Radiotracer Administration for High Temporal Resolution Positron Emission Tomography of the Human Brain: Application to FDG-fPET

The advent of simultaneous MR/PET scanners has sparked renewed interest in FDG-PET imaging in cognitive neuroscience. With these developments, researchers have focused on improving the temporal resolution of FDG-PET to approach the standards of BOLD fMRI. Traditional FDG-PET acquisitions using the bolus method provide a static measure of glucose uptake averaged across the scan period.

In this protocol, we describe two alternate methods of FDG-PET acquisition:constant infusion and hybrid bolus infusion. These techniques provide a superior temporal resolution of up to 16 seconds which compares very favorably to the traditional bolus approach. The improved temporal resolution achieved with these administration protocols will provide important information about the dynamic use of glucose energy in the brain.

To begin, have the nuclear medicine technologist or NMT take into account the estimated start of scanning while preparing the dose. To prepare the dose, aseptically add the radiotracer to the saline bag. Then, prepare the priming dose by withdrawing 20 milliliters from the bag into a syringe and cap it.

Calibrate this 20 milliliter syringe and label. Then, to prepare the dose, use a 50 milliliter syringe to withdraw 60 milliliters from the bag and cap with a red combi-stopper. Store both syringes in the radiochemistry lab until ready to scan.

Next, prepare the scanner room to ensure that all blood collection equipment is within easy reach of the collection site. Place underpads on any surface that will hold blood containers and place bins for regular waste and biohazardous waste within easy reach of the blood collection site. Set up the infusion pump in the scanner room on the side that will be connected to the participant.

Build lead bricks around the base of the pump and place the lead shield in front of the pump. Connect the tubing for the infusion pump that will deliver the infusion to the participant and ensure the correct infusion rate has been entered. Then, connect the 20 milliliter priming dose to the infusion pump.

On the end of the tubing that will be connected to the participant, attach a three-way tap and an empty 20 milliliter syringe. Ensure that the tap is positioned to allow the FDG solution to flow from the priming dose through the tubing and collect only into the empty syringe. Pre-set the infusion pump to prime a volume of 15 milliliters and select the prime button on the pump.

Follow the prompts to prime the line. Lastly, attach the 50 milliliter dose syringe to the infusion pump in place of the priming dose. Begin by escorting the participant to the testing area.

Conduct the informed consent procedure and complete safety screens with the participant. Have the NMT review safety for PET scanning and then have the radiographer review safety for MRI scanning with the participant such as exclusion for pregnancy, medical or nonmedical metallic implants. Then, cannulate the participant with two 22 gauge cannulas, one for dose administration and the other for blood sampling.

Collect a 10 milliliter baseline blood sample while cannulating and disconnect all saline flushes under pressure to maintain patency of the line. Next, position the participant in the scanner and cover with a disposable blanket to maintain a comfortable body temperature. Flush the cannula to ensure it is patent with minimal resistance before connecting the infusion line.

Tape the tubing to the participant's wrist and instruct them to keep their arm straight during the scan. Check the cannula that will be used for plasma samples to ensure that it is able to withdraw blood with minimal resistance. At the start of the scan, situate the NMT in the scanner room to monitor the infusion equipment.

Ensure the NMT wears hearing protection and uses the barrier shield to minimize radiation exposure from the dose where possible. Perform the localizer scan to ensure that the participant is in the correct position and check the details for the PET acquisition. Then, signal the NMT to start the infusion pump 30 seconds after the start of the PET acquisition.

Have the NMT observe the pump to ensure it has started to infuse the FDG and ensure there is no immediate occlusion of the line. Initiate any external stimulus such as the start of a functional run and calculate the times for blood samples. Take blood samples at regular time intervals and at the mid collection point, mark this time on the record form as the actual time of sample.

Finally, connect the 10 milliliter syringe to the vacutainer and then deposit the blood into the relevant blood tube. Quickly flush the cannula with 10 milliliters of saline disconnected under pressure to minimize any chance of line clotting. In the lab, spin all samples at a relative centrifugal force of 724 times g.

After the sample has been spun, place the tube in the pipetting rack. Remove the tube cap to not disturb sample separation and place a labeled counting tube in the rack. Next, ensure the tip is securely fastened to the pipette and have a tissue ready for any drips.

Steadily pipette 1, 000 microliters of plasma from the blood tube, transfer to the counting tube, and replace the lids on the counting tube and blood tube. Finally, place the counting tube into the well counter and count for four minutes. Dispose of any blood product waste in biohazard bags.

The largest peak plasma radioactivity concentration was obtained using the bolus method and the smallest using the constant infusion method. Critically, plasma radioactivity levels were sustained for the longest duration in the hybrid bolus infusion protocol and was minimally varied for a period of approximately 40 minutes. This shows that the hybrid bolus infusion protocol provides a relatively stable plasma radioactivity until the sensation of the infusion.

The PET results indicate that the hybrid bolus infusion participant showed clearer differences between the ROIs compared to bolus only and infusion only participants. In the bolus only protocol, there is a sharp increase in signal following the bolus. In the bolus and infusion protocol, there is a sharp increase in uptake at the start of the scan that is of smaller magnitude than in the bolus only protocol and the uptake continues at a comparatively faster rate for the duration of the scan.

Lastly, the signal increased roughly linearly across the recording period for the three protocols. The slope of the line was highest for the infusion only protocol, intermediate for the bolus only, and smallest for the bolus and infusion protocol. This is consistent with the conclusion that the hybrid protocol provides a more stable signal across the recording period.

The critical point in the protocol is the start of the acquisition. At this point, the beginning of the PET scan must be timed to the start of the BOLD fMRI sequence as well as to the start of the stimulus presentation so as to facilitate accurate analysis. In order for the procedures to fall correctly within the short time period, communication is important to ensure all staff members are adequately prepared prior to the start of the scan.

Simultaneous MRI/PET requires the management of two hazardous scenarios:the presence of the strong magnetic field and the administration of radiation to participants. All staff and participants must comply with the instructions of the supervising radiographer and nuclear medicine technologist.