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Photoacoustic imaging of kidney fibrosis for assessing pretransplant organ quality
Eno Hysi, Xiaolin He, Muhannad N. Fadhel, Tianzhou Zhang, Adriana Krizova, Michael Ordon, Monica Farcas, Kenneth T. Pace, Victoria Mintsopoulos, Warren L. Lee, Michael C. Kolios, Darren A. Yuen
Eno Hysi, Xiaolin He, Muhannad N. Fadhel, Tianzhou Zhang, Adriana Krizova, Michael Ordon, Monica Farcas, Kenneth T. Pace, Victoria Mintsopoulos, Warren L. Lee, Michael C. Kolios, Darren A. Yuen
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Resource and Technical Advance Nephrology

Photoacoustic imaging of kidney fibrosis for assessing pretransplant organ quality

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Abstract

Roughly 10% of the world’s population has chronic kidney disease (CKD). In its advanced stages, CKD greatly increases the risk of hospitalization and death. Although kidney transplantation has revolutionized the care of advanced CKD, clinicians have limited ways of assessing donor kidney quality. Thus, optimal donor kidney–recipient matching cannot be performed, meaning that some patients receive damaged kidneys that function poorly. Fibrosis is a form of chronic damage often present in donor kidneys, and it is an important predictor of future renal function. Currently, no safe, easy-to-perform technique exists that accurately quantifies renal fibrosis. We describe a potentially novel photoacoustic (PA) imaging technique that directly images collagen, the principal component of fibrotic tissue. PA imaging noninvasively quantifies whole kidney fibrotic burden in mice, and cortical fibrosis in pig and human kidneys, with outstanding accuracy and speed. Remarkably, 3-dimensional PA imaging exhibited sufficiently high resolution to capture intrarenal variations in collagen content. We further show that PA imaging can be performed in a setting that mimics human kidney transplantation, suggesting the potential for rapid clinical translation. Taken together, our data suggest that PA collagen imaging is a major advance in fibrosis quantification that could have widespread preclinical and clinical impact.

Authors

Eno Hysi, Xiaolin He, Muhannad N. Fadhel, Tianzhou Zhang, Adriana Krizova, Michael Ordon, Monica Farcas, Kenneth T. Pace, Victoria Mintsopoulos, Warren L. Lee, Michael C. Kolios, Darren A. Yuen

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Figure 4

Three-dimensional photoacoustic (PA) imaging accurately measures intra- and interkidney variations in fibrotic burden in a mouse model of fibrosis.

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Three-dimensional photoacoustic (PA) imaging accurately measures intra- ...
(A) PA imaging and histology orientations for mouse kidneys imaged in 3D. Transverse PA image cross-sections were acquired every 150 μm (blue lines not to scale), while Picrosirius red (PSR) staining was performed on tissue sections collected at 3 locations (orange lines), covering both poles and the middle of the kidney. Representative PA and PSR histology collagen maps are shown from multiple sections within a fibrotic kidney 14 days after unilateral ureteral obstruction surgery (L, left; M, middle; R, right). Scale bars: 5 mm (top) and 100 μm (bottom). (B) Intrakidney collagen variation for both PA-derived (left axis) and PSR-derived collagen measurements (right axis). PSR staining measurements were acquired at 3 locations, while PA images were acquired every 150 μm, across the entire length of the kidney. (C) The mean PSR-based fibrosis scores from each position within the kidney were correlated, with the corresponding mean 3D PA–based collagen scores calculated for each of those same positions (P = 0.00001 for PSR, P = 0.0002 for collagen I, and P = 0.0008 for α-SMA). (D) Pearson correlation analysis between mean 3D PA–based and PSR-based whole kidney fibrosis scores (P = 0.001 for PSR, P = 0.002 for collagen I, and P = 0.02 for α-SMA). Data represent mean ± SEM for n = 5 mice/time point, with n = 3 different PA and histological readings acquired for every mouse, at every time point.

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ISSN 2379-3708

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