Kidney Week

Abstract: SA-OR046

Photoacoustic Ultrasound: A New Way to Assess Kidney Fibrosis

Session Information

• Biomarkers in CKD
  November 09, 2019 | Location: 152, Walter E. Washington Convention Center
  Abstract Time: 06:06 PM - 06:18 PM

Category: CKD (Non-Dialysis)

• 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Yuen, Darren A., Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, Ontario, Canada

Darren A. Yuen, MD, PhD



Dr. Darren Yuen is a Staff Nephrologist, and an Assistant Professor in the Faculty of Medicine at the University of Toronto. His research group is based at the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital. Dr. Yuen’s research is focused on developing new diagnostics and therapeutics for organ fibrosis. He has received funding from multiple national, provincial, and local organizations, and is a scientific co-founder of Fibrocor Therapeutics.

• He, Xiaolin, Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, Ontario, Canada

Xiaolin He,

• Hysi, Eno, Ryerson Univesity, Toronto, Ontario, Canada

Eno Hysi,

• Krizova, Adriana, St. Michael's Hospital, Toronto, Ontario, Canada

Adriana Krizova,

• Kolios, Michael C., Ryerson Univesity, Toronto, Ontario, Canada

Michael C. Kolios,

Background

Despite advances in imaging technology(conventional ultrasound, CT, MRI), the only method for assessing fibrosis is by biopsy. Biopsy is limited by its invasiveness and the fact that it samples < 1% of the kidney. Here we show that combining ultrasound with laser technology (photoacoustic (PA) ultrasound) allows imaging of kidney fibrosis by directly measuring collagen content.

Methods

Kidneys of mice undergoing UUO (left kidney) or sham surgery were imaged ex vivo using a VevoLAZR-X PA ultrasound imaging system at 15 MHz at day 7 and 14 post surgery(n=5 per time point). Human kidney samples were obtained from the non-cancerous pole of radical nephrectomies(n=6). Spectral unmixing was performed on the collected images to produce a PA collagen score for each image. For mouse kidneys, a total of 60 PA ultrasound frames were acquired along the largest longitudinal cross-section. Human kidney cortex specimens were scanned in 60 perpendicular cross-sections(separated by 150 µm increments) to obtain a 3D representation of the collagen distribution across the entire sample. Histology was acquired at 3-4 locations within the mouse and human kidneys stained with picrosirius red (PSR) and an antibody direct against α-SMA. The relationship between PA-derived collagen scores and the above histological parameters was then analyzed by univariate linear regression.

Results

The average PSR score for UUO mouse kidneys increased with time post-surgery [day 7 (0.14±0.01) and day 14 (0.27±0.03]], and was higher than sham kidneys (0.002±0, p<0.001). α-SMA staining increased by 18.8% from 7 to 14 days post-surgery and was 26x higher than sham kidneys by 14 days. PA-derived collagen scores correlated strongly with histologic parameters of fibrosis (PSR, r²=0.98, p<0.05; α-SMA, r²=0.91, p<0.05), suggesting that PA imaging can accurately quantify murine renal collagen content. Human kidney specimens exhibited a 30% variation in PSR staining, which was also strongly correlated with the PA estimates of collagen (r²=0.90, p<0.05). The technique was also capable of generating 3D collagen maps across the entire specimen with sub-mm spatial resolution across the entire kidney cortex.

Conclusion

PA ultrasound can be used to accurately quantify renal collagen content. This non-invasive, easy-to-use technique offers the potential for renal fibrosis imaging in both the pre-clinical and clinical settings.