Multiwave technology introducing shear wave elastography of the kidney: Pre-clinical study on a kidney fibrosis model and clinical feasibility study on 49 human renal transplants

Quantitative Increasing number of patients is affected by chronic kidney disease (CKD) world while with ensuing end-stage renal disease (ESRD). A change in global approach to CKD from costly treatment of ESRD to more aggressive primary and secondary prevention is imperative. This improvement needs: a better understanding of mechanisms underlying renal scarring, a development of specific therapies to slow the progression and a development of modern diagnostic tools to characterize these underlying processes. Number of patients with ESRD underestimates CKD has probably exceeded by a factor 50 this last ten years due to initiation factors as hypertension, diabetes, hyperlipidemia, obesity or smoking. In this work, the Supersonic Shear Imaging technique (SSI) was proved to be able to provide a quantitative follow up of kidney fibrosis on rats. Then, the technique was adapted on curved probes and proposed to map the in vivo viscoelastic properties of human renal transplants and compared with biopsy. The SSI technique is based on the radiation force induced by a conventional ultrasonic probe, to generate a planar shear wave deep into tissues. Then shear wave propagation throughout the medium is caught in real time thanks to an ultrafast ultrasound scanner (5000 frames/s). At last, a time of flight algorithm applied on these data allows to compute a map of the shear wave velocity of the kidney. A follow up study of 8 weeks on a model of glomerulosclerosis induced by L-Name on 50 rats has been conducted in order to investigate the accuracy of the technique. Quantitative maps of the kidney cortex were performed with an 8 MHz linear probe. Regarding human renal transplants, quantitative maps of the cortex elasticity were produced for each patient with a 2.5 MHz curved array. In the animal study the results show an increase of the elasticity of the cortex of the kidney in time with a Young's modulus ranging from 9 to 25 kPa. Results are compared to histological measurement as proteinuria and or quantification of fibrosis with trichrome. On human renal transplants, three groups were studied: a control group, subjects with an early or with a late unfunctional transplant. The results obtained using a curved ultrasonic probe show an 8 cm depth by 10 cm width map of the Young's modulus for the 49 patients. Elasticity varies between groups from 9 to 50 kPa. Results were compared to histology and showed a good agreement between fibrosis markers and Young's modulus. Here we have demonstrated the feasibility of inducing shear waves using the supersonic shear imaging technique in vivo in rats and human kidneys. The good reproducibility and accuracy of the shear elasticity are discussed. The elasticity was proved to be clearly related to kidney fibrosis. As fibrotic process is responsible for the development of most CKD, noninvasive identification and follow-up of this process could improve renal prognosis if adapted targeted therapies can be applied.