Neuroblastoma Imaging 

Neuroblastoma Imaging 

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Neuroblastoma is the most common extracranial pediatric neoplasm and the third most common pediatric malignancy after leukemia and central nervous system (CNS) tumors. In the first year of life, neuroblastoma accounts for 50% of all tumors. [1] Neuroblastoma is associated with a favorable prognosis, with most patients considered to be at low or intermediate risk for recurrence of the disease. [2] Neuroblastomas can arise from anywhere along the sympathetic chain. They have been associated with a number of disorders, such as Hirschsprung disease, fetal alcohol syndrome, DiGeorge syndrome, Von Recklinghausen disease, and Beckwith-Wiedemann syndrome.

CT scanning is the modality most commonly used to diagnose and stage neuroblastomas. [3] About 80-90% of neuroblastomas show stippled calcifications on CT. Intraspinal extension of neuroblastomas can be seen on radiographs. Intravenous pyelography (IVP) and excretory urography were widely used in the past to evaluate patients with adrenal neuroblastomas before the advent of computed tomography (CT), MRI, and ultrasonography. [4]  MRI has some advantages over CT, [5]  such as no need for ionizing radiation; multiplanar imaging capabilities; and, often, the elimination of the need for IV contrast enhancement. [6]  Obstetric ultrasonography can depict fetal neuroblastomas as early as 19 weeks’ gestational age. Most of the cases identified during obstetric ultrasonography are diagnosed during the third trimester (around 36 weeks).

The radiologic characteristics of neuroblastomas are demonstrated in the images below.

Plain radiographs of the abdomen may show a flank mass. Stippled calcifications are present on up to 30% of radiographs. Hepatomegaly may occur secondary to metastatic involvement. Plain images of the chest often show a posterior mediastinal mass. Splaying of the ribs and rib erosion have been seen in patients with thoracic neuroblastomas due to the primary tumor. (See the images below.)

Pleural effusions and pleural nodules have been seen on chest radiographs. Lung parenchymal metastases are rarely seen on radiographs but are often detected on autopsy. Widening of the paraspinal line can be seen secondary to retrocrural extension of retroperitoneal neuroblastomas.

Bone metastases (seen in the images below) usually occur in the long bones and typically present as irregular lucencies or lytic lesions in the metaphysis or submetaphyseal bone.

Lytic lesions may be seen in skull, ribs, and pelvis. Sclerotic lesions have been seen and may be secondary to tumor infarction. Periosteal reaction is common. Widening of the cranial sutures secondary to dural metastasis (demonstrated in the first 2 images below) can be seen in neuroblastoma. The classic hair-on-end appearance (seen in the third image below), albeit unusual in neuroblastoma, can be seen in the skull in destructive lesions.

Intraspinal extension of neuroblastomas can be seen on radiographs. Lateral views of the spine may show widening of the neuroforamina. Vertebral-body scalloping, erosion of the pedicles, and scoliosis have also been seen in patients with intraspinal involvement. Intraspinal involvement may be present in the absence of these findings, and magnetic resonance imaging (MRI) is far superior in evaluating for intraspinal involvement.

Intravenous pyelography (IVP) and excretory urography were widely used in the past to evaluate patients with adrenal neuroblastomas before the advent of computed tomography (CT), MRI, and ultrasonography. [4] Adrenal neuroblastomas typically displace the ipsilateral kidney laterally and downward, producing the classic drooping-lily sign on excretory urograms (as seen in the image below). The drooping-lily sign is also caused by an obstructed upper moiety of a duplex collecting system.

CT scanning is the modality most commonly used to diagnose and stage neuroblastomas. [3] CT can show the organ of origin, extent of the tumor, lymphadenopathy, metastases, and calcifications. About 80-90% of neuroblastomas show stippled calcifications on CT. (See the images below.) [7, 6]

Neuroblastomas often encase or compress adjacent blood vessels. Vessels that are commonly engulfed are the inferior vena cava, the renal veins and arteries, the splenic vein, the aorta, the celiac artery, and the superior mesenteric artery. Neuroblastomas rarely invade into the lumen of blood vessels.

The tumors often appear lobulated and typically have a heterogeneous appearance on contrast-enhanced CT. There are areas of low attenuation in the mass secondary to necrosis and hemorrhage. CT is good for detecting lung metastases and focal liver metastases (which appear as focal hypoattenuating and poorly enhancing masses). [8] Bone-window settings should always also be examined to assess for skeletal metastases.

Diffuse liver metastases may be missed on CT. Cerebral metastases can appear as enhancing meninges secondary to dural metastases, which can simulate meningitis. Sometimes, brain metastases can appear as cystic lesions with peripheral enhancement, which can mimic an abscess. CT is poor for detecting metastatic disease to the bone and is limited in evaluating extradural extension of tumor into the spinal canal without the aid of intrathecal contrast material (CT myelography).

MRI has a number of advantages over CT. [5] One is that MRI does not use ionizing radiation. Other advantages include the multiplanar imaging capabilities of MRI and, often, the elimination of the need to use intravenous contrast enhancement. [6]

MRI is superior to CT in evaluating extradural extension of the tumor and bone marrow involvement and in identifying diffuse hepatic metastases. MRI can show displacement of the spinal cord and/or nerve root displacement or compression and epidural spread of neuroblastoma exceptionally well. MRI results are well correlated with findings from bone marrow biopsy.

MRI utilizes the intrinsic tissue characteristics on T1- and T2-weighted imaging. Neuroblastomas are typically hypointense on T1-weighted images and hyperintense on T2-weighted images. [9] When contrast material is administered, the tumor exhibits inhomogeneous enhancement. Calcifications appear as signal voids on MRIs. Hemorrhagic areas often appear bright on T1-weighted images.

Bone-marrow disease appears bright (hyperintense) and heterogeneous on T2-weighted images and dark (hypointense) on T1-weighted images. Diffuse liver metastases appear bright on T2-weighted MRIs. [10]

The characteristics of neuroblastomas on T1- and T2-weighted MRI scans are demonstrated in the images below.


Neuroblastomas appear as an inhomogeneously echogenic mass on sonograms, as seen in the image below. Calcifications typically appear as focal brightly echogenic areas in the mass. In masses with fine calcifications, images show diffuse, increased echogenicity. Acoustic shadowing from the calcifications may or may not be present. Hemorrhagic or necrotic areas in the tumor appear as hypoechoic or anechoic areas.

Ultrasonography can be used as a screening tool for detecting abdominal or pelvic masses in children. Doppler ultrasonography can be used to identify blood flow through blood vessels encased or compressed by the tumor. Increased vascularity of neuroblastomas has been reported on Doppler sonograms, although typically most lesions show reduced vascularity.

Obstetric ultrasonography can depict fetal neuroblastomas as early as 19 weeks’ gestational age. Most of the cases identified during obstetric ultrasonography are diagnosed during the third trimester (around 36 weeks).

Ultrasonography is used to differentiate adrenal hemorrhage from neuroblastoma. Adrenal hemorrhage is the most common cause of adrenal mass in the neonatal population. It typically appears echogenic in the newborn, as neuroblastomas do, but gradually becomes anechoic and avascular and often becomes smaller on serial sonograms as it regresses.

Sonograms can depict liver metastases, but they are limited in assessing the extent of metastatic disease to the liver. This is better evaluated with CT scanning or MRI, although all of these techniques may be complementary (eg, a metastasis may be visible on sonograms but not on CT scans, or vice versa).

Bone scans obtained by using technetium-99m (99mTc) methylene diphosphate (MDP), an example of which appears below, are performed in many patients with neuroblastoma to assess metastatic disease. Approximately 74% of primary tumors in neuroblastoma take up 99mTc MDP. Uptake may be seen in liver and lung metastases as well.

Tc-99m MDP scans cannot be used to differentiate between cortical and bone marrow metastases; this limits their usefulness in accurately staging the disease, particularly in differentiating stage 4 from stage 4s neuroblastomas in the Evans classification system. In stage 4, distant metastases are present. Stage 4s occurs in infants who have a localized tumor that does not cross the midline, with metastatic disease confined to the liver, skin, and bone marrow and with no evidence of cortical bone involvement observed. [11]

Iodine-131 (131I) metaiodobenzylguanidine (MIBG) and iodine-123 (123I) MIBG [12] are used to identify sites of primary neuroblastomas. Tumors that contain sympathetic tissue, such as neuroblastomas, ganglioneuroblastomas, ganglioneuromas, medullary thyroid carcinomas, pheochromocytomas, and carcinoids, take up MIBG. However, MIBG scanning cannot be used to differentiate these lesions. In the age group in which neuroblastoma (and its more benign forms, ganglioneuroblastoma and ganglioneuroma) is prevalent, the other tumors are rare. In patients with high-risk neuroblastoma, Papathanasiou et al found that 123I MIBG was superior to fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in assessing extent of disease. [13, 14, 15, 16, 17]

MIBG has also been used to follow up the response to treatment in neuroblastoma patients. One of the drawbacks of using MIBG is that up to 30% of neuroblastomas may not take up MIBG, although 95% of neuroblastomas secrete catecholamines. Also, up to 50% of recurrent neuroblastomas do not take up MIBG even if they did so before therapy. [18]

I-131 MIBG has a high principal proton energy (364 KeV). It emits beta particles, thus giving a large dose of radiation to the patient.I-123 MIBG has a lower principal photon energy (159 KeV). It also does not emit beta particles, giving less radiation dose to the patient.I-123 MIBG has a shorter half-life (13 hr) than that of 131I MIBG (8 days), and it must be used the day it is produced, making it more expensive and less readily available.

In a retrospective study of 28 patients with neuroblastoma, PET/CT was found to be superior to I-MIBG (iodine-131 metaiodobenzylguanidine) scintigraphy in detecting lymph node and bone/bone marrow lesions. Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of F-FDG PET/CT were 100%, 60%, 92%, 100%, and 92.80%, respectively; and those of I-MIBG were 95.65%, 60%, 91.67%, 75%, and 89.20%, respectively. In these patients, PET/CT detected 107 lesions, and I-MIBG scintigraphy detected 74 lesions. [19]

Another isotope that can be used in detecting primary neuroblastomas is indium-111 (111In) pentetreotide, which is a somatostatin analogue. Studies have shown that it is as sensitive as MIBG in detecting neuroblastoma and other catecholamine-secreting tumors.In-111 pentetreotide has 2 principal photon energies (174 and 245 KeV), both of which are lower than that of 131I MIBG. It also does not emit beta particles, giving a lower radiation dose to the patient.In-111 pentetreotide also requires less patient preparation and produces images with better resolution than MIBG images have on gamma scintillation cameras, but it is not widely used in pediatric oncology imaging.

Castel V, Grau E, Noguera R, Martínez F. Molecular biology of neuroblastoma. Clin Transl Oncol. 2007 Aug. 9(8):478-83. [Medline].

Interiano RB, Davidoff AM. Current Management of Neonatal Neuroblastoma. Curr Pediatr Rev. 2015. 11 (3):179-87. [Medline].

Xia J, Zhang H, Hu Q, Liu SY, Zhang LQ, Zhang A, et al. Comparison of diagnosing and staging accuracy of PET (CT) and MIBG on patients with neuroblastoma: Systemic review and meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2017 Oct. 37 (5):649-660. [Medline]. [Full Text].

Currarino G. The Genitourinary Tract. In: Silverman FN, Kuhn JP, eds. Essentials of Caffey’s Pediatric X-Ray Diagnosis. 1990: 724-9.

Callahan MJ, MacDougall RD, Bixby SD, Voss SD, Robertson RL, Cravero JP. Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations. Pediatr Radiol. 2018 Jan. 48 (1):21-30. [Medline]. [Full Text].

Liu W, Zheng J, Li Q. Application of imaging modalities for evaluating neuroblastoma. J Pediatr Endocrinol Metab. 2013. 26(11-12):1015-20. [Medline].

Shore RM. Positron emission tomography/computed tomography (PET/CT) in children. Pediatr Ann. 2008 Jun. 37(6):404-12. [Medline].

Rozovsky K, Koplewitz BZ, Krausz Y, Revel-Vilk S, Weintraub M, Chisin R, et al. Added value of SPECT/CT for correlation of MIBG scintigraphy and diagnostic CT in neuroblastoma and pheochromocytoma. AJR Am J Roentgenol. 2008 Apr. 190(4):1085-90. [Medline].

Aslan M, Aslan A, Arıöz Habibi H, Kalyoncu Uçar A, Özmen E, Bakan S, et al. Diffusion-weighted MRI for differentiating Wilms tumor from neuroblastoma. Diagn Interv Radiol. 2017 Sep-Oct. 23 (5):403-406. [Medline]. [Full Text].

Sofka CM, Semelka RC, Kelekis NL, et al. Magnetic resonance imaging of neuroblastoma using current techniques. Magn Reson Imaging. 1999 Feb. 17(2):193-8. [Medline].

Thrall JH, Ziessman HA. Nuclear Medicine: The Requisites. 1995: 47-8.

Schmidt M, Simon T, Hero B, Schicha H, Berthold F. The prognostic impact of functional imaging with (123)I-mIBG in patients with stage 4 neuroblastoma >1 year of age on a high-risk treatment protocol: Results of the German Neuroblastoma Trial NB97. Eur J Cancer. 2008 Jul. 44(11):1552-8. [Medline].

Papathanasiou ND, Gaze MN, Sullivan K, Aldridge M, Waddington W, Almuhaideb A, et al. 18F-FDG PET/CT and 123I-Metaiodobenzylguanidine Imaging in High-Risk Neuroblastoma: Diagnostic Comparison and Survival Analysis. J Nucl Med. 2011 Apr. 52(4):519-25. [Medline].

Piccardo A, Lopci E, Conte M, Foppiani L, Garaventa A, Cabria M, et al. PET/CT imaging in neuroblastoma. Q J Nucl Med Mol Imaging. 2013 Mar. 57(1):29-39. [Medline].

Piccardo A, Lopci E, Conte M, Garaventa A, Foppiani L, Altrinetti V, et al. Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study. Eur J Nucl Med Mol Imaging. 2012 Jan. 39(1):57-71. [Medline].

Piccardo A, Lopci E, Conte M, Cabria M, Cistaro A, Garaventa A, et al. Bone and Lymph Node Metastases From Neuroblastoma Detected by 18F-DOPA-PET/CT and Confirmed by Posttherapy 131I-MIBG but Negative on Diagnostic 123I-MIBG Scan. Clin Nucl Med. 2013 Apr 10. [Medline].

Piccardo A, Lopci E, Conte M, Foppiani L, Garaventa A, Cabria M, et al. PET/CT imaging in neuroblastoma. Q J Nucl Med Mol Imaging. 2013 Mar. 57(1):29-39. [Medline].

Lonergan GJ, Schwab CM, Suarez ES. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. Radiographics. 2002 Jul-Aug. 22(4):911-34. [Medline].

Dhull VS, Sharma P, Patel C, Kundu P, Agarwala S, Bakhshi S, et al. Diagnostic value of 18F-FDG PET/CT in paediatric neuroblastoma: comparison with 131I-MIBG scintigraphy. Nucl Med Commun. 2015 Jun 5. [Medline].

Steven West, DO Consulting Staff, Department of Radiology, Brookhaven Memorial Hospital Medical Center

Steven West, DO is a member of the following medical societies: American College of Radiology, American Society of Neuroradiology, American Medical Association, American Roentgen Ray Society, Radiological Society of North America

Disclosure: Nothing to disclose.

Jennith D Correa, DO Staff Physician, Department of Emergency Medicine, Mount Sinai Medical Center

Jennith D Correa, DO is a member of the following medical societies: American Osteopathic Association

Disclosure: Nothing to disclose.

Michele Germaine, DO Attending Physician, Department of Obstetrics and Gynecology, Queens-Long Island Medical Group and North Shore at Forest Hills

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Kieran McHugh, MB, BCh Honorary Lecturer, The Institute of Child Health; Consultant Pediatric Radiologist, Department of Radiology, Great Ormond Street Hospital for Children, London, UK

Kieran McHugh, MB, BCh is a member of the following medical societies: American Roentgen Ray Society, Royal College of Radiologists

Disclosure: Nothing to disclose.

Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Nothing to disclose.

Fredric A Hoffer, MD, FSIR Affiliate Professor of Radiology, University of Washington School of Medicine; Member, Quality Assurance Review Center

Fredric A Hoffer, MD, FSIR is a member of the following medical societies: Children’s Oncology Group, Radiological Society of North America, Society for Pediatric Radiology, Society of Interventional Radiology

Disclosure: Nothing to disclose.

Dvorah Balsam, MD Chief, Division of Pediatric Radiology, Nassau University Medical Center; Professor, Department of Clinical Radiology, State University of New York at Stony Brook

Disclosure: Nothing to disclose.

Joel Rosen, MD Chief, Department of Nuclear Medicine, Nassau University Medical Center

Disclosure: Nothing to disclose.

Neuroblastoma Imaging 

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