Multi-modality detection of RCC Recurrence Post Ablation - Project Summary: Renal cell carcinoma (RCC) accounts for 3-5% of all cancers. Localized ablation is a recommended treatment for T1a renal cancers (approximately 25% of all RCC) and particularly important for the treatment of patients who are poor surgical candidates due to diminished renal function or with a solitary kidney. Post-ablation imaging protocols for detection of recurrence vary, but mainly rely on contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) at 3-12 months intervals. However, detection of relapse based on detection of contrast enhancement within the ablation cavity can be challenging on both modalities – due to most imaging findings of recurrence being nonspecific because of changes in tumor size, enhancement from fat necrosis and scarring, and the development of calcifications following therapy. Additionally, these techniques can be problematic due to modality and contrast agent contraindications. As an alternative to CECT and CEMRI, contrast-enhanced ultrasound (CEUS) has gained acceptance for a variety of clinical applications. In small pilot studies, our group has demonstrated the ability of CEUS to monitor for both residual and recurrent RCC following percutaneous ablation with 100% sensitivity and no adverse events. While encouraging, our findings were based on a relatively small sample size and, with an overall specificity of the technique that ranged from 75-96%, primarily due to an inability to properly identify the boundaries of the ablation cavity from the surrounding renal cortex. To assess the clinical promise of CEUS, we propose a larger, fully powered study, recruiting patients across multiple institutions and using multi-modality imaging techniques to overcome these limitations and enable clinical adoption. In our first specific aim, we will characterize the sensitivity, specificity, positive and negative predictive value, and inter-reader agreement of both 2D CEUS and contrast-enhanced cross-sectional imaging for detecting recurrent RCC following ablation; we will use a combination of long-term follow-up imaging and tissue pathology as a reference standard, instead of relying on CECT or CEMRI. At each site, blinded radiologists with varying experience levels in CEUS will interpret exams, enabling us to define these parameters while also quantifying reader variability. In the second aim, we will evaluate the potential improvement to the qualitative assessments of 2D CEUS when fused with the patient's pre-treatment cross-sectional imaging, which we hypothesize will provide better delineation of the initial tumor boundary. In the third aim, we will assess the potential added value of using multi-modality volumetric CEUS for detecting RCC recurrence post ablation and also an advanced Doppler non-contrast technique as an exploratory sub-aim. Finally, we will explore use of quantitative parameters extracted from 2D/3D CEUS exams to determine if this improves the overall performance of CEUS. At the study's conclusion, we hope to address the current limitations in RCC recurrence surveillance imaging with fully powered CEUS study to support clinical adoption, while also addressing prior limitations through the use of multi-modality and quantitative imaging.