Background: Inflammation, fibrosis, and muscular hypertrophy lead to thickened bowel in Crohn's disease forming strictures. Ultrasound shear wave elastography (SWE) measures bowel wall stiffness. Contrast-enhanced ultrasound (CEUS) uniquely detects bowel wall inflammation. We aim to correlate SWE of ileal Crohn's disease in vivo to CEUS peak enhancement and pathology grades of inflammation, fibrosis, and muscular hypertrophy. Methods: In a prospective institutional review board-approved study, 105 consecutive ileal patients with Crohn's disease received ultrasound. At maximal bowel wall thickness (>4 mm), SWE and CEUS were performed. Fifteen patients had ileal resection within a mean time interval of 71.0 +/- 66.9 days. Pathology scores for inflammation, fibrosis, and muscular hypertrophy were compared with SWE and CEUS measurements. Results: Mean in vivo SWE velocity for patients with and without surgery was 2.8 +/- 0.7 and 2.2 +/- 0.8 m/s (P < 0.01), respectively. In all ileal specimens, chronic exceeded active inflammatory change (P < 0.001). There was an inverse relationship between CEUS peak enhancement and both fibrosis, r = 20.59, P = 0.02, and SWE velocity measurements, r = 20.61, P = 0.03. Strictured bowel specimens had more smooth muscle hypertrophy than fibrosis, P0.05). Conclusions: Stiffer bowel from smooth muscle hypertrophy increases SWE measurements. We report a novel relation of high SWE with muscle hypertrophy, and inverse relationship with CEUS peak enhancement; providing differentiation between active and chronic bowel wall inflammation to improve selection between medical therapy and surgery.