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 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.
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, 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 "one stop" 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.
All methods presented here have been established under a research study, which was approved by the institutional review board of Stanford University. The "off label" 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
2. 1-2 h Before the PET/MRI Scan: Patient Preparation
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.
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.
5. Image Analysis and SUV Measurement
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 receive a dedicated scan of the primary tumor, in addition to the whole-body head-to-toe PET/MR image acquisition, the combined scan can be performed in 60-90 min, depending on the location and size of the primary tumor and the length of the patient.
Figure 1: Result of whole-body PET/MRI acquisition using protocol. 18F-FDG PET and ferumoxytol-enhanced MRI images of pulmonary and cardiac metastases of a 10 year-old boy with status post-resection of an undifferentiated sarcoma of the 12th rib. Images show multiple hypermetabolic pulmonary metastases as well as a metastasis in the right ventricular outflow tract of the heart. Whole-body coronal (A) LAVA MRI data, (B) MRI Attenuation Corrected PET-data, and (C) co-registered PET and merged LAVA MRI data. Please click here to view a larger version of this figure.
Pulse Sequence Parameter | Localizers | Coronal thoracic LAVA | Axial thoracic T2-FSE PROPELLER | Axial low-resolution LAVA MRAC | Axial LAVA | Axial DWI |
Acquisition time (min) | 1:45 | 0:16 | 5:48 | 0:18 | 0:16 | 1:47 |
TE (ms) | 80 | 1.1 | 119 | 1.7, 3.4 | 1.7, 3.4 | 56 |
TR (ms) | 1519 | 4.1 | 12500 | 4 | 4.2 | 7824 |
Matrix Size | 288 x 192 | 320 x 224 | 384 x 384 | 256 x 256 | 320 x 224 | 80×128 |
Slice Thickness (mm) | 10 | 3.4 | 4 | 5.2 | 3.4 | 8 |
FOV (cm) | (whole-body or head to mid-thigh coverage) | 46 | 48 | 50 | 48 | 40 |
Flip Angle (degrees) | – | 15 | 110 | 5 | 15 | 90 |
B-value (s/mm2) | – | – | – | – | – | 50, 600 |
Table 1: Magnetic resonance imaging pulse sequence parameters for whole-body scan. MRI pulse sequence parameters for each acquisition of the whole-body PET/MRI scan.
Pulse Sequence Parameter | High-resolution LAVA | T1 FSE IDEAL | T2 FSE (Head & Neck) | T2 FSE (Abdomen) | RT T2 FRFSE | T1 FSE (Pelvis) | T2 FSE (Pelvis) | T1 FSE (Extremity) | T2 FSE (Extremity) |
Acquisition time (min) | 1:38 | 4:26 | 3:12 | 1:13 | 3:00-6:00 | 4:07 | 6:43 | 6:13 | 6:08 |
TE (ms) | 1.3 | 9.8-39.3 | 116 | 102 | 102 | 9.1 | 102 | 7.8 | 116 |
TR (ms) | 9.5 | 884 | 4000 | 2400 | 1100-1300 | 709 | 9823 | 709 | 4000 |
Matrix Size | 160 x 256 | 384 x 192 | 320 x 224 | 320 x 224 | 384 x 256 | 448 x 256 | 384 x 320 | 416 x 320 | 320 x 224 |
Slice Thickness (mm) | 3.4 | 5 | 4 | 4 | 4 | 4 | 4 | 3 | 3 |
FOV (cm) | 21 | 20 | 20 | 38 | 38 | 30 | 30 | 28 | 28 |
Flip Angle (degrees) | 15 | 111 | 142 | 111 | 111 | 111 | 111 | 111 | 111 |
Table 2: Magnetic resonance imaging pulse sequence parameters for local tumor scan. MRI pulse sequence parameters for the primary tumor scan. Note that not all sequences are applied for each tumor (see Table 3). Respiratory-triggered (RT), Fast Recovery Fast Spin Echo (FRFSE).
Protocol | Magnetic Resonance Imaging Sequences |
Head & Neck Tumor | Whole-body scan + High-resolution LAVA + T1 FSE IDEAL + T2 FSE (Head & Neck) |
Abdominal Tumor | Whole-body scan + High-resolution LAVA + T2 FSE (Abdomen) + RT T2 FRFSE |
Pelvic Tumor | Whole-body scan + T1 FSE (Pelvis) + T2 FSE (Pelvis) |
Extremity Tumor | Whole-body scan + T1 FSE (Extremity) + T2 FSE (Extremity) |
Lymphoma | Whole-body scan only |
Table 3: Magnetic resonance imaging sequences for local tumor scan. MRI sequences for the primary tumor scan depending on tumor localization.
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 start to move or abort the exam if it takes too long. Therefore, it is important to carefully choose the direction of the scan (head-to-toe or toe-to-head, primary tumor first or whole body first, depending on priority). Apparently simple preparation steps such as asking the patient to void directly before entering the scanner can have major impact on image quality. Pediatric tumors can usually not be scanned with a “one fits all” approach and require prescription of tailored PET and MRI scan parameters for evaluation of the primary tumor.
Our PET/MRI protocol has been tailored to the specific needs of children with regards to both the chronological sequence of image acquisitions and the specific scanning parameters4. Our goal was to devise a protocol which would acquire high-quality diagnostic images, while keeping scan time at a minimum.
This protocol was originally developed for children above 6 years,or old enough to comply with breath-hold instructions. The protocol can be also applied for younger patients under general anesthesia by either also using breath-hold MRI sequences for anatomical orientation or by using ultrafast sequences with free breathing acquisition modes. Furthermore, while table 3 provides our choice of MRI pulse sequences for assessment of the primary tumor, these can easily be modified or expanded to fit institutional preferences.
In conclusion, the protocol presented here shows how acquisition of whole-body PET/MRI for pediatric cancer staging can be realized. Given that PET/MRI has several advantages over PET/CT including markedly reduced radiation exposure, better soft tissue contrast and equal or improved sensitivity for cancer staging, it appears possible to replace some pediatric PET/CT studies by PET/MRI.
The authors have nothing to disclose.
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.
Integrated PET/MRI scanner | |||
SIgna PET/MR | GE | 3.0 T integrated PET/MRI scanner | |
Software | |||
MP24_R03 | GE | PET/MRI scanner software | |
MIM software version 6.6.13 | MIM Software Inc. | PET/MRI analysis software | |
Contrast Agents | |||
Ferumoxytol | AMAG Pharmaceuticals | Iron Oxide nanoparticles | |
18F-FDG | – | 2-Deoxy-2-(18F)fluoro-D-glucose | |
MRI coils available on the scanner | |||
Nova 32 Channel Head coil | Nova | ||
Neocoil 1H 16 channel GEM Flex Large Array | GE | M7000SK | |
Neocoil 1H 16 channel GEM Flex Medium Array | GE | M7000SL | |
Neocoil 1H 16 channel GEM Flex Small Array | GE | M7000SM | |
Everest Central Molecular Imaging Array (CMA) | GE | M8000RB | |
Everest Head Neck Unit | GE | M8000CB | |
Everest Lower and Upper Anterior Array | GE | M8000CC & M8000CA | |
Invivo 1H 8 channel High Res Brain Array | GE | M8000RA | |
3.0T HD Breast Array Coil | GE | M7000GG | |
3.0T Split-Top Head TR Single Ch Coil | GE | G6000BH |