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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 6

PA imaging can detect intrarenal variations in collagen content in human kidneys.

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PA imaging can detect intrarenal variations in collagen content in human...
(A) Human kidney PA imaging setup. Imaging was performed in a 4°C saline bath. (B) Three-dimensional whole kidney PA imaging strategy. The bottom and top surfaces of the kidney were imaged in the orientation shown, with slices taken every 0.5 mm. (C and D) PA- and Picrosirius red–derived (PSR-derived) collagen scores from selected positions within the top (C) and bottom (D) of the kidney. Labelled positions (P1–P4) represent the locations where histological sampling was performed. (E) Correlation of PA-derived collagen estimates with PSR-derived collagen scores for all measured sites (n = 8). The Pearson correlation coefficient was statistically significant (r = 0.97, P = 0.0001). Representative PA- and PSR-stained images are also shown for both sides of the kidney. Scale bar: 5 mm (PA) and 100 μm (histology). (F) Photographs of the human kidney nephrectomy specimens. The 3D imaging orientation strategy shown in kidney 2 applies to all imaged specimens. (G) Intrakidney collagen variation in nephrectomy specimens, as measured by both PA-derived (left axis, red) and PSR-derived collagen scores (right axis, blue). (H) PA-based collagen scores and histology-derived fibrosis measurements (PSR and Masson’s trichrome) were compared at 4 locations within each kidney, using Pearson correlation analysis (P = 9 × 10–8 for PSR, P = 1 × 10–6 for Masson’s trichrome). The Data represent mean ± SEM for n = 4 PA and histological locations for n = 5 kidney samples.

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