Name: semi-quantitative assessment using [18f]fdg tracer in patients with severe brain injury
Uploaded: 2018-11-09T15:00:00
Description: Watch this Scientific Journal Video about Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury at JoVE.com

The authors wish to thank Dr. Uchino in Sousen hospital for all procedures. The authors also thank Adam Phillips from the Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

This study was performed in compliance with the institutional review board (approval No. 07-01) and adhered to the tenets of the Declaration of Helsinki. Informed consent for medical record and brain image use was obtained from the patients&#8217; legal representatives. The study was conducted after approval by the institutional ethics committee (2017-14). This protocol was made following the guidelines of the Japanese Society of Nuclear Medicine and European Association of Nuclear Medicine as a reference<sup class="xref...

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This protocol provides the means to conduct a series of brain-glucose metabolic assessments with [18F]FDG-PET/CT using self-produced [18F]FDG tracer at a single institution.
The production of [18F]FDG tracer follows the procedure described in the FDG synthesizer operator manual; however, caution is necessary regarding three points. First, the bombardment time and energy (step 2.5) should be adjusted according to the number of patients. Second, attention should ...

Patients with sTBI are presented with unforeseeable neurological difficulties over the course of rehabilitation that include motor deficits, sensory deficits, and psychiatric instability1. Although clinical assessment is generally performed verbally, patients with sTBI such as unresponsive wakefulness syndrome or minimally conscious state have particular difficulty in knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances2,3. Family members, medical staff, and caregivers are sometimes confounded by unforeseeable neurological changes or the lack of response that can result from insufficient communicatory ability4,5.
Recently, multimodal brain imaging has been used to explore regional brain function6,7,8,9. The brain is the main consumer of glucose-derived energy, with glucose metabolism providing approximately 95% of the adenosine triphosphate (ATP) required for the brain to function10. The uptake of [18F]-fluorodeoxyglucose (FDG) is a marker for the uptake of glucose by brain tissue. [18F]FDG-PET/CT can detect [18F]FDG uptake and is, therefore, a useful tool for examining brain function11. In general, [18F]FDG image analysis is divided into two categories: ROI analysis and voxel-based analysis (VBA)12. Previous reports show that ROI analysis is preferred for studying specific regions of traumatic injury. This is because VBA (such as statistical parametric mapping [SPM]) requires coregistration and normalization to a standard brain, which does not work well in cases of TBI due to brain tissue deformation such as brain atrophy, swelling, enlargement, and shrinking of ventricular space7,12. Although various algorithms and software have been developed for analyzing magnetic resonance imaging (MRI) data, metals used in neurosurgical and orthopedic surgery generate noise artefacts7,12,13. Recently, the use of photomultipliers with PET/CT devices has improved the spatial resolution of PET/CT-derived brain images14. The current protocol focuses on semi-quantitatively measuring glucose uptake via ROI analysis in [18F]FDG-PET/CT using self-produced [18F]FDG tracers in patients with sTBI.

<table>
	<tbody>
		<tr>
			<td>20ml syringe</td>
			<td>Terumo</td>
			<td>SS-20ESZ</td>
			<td></td>
		</tr>
		<tr>
			<td>10ml syringe</td>
			<td>Terumo</td>
			<td>SS-10ESZ</td>
			<td></td>
		</tr>
		<tr>
			<td>1ml syringe</td>
			<td>Terumo</td>
			<td>SS-01T</td>
			<td></td>
		</tr>
		<tr>
			<td>Protective plug</td>
			<td>Top</td>
			<td>ML-KS</td>
			<td></td>
		</tr>
		<tr>
			<td>Three-way cock L type 180&#176;</td>
			<td>Terumo</td>
			<td>TS-TL2K</td>
			<td></td>
		</tr>
		<tr>
			<td>Extension tube</td>
			<td>Top</td>
			<td>X1-50</td>
			<td></td>
		</tr>
		<tr>
			<td>Indwelling needle 22G or 24G</td>
			<td>Terumo</td>
			<td>SR-OT2225C</td>
			<td></td>
		</tr>
		<tr>
			<td>Tegaderm transparent dressing</td>
			<td>3M</td>
			<td>1624W</td>
			<td></td>
		</tr>
		<tr>
			<td>Hepaflash 10U/ml 10ml</td>
			<td>Terumo</td>
			<td>PF-10HF10UA</td>
			<td></td>
		</tr>
		<tr>
			<td>Auto dispensing and injection system</td>
			<td>Universal Giken Co., Ltd.</td>
			<td>UG-01</td>
			<td></td>
		</tr>
		<tr>
			<td>Fluid for auto dispensing and injection system</td>
			<td>Universal Giken Co., Ltd.</td>
			<td>UG-01-001</td>
			<td></td>
		</tr>
		<tr>
			<td>Millex-GS Syringe Filter Unit</td>
			<td>Millipore</td>
			<td>SLGSV255F</td>
			<td></td>
		</tr>
		<tr>
			<td>Air needle</td>
			<td>Terumo</td>
			<td>XX-MFA2038</td>
			<td></td>
		</tr>
		<tr>
			<td>Check valve</td>
			<td>Hakko</td>
			<td>23310100</td>
			<td></td>
		</tr>
		<tr>
			<td>Saline 500ml</td>
			<td>HIKARI pharmaceutical Co., Ltd.</td>
			<td>18610155-3</td>
			<td></td>
		</tr>
		<tr>
			<td>Yukiban 25x7mm</td>
			<td>Nitto</td>
			<td>3252</td>
			<td></td>
		</tr>
		<tr>
			<td>Elascot No.3</td>
			<td>Alcare</td>
			<td>44903221</td>
			<td></td>
		</tr>
		<tr>
			<td>Presnet No.3 27x20mm</td>
			<td>Alcare</td>
			<td>11674</td>
			<td></td>
		</tr>
		<tr>
			<td>Steri Cotto a 4x4cm</td>
			<td>Kawamoto</td>
			<td>023-720220-00</td>
			<td></td>
		</tr>
		<tr>
			<td>StatstripXp3</td>
			<td>Nova Biomedical</td>
			<td>11-110</td>
			<td></td>
		</tr>
		<tr>
			<td>Statstrip Glucose strips</td>
			<td>Nova Biomedical</td>
			<td>11-106</td>
			<td></td>
		</tr>
		<tr>
			<td>JMSsheet</td>
			<td>JMS</td>
			<td>JN-SW3X</td>
			<td></td>
		</tr>
		<tr>
			<td>Injection pad</td>
			<td>Nichiban</td>
			<td>No.30-N</td>
			<td></td>
		</tr>
		<tr>
			<td>Stepty</td>
			<td>Nichiban</td>
			<td>No.80</td>
			<td></td>
		</tr>
		<tr>
			<td>Advantage Workstation</td>
			<td>GE Healthcare</td>
			<td>Volume Share 7. version 4.7</td>
			<td></td>
		</tr>
		<tr>
			<td>Discovery MI PET/CT</td>
			<td>GE Healthcare</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>EV Insite</td>
			<td>PSP</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>GE TRACERlab MXFDG synthesizer reagent kit</td>
			<td>ABX</td>
			<td>K-105TM</td>
			<td></td>
		</tr>
		<tr>
			<td>TRACERlab MXFDG cassette</td>
			<td>GE Healthcare</td>
			<td>P5150ME</td>
			<td></td>
		</tr>
		<tr>
			<td>Extension tube</td>
			<td>Universal Giken Co., Ltd</td>
			<td>AT511-ST-001</td>
			<td></td>
		</tr>
		<tr>
			<td>TSK sterilized injection needle 18x100</td>
			<td>Tochigiseiko</td>
			<td>AT511-ST-004</td>
			<td></td>
		</tr>
		<tr>
			<td>TSK sterilized injection needle 18x60</td>
			<td>Tochigiseiko</td>
			<td>AT511-ST-002</td>
			<td></td>
		</tr>
		<tr>
			<td>TSK sterilized injection needle 21x65</td>
			<td>Tochigiseiko</td>
			<td>AT511-ST-003</td>
			<td></td>
		</tr>
		<tr>
			<td>Seal sterile vial -N 5ml</td>
			<td>Mita Rika Kogyo Co., Ltd.</td>
			<td>SSVN5CBFA</td>
			<td></td>
		</tr>
		<tr>
			<td>k222 TLC plate</td>
			<td>Universal Giken Co., Ltd.</td>
			<td>AT511-01-005</td>
			<td></td>
		</tr>
		<tr>
			<td>Anion-cation test paper</td>
			<td>Toyo Roshi Kaisha</td>
			<td>7030010</td>
			<td></td>
		</tr>
		<tr>
			<td>Endospecy ES-24S set</td>
			<td>Seikagaku corporation</td>
			<td>20170</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile evacuated vial</td>
			<td>Gi phama</td>
			<td>10214</td>
			<td></td>
		</tr>
		<tr>
			<td>5ml syringe</td>
			<td>Terumo</td>
			<td>SS-05SZ</td>
			<td></td>
		</tr>
		<tr>
			<td>Extension tube</td>
			<td>Top</td>
			<td>X-120</td>
			<td></td>
		</tr>
		<tr>
			<td>Finefilter F</td>
			<td>Forte grow medical Co.Ltd.</td>
			<td>F162</td>
			<td></td>
		</tr>
		<tr>
			<td>Millex FG</td>
			<td>Merck</td>
			<td>SLFG I25 LS</td>
			<td></td>
		</tr>
		<tr>
			<td>Vented Millex GS</td>
			<td>Merck</td>
			<td>SLGS V25 5F</td>
			<td></td>
		</tr>
		<tr>
			<td>Injection needle 18x38</td>
			<td>Terumo</td>
			<td>NN-1838R</td>
			<td></td>
		</tr>
		<tr>
			<td>Injection needle 21x38</td>
			<td>Terumo</td>
			<td>NN-2138R</td>
			<td></td>
		</tr>
		<tr>
			<td>Water-18O</td>
			<td>Taiyo Nippon Sanso</td>
			<td>F03-0027</td>
			<td></td>
		</tr>
		<tr>
			<td>Distilled water</td>
			<td>Otsuka phrmaceutical</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hydrogen gas G1</td>
			<td>Hosi Iryou Sanki</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Helium gas G1</td>
			<td>Hosi Iryou Sanki</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Nitrogen G1</td>
			<td>Hosi Iryou Sanki</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>TRACERlabMXFDG</td>
			<td>GE Healthcare</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sep-Pak Light Accell Plus QMA</td>
			<td>WATERS</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sep-Pak Plus tC18</td>
			<td>WATERS</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sep-Pak Plus Alumina N</td>
			<td>WATERS</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>HPLC with 3.9 X 300 mm columns</td>
			<td>WATERS</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>US-2000</td>
			<td>Universal Giken CO. Ltd.</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Kryptofix222</td>
			<td>Merck</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>EG Reader SV-12</td>
			<td>Seikagaku Corporation</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>UG-01</td>
			<td>Universal Giken Co., Ltd.</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>syngo.via</td>
			<td>Siemens Healthineers</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Advantage Workstation Volume Share 7, version 4.7</td>
			<td>GE Healthcare</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Q clear</td>
			<td>GE Healthcare</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>CRC-15PET dose calibrator</td>
			<td>CAPINTEC, INC.</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

semi-quantitative assessment using [18f]fdg tracer in patients with severe brain injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient&#39;s condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

A 63-year-old man who had been run over by a car while cycling was brought to the emergency room via ambulance. The examination revealed a Glasgow Coma Scale score of 7 (eye opening = 1, best verbal response = 2, best motor response = 4), anisocoria (right: 2 mm, and left: 3 mm), and a negative corneal response17. A CT of the head showed subarachnoid and intracranial hemorrhage and a skull fracture of the left zygoma, temporal bones, and parietal bones. Th...

Watch this Scientific Journal Video about Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury at JoVE.com

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is useful for studying glucose metabolism related to brain function. Here, we present a protocol for an [18F]FDG tracer set-up and semiquantitative assessment of the region-of-interest analysis for targeted brain areas associated with clinical manifestations in patients with severe traumatic brain injury.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of ...

This list can help us with key questions in the neuro-rehabilition field. Regarding Unresponsive Wakefulness Syndrome and minimal conscious states following cerebral traumatic brain injury. The main advantage of this technique is that, patients with brain tissue deformation such as, atrophy, swelling, enlargement and shrinking of ventricular spaces can be assisted in the chronic stage.Demonstrating the procedure will be Tomoki Uchida, our pharmacist, Kazuaki Yokoyama, our skilled operator, Mizuho Kamezawa, our nurse, Shinji Onodera and Yoshihiro Ozaki, Radio Technologist from my laboratory. Begin manufacturing reagent kits for the automated production of FDG, tailored to the synthesizer in use. Set the syringes for the manufacturing reagent kits on to the corresponding syringe drivers in the automated FDG Synthesizer.Be sure to use the automatic program to check the mobility of the pumping system. Check the volume of the Oxygen-16 and 18 water, and the volume of helium, hydrogen and nitrogen gases. Also ensure that the tap water is under 25 degrees celsius for primary cooling and under 22 degrees celsius for secondary cooling.After one hour, ensure that air cannot leak from the reagent kit. Set out vials of acetonitrile, mannose triflate, ethanol, and PH buffer solution. Begin preliminary irradiation of Oxygen-16 in the cyclotron.Check that two to three milliliters of water is irradiated in optimal conditions in the target area. Next, begin the irradiation of Oxygen-18 water in the cyclotron 90 minutes after starting. Set the bombardment time for up to 20 minutes, and the energy of the impinging protons to 16.5 mega electron volts.Ensure that the lamp lights up, when the cyclotron is running. After irradiation, use helium gas to transfer two to three milliliters of the Oxygen-18 water from the cyclotron to the polypropylene receiver of the FDG Synthesizer. Hook syringes on to the corresponding syringe drivers and the pressurized reagent vials.Then, dissolve the mannose triflate in one vial of 99.5 percent pure acetonitrile, then rinse the cassette with acetonitrile. Transfer the irradiate Oxygen-18 water to the FDG synthesizer. Then, after transferring the eluent to the containing Fluorine-18 without liquid into the reaction vessels.Allow the solvents to evaporate until dry. During the drying process, add 80 microliters of acetonitrile to the reaction vessel three times. Perform the evaporation at 95 degrees celsius under nitrogen flow and vacuum.Dissolve 25 milligrams of mannose triflate precursor in about 3.5 milliliters of 99.5 percent pure acetonitrile, then add it to the dry residue. A nucleophilic substitution reaction occurs at 85 degrees Celsius in the FDG Synthesizer. As a preliminary purification, mixed the labeled solution with 26 milliliters of distilled water.Then, send about four milliliters of the diluted labeling solution back to the reaction vessel to recover the remaining activity. Next, pass the solution through the reverse phase cartridge. Then, rinse the cartridge containing the trapped labeled precursor four times using distilled water.Now, convert the acetylated compound into FDG within the cartridge via alkaline hydrolysis. Using 750 microliters of 2 N sodium hydroxide for 90 seconds at room temperature. After hydrolysis is complete, collect the alkaline FDG solution in 70 milliliters of water, and mix it with a neutralization solution.Then, purify the resulting neutralized FDG solution. Pass the neutralized FDG solution through a second reverse phase cartridge retaining the partially hydrolyzed compounds and non-bipolar byproducts. Then, pass it through an Alumina-N cartridge retaining the last trace of unreacted F-18 flouride ions, then pass it through a 0.22 micrometer filter.Next, rinse the cassette and cartridges and filter with 3 milliliters of water to recover the residual FDG in the lines. Then, drain the FDG into the final vial which should contain 15 to 17 milliliters of liquid. After two hours and 30 minutes from start of preparation, perform a qualitative analysis by examining the vial to confirm that it is transparent without particles.Also, measure the amount of liquid using a robe revolves balance. And measure the radioactivity and half-life using a radioisotope dose calibrator. Now, measure the PH as well as the residual cryptand-22 using test paper.Also, measure the endotoxins with the appropriate device through the absorbance measuring. Next, dispense 0.5 milliliters from the vial and perform a radiochemical purity test via carbohydrated analysis. Use columns of 3.9 by 300 millimeters for high performance liquid chromatography to detect the peak radioactivity.Finally, fill the vial covered by lead and tungsten with the FDG Tracer, at a dosage of 5 megabecquerel per kilogram of body weight. Then, three hours and 25 minutes after the start time, transfer the Tracer from the Hot Lab to the working room. Begin by preparing the intravenous route for the FDG Tracer administration.Secure a 22 to 24 gauge needle with 5 milliliters of heparin sodium, on one of the lower limbs. The patient should then lie down for 30 minutes before entering the radiation controlled area. Next, recheck the patency of the intravenous route by drawing blood and measure the patient's blood glucose level.Then, transfer the FDG Tracer from the Hot Lab to the working room through the window. Set the tracer up in the Auto Dispensing and Injection System. Check the aspiration of the FDG Tracer from the vial on the monitor.Connect the tube between the patient and the Auto Dispensing Injection System. Push the bottom and inject the FDG Tracer to the patient. At this point, stop to confirm the Tracer amount and lot number, programmed radioactivity, injection time, injection speed, and measured radioactivity level.Now, record the automatic measurement of pre-injected radioactivity that appears on the display of the Auto Display and Injection System. Then, inject the Tracer via the intravenous route at three hours and 30 minutes, after the start. Have the patient wait in the waiting room of the radiation controlled area for 50 minutes.Then, four hours and 30 minutes after the start time, transfer the patient from the waiting room to the PET/CT machine, and record brain images for 10 minutes. After imaging, check the injection area for extravasation. Once all data is acquired, evaluation all image data for a standardized uptake value measurement using imaging software and compare the clinical assessment with the FDG-PET/CT images.This figure shows a representative FDG-PET/CT brain image. Shown here is the measurement of the right thalamic glucose metabolism in a 3-dimensional image browser. Here we see a representative color mapped image after FDG-PET and CT fusion.The blood glucose level at the time of the scan as depicted as red with a 50 percent SUV max threshold. This panel, shows representative 3-dimensional brain surface FDG-PET images. The red regions have a higher glucose metabolism than the green regions.The blood glucose level at the time of scan is shown in red. While attempting this procedure, it's important that bombardment time and energy are adjusted according to the number of patients. Also, attention should be paid to the cryptand-222 tube, because it can be easily become stopped up by crystallization.Also know that the hook of syringes should be handled carefully because it can be easily broken. In addition, be aware that a patient with cerebral traumatic brain injury can sometimes make unforeseen movements during image acquisition. Follow this procedure, add in many ways various radioactive tests can be applied in order to answer additional questions involving amino acid metabolism.Don't forget that working with radioactive materials can be extremely hazardous and precautions such as radiation protection should always be taken while performing this procedure.

Research

JoVE Journal

Medicine

Non-invasive Imaging of Acute Allograft Rejection after Rat Renal Transplantation Using 18F-FDG PET

Non-invasive Imaging of Acute Allograft Rejection after Rat Renal Transplantation Using 18F-FDG PET

The number of patients with end-stage renal  disease, and the number of kidney allograft recipients continuously increases.  Episodes of acute cellular ...

A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic ...

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this ...

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

Stroke is the third leading cause of death among Americans 65 years of age or older1. The quality of life for patients who suffer from a stroke fails to ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT

This paper describes the use of 18F-FDG and micro-PET/CT imaging to determine in vivo glucose metabolism kinetics in mice (and is transferable to rats). ...

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT&#39;s ability to ...