in vivo VisR Measurements of Viscoelasticity and Viscoelastic Anisotropy in Human Allografted Kidneys Differentiate Interstitial Fibrosis and Graft Rejection

Assessment of renal transplant failure typically in-volves nonspecific biomarkers or invasive biopsies, presenting a clinical need for noninvasive imaging modalities that can identify pathologic changes in renal allografts. One approach is Viscoelastic Response (VisR) ultrasound, an acoustic radiation force (ARF)-based imaging method that qualitatively evaluates, relative to the applied ARF amplitude, tissue elasticity (RE) and viscosity (RV). We hypothesize that, by measuring the RE and RV degree of anisotropy (DoA) along versus across nephrons in the cortex and the regional ratio (RR) of RE and RV in the outer versus inner cortex, VisR can discriminate transplanted kidneys with fibrosis and rejection in humans in vivo. VisR imaging was performed in renal transplant patients from 3 to 36 months after transplantation at 3 mo. (quarterly) intervals, coincident with routine clinic visits. RE and RV-based DoA in outer and inner cortices were significantly different between patients with and without biopsy-confirmed interstitial fibrosis up to 4 quarters before the time of clinically indicated biopsies. VisR RE-based RR had similar performance but also differentiated rejected from fibrotic kidney. These results suggest that noninvasive VisR imaging is relevant to early detection of transplant kidney fibrosis and rejection, which could enable timely interventions that extend graft life.