Image of Youth: Progress in Molecular Pediatric Medicine

Molecular imaging has become increasingly important in the non-invasive diagnosis and monitoring of pediatric disease, whether known or suspected. Innovations in molecular oncology, neuroimaging and hybrid imaging are shaping how clinicians approach a range of diseases in children and young adults. Radiation exposure continues to be a concern in pediatric imaging, especially when children require multiple exams throughout the course of their treatment.

Over the past 20 years, there has been an increase in the incidence of children diagnosed with all forms of malignant disease. Molecular imaging techniques also have become much more targeted and recent fine-tuning of technology allows more precision and higher resolution imaging than ever before.

Pediatric oncology

According to the National Cancer Institute, among the 12 major types of childhood cancers, leukemias and cancers of the brain and central nervous system account for more than half of all new cases. The most common solid tumors are brain tumors such as gliomas and medulloblastomas, followed by other solid tumors such as neuroblastomas, Wilms tumors, and sarcomas including rhabdomyosarcoma and osteosarcoma.

Oncology likely represents the broadest area of current applications for pediatric molecular imaging. Hybrid imaging techniques using PET or SPECT combined with CT demonstrate significant benefits in the evaluation, staging and response assessment of malignancies in children.

“PET/CT has changed how we manage solid tumors,” says Helen Nadel, MD, pediatric radiologist and head of nuclear medicine at Radiology British Columbia Children’s Hospital and associate professor of radiology at University of British Columbia, Vancouver. “It provides whole-body staging in one sitting and the ability to see if treatment has been effective. There’s always a concern about monitoring patients’ exposure [to ionizing radiation], and there are a lot of ways to effectively reduce dose. In our facility, the CT portion of the PET/CT suffices as the patient’s diagnostic study that I need. A separate study for attenuation correction is not needed.”

SPECT/CT is quickly becoming a part of the diagnostic path to discover common pediatric tumors such as neuroblastoma, an neuroendocrine tumor. According to the American Cancer Society, neuroblastoma is by far the most common cancer in infants (less than 1 year old) and accounts for about 7 percent of all cancers in children.

In most cases, the disease has already spread to the lymph nodes or other parts of the body when it is diagnosed. Because of its high sensitivity and specificity, SPECT/CT using I-123 metaiodobenzylguanidine (I-123 MIBG) offers a complete whole-body map of the disease for detection of both primary tumors and metastases demonstrating the precise location of the lymph nodes that have been affected.

“We’re using SPECT/CT in oncology for neuroblastoma with I-123 MIBG. SPECT alone is very specific but doesn’t localize the disease. Artifacts may look inconsequential on standard I-123 MIBG SPECT, when in fact, they are metastases,” Nadel says. Her recent study, SPECT/CT in Pediatric Patient Management, published in the January issue of the European Journal of Nuclear Medicine and Molecular Imaging, reviews the current standard of care in pediatric SPECT/CT imaging. 

Neuroblastoma also can be effectively diagnosed with PET/CT. The uptake of the tracer F-18 fluorodeoxyglucose (FDG) is proportional to tumor burden and cell proliferation. These characteristics make it very effective for staging and monitoring patient’s response to treatment.

Neuroimaging

Currently, PET is widely used as an accurate and noninvasive method to study brain activity and to understand pediatric neurological disease processes such as the evaluation of head and neck lymphoma and pediatric brain tumors.

Pediatric brain tumors are often imaged with contrast-enhanced structural MRI, but MR is limited in its ability to demonstrate tumor progression and recurrence. Research presented at the 2013 annual meeting of the Society of Nuclear Medicine and Molecular Imaging reported using an amino acid imaging agent, O-(2-[18F]-fluoroethyl)-L-tyrosine (F-18 FET), because of its diagnostic benefit for imaging pediatric gliomas when conventional MRI cannot make out a clear picture of disease.

The authors postulated that PET and F-18 FET can be used to evaluate the extent of tumors and also to help plan for biopsies, surgeries, radiation therapies and to track therapy effectiveness after treatment. F-18 FET also has a radioactive half-life of approximately 110 minutes and does not require a cyclotron.

“The one application for PET/CT that hasn’t increased as much as I’d like to see is brain imaging,” Nadel remarked. “I feel that PET/MR in the near future will come to dominate that field with significant advances in imaging disease in the brain.”

PET/MR

The MR piece of the equation not only provides more biological and functional data than CT, it does so without radiation. Thus,  the PET/MR offers a big advantage for pediatric patients, especially those needing multiple scans. 

MR offers better definition of tumor volume and disease extent than CT for staging tumors in the brain. Instead of using MR for attenuation correction, it can be used to evaluate perfusion and blood flow to affected tissue in the brain and inform treatment decisions based on whether or not the tumor is likely to respond.

Initial reports indicate the effective dose of a PET/MR scan was about 20 percent that of the equivalent PET/CT examination. In an article published last July in Pediatric Radiology, initial reporting on PET/MR in pediatrics was presented by the University of Leipzig in Germany. The authors noted one of the positives of the new hybrid scanner was whole-body diffusion-weighted imaging. However, a longer examination time was a noted disadvantage. 

Reducing radiation exposure

Reducing radiation exposure to pediatric patients continues to be a topic of concern as policy makers and healthcare providers work together toward cumulative exposure tracking and monitoring. The American College of Cardiology’s Committee on Clinical Quality recently published the 2014 Health Policy Statement on Use of Noninvasive Cardiovascular Imaging. The issue of patient risk/safety following exposure to ionizing radiation from CT, nuclear medicine, and invasive angiographic studies has been added to the debate about the increased use of medical imaging.

In molecular imaging specifically, modifications can be made to adjust the dosage to pediatric patients. In some cases, the radiation dose can be cut in half while maintaining image quality.

“Each examination must start with justification,” Nadel says, citing that careful consideration for dose optimization and reduction must be included for each study performed. “The key to these studies is not imaging more than you need to,” insists Nadel. “We use optimal minimal exposure, looking for localization and always use dose modulation to get a 50 percent reduction in dose.”

Imaging studies using PET/MR scanners can further decrease the radiation exposure to children.

“Using PET/MR eliminates the dose entirely from the CT, and because the MR study takes longer to complete, you can reduce the PET dose due to the extended imaging time,” adds Nadel.

Reimbursement is another big question. Private coverage across pediatrics is currently limited. For adults covered by Medicare and Medicaid, CMS amended coverage for oncologic PET in June 2013 to include one initial PET scan and three follow-up scans. This was to include PET/CT and PET/MR modalities. Time will tell what private insurors will cover. Stay tuned.