Devices, systems, and methods for evaluating a physiological condition of a vessel are disclosed. In an embodiment, a medical system is disclosed. One embodiment of the medical system comprises a medical processing unit in communication with a first sensor, a second sensor, and an imaging source configured to obtain images of at least one intravascular instrument positioned within a body lumen. The medical processing unit is configured to: receive the images obtained by the imaging source; detect, using the images, when the first sensor is in a pre-determined spatial configuration with respect to the second sensor; and automatically initiate normalization of the first sensor and the second sensor in response to detecting that the first sensor is in the pre-determined spatial configuration with respect to the second sensor.