Name: radiotracer administration for high temporal resolution positron emission tomography of the human brain: application to fdg-fpet
Uploaded: 2019-10-22T14:00:00
Description: Watch this Scientific Journal Video about Radiotracer Administration for High Temporal Resolution Positron Emission Tomography of the Human Brain: Application to FDG-fPET at JoVE.com

Jamadar is supported by an Australian Council for Research (ARC) Discovery Early Career Researcher Award (DECRA DE150100406). Jamadar, Ward, and Egan are supported by the ARC Centre of Excellence for Integrative Brain Function (CE114100007). Chen and Li are supported by funding from the Reignwood Cultural Foundation.
Jamadar, Ward, Carey, and McIntyre designed the protocol. Carey, McIntyre, Sasan, and Fallon collected the data. Jamadar, Ward, Parkes, and Sasan analyzed the data. Jamadar, Ward, Carey, and McIntyre wrote the first draft of the manuscript. All authors have reviewed and approved the final version.

This protocol has been reviewed and approved by the Monash University Human Research Ethics Committee (approval number CF16/1108 - 2016000590) in accordance with the Australian National Statement on Ethical Conduct in Human Research24. Procedures were developed under the guidance of an accredited Medical Physicist, Nuclear Medicine Technologist, and clinical radiographer. Researchers should refer to their local experts and guidelines for the administration of ionizing radiation in humans.
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FDG-PET is a powerful imaging technology that measures glucose uptake, an index of cerebral glucose metabolism. To date, most neuroscience studies using FDG-PET use a traditional bolus administration approach, with a static image resolution that represents the integral of all metabolic activity over the course of the scan2. This manuscript describes two alternative radiotracer administration protocols: the infusion-only (e.g., Villien et al., Jamadar et al.19,<su...

Positron emission tomography (PET) is a powerful molecular imaging technique that is widely used in both clinical and research settings (see Heurling et al.1 for a recent comprehensive review). The molecular targets that can be imaged using PET are only limited by the availability of radiotracers, and numerous tracers have been developed to image neural metabolism receptors, proteins, and enzymes2,3. In neuroscience, one of the most used radiotracers is 18F-fluorodeoxyglucose (FDG-PET), which measures glucose uptake, usually interpreted as an index of cerebral glucose metabolism. The human brain requires a constant and reliable supply of glucose to satisfy its energy requirements4,5, and 70-80% of cerebral glucose metabolism is used by neurons during synaptic transmission6. Changes to cerebral glucose metabolism are thought to initiate and contribute to numerous conditions, including psychiatric, neurodegenerative, and ischemic conditions7,8,9. Furthermore, as FDG uptake is proportional to synaptic activity10,11,12, it is considered a more direct and less confounded index of neuronal activity compared to the more widely used blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) response. BOLD-fMRI is an indirect index of neural activity and measures changes in deoxygenated hemoglobin that occur following a cascade of neurovascular changes following neuronal activity.
Most FDG-PET studies of the human brain acquire static images of cerebral glucose uptake. The participant rests quietly for 10 min with their eyes open in a darkened room. The full radiotracer dose is administered as a bolus over a period of seconds, and the participant then rests for a further 30 min. Following the uptake period, participants are placed in the center of the PET scanner, and a PET image that reflects the cumulative FDG distribution over the course of the uptake and scanning periods is acquired. Thus, the neuronal activity indexed by the PET image represents the cumulative average of all cognitive activity over uptake and scan periods and is not specific to cognitive activity during the scan. This method has provided great insight into the cerebral metabolism of the brain and neuronal function. However, the temporal resolution is equal to the scan duration (often ~45 min, effectively yielding a static measurement of glucose uptake; this compares unfavourably to neuronal response during cognitive processes and common experiments in neuroimaging. Due to the limited temporal resolution, the method provides a non-specific index of glucose uptake (i.e., not locked to a task or cognitive process) and cannot provide measures of within-subject variability, which can lead to erroneous scientific conclusions due to Simpson&#39;s Paradox13. Simpson&#8217;s Paradox is a scenario, where brain-behavior relationships calculated across-subjects are not necessarily indicative of the same relationships tested within-subjects. Furthermore, recent attempts to apply functional connectivity measures to FDG-PET can only measure across-subjects connectivity. Thus, differences in connectivity can only be compared between groups and cannot be calculated for individual subjects. While it is debatable what exactly across-subject connectivity measures14, it is clear that measures calculated across-but not within-subjects cannot be used as a biomarker for disease states or used to examine the source of individual variation.
In the past five years, the development and wider accessibility of clinical-grade simultaneous MRI-PET scanners has sparked renewed research interest in FDG-PET imaging2 in cognitive neuroscience. With these developments, researchers have focused on improving the temporal resolution of FDG-PET to approach the standards of BOLD-fMRI (~0.5&#8722;2.5 s). Note that the spatial resolution of BOLD-fMRI can approach submillimeter resolutions but the spatial resolution of FDG-PET is fundamentally limited to around 0.54 mm full width at half maximum (FWHM) due to the positron range15. Dynamic FDG-PET acquisitions, which are often used clinically, use the bolus administration method and reconstruct the list-mode data into bins. The bolus dynamic FDG-PET method offers a temporal resolution of around 100 s (e.g., Tomasi et al.16). This is clearly much better compared to static FDG-PET imaging but is not comparable to BOLD-fMRI. Additionally, the window in which brain function may be examined is limited, because the blood plasma concentration of FDG diminishes soon after the bolus is administered.
To expand this experimental window, a handful of studies17,18,19,20,21 have adapted the radiotracer infusion method previously proposed by Carson22,23. In this method, sometimes described as &#39;functional FDG-PET&#39; (FDG-fPET, analogous to BOLD-fMRI), the radiotracer is administered as a constant infusion over the course of the entire PET scan (~90 min). The goal of the infusion protocol is to maintain a constant plasma supply of FDG to track dynamic changes in glucose uptake across time. In a proof-of-concept study, Villien et al.21 used a constant infusion protocol and simultaneous MRI/FDG-fPET to show dynamic changes in glucose uptake in response to checkerboard stimulation with a temporal resolution of 60 s. Subsequent studies have used this method to show task-locked FDG-fPET (i.e., time-locked to an external stimulus19) and task-related FDG-fPET (i.e., not time-locked to an external stimulus17,18) glucose uptake. Using these methods, FDG-fPET temporal resolutions of 60 s have been obtained, which is a substantial improvement over bolus methods. Preliminary data show that the infusion method can provide temporal resolutions of 20&#8722;60 s19.
Despite the promising results from the constant infusion method, the plasma radioactivity curves of these studies show that the infusion method is not sufficient to reach a steady-state within the timeframe of a 90 min scan19,21. In addition to the constant infusion procedure, Carson22 also proposed a hybrid bolus/infusion procedure, where the goal is to quickly reach equilibrium at the beginning of the scan, and then sustain plasma radioactivity levels at equilibrium for the duration of the scan. Rischka et al.20 recently applied this technique using a 20% bolus plus 80% infusion. As expected, the arterial input function quickly rose above baseline levels and was sustained at a higher rate for a longer time, compared to results using an infusion-only procedure19,21.
This paper describes the acquisition protocols for acquiring high temporal resolution FDG-fPET scans using infusion-only and bolus/infusion radiotracer administration. These protocols have been developed for use in a simultaneous MRI-PET environment with a 90&#8722;95 min acquisition time19. In the protocol, blood samples are taken to quantify plasma serum radioactivity for subsequent quantification of PET images. While the protocol&#39;s focus is the application of infusion methods for functional neuroimaging using BOLD-fMRI/FDG-fPET, these methods can be applied to any FDG-fPET study regardless of whether simultaneous MRI, BOLD-fMRI, computed tomography (CT), or other neuroimages are acquired. Figure 1 shows the flowchart of procedures in this protocol.

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			<td>Blood Collection Equipment</td>
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			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>--12-15 vacutainers</td>
			<td>Becton Dickinson, NJ USA</td>
			<td>364880</td>
			<td>Remain in sterile packaging until required to put blood in tube</td>
		</tr>
		<tr>
			<td>--12-15 10mL LH blood collecting tubes</td>
			<td>Becton Dickinson</td>
			<td>367526</td>
			<td>Marked with the sample number (e.g., S1, S2&#8230;) and subsequently marked with the sample time (e.g., time 0 + x min [T0+x])</td>
		</tr>
		<tr>
			<td>--2-15 10mL Terumo syringe</td>
			<td>Terumo Tokyo, Japan</td>
			<td>SS+10L</td>
			<td>These are drawn up on the day of the study and capped with the ampoule that contained the saline</td>
		</tr>
		<tr>
			<td>-- pre-drawn 0.9% saline flushes</td>
			<td>Pfizer, NY, USA</td>
			<td>61039117</td>
			<td></td>
		</tr>
		<tr>
			<td>--12-15 5mL Terumo syringes</td>
			<td>Terumo Tokyo, Japan</td>
			<td>SS+05S</td>
			<td>Remain in sterile packaging until ready to withdraw a blood sample</td>
		</tr>
		<tr>
			<td>Safety &#38; Waste Equipment</td>
			<td></td>
			<td></td>
			<td>All objects arranged on a plastic chair inside the scanner room on the same side as the arm from which the blood samples will be taken. Biohazard and non-biohazard waste bags to be used. Gloves and waste bags to be easily accessible when preparing the radioactivity in the dispensing area and when pipetting the plasma samples. Biohazard and non-biohazard waste bags to be used. All waste generated is checked with the Geiger counter to ensure that radioactive contaminated waste is stored until it is safe to be disposed of according to Australian Radiation Protection and Nuclear Safety Agency (APRANSA) guidelines for Radiation protection series No.6 (2017).</td>
		</tr>
		<tr>
			<td>-- Gloves</td>
			<td>Westlab, VIC, Australia</td>
			<td>663-219</td>
			<td></td>
		</tr>
		<tr>
			<td>-- waste bags</td>
			<td>Austar Packaging, VIC, Australia</td>
			<td>YIW6090</td>
			<td></td>
		</tr>
		<tr>
			<td>--cello underpads &#8216;blueys&#8217; Underpads 5 Ply</td>
			<td>Halyard Health, NSW, Australia</td>
			<td>2765A</td>
			<td></td>
		</tr>
		<tr>
			<td>--Blue Sharpie pen</td>
			<td>Sharpie, TN, USA</td>
			<td>S30063</td>
			<td></td>
		</tr>
		<tr>
			<td>Dose Syringes</td>
			<td></td>
			<td></td>
			<td>Remain in sterile packaging until ready for use. All syringes used in this facility have an additional 20% volume capacity above the stated volume on the packaging. This is important for the 50mL syringe where the total capacity of 60mL is used</td>
		</tr>
		<tr>
			<td>--5mL</td>
			<td>Terumo Tokyo, Japan</td>
			<td>SS+05S</td>
			<td></td>
		</tr>
		<tr>
			<td>-- 20mL</td>
			<td>Terumo Tokyo, Japan</td>
			<td>SS+20L</td>
			<td></td>
		</tr>
		<tr>
			<td>--50mL</td>
			<td>Terumo Tokyo, Japan</td>
			<td>SS*50LE</td>
			<td></td>
		</tr>
		<tr>
			<td>--1 Terumo 18-gauge needle</td>
			<td>Terumo Tokyo, Japan</td>
			<td>NN+1838R</td>
			<td>Remain in sterile packaging until ready to inject [18F]FDG into the saline bag</td>
		</tr>
		<tr>
			<td>--100mL 0.9% saline bag</td>
			<td>Baxter Pharmaceutical, IL, USA</td>
			<td>AHB1307</td>
			<td>Remain in sterile packaging until ready to inject [18F]FDG</td>
		</tr>
		<tr>
			<td>Radiochemistry Lab Supplies</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>--Heraeus Megafuge 16 centrifuge; Rotor Bioshield 720</td>
			<td>ThermoScientific MA, USA</td>
			<td>75004230</td>
			<td>Relative Centrifugal Force = 724 Our settings are 2000RPM for 5mins. Acceleration and deceleration curves set to 8</td>
		</tr>
		<tr>
			<td>--Single well counter</td>
			<td>Laboratory Technologies, Inc. IL, USA</td>
			<td>630-365-1000</td>
			<td>Complete daily quality control (includes background count) and protocol set to 18F and 4mins. Cross calibration is performed between the well counter, dose calibrator and scanner on a bi-monthly basis.</td>
		</tr>
		<tr>
			<td>--Pipette</td>
			<td>ISG Xacto, Vienna, Austria</td>
			<td>LI10434</td>
			<td>We use a 100-1000 &#956;L set to 1000&#956;L. It is calibrated annually.</td>
		</tr>
		<tr>
			<td>--12-15 plasma counting tubes</td>
			<td>Techno PLAS; SA Australia</td>
			<td>P10316SU</td>
			<td>Marked in the same manner as the LH blood tubes</td>
		</tr>
		<tr>
			<td>--12-15 pipette tips</td>
			<td>Expell Capp, Denmark</td>
			<td>5130140-1</td>
			<td></td>
		</tr>
		<tr>
			<td>--3 test tube racks</td>
			<td>Generic</td>
			<td></td>
			<td>Checked with a Geiger counter to ensure there is no radiation contamination on them</td>
		</tr>
		<tr>
			<td>--500mL volumetric flask and distilled water</td>
			<td>Generic</td>
			<td></td>
			<td>Need approximately 500mL of distilled water to prepare the reference for gamma counting</td>
		</tr>
		<tr>
			<td>--Synchronised clocks in scanner room, console and radiochemistry lab</td>
			<td>Generic</td>
			<td></td>
			<td>Synchronisation checks are routinely completed in the facility on a weekly basis</td>
		</tr>
		<tr>
			<td>--Haemoglobin Monitor</td>
			<td>EKF Diagnostic Cardiff, UK Haemo Control.</td>
			<td>3000-0810-6801</td>
			<td>Manufacturer recommended quality control performed before testing on participant&#8217;s blood sample.</td>
		</tr>
		<tr>
			<td>--Glucometre</td>
			<td>Roche Accu-Chek</td>
			<td>6870252001</td>
			<td>Accu-Chek Performa is used to measure participant blood sugar levels in mmol/L. Quality control is performed daily using high and low concentration solution control test.</td>
		</tr>
		<tr>
			<td>Cannulating Equipment</td>
			<td></td>
			<td></td>
			<td>Check expiry dates and train NMT to prepare aseptically for cannulation.</td>
		</tr>
		<tr>
			<td>--Regulation tourniquet</td>
			<td>CBC Classic Kimetec GmBH</td>
			<td>K5020</td>
			<td></td>
		</tr>
		<tr>
			<td>--20, 22 and 24 gauge cannulas</td>
			<td>Braun, Melsungen Germany</td>
			<td>4251644-03; 4251628-03; 4251601-03</td>
			<td></td>
		</tr>
		<tr>
			<td>--tegaderm dressings</td>
			<td>3M, MN USA</td>
			<td>1624W</td>
			<td></td>
		</tr>
		<tr>
			<td>--alcohol and chlorhexidine swabs</td>
			<td>Reynard Health Supplies, NSW Australia</td>
			<td>RHS408</td>
			<td></td>
		</tr>
		<tr>
			<td>--0.9% saline 10mL ampoules; for flushes</td>
			<td>Pfizer, NY, USA</td>
			<td>61039117</td>
			<td></td>
		</tr>
		<tr>
			<td>--10mL syringes</td>
			<td>Terumo Tokyo, Japan</td>
			<td>SS+10L</td>
			<td></td>
		</tr>
		<tr>
			<td>--3-way tap</td>
			<td>Becton Dickinson Connecta</td>
			<td>394600</td>
			<td></td>
		</tr>
		<tr>
			<td>--IV bung</td>
			<td>Safsite Braun PA USA</td>
			<td>415068</td>
			<td></td>
		</tr>
		<tr>
			<td>--Optional extension tube, microbore extension set</td>
			<td>M Devices, Denmark</td>
			<td>IV054000</td>
			<td></td>
		</tr>
		<tr>
			<td>Scanner Room Equipment</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>--Siemens Biograph 3T mMR</td>
			<td>Siemens, Erlangen, Germany</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>--Portable lead barrier shield</td>
			<td>Gammasonics</td>
			<td>Custom-built</td>
			<td>MR-conditional lead barrier shield. Positioned at the 2000 Gauss line with the castors locked to provide additional shielding of the radioactivity connected to the infusion pump.</td>
		</tr>
		<tr>
			<td>--Infusion pump BodyGuard 323 MR-conditional infusion pump</td>
			<td>Caesarea Medical Electronics</td>
			<td>300-040XP</td>
			<td>MR-compatible. This model is cleared for use on 1.5 and 3T scanners at 2000 Gauss with castors locked.</td>
		</tr>
		<tr>
			<td>--Infusion pump tubing</td>
			<td>Caesarea Medical Electronics</td>
			<td>100-163X2YNKS</td>
			<td>Tubing is administration set with an anti-siphon valve and male luer lock (REF 100-163X2YNKS).</td>
		</tr>
		<tr>
			<td>--Lead bricks</td>
			<td>Custom built</td>
			<td></td>
			<td>Tested for ferromagnetic translational force</td>
		</tr>
		<tr>
			<td>Other Equipment</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>--Syringe shields</td>
			<td>Biodex, NY USA</td>
			<td>Custom-built</td>
			<td>There is a 5mL tungsten syringe shield that is MR-safe, as well as a 50mL lead shield that has been tested for ferromagnetic attraction prior to use in the MR-PET scanner. It is used to transport the radioactive dose from the radiochemistry lab into the scanner to minimise radiation exposure to the NMT.</td>
		</tr>
		<tr>
			<td>--Geiger counter Model 26-1 Integrated Frisker</td>
			<td>Ludlum Measurements, Inc. TX USA</td>
			<td>48-4007</td>
			<td>This is calibrated annually and used to monitor potential contamination and waste. It is not taken into the MR-PET scanner.</td>
		</tr>
	</tbody>
</table>

radiotracer administration for high temporal resolution positron emission tomography of the human brain: application to fdg-fpet

Functional positron emission tomography (fPET) provides a method to track molecular targets in the human brain. With a radioactively-labelled glucose analogue, 18F-fluordeoxyglucose (FDG-fPET), it is now possible to measure the dynamics of glucose metabolism with temporal resolutions approaching those of functional magnetic resonance imaging (fMRI). This direct measure of glucose uptake has enormous potential for understanding normal and abnormal brain function and probing the effects of metabolic and neurodegenerative diseases. Further, new advances in hybrid MR-PET hardware make it possible to capture fluctuations in glucose and blood oxygenation simultaneously using fMRI and FDG-fPET.
The temporal resolution and signal-to-noise of the FDG-fPET images is critically dependent upon the administration of the radiotracer. This work presents two alternative continuous infusion protocols and compares them to a traditional bolus approach. It presents a method for acquiring blood samples, time-locking PET, MRI, experimental stimulus, and administering the non-traditional tracer delivery. Using a visual stimulus, the protocol results show cortical maps of the glucose-response to external stimuli on an individual level with a temporal resolution of 16 s.

Study-specific methods 
Here, study-specific details for the representative results are reported. These details are not critical to the procedure and will vary across studies.
Participants and task design 
Participants (n = 3, Table 2) underwent a simultaneous BOLD-fMRI/FDG-fPET study. As this manuscript focuses on the PET acquisition protocol, MRI re...

Watch this Scientific Journal Video about Radiotracer Administration for High Temporal Resolution Positron Emission Tomography of the Human Brain: Application to FDG-fPET at JoVE.com

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

This manuscript describes two radiotracer administration protocols for FDG-PET (constant infusion and bolus plus infusion) and compares them to bolus administration. Temporal resolutions of 16 s are achievable using these protocols.

Functional positron emission tomography (fPET) provides a method to track molecular targets in the human brain. With a radioactively-labelled glucose ...

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.

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