Abstract
The goals of tumor imaging include tumor detection, tumor characterization and differential diagnosis, imaging-guided biopsy, evaluation of tumor extent and staging, assessment of treatment responses, and surveillance for residual tumor or tumor recurrence. In clinical practice, various combinations of imaging modalities are used to achieve these goals. Recently introduced tumor imaging methods, such as diffusion MRI, perfusion MRI, whole-body MRI, and positron emission tomography (PET-CT), have shown promising results. Depending on tumor type and management plan, imaging protocols for children should be individually optimized to achieve the shortest examination time, the highest image quality, the lowest risk, and maximum clinical benefits. In this article, the roles of regional and whole-body tumor imaging will be reviewed, and several important issues related to recent technical developments will be discussed.
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The roles of tumor imaging include tumor detection, tumor characterization and differential diagnosis, imaging-guided biopsy, evaluation of tumor extent and staging, assessment of treatment responses, and surveillance for residual tumor or tumor recurrence. In clinical practice, various combinations of imaging modalities, including radiography, sonography, CT, MRI, and scintigraphy, have been used for the accurate assessment of pediatric tumors [1]. Imaging protocols should be individualized depending on tumor type and management plan, and should be updated as new imaging techniques are introduced. Recently developed techniques include contrast-enhanced sonography, diffusion MRI, perfusion MRI, whole-body MRI, and positron emission tomography (PET)-CT [2]. In this paper, the roles of regional and whole-body tumor imaging, excluding scintigraphy, will be reviewed, and several important issues related to recent technical developments will be discussed.
Radiography
Radiography can be used to identify high-contrast lesions, typically in lung and bone; calcification and/or ossification; and abnormal gas. Because the diagnostic yield is generally not very high, further evaluation with cross-sectional imaging modalities is usually required. Radiography is generally performed only in areas of clinical interest. Whole-body radiography is rarely conducted, with some exceptions, e.g., skeletal survey in Langerhans cell histiocytosis [3, 4].
Sonography
Gray-scale and Doppler sonography is used frequently as an initial imaging method for abdominal, pelvic, and soft-tissue tumors. In addition to localizing and characterizing (e.g., cystic, solid, or mixed) tumors, sonography may be used to evaluate loco-regional associated abnormalities, such as neovascularity (Fig. 1), vascular encasement, and lymphadenopathy. Real-time sonographic sliding signs are greatly helpful in localizing tumors, especially in pediatric patients with a paucity of intervisceral fat [5]. If necessary, a portable sonographic unit may be used to examine patients in the intensive care unit or the emergency department. However, sonography is limited by operator dependency and by restricted fields of view. Recent technical developments in sonography that may have additional value in tumor imaging include three-dimensional [6], extended field-of-view [7, 8] (Fig. 2), and contrast-enhanced sonography [2].
CT
CT is commonly used for initial and follow-up examinations. Because of the short scan time, CT can be used in severely ill patients. In addition, multi-slice CT with near-isotropic high spatial resolution can yield good-quality multi-planar reformatted images (Fig. 3) as well as three-dimensional images that may improve the accuracy of evaluation of the tumor extent [9–11]. Multi-slice chest CT facilitates the detection of lung nodules by reducing motion artifacts. The use of partial reconstruction [12] or electrocardiogram (ECG)-triggered data acquisition [13] can substantially reduce cardiac pulsation artifacts on chest CT, resulting in improved detection of small lung nodules (Fig. 4). Recently, combined ECG- and respiratory-triggered data acquisition has been utilized in free-breathing children to eliminate cardiac and respiratory motion artifacts on chest CT [14]. Despite the improved detection of lung nodules when CT is used, recent studies have shown that single or multi-slice spiral chest CT could not adequately distinguish malignant from benign nodules [15, 16]. Prone CT scanning is useful for differentiating true posterior subpleural nodules from nodular atelectasis [17], a frequent diagnostic dilemma in children (Fig. 5). CT is fairly sensitive when used to detect calcification or fat in a tumor. The limitations of CT are associated with the use of ionizing radiation and iodinated contrast agents, as well as relatively inferior soft tissue contrast resolution. To minimize radiation exposure during diagnostic CT, low-dose CT protocols should be appropriately tailored to age or body size [18, 19]. A recent study [20] found that 40% of surveillance imaging studies using ionizing radiation, predominantly CT (94%) and nuclear scintigraphy, were performed in children with low risk of recurrence and/or with no clear indication. These findings emphasize the need for guidelines for surveillance imaging, which should be justified by the probability of recurrence [20].
MRI
MRI is used increasingly for pediatric tumor imaging because of inherent advantages compared to other imaging modalities, including the absence of ionizing radiation and excellent soft-tissue contrast resolution. MRI has limitations when used to evaluate the lungs because of low proton density and high susceptibility effect. However, lung nodules of diameter larger than 3–4 mm can be detected with MRI at 1.5 T [21] (Fig. 6). In general, MRI is limited by long scan times and associated motion artifact. The combination of a state-of-the-art multichannel (e.g., 32-channel) body-array coil and parallel imaging can reduce scan time without degrading images; it may in fact improve image quality [22]. Among the strategies available to reduce physiologic motion artifacts are placing of a presaturation band in the anterior body wall (Fig. 7), multiple signal averaging, parallel imaging [23], single-shot acquisition [24], respiratory triggering, gating [25], and use of periodically rotated overlapping parallel lines with enhanced reconstruction [26]. The potential advantages and disadvantages of 3.0 T MRI in children have been described [27, 28]. Although dielectric shading artifacts and specific absorption rate-related issues are less problematic in children, the recently introduced dual-source parallel radiofrequency excitation technology seems to be preferable, offering the full benefits of 3.0 T in body MRI [29].
An MRI protocol for pediatric oncology patients basically consists of T2- and T1-weighted imaging. A fat-suppression technique may be used to identify lesions in fatty bone marrow and subcutaneous fat as well as to identify fat-containing lesions. The balanced steady-state free precession-sequence has been considered to represent a fast imaging technique with a high signal-to-noise ratio, but the clinical utility of this method in oncologic imaging remains unclear. Post-contrast T1-weighted imaging is usually performed to assess delayed hyper-enhancement of a tumor. Recently, dynamic contrast-enhanced T1-weighted MRI [30] (Fig. 8) and diffusion-weighted MRI [31, 32] (Fig. 7) have been regarded as useful biomarkers in oncologic imaging. Free-breathing real-time chest MRI can assess for mediastinal or chest wall tumor invasion [33] (Fig. 9). The prudent use of gadolinium-based contrast agents to avoid or minimize the risk of nephrogenic systemic fibrosis cannot be overemphasized, as pediatric oncologic patients are more likely to have impaired renal function secondary to anti-cancer therapy [34].
Whole-body MRI
In pediatric oncology, whole-body MRI offers great potential to provide critical information for initial and follow-up assessments [4, 35–45]. Coronal and sagittal short tau inversion recovery (STIR) images have been regarded as fundamental (Fig. 10). The total scan time for coronal and sagittal whole-body STIR is approximately 15–50 min, depending on patient height. The STIR sequence, which is fairly insensitive to magnetic field inhomogeneity, provides excellent fat suppression in a large field-of-view, which is essential to obtain high-quality images. To ensure optimal image contrast, appropriate inversion times should be used (i.e., 150–160 ms at 1.5 T and 210–230 ms at 3.0 T) [27, 28, 45]. In fact, any pulse sequence may be used for whole-body MRI. However, the whole-body MRI protocol should be made acceptably short for children. Currently, 1.5 T offers better image quality than does 3.0 T for whole-body MRI. In addition to a quadrature body coil system, other coil systems can be employed to achieve high signal-to-noise ratios and high spatial resolution. The body-size-adapted coil selection for whole-body MRI used at our institution is described in Table 1. Whole-body MRI has been shown to be consistently superior to bone scintigraphy in detecting bone metastases [4, 35, 40, 41], whereas whole-body MRI and PET-CT are complementary [41, 44]. MRI is usually better for evaluating the brain, liver, and bone marrow, whereas PET-CT is generally better for lungs and the lymph nodes. Recently, whole-body diffusion-weighted MRI was found to be useful to stage patients with lymphoma [46, 47]. This imaging technique is particularly promising in children because most pediatric malignant tumors are small round cell tumors with restricted water diffusion (Fig. 11). In contrast, diffusion-weighted MRI may not be useful for evaluating spindle cell tumors or Langerhans cell histiocytosis [4].
Conclusion
Pediatric oncologic imaging protocols should be individually optimized to achieve the shortest examination time, the highest image quality, the lowest risks of radiation exposure and other adverse effects, and the maximum clinical benefits. Moreover, every effort should be made to eliminate redundant examinations, which are unnecessary burdens to the child. In this regard, bone scintigraphy may be omitted when another superior imaging modality is available. CT and scintigraphy should be used cautiously in children due to ionizing radiation exposure. Whole-body MRI and PET-CT may become the mainstays of pediatric tumor imaging.
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The supplement this article is part of is not sponsored by the industry. Dr. Goo has no financial interests, investigational or off-label uses to disclose.
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