Testing for neurovascular uncoupling in multiple sclerosis using sequential gas delivery versus fixed inspired CO2

An apparatus for providing a vasoactive stimulus to a subject with multiple sclerosis to assess vascular compliance with regard to multiple sclerosis-related cognition of the subject, the apparatus comprising:

• (a) a gas delivery device;
• and
• (b) a processor connected to the gas delivery device,
• wherein the processor is configured to:
• control the gas delivery device to target a first end-tidal concentration of carbon dioxide for a first series of repeated inspirations by the subject, and control the gas delivery device to target a second end-tidal concentration of carbon dioxide for a second series of repeated inspirations by the subject, wherein targeting the first and second end-tidal concentrations of carbon dioxide comprises:
• during an inspiration by a subject with multiple sclerosis, controlling the gas delivery device to deliver a first gas to the subject, the first gas provided in a volume that is less than a tidal volume minus an anatomical dead space, the first gas containing a concentration of oxygen to meet a respiratory need of the subject and to target an end-tidal partial concentration of oxygen, the first gas further containing a concentration of carbon dioxide to target an end-tidal concentration of carbon dioxide;
• and
• during the same inspiration and after delivering the first gas to the subject, controlling the gas delivery device to deliver a second gas to the subject, wherein the second gas contains a concentration of carbon dioxide approximately equal to the target end-tidal concentration of carbon dioxide or, if at a resting state, equilibrated with an arterial partial pressure of carbon dioxide of the subject,
• when the first end-tidal concentration of carbon dioxide is reached, control a sensor to measure blood flow in the subject's brain;
• when the second end-tidal concentration of carbon dioxide is reached, control the sensor to measure blood flow in the subject's brain;
• and
• calculate a cardiovascular response using the difference between the blood flow measured at the first and second end-tidal concentrations of carbon dioxide.

A method of using sequential gas delivery to test for neurovascular uncoupling in a subject with multiple sclerosis, the method comprising:

• targeting a first end-tidal concentration of carbon dioxide for a first series of repeated inspirations by the subject;
• when the first end-tidal concentration of carbon dioxide is reached, measuring blood flow in the subject's brain;
• targeting a second end-tidal concentration of carbon dioxide for a second series of repeated inspirations by the subject;
• when the second end-tidal concentration of carbon dioxide is reached, measuring blood flow in the subject's brain;
• and
• calculating a cardiovascular response using a difference between the blood flow measured at the first and second end-tidal concentrations of carbon dioxide.

A method of using sequential gas delivery to determine vascular compliance in a subject with multiple sclerosis;

• the method comprising:
• targeting a first end-tidal concentration of carbon dioxide for a first series of repeated inspirations by the subject;
• when the first end-tidal concentration of carbon dioxide is reached, measuring blood flow in the subject's brain;
• targeting a second end-tidal concentration of carbon dioxide for a second series of repeated inspirations by the subject;
• when the second end-tidal concentration of carbon dioxide is reached, measuring blood flow in the subject's brain;
• and
• calculating a cardiovascular response using a difference between the blood flow measured at the first and second end-tidal concentrations of carbon dioxide.