Pint-size Power: PET/CT and SPECT/CT in Pediatrics
PET/CT—a technology whose potential is now being appreciated, but has yet to be fully realized—has proven successful in the accurate staging and monitoring of oncology patient therapy for a variety of cancers. SPECT/CT, while relatively new, is beginning to make its mark in areas such as oncology, cardiology, neurology imaging. Across the spectrum of specialties, PET/CT and SPECT/CT offer new, advanced techniques to improve the diagnosis, treatment and management of a variety of diseases in adults as well as in children.
Addressing the challenges
Molecular imaging within the field of pediatrics is challenging due to the very nature of the patient population. Children are inherently different than adults in their range of body sizes, behaviors and the rather unique types of diseases affecting them, says S. Ted Treves, MD, chief of Nuclear Medicine/PET at Children’s Hospital in Boston and professor of radiology and director of the Joint Program in nuclear medicine at Harvard Medical School. “One of the biggest challenges in imaging children is the need for high spatial resolution,” he says. “The equipment is normally designed for adult use and we have to adapt our techniques and equipment for the benefit of children.”
Treves directs his research along two paths: optimizing the use of nuclear medicine in pediatrics with a recent focus on reducing radiation dose in children; and integrating modalities in medical imaging. An important challenge to pediatric imaging is obtaining high-quality studies using the lowest possible radiation dose, he adds. Improved use of technology combined with careful screening of indications can help lower radiation dose and still provide the necessary diagnostic information.
One of the common dangers in treating children is over-treating disease, says Richard L. Wahl, MD, FACR, professor of nuclear medicine, director of nuclear medicine/PET facility, vice chair radiology for technology and business development at Johns Hopkins University School of Medicine in Baltimore. “Both under- and over-treatment can occur in children if you don’t have the right technology,” he says. While the combination of PET and CT is more potent than either alone, it is a good method to use to avoid many false positives and negatives on CT and to add specificity to PET.
Helen R. Nadel, MD, pediatric radiologist, division head of nuclear medicine, British Columbia Children’s Hospital in Vancouver, Canada, agrees that it is necessary to accommodate the varying needs within pediatrics, while minimizing radiation exposure. “Given that we run the gamut of all age groups from newborns to the cusp of adulthood for the diseases we face in pediatrics, we cannot always standardize and set up one way to do a test for everyone,” Nadel says.
Optimizing hybrid molecular imaging for pediatrics requires a little more flexibility and creativity in how tests are performed. Standardizing protocols can be a good start, but such protocols may require modification. “In nuclear medicine [there] is a movement toward optimized workflow and batch processing,” she says. “We would love to do this in pediatrics, but when you deal with a population that can range from 5 pounds to 200 pounds, it is not possible. You cannot possibly do them the same way—you must adapt.”
Clinical indications for PET/CT
“Just because it is difficult, does not mean it is impossible for these technologies to make a difference in pediatrics,” says Wahl. These hybrid technologies are proving their value in pediatric neurology, orthopedics and oncology, Treves says.
In neurology, PET fused with MR has proven an effective tool for the localization of focal epilepsy in the brain. “In addition, PET/MR fusion is effective for assessing the effect of therapy and also to detect the residual or recurrent brain tumor activity,” Treves says. “At Children’s Hospital Boston, PET/MR image fusion is considered a necessity and it is done routinely in all brain studies so that the anatomic-functional relationships can be assessed more easily. Emerging PET agents beyond FDG hold promise in improving the assessment of brain tumors in children.”
It has been proven that PET’s metabolic assessment shows other areas of abnormality that cannot be detected by other modalities, which aids in surgical planning. “It is proven but requires a dedicated epilepsy surgery service that can act on the results,” Nadel says. Despite its proven ability, with the limited availability of PET/CT in pediatrics, the British Columbia’s Children’s Hospital has been providing their assessment of children with other modalities such as functional MRI (fMRI), but Nadel admits this is an area of potential growth for PET.
Treves says that PET/CT, using 18F sodium fluoride (18F NaF PET), a skeletal PET imaging agent, is being used in orthopedics and sports medicine to assess various bone disorders, osteomyelitis, bone tumors, non-accidental trauma, or any of the well-established indications of skeletal scintigraphy. “PET with 18F NaF has certain advantages including a high sensitivity, exquisite spatial resolution and rapid imaging at a similar radiation exposure to that of conventional skeletal scintigraphy,” he adds. “The combination of PET and CT provides improved lesion localization.”
In the case of pediatric oncology, the majority of childhood cancers are clinically aggressive, high-grade tumors such as malignant lymphomas, bone and soft-tissue sarcomas, germ cell tumors and neuroblastoma.
Pediatric cancer is a heterogeneous group of diseases and there is great interest in integrating PET into the evaluation of children and adolescents with cancer to help adjust treatment strategies and possibly improve outcomes, says Edita Kabickova, MD, pediatric oncologist and assistant professor, department of pediatric hematology and oncology, Charles University, Prague, Czech Republic. PET with 18F-fluorodeoxygluclose allows for a functional assessment of tumor metabolism and has increased sensitivity for lesions that may be undetectable by anatomic-based methods of imaging.
“PET is now widely used in our patients and is helpful in the primary staging, treatment and follow-up of children with cancer,” Kabickova says. “Today, PET/CT is incorporated into the diagnostic work-up of our patients with lymphomas, germ cell tumors, sarcomas and some types of rare pediatric malignancies, such as colorectal carcinoma, thyroid cancer and melanoma.”
Using PET with FDG allows a physician to ascertain the extent of cancer in the body in rather unique ways because it does not rely on anatomic changes or the detection of masses, says Treves. “Instead, it allows the physician to portray the actual [metabolic] activity of the tumors. It has really been a powerful tool to give us a more complete picture of disease.”
Kabickova adds that small cancer manifestations, for example, normal size lymph nodes in children with lymphomas or sarcomas, can be visualized due to high FDG uptake. This can improve the clinical staging of untreated patients. PET/CT also is being used to evaluate tumor viability after chemotherapy and to identify children at risk for early relapse.
“The current treatment strategy for childhood malignancies is risk-based and the rapidity of response to the first few cycles of chemotherapy is used to determine the subsequent treatment intensity,” says Kabickova. “PET/CT imaging allows identification of responding and non-responding tumors early in the course of therapy. With this information, we can rapidly modify ineffective therapies for these patients and thereby potentially improve their outcomes.”
While PET/CT is effective in staging lymphomas, bone, and soft-tissue tumors, and for evaluating tumor response, it is not helpful for routine follow-up on surveillance of children for bone and soft-tissue tumors with no evidence of recurrent or metastatic disease and no symptoms, according to Nadel.
“We have determined in a series of studies that the least value of PET/CT is in surveillance monitoring in the absence of symptoms, where we get a very low rate of abnormality,” Nadel says. “Where we do get a high rate of pick-up and change in management is either at diagnosis for staging and picking up unexpected, more widespread, disease at the time of assessment for local control before surgical planning and at the end of treatment.” Other studies have shown value in surveillance monitoring.
Another area of growth in pediatrics is infection imaging, or inflammation, particularly in musculoskeletal disease and fever of unknown origins. “PET/CT can help us to look at infections in children more easily and avoid the need to label their white blood cells,” Wahl says.
Clinical indications for SPECT/CT
SPECT/CT is relatively new in pediatrics—it has not penetrated the field to the degree PET/CT has, but it holds promise. “SPECT/CT has a growing role within pediatrics, but it is going to be a more limited role compared to PET/CT,” says Wahl. Currently, the technology is being used more for Meta-Iodo-Benzyl-Guanidine (MIBG) scans for neuroblastoma, and in some patients with osteosarcoma, he adds.
With SPECT/CT, a physician gains improved anatomical localization and the acquisition of attenuation maps for attenuation correction. “It is the uniqueness of the information that studies provide that make the technology so desirable,” says Treves. SPECT/CT is used for imaging of the brain and the body in routine applications for epilepsy, tumors and whole-body imaging, including myocardial perfusion imaging.
British Columbia Children’s Hospital has slowly been increasing its SPECT/CT workload over the last nine months, Nadel says. The hospital is utilizing the technology to do diagnostic CT scans and correlated imaging tests when the child was already scheduled to have a CT scan, for example, in patients with neuroblastoma. By doing SPECT MIBGs with contrast enhanced CT scans, Nadel says they have found economies of time—the child is saved an extra trip; economies of radiation exposure—minimizing radiation dosing; and economies of efficiency, reading both diagnostic scans simultaneously.
“Two heads are better than one,” she says. “When you put the two studies together, you can see things that could not be matched up alone.”
For example, a child at the Children’s Hospital had an initial SPECT/CT study done, Nadel says, for staging; the next study done prior to reaching a treatment decision point was done as one modality; the next time as the other modality. Although done correctly, they each missed one observation. A fourth combined study was done. “It was clear that the stand-alone studies showed what they could, the best they could,” she says. “However, the combined study of SPECT and CT clearly helped in disease evaluation and was better than the two [separately].”
Another area where SPECT/CT is found to be beneficial is in small bone lesion localization and diagnosis. “We are finding things hot on bone scans that we did not know exactly where they were, but in finding their location, we were able to better suggest the correct diagnosis,” Nadel adds.
Assessing future potential
The recent proliferation of hybrid imaging systems has been revolutionary and has added a new and important dimension in imaging, Treves says.
Molecular imaging has helped to highlight the great advantages of radionuclide imaging in the diagnosis and monitoring of disease in children. Ongoing research will continue to expand the effectiveness and potential of value of PET/CT and SPECT/CT in pediatric care.
Addressing the challenges
Molecular imaging within the field of pediatrics is challenging due to the very nature of the patient population. Children are inherently different than adults in their range of body sizes, behaviors and the rather unique types of diseases affecting them, says S. Ted Treves, MD, chief of Nuclear Medicine/PET at Children’s Hospital in Boston and professor of radiology and director of the Joint Program in nuclear medicine at Harvard Medical School. “One of the biggest challenges in imaging children is the need for high spatial resolution,” he says. “The equipment is normally designed for adult use and we have to adapt our techniques and equipment for the benefit of children.”
Treves directs his research along two paths: optimizing the use of nuclear medicine in pediatrics with a recent focus on reducing radiation dose in children; and integrating modalities in medical imaging. An important challenge to pediatric imaging is obtaining high-quality studies using the lowest possible radiation dose, he adds. Improved use of technology combined with careful screening of indications can help lower radiation dose and still provide the necessary diagnostic information.
One of the common dangers in treating children is over-treating disease, says Richard L. Wahl, MD, FACR, professor of nuclear medicine, director of nuclear medicine/PET facility, vice chair radiology for technology and business development at Johns Hopkins University School of Medicine in Baltimore. “Both under- and over-treatment can occur in children if you don’t have the right technology,” he says. While the combination of PET and CT is more potent than either alone, it is a good method to use to avoid many false positives and negatives on CT and to add specificity to PET.
Helen R. Nadel, MD, pediatric radiologist, division head of nuclear medicine, British Columbia Children’s Hospital in Vancouver, Canada, agrees that it is necessary to accommodate the varying needs within pediatrics, while minimizing radiation exposure. “Given that we run the gamut of all age groups from newborns to the cusp of adulthood for the diseases we face in pediatrics, we cannot always standardize and set up one way to do a test for everyone,” Nadel says.
Optimizing hybrid molecular imaging for pediatrics requires a little more flexibility and creativity in how tests are performed. Standardizing protocols can be a good start, but such protocols may require modification. “In nuclear medicine [there] is a movement toward optimized workflow and batch processing,” she says. “We would love to do this in pediatrics, but when you deal with a population that can range from 5 pounds to 200 pounds, it is not possible. You cannot possibly do them the same way—you must adapt.”
Clinical indications for PET/CT
“Just because it is difficult, does not mean it is impossible for these technologies to make a difference in pediatrics,” says Wahl. These hybrid technologies are proving their value in pediatric neurology, orthopedics and oncology, Treves says.
In neurology, PET fused with MR has proven an effective tool for the localization of focal epilepsy in the brain. “In addition, PET/MR fusion is effective for assessing the effect of therapy and also to detect the residual or recurrent brain tumor activity,” Treves says. “At Children’s Hospital Boston, PET/MR image fusion is considered a necessity and it is done routinely in all brain studies so that the anatomic-functional relationships can be assessed more easily. Emerging PET agents beyond FDG hold promise in improving the assessment of brain tumors in children.”
It has been proven that PET’s metabolic assessment shows other areas of abnormality that cannot be detected by other modalities, which aids in surgical planning. “It is proven but requires a dedicated epilepsy surgery service that can act on the results,” Nadel says. Despite its proven ability, with the limited availability of PET/CT in pediatrics, the British Columbia’s Children’s Hospital has been providing their assessment of children with other modalities such as functional MRI (fMRI), but Nadel admits this is an area of potential growth for PET.
Treves says that PET/CT, using 18F sodium fluoride (18F NaF PET), a skeletal PET imaging agent, is being used in orthopedics and sports medicine to assess various bone disorders, osteomyelitis, bone tumors, non-accidental trauma, or any of the well-established indications of skeletal scintigraphy. “PET with 18F NaF has certain advantages including a high sensitivity, exquisite spatial resolution and rapid imaging at a similar radiation exposure to that of conventional skeletal scintigraphy,” he adds. “The combination of PET and CT provides improved lesion localization.”
In the case of pediatric oncology, the majority of childhood cancers are clinically aggressive, high-grade tumors such as malignant lymphomas, bone and soft-tissue sarcomas, germ cell tumors and neuroblastoma.
 |
“PET is now widely used in our patients and is helpful in the primary staging, treatment and follow-up of children with cancer,” Kabickova says. “Today, PET/CT is incorporated into the diagnostic work-up of our patients with lymphomas, germ cell tumors, sarcomas and some types of rare pediatric malignancies, such as colorectal carcinoma, thyroid cancer and melanoma.”
Using PET with FDG allows a physician to ascertain the extent of cancer in the body in rather unique ways because it does not rely on anatomic changes or the detection of masses, says Treves. “Instead, it allows the physician to portray the actual [metabolic] activity of the tumors. It has really been a powerful tool to give us a more complete picture of disease.”
Kabickova adds that small cancer manifestations, for example, normal size lymph nodes in children with lymphomas or sarcomas, can be visualized due to high FDG uptake. This can improve the clinical staging of untreated patients. PET/CT also is being used to evaluate tumor viability after chemotherapy and to identify children at risk for early relapse.
“The current treatment strategy for childhood malignancies is risk-based and the rapidity of response to the first few cycles of chemotherapy is used to determine the subsequent treatment intensity,” says Kabickova. “PET/CT imaging allows identification of responding and non-responding tumors early in the course of therapy. With this information, we can rapidly modify ineffective therapies for these patients and thereby potentially improve their outcomes.”
While PET/CT is effective in staging lymphomas, bone, and soft-tissue tumors, and for evaluating tumor response, it is not helpful for routine follow-up on surveillance of children for bone and soft-tissue tumors with no evidence of recurrent or metastatic disease and no symptoms, according to Nadel.
“We have determined in a series of studies that the least value of PET/CT is in surveillance monitoring in the absence of symptoms, where we get a very low rate of abnormality,” Nadel says. “Where we do get a high rate of pick-up and change in management is either at diagnosis for staging and picking up unexpected, more widespread, disease at the time of assessment for local control before surgical planning and at the end of treatment.” Other studies have shown value in surveillance monitoring.
Another area of growth in pediatrics is infection imaging, or inflammation, particularly in musculoskeletal disease and fever of unknown origins. “PET/CT can help us to look at infections in children more easily and avoid the need to label their white blood cells,” Wahl says.
Clinical indications for SPECT/CT
SPECT/CT is relatively new in pediatrics—it has not penetrated the field to the degree PET/CT has, but it holds promise. “SPECT/CT has a growing role within pediatrics, but it is going to be a more limited role compared to PET/CT,” says Wahl. Currently, the technology is being used more for Meta-Iodo-Benzyl-Guanidine (MIBG) scans for neuroblastoma, and in some patients with osteosarcoma, he adds.
With SPECT/CT, a physician gains improved anatomical localization and the acquisition of attenuation maps for attenuation correction. “It is the uniqueness of the information that studies provide that make the technology so desirable,” says Treves. SPECT/CT is used for imaging of the brain and the body in routine applications for epilepsy, tumors and whole-body imaging, including myocardial perfusion imaging.
British Columbia Children’s Hospital has slowly been increasing its SPECT/CT workload over the last nine months, Nadel says. The hospital is utilizing the technology to do diagnostic CT scans and correlated imaging tests when the child was already scheduled to have a CT scan, for example, in patients with neuroblastoma. By doing SPECT MIBGs with contrast enhanced CT scans, Nadel says they have found economies of time—the child is saved an extra trip; economies of radiation exposure—minimizing radiation dosing; and economies of efficiency, reading both diagnostic scans simultaneously.
“Two heads are better than one,” she says. “When you put the two studies together, you can see things that could not be matched up alone.”
For example, a child at the Children’s Hospital had an initial SPECT/CT study done, Nadel says, for staging; the next study done prior to reaching a treatment decision point was done as one modality; the next time as the other modality. Although done correctly, they each missed one observation. A fourth combined study was done. “It was clear that the stand-alone studies showed what they could, the best they could,” she says. “However, the combined study of SPECT and CT clearly helped in disease evaluation and was better than the two [separately].”
Another area where SPECT/CT is found to be beneficial is in small bone lesion localization and diagnosis. “We are finding things hot on bone scans that we did not know exactly where they were, but in finding their location, we were able to better suggest the correct diagnosis,” Nadel adds.
Assessing future potential
The recent proliferation of hybrid imaging systems has been revolutionary and has added a new and important dimension in imaging, Treves says.
Molecular imaging has helped to highlight the great advantages of radionuclide imaging in the diagnosis and monitoring of disease in children. Ongoing research will continue to expand the effectiveness and potential of value of PET/CT and SPECT/CT in pediatric care.