Catheter systems and methods for determining blood flow rates based on speed of sound measurements. The catheter may include a lumen extending between a proximal end of the catheter and a distal end of the catheter. The catheter may include fluid infusion openings at the distal end region of the catheter that are configured to permit the indicator fluid to exit the catheter from the lumen. The catheter system may include a guidewire having one or more sensors thereon for sensing speed of sound in a body vessel lumen and/or in a lumen of the catheter. The sensors may sense a sound sent through the catheter to the body vessel lumen. A blood flow rate may be calculated based on the measured speeds of sound.