Multi-Tracer Studies of Brain Oxygen and Glucose Metabolism Using a Time-of-Flight Positron Emission Tomography-Computed Tomography Scanner

Brain glucose and oxygen metabolism is closely involved in many physiological and pathological processes in the brain. Our research helps to understand how it's involved in aging, and whether it delays auxiliary biodegeneration in the brain. We use positron emission tomography which help and allow us to study metabolism in humans in vivo.

Measurements of human brain metabolism in vivo, traditionally required invasive techniques, even including catheters snaked into vessels of the brain. Imaging has changed all that. Now, PET and MRI are the two most commonly used methods to study human brain metabolism in vivo.

Our protocol addresses research needs for absolute quantitation in metabolism so that physiologically meaningful measurements of blood volume, tissue oxygen extraction, blood flow, and metabolic rate of glucose utilization can be compared across subjects, across studies, and across modalities and methodologies. Compared to SUVR, our protocol provides physiologic measurements that can be assessed against existing information from published literature. These inform future methodologies that may have variations of instrumentation. Most importantly, our measurements are informative of variability in human study populations, especially the variability brought on by disease processes.

Our advancements in PET imaging allow us to probe more specifically how glucose and oxygen metabolism are affected in specific regions of the human brain by aging, Alzheimer's disease, and white matter disease. The resolution of state-of-the-art PET scanners is now comparable to functional MRI, and this allows us to integrate our understanding of brain metabolism and function in a multimodal fashion.

[Presenter] To begin, prepare the shielded gas storage container equipped with a pico-ammeter dose calibrator. Connect the expandable bellows to the rigid, narrow-diameter nylon line from the cyclotron and to a semi-rigid, large diameter plastic polymer tube that is kept clamped, except during administration. Place a virus-capturing particulate filter in line with the large diameter tube, and attach a disposable plastic mouthpiece to the end of the tubing. Get gaseous radiopharmaceuticals delivered to the gas container from the cyclotron facility. Begin the PET-CT scanning preparation by informing the participant about the importance of avoiding head movements during the scanning process. Ensure the participant follows all standard protocols for human PET-CT scanning. Position the participant to allow for head-first or feet-first positioning. Next, assist the participant in lying down on the lowered gantry table. Before the gantry table moves into the scanner board, check the integrity of all arterial and venous lines. Maintain a continuous connection of arterial lines with pressurized saline sources. Check the comfort of the participant by ensuring adequate cushioning for positioning the head, neck, spine, hips, and leg flexion. After the participant comfortably positions the head on freely adjustable foam headrests, secure their forehead to the gantry table using an elastic self-adhesive and self-removable wrap. Instruct the participant once again to avoid any head movement throughout the scanning. Let the gantry table pass through the scanner bore until the participant's extremities and torso are beyond the CT gantry and their head is centered inside the gantry. Now, with the participant properly positioned in the CT gantry, perform the CT scan. Once the CT scan is done, pass the gantry table further through the scanner bore until the participant's head rests at the center of the PET gantry. Proceed to perform CT and PET scans. Continuously monitor and assess the comfort of the participant during the scan via minimal verbal communication. To begin, position the study participant in the PET-CT scanner. To administer the gaseous radiopharmaceuticals as boluses, using the pico-ammeter dose calibrator, monitor the activity of each gas delivered to the expandable bellows till it peaks, and then wait for the activity to fall below the maximum dose of 55 millicuries permitted by the Radioactive Drug Research Committee. Commence scanning immediately prior to the start of inhalation to ensure the acquisition of the start of the time-activity curve. Obtain six to seven minutes of time activity curve for emissions with the frame setting displayed on the screen. After placing the mouthpiece in the participant's mouth, ask them to form a tight seal around the mouthpiece with their lips before inhaling as much as possible. Ask them to hold their breath for a few seconds to let the lungs absorb the radiopharmaceutical. Ask the participant to exhale again through the tube, blowing residual gaseous radiopharmaceutical back into the bellows. After reclamping the tube, retrieve it from the participant. Monitor the gas activity in the bellows from the start of inhalation to the end of exhalation. Calculate the total administered dose by the difference in activities and aim for a total dose that exceeds 20 millicuries. Monitor arterial measurements for nominal time-activity curves after administering the desired gas doses. After positioning the study participant in the PET-CT scanner, prepare all devices needed for arterial measurements of radiopharmaceutical activities. Verify the integrity of all connections and check the priming to ensure no air bubbles enter the radial artery or interfere with peristaltic pumping while extracting blood. For the gamma detector, use appropriate microbore catheter extension sets. Set the maximum allowable occlusion pressure limit for the peristaltic pump, and if it is an infusion pump operating with reversed flow directions, select the minimum flow rate to keep the vessel open. Immediately prior to administering radiopharmaceuticals, close the stopcock to the pressure bag and monitor, and operate the pump at 300 milliliters per hour. Confirm the extraction of blood from the radial artery and its passage through extension catheter sets to the gamma detector and the collection pump. While pumping at 300 milliliters per hour, check activity measurements on the gamma detectors for each administered radiopharmaceutical for the appropriate time, depending on the particular radio tracer. After each arterial measurement, reconfigure the arterial lines to flush the radial artery catheter, followed by the supply line circuit to the gamma detectors and pump. For the isolated circuit through the pump, set pump rates at 300 milliliters per hour. The radiopharmaceuticals administered were easily incorporated into non-quantitative maps of specific activities. Whole-brain time-activity curves helped identify significant head movements and provided characteristic features of tracers after decay correction.