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Multimodal Imaging Bacterial Infection

Bacterial infection is a major cause of morbidity and mortality, especially in the case of antibiotic-resistant strains of S. aureus. A small animal model that uses noninvasive imaging provides a valuable system to study pathogenesis, its treatments and diagnostic approaches.

In collaboration with Lloyd Miller, Associate Professor in the Department of Dermatology at Johns Hopkins University, we used microultrasound and photoacoustic imaging with the Vevo LAZR system to investigate such a model.

Bacteria were labeled with a genetic reporter (luciferase) and imaged with bioluminescence to determine bacterial burden. Then, an antibiotic tagged with an optical dye called indocyanine green (ICG) or the dye alone was administered intravenously to animals that had a subdermal S. aureus infection in the hindlimb. The antibiotic-dye compound was visualized both with fluorescent whole-body imaging and with ultrasound and phtotoacoustic imaging with the Vevo LAZR. Co-registered ultrasound and multispectral photoacoustic images were acquired in 3D (ultrasound/photoacoustic image) and spectral unmixing was performed on these images to separate the antibiotic-ICG compound (green) from the background blood signal (not shown). As expected, the antibiotic-ICG conjugate was seen both with fluorescence imaging and with high resolution at depth with the photoacoustic system. The negative control (ICG alone) showed no such signal indicating that the dye was excreted and did not non-selectively label the bacteria.

Using the Vevo LAZR ultrasound and photoacoustic imaging system, precise anatomical localization and quantification of the signal can be performed, thus yielding data about the extent and precise location of the bacterial infection.