This work was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, grant number R01 HD081123-01A1. Anuj Pareek is a visiting Ph.D. student from the Department of Radiology, Aarhus University Hospital, Denmark. The authors acknowledge technologists Dawn Holley and Harsh Gandhi from the PET/MRI Metabolic Service Centre for their assistance with the acquisition of PET/MRI scans. We thank members of the Daldrup-Link lab, the PET/MRI service center, the Molecular Imaging Program at Stanford, the Radiological Science Lab, the Pediatric Radiology Section, the Stanford Cancer Institute and the pediatric oncology team at Lucile Packard Children's Hospital for helpful discussions and support of this project.

All methods presented here have been established under a research study, which was approved by the institutional review board of Stanford University. The &#34;off label&#34; use of ferumoxytol was performed under an investigator-initiated investigational new drug application (IND 111,154).
1. 24 h Prior to PET/MRI Scan: Patient Safety Screening
<ol>
	<li>Screen the patient for potential magnetic field hazards using an MRI safety questionnaire. If the administration of intravenous MRI contrast agent is planned, check contraindications, such as history of allergies and kidney function, among others.</li>
	<li>Inform the patient of purpose, procedure, risks and benefits prior to the scan.</li>
	<li>Weigh the patient for calculation of radiotracer and contrast agent dose.</li>
	<li>Ask the patient to fast for at least 4 hours before the scan.</li>
</ol>
2. 1-2 h Before the PET/MRI Scan: Patient Preparation
<ol>
	<li>Ask the patient to remove all metallic objects and change into a gown. If there are any implanted metallic objects, make sure that they are safe for MRI scanning. Use a metal detector as needed. Do not perform the PET/MRI if there is a concern for patient safety.</li>
	<li>Place an intravenous line in a peripheral superficial vein or access a port-catheter.</li>
	<li>Dilute ferumoxytol (5 mg Fe/kg bodyweight) 1:4 in saline, and infuse slowly over at least 15 min according to FDA protocols10. 
	Note: Ferumoxytol can be used &#34;off label&#34; as a contrast agent through an investigator-initiated IND, because it provides long lasting vascular and tissue enhancement for the duration of the entire scan. Alternatively, a cyclic gadolinium chelate can be administered directly before start of the PET/MRI scan. For patients with liver lesions, gadoxetate disodium may be chosen.</li>
	<li>Check the patient&#39;s blood-glucose levels with a glucometer.If the patient&#39;s blood-glucose levels are above 200 mg/dL, consider re-scheduling the PET/MRI scan.</li>
	<li>45 min prior to the PET/MRI scan, administer 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) at a dose of 2 MBq/kg bodyweight in 1 mL of saline through the intravenous line.</li>
</ol>
3. PET/MR Image Acquisition
Note: For this protocol, we used a 3.0 Tesla GE Signa integrated PET/MRI system bundled with MP24_R03 scanner software.
<ol>
	<li>Save the protocol for the whole-body scan (Table 1) and local tumor scan (Table 2) on the scanner, so that these can be easily retrieved without losing much time to search sequences or adjust protocols.</li>
	<li>For patients with lymphoma, prescribe a whole-body scan only, either extending from head to toe or extending from head to mid-thigh level, according to the clinical oncologist&#39;s request. For all other patients, prescribe a whole-body scan from head to toe followed by a separate local tumor scan.
	<ol>
		<li>If a tumor is already appropriately centered in one of the whole-body PET slabs, prescribe and run the dedicated MRI sequences during the whole-body scan in order to save time; e.g., an abdominal tumor can be scanned with the whole-body coil.</li>
	</ol>
	</li>
	<li>To enable easy retrieval and review of PET/MRI data for the Radiologist, save the &#34;diagnostic&#34; images under one accession number. Later (see step 4.3.5) save the source images under a second accession number in the PACS system.</li>
	<li>Use the same localizers throughout the scan and make sure the patient doesn&#39;t move for the duration of the scan. This enables co-registration of the acquired PET and MRI data later.</li>
	<li>Prescribe the necessary MRI sequences within each PET slab. The integrated PET/MRI system then allows for the simultaneous acquisition of PET data and MRI data.</li>
	<li>Ask the patient to void directly before entering the scanner room.</li>
	<li>Whole-Body PET/MRI Scan
	<ol>
		<li>Position the patient on the PET/MRI table in a supine position. If the patient cannot lay supine, scan the head supine and the whole body in prone position. For very tall patients, acquire the lower legs in a second step. For patients with bone or soft tissue sarcoma, make sure to cover the whole affected bone from joint to joint (e.g., whole femur from hip to knee joint).</li>
		<li>Close a breathing belt around the patient. Then position a head coil and 2-3 surface coils on the neck, chest, abdomen, pelvis and extremities of the patient.</li>
		<li>Acquire whole-body localizers in three planes; axial, coronal and sagittal (Table 1) using the generic localizer protocol. Select the number of stations according to patient height. Scanning direction can be either from head to feet or feet towards head.</li>
		<li>Prescribe the entire protocol before starting the whole-body scan. Streamline this process and use a pre-saved protocol so that children do not lose patience.</li>
		<li>Prescribe axial PET slabs first, using the maximum axial field of view (FOV, typically 25 cm) and 3 min data acquisition. Depending on patient size, 4-5 slabs will cover head to mid-thigh and 9-10 slabs will cover the whole body.</li>
		<li>In the scanner software, enable two separate reconstructions for the PET data: one non-attenuation corrected (NAC) PET and one MRI attenuation corrected (MAC) PET. Use a matrix size of 192 x 192. Use 28 subsets with 2 iterations. The PET/MRI software allows for attenuation correction accounting for patient, patient cradle and dedicated MRI coils using sequences described under 3.7.7 below.</li>
		<li>Fill each PET slab with a low-resolution Liver Acquisition with Volume Acquisition (LAVA) sequencefor Attenuation Correction (MRAC) and a higher resolution LAVA sequence for anatomical co-registration of 18F-FDG-PET data. Diffusion-Weighted Images (DWI) can be added as deemed appropriate (Table 1).</li>
		<li>In the Task menu select the PET Task, click Add Task, click Add Postprocessing, choose MRAC Autobind (User) and then click Setup which will bring up an additional menu. Select all consecutive Water MRAC for the PET slabs and click Accept. This will enable the software to automatically merge the MRAC.</li>
		<li>Apply similar steps to merge the DWI. In this case, choose the first PET slab and click on the DWI sequence. Then click Add Task and follow the same additional steps as in 3.7.8.</li>
		<li>Add a dedicated T2-sequence for evaluation of the lungs and/or mediastinum (Table 1).</li>
	</ol>
	</li>
	<li>Local PET/MRI scan
	<ol>
		<li>Place an appropriate coil over the primary tumor. For extremity tumors, a flex coil may be used. For bone tumors, make sure to cover the adjacent joint (e.g., for an osteosarcoma of the distal femur metaphysis, include the distal femoral epiphysis and knee joint). For primary tumors of the neck, chest, abdomen and pelvis, placement of coils for local tumor and whole body staging can be done at once (see step 3.7.2). The separate materials/equipment list provides an overview of PET-compatible MRI coils available on the scanner.</li>
	</ol>
	</li>
</ol>
4. Image Data Processing
Note: To obtain the merged whole-body PET/MRI scan, the following four steps must be done: 1) reconstruct the PET image data, 2) merge the individual MRI data acquisitions to a single image volume, 3) co-register the PET to the MRI data, and 4) generate a PET whole-body maximum intensity projection (MIP). The scanner software greatly simplifies these steps.
<ol>
	<li>Merging of individual MRI data
	<ol>
		<li>Select all individual MRI data sets of a specific sequence, e.g.,LAVA 1 through 9, and press the Autobind button. The software then constructs a merged MRI data set. Save the merged MRI data set. The software automatically names the data set and adds it to the series list.</li>
	</ol>
	</li>
	<li>Co-registration of PET and MRI data
	<ol>
		<li>To co-register the merged MAC PET-data and merged LAVA-data, select each data set which needs to be co-registered and press the ImageQC button. The software then shows both the individual non-co-registered data sets and the co-registered data set in two planes in six separate windows.</li>
		<li>Select the MRI data and window-level appropriately, since this cannot be adjusted once the co-registered scan is finalized and saved.</li>
		<li>Similarly select the co-registered PET/MRI data set and window-level the PET data. It is also possible to adjust opacity, zoom and position of the co-registered data before saving.</li>
		<li>Choose the appropriate slice orientation for the co-registered data set, i.e., axial or coronal.</li>
		<li>Lastly, save the adjusted co-registered PET/MRI data set:
		<ol>
			<li>Choose Batch in the Film/Save menu. Select Loop and scroll all the way to the most cranial slice and click Set Start, then scroll down to the most caudal slice and click Set End.</li>
			<li>In the description field, choose an appropriate filename. Use a consistent and easily recognizable file name for all studies, so that the radiologist and clinician can easily find a specific data set (e.g., PET-LAVA Whole-Body).</li>
			<li>Click Preview and let the scan scroll from head to toe while checking that the final result is acceptable in terms of fusion accuracy and window levels. Close the preview and then select OK to start rendering the PET/MRI scan. The rendering process can be followed by observing the image index track bar.</li>
		</ol>
		</li>
		<li>Follow the same steps to co-register the MAC PET-data and the dedicated T2 MRI sequence for evaluation of the lungs. Since the PET-data FOV extends beyond the MRI, set the start and end of the scan to include only the co-registered part. 
		Note: The local PET/MRI can be co-registered following the same steps.</li>
	</ol>
	</li>
	<li>Generate PET whole-body MIP overview
	<ol>
		<li>To generate a PET whole-body maximum intensity projection (MIP), select the MAC PET and any MRI data set and press the ImageQC button.</li>
		<li>Double-click on the window with PET data only, and hover the cursor in the upper left corner to select View Type, and then select VR. This will create a 3D reconstruction of the PET data. Again, hover the mouse in the upper left corner to select rendering mode and then select HD MIP to finally create the PET whole-body MIP overview.</li>
		<li>To save the MIP overview choose Batch in the Film/Save menu and select Rotate. Adjust the number of images to 60. In the description field choose an appropriate file name. Click Preview and check that the final result is acceptable. Close the preview and then select OK to start rendering the MIP overview. Make sure the rendering is complete before you exit.</li>
		<li>Send the diagnostic image data sets to the institutions Picture Archiving and Communication System (PACS) by selecting the appropriate series and click on the desired Network in the Destinations menu.</li>
		<li>To save the source images under a different accession number, click Edit Patient and change the accession number. Then repeat the send procedure.</li>
	</ol>
	</li>
</ol>
5. Image Analysis and SUV Measurement
<ol>
	<li>Load the co-registered PET/MRI data in an FDA-approved medical imaging viewer to read and analyze the scan. Commercial PET/MRI viewers allow for measurement of the maximum Standardized Uptake Values (SUV) in 3D. 
	Note: For this specific protocol, we used MIM version 6.6.</li>
	<li>Choose Calculate SUV statistics from the tool bar. Position the region of interest (ROI) around the tissue exhibiting pathological 18F-FDG uptake on the co-registered PET/MRI. The ROI diameter can be enlarged by holding and dragging with the right mouse button. The software will determine both the mean and maximum SUV value. For patients with lymphoma, measure the liver and mediastinal blood pool as a standard of reference. Follow institution-specific guidelines for reporting of SUV measurements.</li>
</ol>

<ol>
	<li>Pichler, B. J., Judenhofer, M. S., Wehrl, H. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET/MRI+hybrid+imaging:+Devices+and+initial+results.">PET/MRI hybrid imaging: Devices and initial results.</a> Eur. Radiol. 18 (6), 1077-1086 (2008).</li><li>Torigian, D. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET+/+MR+Imaging+:+Technical+Aspects+and+Potential+Clinical+Applications.">PET / MR Imaging : Technical Aspects and Potential Clinical Applications.</a> Radiology. 267 (1), 26-44 (2013).</li><li>Daldrup-Link, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+PET/MR+Can+Add+Value+For+Children+With+Cancer.">How PET/MR Can Add Value For Children With Cancer.</a> Curr. Radiol. Rep. 5 (3), (2017).</li><li>Muehe, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+to+Provide+Gadolinium-Free+PET/MR+Cancer+Staging+of+Children+and+Young+Adults+in+Less+than+1+h:+the+Stanford+Approach.">How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1 h: the Stanford Approach.</a> Mol Imaging Biol. , (2017).</li><li>Spick, C., Herrmann, K., Czernin, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=18F-FDG+PET/CT+and+PET/MRI+perform+equally+well+in+cancer+patients:+Evidence+from+studies+in+more+than+2300+patients.">18F-FDG PET/CT and PET/MRI perform equally well in cancer patients: Evidence from studies in more than 2300 patients.</a> J. Nucl. Med. 57 (310), 1-38 (2016).</li><li>Sher, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+sequential+PET/MRI+in+comparison+with+PET/CT+of+pediatric+lymphoma:+A+prospective+study.">Assessment of sequential PET/MRI in comparison with PET/CT of pediatric lymphoma: A prospective study.</a> Am. J. Roentgenol. 206 (3), 623-631 (2016).</li><li>Jadvar, H., Colletti, P. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Competitive+Advantage+of+PET/MRI.">Competitive Advantage of PET/MRI.</a> Eur. J. Radiol. 83 (1), 84-94 (2014).</li><li>Wan, J. C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liquid+biopsies+come+of+age:+towards+implementation+of+circulating+tumour+DNA.">Liquid biopsies come of age: towards implementation of circulating tumour DNA.</a> Nat. Rev. Cancer. 17 (4), 223-238 (2017).</li><li>Grant, A. M., Deller, T. W., Khalighi, M. M., Maramraju, S. H., Delso, G., Levin, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NEMA+NU+2-2012+performance+studies+for+the+SiPM-based+ToF-PET+component+of+the+GE+SIGNA+PET/MR+system.">NEMA NU 2-2012 performance studies for the SiPM-based ToF-PET component of the GE SIGNA PET/MR system.</a> Med. Phys. 43 (5), 2334-2343 (2016).</li><li>. FDA Drug Safety Communication: FDA strengthens warnings and changes prescribing instructions to decrease the risk of serious allergic reactions with anemia drug Feraheme (ferumoxytol) Available from: <a target="_blank" href="https://www.fda.gov/Drugs/DrugSafety/ucm440138.htm">https://www.fda.gov/Drugs/DrugSafety/ucm440138.htm</a> (2015)</li><li>Mattsson, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radiation+Dose+to+Patients+from+Radiopharmaceuticals:+a+Compendium+of+Current+Information+Related+to+Frequently+Used+Substances.">Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances.</a> Ann. ICRP. 44 (2 Suppl), 7-321 (2015).</li></ol>

The authors have nothing to disclose.

We have shown a step-by-step protocol for PET/MRI studies of pediatric cancer patients. The most critical part of the protocol is time-efficient planning and prescribing the PET-slabs and MRI sequences with the correct parameters and in the correct consecutive order before initiating the whole-body scan. This enables continuous acquisition of the entire body. Efficient scanning is especially important in the pediatric setting, where unsedated patients can easily lose patience and either s...

Integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) enables cancer staging and treatment monitoring with high sensitivity, high soft tissue contrast, and added metabolic information1,2,3,4. In adult patients, PET/MRI performed equally well as PET/CT for staging of established cancers5,6,7. In the future, liquid biopsies will likely lead to earlier detection of cancer development (e.g., through transcriptomes and circulating DNA) and require more sensitive imaging tests than are currently available to find small tumors in the body8. This might put PET/MRI into a superior position to evaluate the whole body and detect cancers in anatomical areas that have been classically evaluated with MRI alone, such as the brain, neck, abdomen/pelvis,&#160;and musculoskeletal system.
For pediatric patients, PET/MRI has several advantages over PET/CT: First, PET/MRI provides a markedly reduced radiation exposure of the patient by up to 74%4. This can be achieved by using ionizing radiation-free MRI instead of CT technologies for anatomical co-registration of PET data. In addition, the increased sensitivity of modern PET detector systems9 and longer PET data acquisition during an MRI scan enables significant reduction of administered radiotracer doses by 30-50% compared to current PET/CT protocols4. Second, the possibility of combining staging scans of the primary tumor and the whole body saves time and avoids duplicate sedations for some patients, such as patients with bone and soft tissue sarcomas. However, a &#34;one stop&#34; staging scan is only clinically feasible if all PET/MRI data (local tumor and whole body) can be acquired in an efficient manner and if the abundance of resultant image data is presented in an easily digestible format to the radiologist. The protocol presented here will provide step-by-step instructions for the acquisition of PET/MRI data that can be used for clinical staging of children with cancer, with particular attention to specific needs of the pediatric population.

<table><tbody><tr><td>&lt;strong&gt;Integrated PET/MRI scanner&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>SIgna PET/MR</td><td>GE</td><td></td><td>3.0 T integrated PET/MRI scanner</td></tr><tr><td>&lt;strong&gt;Software&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>MP24_R03</td><td>GE</td><td></td><td>PET/MRI scanner software</td></tr><tr><td>MIM software version 6.6.13</td><td>MIM Software Inc.</td><td></td><td>PET/MRI analysis software</td></tr><tr><td>&lt;strong&gt;Contrast Agents&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Ferumoxytol</td><td>AMAG Pharmaceuticals</td><td></td><td>Iron Oxide nanoparticles</td></tr><tr><td>18F-FDG</td><td>-</td><td></td><td>2-Deoxy-2-(18F)fluoro-D-glucose</td></tr><tr><td>&lt;strong&gt;MRI coils available on the scanner&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Nova 32 Channel Head coil</td><td>Nova&amp;nbsp;</td><td></td><td></td></tr><tr><td>Neocoil 1H 16 channel GEM Flex Large Array</td><td>GE</td><td>M7000SK</td><td></td></tr><tr><td>Neocoil 1H 16 channel &amp;nbsp;GEM Flex Medium Array</td><td>GE</td><td>M7000SL</td><td></td></tr><tr><td>Neocoil 1H 16 channel GEM Flex Small Array</td><td>GE</td><td>M7000SM</td><td></td></tr><tr><td>Everest Central Molecular Imaging Array (CMA)</td><td>GE</td><td>M8000RB</td><td></td></tr><tr><td>Everest Head Neck Unit</td><td>GE</td><td>M8000CB</td><td></td></tr><tr><td>Everest Lower and Upper Anterior Array</td><td>GE</td><td>M8000CC &amp;amp; M8000CA</td><td></td></tr><tr><td>Invivo 1H 8 channel High Res Brain Array</td><td>GE</td><td>M8000RA</td><td></td></tr><tr><td>3.0T HD Breast Array Coil</td><td>GE</td><td>M7000GG</td><td></td></tr><tr><td>3.0T Split-Top Head TR Single Ch Coil</td><td>GE</td><td>G6000BH</td><td></td></tr></tbody></table>

whole-body pet/mri of pediatric patients: the details that matter

Integrated PET/MRI is a hybrid imaging technique enabling clinicians to acquire diagnostic images for tumor assessment and treatment monitoring with both high soft tissue contrast and added metabolic information. Integrated PET/MRI has shown to be valuable in the clinical setting and has many promising future applications. The protocol presented here will provide step-by-step instructions for the acquisition of whole-body 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/MRI data in children with cancer. It also provides instructions on how to combine a whole-body staging scan with a local tumor scan for evaluation of the primary tumor. The focus of this protocol is to be both comprehensive and time-efficient, which are two ubiquitous needs for clinical applications. This protocol was originally developed for children above 6 years, or old enough to comply with breath-hold instructions, but can also be applied to patients under general anesthesia. Similarly, this protocol can be modified to fit institutional preferences in terms of choice of MRI pulse sequences for both the whole-body scan and local tumor assessment.

We demonstrate an integrated whole-body (head to toe) data set of MRI, PET and fused PET/MR images, respectively, respectively, of a 10 year-old boy with status post resection of an undifferentiated sarcoma of the 12th rib, who presented with pulmonary and cardiac metastases (Figure 1). The data set shown here was acquired within 40 min. The effective dose of the patient during this exam was 3.3 mSv11.
For patients who rece...

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Whole-body PET/MRI of Pediatric Patients: The Details That Matter

This article provides comprehensive step-by-step instructions for the acquisition of whole-body 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/MRI scans for cancer staging of pediatric patients. The protocol was developed for children above 6 years, or old enough to comply with breath-hold instructions, but can be used for general anesthesia patients as well.

Integrated PET/MRI is a hybrid imaging technique enabling clinicians to acquire diagnostic images for tumor assessment and treatment monitoring with both ...

whole-body-petmri-of-pediatric-patients-the-details-that-matter

Research

JoVE Journal

Cancer Research

14.5K Views.  Stanford University. Dit artikel bevat uitgebreide stapsgewijze instructies voor de overname van het gehele lichaam 2-deoxy - 2-(18F) fluoro-D-glucose (18F-FDG) PET/MRI scans voor kanker enscenering van pediatrische patiënten. Het protocol werd ontwikkeld voor kinderen boven de 6 jaar, of oud genoeg om te voldoen aan adem-hold instructies, maar kan worden gebruikt voor algemene anesthesie patiënten zo goed.

Video: Whole-body PET/MRI of Pediatric Patients: The Details That Matter

PET and MRI Guided Irradiation of a Glioblastoma Rat Model Using a Micro-irradiator

For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without the ability to target a specific or well-delineated tumor volume. The delivery of radiation was achieved using fixed radiation sources or linear accelerators producing megavoltage (MV) X-rays. These devices are unable to achieve sub-millimeter precision required for small animals. Furthermore, the high doses delivered to healthy surrounding tissue hamper response assessment. To increase the translation between small animal studies and humans, our goal was to mimic the treatment of human glioblastoma in a rat model. To enable a more accurate irradiation in a preclinical setting, recently, precision image-guided small animal radiation research platforms were developed. Similar to human planning systems, treatment planning on these micro-irradiators is based on computed tomography (CT). However, low soft-tissue contrast on CT makes it very challenging to localize targets in certain tissues, such as the brain. Therefore, incorporating magnetic resonance imaging (MRI), which has excellent soft-tissue contrast compared to CT, would enable a more precise delineation of the target for irradiation. In the last decade also biological imaging techniques, such as positron emission tomography (PET) gained interest for radiation therapy treatment guidance. PET enables the visualization of e.g., glucose consumption, amino-acid transport, or hypoxia, present in the tumor. Targeting those highly proliferative or radio-resistant parts of the tumor with a higher dose could give a survival benefit. This hypothesis led to the introduction of the biological tumor volume (BTV), besides the conventional gross target volume (GTV), clinical target volume (CTV), and planned target volume (PTV).
At the preclinical imaging lab of Ghent University, a micro-irradiator, a small animal PET, and a 7 T small animal MRI are available. The goal was to incorporate MRI-guided irradiation and PET-guided sub-volume boosting in a glioblastoma rat model.

In the past, small animal irradiation was usually performed without the ability to target a well-delineated tumor volume. The goal was to mimic the treatment of human glioblastoma in rats. Using a small animal irradiation platform, we performed MRI-guided 3D conformal irradiation with PET-based sub-volume boosting in a preclinical setting.

For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without ...

Making MR Imaging Child's Play - Pediatric Neuroimaging Protocol, Guidelines and Procedure

Within the last decade there has been an increase in the use of structural and functional magnetic resonance imaging (fMRI) to investigate the neural basis of human perception, cognition and behavior 1, 2. Moreover, this non-invasive imaging method has grown into a tool for clinicians and researchers to explore typical and atypical brain development. Although advances in neuroimaging tools and techniques are apparent, (f)MRI in young pediatric populations remains relatively infrequent 2. Practical as well as technical challenges when imaging children present clinicians and research teams with a unique set of problems 3, 2. To name just a few, the child participants are challenged by a need for motivation, alertness and cooperation. Anxiety may be an additional factor to be addressed. Researchers or clinicians need to consider time constraints, movement restriction, scanner background noise and unfamiliarity with the MR scanner environment2,4-10. A progressive use of functional and structural neuroimaging in younger age groups, however, could further add to our understanding of brain development. As an example, several research groups are currently working towards early detection of developmental disorders, potentially even before children present associated behavioral characteristics e.g.11. Various strategies and techniques have been reported as a means to ensure comfort and cooperation of young children during neuroimaging sessions. Play therapy 12, behavioral approaches 13, 14,15, 16-18 and simulation 19, the use of mock scanner areas 20,21, basic relaxation 22 and a combination of these techniques 23 have all been shown to improve the participant's compliance and thus MRI data quality. Even more importantly, these strategies have proven to increase the comfort of families and children involved 12. One of the main advances of such techniques for the clinical practice is the possibility of avoiding sedation or general anesthesia (GA) as a way to manage children's compliance during MR imaging sessions 19,20. In the current video report, we present a pediatric neuroimaging protocol with guidelines and procedures that have proven to be successful to date in young children.

Despite an increase in the use of structural and functional magnetic resonance imaging (fMRI) in humans, the study of young pediatric populations remains a challenge. We present a hands-on, step-by-step video protocol including guidelines for clinicians and researchers intending to perform (f)MRI in young children.

Within the last decade there has been an increase in the use of structural and functional magnetic resonance imaging (fMRI) to investigate the neural ...

Biology

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.

We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

Medicine

A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which&#160;11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of 11C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of 11C-AcAc and 18F-FDG brain uptake (cerebral metabolic rate; &#956;mol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer&#39;s and Parkinson&#39;s diseases.

Small-animal positron emission tomography enables the assessment of the brain&#39;s two main energy substrates:&#160;glucose and ketones. In the present method, 11C-acetoacetate and 18F-fluorodeoxyglucose are injected sequentially in each animal, and their uptake is measured quantitatively in specific brain regions determined from the magnetic resonance images.

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the ...

Neuroscience

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer 18F-Fluorodeoxyglucose (18F-FDG) into adipose tissue depots, as measured by positron emission tomography/computed tomography (PET-CT) scans after exposing the subject to cold stimulus. Fat-water separated magnetic resonance imaging (MRI) has the ability to distinguish BAT without the use of a radioactive tracer. To date, MRI of BAT in adult humans has not been co-registered with cold-activated PET-CT. Therefore, this protocol uses 18F-FDG PET-CT scans to automatically generate a BAT mask, which is then applied to co-registered MRI scans of the same subject. This approach enables measurement of quantitative MRI properties of BAT without manual segmentation. BAT masks are created from two PET-CT scans: after exposure for 2 hr to either thermoneutral (TN) (24 &#176;C) or cold-activated (CA) (17 &#176;C) conditions. The TN and CA PET-CT scans are registered, and the PET standardized uptake and CT Hounsfield values are used to create a mask containing only BAT. CA and TN MRI scans are also acquired on the same subject and registered to the PET-CT scans in order to establish quantitative MRI properties within the automatically defined BAT mask. An advantage of this approach is that the segmentation is completely automated and is based on widely accepted methods for identification of activated BAT (PET-CT). The quantitative MRI properties of BAT established using this protocol can serve as the basis for an MRI-only BAT examination that avoids the radiation associated with PET-CT.

The method presented here uses 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET-CT) and fat-water separated magnetic resonance imaging (MRI), each scanned following 2 hr exposure to thermoneutral (24 &#176;C) and cold conditions (17 &#176;C) in order to map brown adipose tissue (BAT) in adult human subjects.

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in ...

Dynamic Contrast Enhanced Magnetic Resonance Imaging of an Orthotopic Pancreatic Cancer Mouse Model

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been limitedly used for orthotopic pancreatic tumor xenografts due to severe respiratory motion artifact in the abdominal area. Orthotopic tumor models offer advantages over subcutaneous ones, because those can reflect the primary tumor microenvironment affecting blood supply, neovascularization, and tumor cell invasion. We have recently established a protocol of DCE-MRI of orthotopic pancreatic tumor xenografts in mouse models by securing tumors with an orthogonally bent plastic board to prevent motion transfer from the chest region during imaging. The pressure by this board was localized on the abdominal area, and has not resulted in respiratory difficulty of the animals. This article demonstrates the detailed procedure of orthotopic pancreatic tumor modeling using small animals and DCE-MRI of the tumor xenografts. Quantification method of pharmacokinetic parameters in DCE-MRI is also introduced. The procedure described in this article will assist investigators to apply DCE-MRI for orthotopic gastrointestinal cancer mouse models.

The goal of this protocol is to apply dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for orthotopic pancreatic tumor xenografts in mice. DCE-MRI is a non-invasive method to analyze microvasculature in a target tissue, and useful to assess vascular response in a tumor following a novel therapy.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been limitedly used for orthotopic pancreatic tumor xenografts due to severe ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Several in vivo pre-clinical studies in Polycystic Kidney Disease (PKD) utilize orthologous rodent models to identify and study the genetic and molecular mechanisms responsible for the disease, and are very convenient for rapid drug screening and testing of promising therapies. A limiting factor in these studies is often the lack of efficient non-invasive methods for sequentially analyzing the anatomical and functional changes in the kidney. Magnetic resonance imaging (MRI) is the current gold standard imaging technique to follow autosomal dominant polycystic kidney disease (ADPKD) patients, providing excellent soft tissue contrast and anatomic detail and allowing Total Kidney Volume (TKV) measurements.A major advantage of MRI in rodent models of PKD is the possibility for in vivo imaging allowing for longitudinal studies that use the same animal and therefore reducing the total number of animals required. In this manuscript, we will focus on using Ultra-high field (UHF) MRI to non-invasively acquire in vivo images of rodent models for PKD. The main goal of this work is to introduce the use of MRI as a tool for in vivo phenotypical characterization and drug monitoring in rodent models for PKD.

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

The use of ultra-high field MRI as a non-invasive way to obtain phenotypic information of rodent models for polycystic kidney disease and to monitor interventions is described. Compared with the traditional histological approach, MRI images can be acquired in vivo, allowing for longitudinal follow-up.

Several in vivo pre-clinical studies in Polycystic Kidney Disease (PKD) utilize orthologous rodent models to identify and study the genetic and molecular ...

Functional Imaging of Brown Fat in Mice with 18F-FDG micro-PET/CT

Brown adipose tissue (BAT) differs from white adipose tissue (WAT) by its discrete location and a brown-red color due to rich vascularization and high density of mitochondria. BAT plays a major role in energy expenditure and non-shivering thermogenesis in newborn mammals as well as the adults 1. BAT-mediated thermogenesis is highly regulated by the sympathetic nervous system, predominantly via &beta; adrenergic receptor 2, 3. Recent studies have shown that BAT activities in human adults are negatively correlated with body mass index (BMI) and other diabetic parameters 4-6. BAT has thus been proposed as a potential target for anti-obesity/anti-diabetes therapy focusing on modulation of energy balance 6-8. While several cold challenge-based positron emission tomography (PET) methods are established for detecting human BAT 9-13, there is essentially no standardized protocol for imaging and quantification of BAT in small animal models such as mice. Here we describe a robust PET/CT imaging method for functional assessment of BAT in mice. Briefly, adult C57BL/6J mice were cold treated under fasting conditions for a duration of 4 hours before they received one dose of 18F-Fluorodeoxyglucose (FDG). The mice were remained in the cold for one additional hour post FDG injection, and then scanned with a small animal-dedicated micro-PET/CT system. The acquired PET images were co-registered with the CT images for anatomical references and analyzed for FDG uptake in the interscapular BAT area to present BAT activity. This standardized cold-treatment and imaging protocol has been validated through testing BAT activities during pharmacological interventions, for example, the suppressed BAT activation by the treatment of &beta;-adrenoceptor antagonist propranolol 14, 15, or the enhanced BAT activation by &beta;3 agonist BRL37344 16. The method described here can be applied to screen for drugs/compounds that modulate BAT activity, or to identify genes/pathways that are involved in BAT development and regulation in various preclinical and basic studies.

Functional Imaging of Brown Fat in Mice with 18F-FDG micro-PET/CT

A method of functional imaging of mouse brown adipose tissue (BAT) is described in which cold-stimulated uptake of 18F-Fluorodeoxyglucose (FDG) in BAT is non-invasively assessed with a standardized micro-PET/CT protocol. This method is robust and sensitive to detect differences in BAT activities in mouse models.

Brown adipose tissue (BAT) differs from white adipose  tissue (WAT) by its discrete location and a brown-red color due to rich  vascularization and high ...

Clinical Indications for Rapid Sequence MRI in Pediatric Neurosurgical Patients and the Limitations and Barriers to Implementation

Rapid and fast magnetic resonance imaging (MRI) protocols have become increasingly popular for pediatric neurosurgical patients as they are a great way to reduce ionizing radiation and sedation. While their popularity has increased, there are hurdles to overcome when transitioning to using them clinically, such as cost, staffing training, and motion artifact. Through this paper, we developed a protocol for clinical applications where rapid MRI can be a substitute or adjuvant in diagnostic workup. Further, we outline the relevant literature for the use of RS-MRI for the spine, TBI, and hydrocephalus pathologies while expanding upon the limitations and logistical barriers when transitioning to their use, a few of which are discussed above. Through this, we conclude that RS-MRI can be used diagnostically for spinal pathologies such as syrinx and hydrocephalus. Further, its lack of sensitivity for TBI findings makes rapid sequence magnetic resonance imaging (RS-MRI) a strong adjuvant with other advanced imaging or computed tomography (CT) for traumatic brain injury (TBI) pathologies.

Here, we present a protocol to increase the use of rapid sequence magnetic resonance imaging (RS-MRI) for pediatric patients for spine, traumatic brain injury (TBI), and hydrocephalus while documenting limitations and barriers to universal implementation.

Rapid and fast magnetic resonance imaging (MRI) protocols have become increasingly popular for pediatric neurosurgical patients as they are a great way to ...

Whole-body PET/MRI of Pediatric Patients: The Details That Matter

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