In the kidney and liver, fibrosis is a powerful predictor of outcomes. Unfortunately, accurate fibrosis quantification cannot be done non-invasively. Photoacoustic (PA) imaging offers the potential for measuring collagen, the principal component of the fibrotic matrix. Here, we demonstrate the potential of PA imaging for fibrosis quantification in preclinical kidney and liver fibrosis models. To induce kidney fibrosis, the left ureter was obstructed for 0 (n = 5), 7 (n = 5) or 14 days (n =5). The right kidneys at each day (n = 15) served as controls. To induce liver fibrosis, carbon tetrachloride (CCl4) injections were given to mice (n = 31). Control mice (n = 12) received corn oil vehicle injections. A PA unmixing algorithm based on the use of the variance inflation coefficient for detecting the multicollinearity of collagen/oxy/deoxyhemoglobin was developed and validated against gold standard histology measurements. The VevoLAZR-X system was used in the 680-930 nm illumination range at 15 MHz. PA imaging revealed 4x more collagen by day 14 post ureteral obstruction compared to sham kidneys. Similarly, PA imaging suggested that fibrotic livers 6 weeks post-CCl4 injection contained about 125% more collagen than control livers. Comparisons with histological gold standards revealed a strong linear correlation (r = 0.89 – 0.99). This work demonstrates the potential of PA imaging to accurately and non-invasively assess fibrotic burden in livers and kidneys. We postulate that this technology will accelerate the preclinical assessment of antifibrotic drugs.
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