This study aimed at evaluating hybrid multispectral optoacoustic tomography/ultrasound for imaging of thyroid disorders, including Graves' disease and thyroid nodules. Methods: The functional biomarkers and tissue parameters deoxygenated hemoglobin, oxygenated hemoglobin, total hemoglobin, saturation of hemoglobin, fat content, and water content were analyzed in thyroid lobes affected by Graves' disease (n 5 6), thyroid lobes with healthy tissue (n 5 8), benign thyroid nodules (n 5 13), and malignant thyroid nodules (n 5 3). Results: In Graves' disease, significantly higher deoxygenated hemoglobin (3.18 ± 0.52 vs. 2.13 ± 0.62; P 5 0.0055) and total hemoglobin (8.34 ± 0.88 vs. 6.59 ± 1.16; P 5 0.0084) and significantly lower fat content (0.64 ± 0.37 vs. 1.69 ± 1.25; P 5 0.0293) were found than in healthy controls. Malignant thyroid nodules showed significantly lower saturation of hemoglobin (55.4% ± 2.6% vs. 60.8% ± 7.2%; P 5 0.0393) and lower fat content (0.62 ± 0.19 vs. 1.46 ± 0.87; P 5 0.1295) than benign nodules. Conclusion: This pilot study showed the applicability and the potential of hybrid multispectral optoacoustic tomography/ultrasound to semiquantitatively provide tissue characterization and functional parameters in thyroid disorders for improved noninvasive diagnostics of thyroid diseases.
Short-lived reactive intermediates such as reactive oxygen species (ROS) regulate many physiological processes, but overproduction can also lead to severe tissue dysfunction. Thus, there is a high demand for noninvasive detection of reactive molecules, which, however, is challenging. Herein, we report photoacoustic detection of ROS using conjugated BODIPY probes (ROS-BODIPYs). The ROS reaction with conjugated BODIPYs induced a redshift in absorption by ∼100 nm into the near infrared (from ∼700 to ∼800 nm), quenched fluorescence, and generated strong photoacoustic (PA) signals. Thus, the ROS-activated and ROS-nonactivated states of ROS-BODIPYs can be detected in vivo by PA and fluorescence imaging. Interestingly, ROS activation is reversible, in the presence of excess reducing agents, e.g., citric acid, converted back to its original state, suggesting that ROS-BODIPYs can be useful for the detection of over production of ROS but not physiological amounts. This makes the imaging independent of accumulation of the activated probe with the physiological ROS amounts and thus strongly improves applicability and highlights the translational potential of ROS-BODIPYs for detecting overexpression of ROS in vivo by optical and photoacoustic imaging methods.
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