imaging biomarker for Ebola virus liver disease progression in nonhuman primates

The main goal of this work is to evaluate R-2* 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., R-2* relaxivity from MRI) are attractive targets to monitor changes of paramagnetic substances that occur from hemorrhage and liver dysfunction during EBOV infection. R-2 maps exhibit a decreased relaxivity in edematous tissue due to higher T-2 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 R-2* because of local field inhomogeneities caused by paramagnetic molecules such as deoxyhemoglobin. In this study, R-2* 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 R-2* 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, R-2* curve roughly followed later changes in liver function tests. Lower variability of R-2* in paravertebral muscles, hematocrit, and oxygen saturation, suggests that R-2* changes may be liver-specific.

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