A patient monitoring system may provide photoacoustic sensing based on an indicator dilution to determine one or more physiological parameters of a subject. The system may detect an acoustic pressure signal, which may include one or more thermo-dilution responses, one or more hemo-dilution responses, or a combination thereof, using one or more sensor units. The system may use multiple light sources and/or detectors to diagnose and/or improve signal to noise ratio, distinguish between arterial and venous signals, prevent under-sampling, and separate the effects of hemo-dilution and thermo-dilution.