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Kidney Week

Abstract: TH-PO876

Photoacoustic Ultrasound Can Non-Invasively Detect Kidney Fibrosis

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • He, Xiaolin, St. Michael''s Hospital, Toronto, Ontario, Canada
  • Dong, Jiayin, Ryerson University, Toronto, Ontario, Canada
  • Berndl, Elizabeth S. L., Ryerson University, Toronto, Ontario, Canada
  • Zhang, Tianzhou, St. Michael''s Hospital, Toronto, Ontario, Canada
  • Kolios, Michael C., Ryerson University, Toronto, Ontario, Canada
  • Yuen, Darren A., St. Michael''s Hospital, Toronto, Ontario, Canada
Background

Fibrosis is a key manifestation and driver of chronic kidney injury. Despite its importance, the options for measuring fibrosis are limited. The only available test is a needle biopsy, a time-consuming, invasive procedure that at best samples < 1% of one kidney, leading to the potential for sampling bias.

Unlike biopsy, ultrasound can quickly and non-invasively image the entire kidney. While historically limited to the imaging of gross abnormalities, the recent combination of laser technology with ultrasound (“photoacoustic (PA) ultrasound”) has dramatically expanded its capabilities. Based on the principle that each molecule has its own unique light absorption spectrum, PA ultrasound can be used to non-invasively image specific molecules. We have previously demonstrated that PA ultrasound can specifically detect extracellular matrix in a model of ischemia-reperfusion injury (doi: 10.1117/12.2291199). Our goal was to test whether PA ultrasound could detect milder degrees of fibrosis in a clinically relevant model of diabetic nephropathy.

Methods

Diabetes was induced in renin-overexpressing, hypertensive TTRhRen mice using a low dose STZ injection protocol (Ren-STZ mice, n=7). Ren-STZ mice develop hypertension, hyperglycemia, albuminuria, and renal fibrosis (Thibodeau et al, PLoS ONE 2014). Kidneys were imaged in vivo using a VevoLAZR system at 21 MHz by Photoacoustic (PA) spectral sweep from 680 to 970 nm at 0 and 20 wks post-STZ, and compared with wild-type littermates injected with citrate (WT-citrate, n=9). 20 wks post-injection, kidneys were assessed by picrosirius red (PSR) staining to quantify fibrosis.

Results

Ren-STZ mice developed hypertension (138±7vs. 98±5 mmHg) and hyperglycemia (28.0±2.6 vs. 9.7±0.3 mmol/L) compared to WT-citrate mice 20 wks post-STZ injection. As expected, Ren-STZ kidneys were more fibrotic than WT-citrate controls (PSR intensity: 5.4±0.1 vs. 2.8±0.1). Prior to STZ injection, the photoacoustic spectra of Ren-STZ and WT-citrate kidneys were similar. However, 20 wks post-STZ, Ren-STZ kidneys demonstrated significantly different photoacoustic spectra compared to their WT-citrate counterparts, in line with the fibrosis observed histologically.

Conclusion

Our data suggest that photoacoustic ultrasound may enable the non-invasive, whole organ imaging of kidney fibrosis.

Funding

  • Private Foundation Support