Methods for diagnosing and/or treating a multi-lesion intravascular region are disclosed. The methods may include advancing a pressure sensing device to a first position that is distal of a first lesion and that is distal of a second lesion, proximally retracting the pressure sensing device to a second position that is proximal of the first lesion and that is proximal of the second lesion, calculating a first estimated post-treatment fractional flow reserve based on treatment of the first lesion, calculating a second estimated post-treatment fractional flow reserve based on treatment of the second lesion, and treating the first lesion, the second lesion, or both based on the first estimated post-treatment fractional flow reserve and the second estimated post-treatment fractional flow reserve.