Advertisement

Molecular Imaging and Biology

, Volume 20, Issue 2, pp 324–335 | Cite as

How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1 h: the Stanford Approach

  • Anne M. Muehe
  • Ashok J. Theruvath
  • Lillian Lai
  • Maryam Aghighi
  • Andrew Quon
  • Samantha J. Holdsworth
  • Jia Wang
  • Sandra Luna-Fineman
  • Neyssa Marina
  • Ranjana Advani
  • Jarrett Rosenberg
  • Heike E. Daldrup-Link
Research Article

Abstract

Purpose

To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h.

Procedures

In this prospective clinical trial, 20 children and young adults (11–30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [18F]FDG (2–3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher’s exact tests.

Results

Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol “off label” as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [18F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %).

Conclusion

Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.

Key words

Positron-emission tomography Magnetic resonance imaging Nanoparticles Cancer Pediatrics 

Notes

Acknowledgements

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. We thank Praveen Gulaka, Dawn Holley, and Harsh Gandhi from the PET/MR Metabolic Service Centre for their assistance with the acquisition of PET/MR scans. We thank the members of Daldrup-Link lab for valuable input and discussions regarding this project.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2017_1105_MOESM1_ESM.pdf (664 kb)
ESM 1 (PDF 664 kb)

References

  1. 1.
    Federman N, Feig SA (2007) PET/CT in evaluating pediatric malignancies: a clinician’s perspective. J Nucl Med 48:1920–1922CrossRefPubMedGoogle Scholar
  2. 2.
    Kleis M, Daldrup-Link H, Matthay K et al (2009) Diagnostic value of PET/CT for the staging and restaging of pediatric tumors. Eur J Nucl Med Mol Imaging 36:23–36CrossRefPubMedGoogle Scholar
  3. 3.
    Tatsumi M, Miller JH, Wahl RL (2007) 18F-FDG PET/CT in evaluating non-CNS pediatric malignancies. J Nucl Med 48:1923–1931CrossRefPubMedGoogle Scholar
  4. 4.
    London K, Cross S, Onikul E et al (2011) 18F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging. Eur J Nucl Med Mol Imaging 38:274–284CrossRefPubMedGoogle Scholar
  5. 5.
    Cheng G, Servaes S, Zhuang H (2013) Value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan versus diagnostic contrast computed tomography in initial staging of pediatric patients with lymphoma. Leukemia Lymphoma 54:737–742CrossRefPubMedGoogle Scholar
  6. 6.
    London K, Stege C, Cross S et al (2012) 18F-FDG PET/CT compared to conventional imaging modalities in pediatric primary bone tumors. Pediatr Radiol 42:418–430CrossRefPubMedGoogle Scholar
  7. 7.
    Walter F, Czernin J, Hall T et al (2012) Is there a need for dedicated bone imaging in addition to 18F-FDG PET/CT imaging in pediatric sarcoma patients? J Pediatr Hematol Oncol 34:131–136CrossRefPubMedGoogle Scholar
  8. 8.
    Ponisio MR, McConathy J, Laforest R, Khanna G (2016) Evaluation of diagnostic performance of whole-body simultaneous PET/MRI in pediatric lymphoma. Pediatr Radiol 46:1258–1268CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Miglioretti DL, Johnson E, Williams A et al (2013) The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. J Am Med Assoc Pediatr 167:700–707Google Scholar
  10. 10.
    Weiser DA, Kaste SC, Siegel MJ, Adamson PC (2013) Imaging in childhood cancer: a Society for Pediatric Radiology and Children's oncology group joint task force report. Pediatr Blood Cancer 60:1253–1260CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Grueneisen J, Nagarajah J, Buchbender C et al (2015) Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging. Investig Radiol 50:505–513CrossRefGoogle Scholar
  12. 12.
    Souvatzoglou M, Eiber M, Takei T et al (2013) Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer. Eur J Nucl Med Mol Imaging 40:1486–1499CrossRefPubMedGoogle Scholar
  13. 13.
    Uslu L, Donig J, Link M et al (2015) Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies. J Nucl Med 56:274–286CrossRefPubMedGoogle Scholar
  14. 14.
    Hirsch FW, Sattler B, Sorge I et al (2013) PET/MR in children. Initial clinical experience in paediatric oncology using an integrated PET/MR scanner. Pediatr Radiol 43:860–875CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Huellner MW, Appenzeller P, Kuhn FP et al (2014) Whole-body nonenhanced PET/MR versus PET/CT in the staging and restaging of cancers: preliminary observations. Radiology 273:859–869CrossRefPubMedGoogle Scholar
  16. 16.
    McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 275:772–782CrossRefPubMedGoogle Scholar
  17. 17.
    Jiang W, Tao X, Fang F, Zhang S, Xu C (2013) Benign and malignant ovarian steroid cell tumors, not otherwise specified: case studies, comparison, and review of the literature. J Ovarian Res 6:53CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Schafer JF, Gatidis S, Schmidt H et al (2014) Simultaneous whole-body PET/MR imaging in comparison to PET/CT in pediatric oncology: initial results. Radiology 273:220–231CrossRefPubMedGoogle Scholar
  19. 19.
    Gatidis S, Schmidt H, Gucke B et al (2016) Comprehensive oncologic imaging in infants and preschool children with substantially reduced radiation exposure using combined simultaneous (1)(8)F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging: a direct comparison to (1)(8)F-fluorodeoxyglucose positron emission tomography/computed tomography. Investig Radiol 51:7–14CrossRefGoogle Scholar
  20. 20.
    Sher AC, Seghers V, Paldino MJ et al (2016) Assessment of sequential PET/MRI in comparison with PET/CT of pediatric lymphoma: a prospective study. Am J Roentgenol 206:623–631CrossRefGoogle Scholar
  21. 21.
    Ricard F, Cimarelli S, Deshayes E et al (2011) Additional benefit of F-18 FDG PET/CT in the staging and follow-up of pediatric rhabdomyosarcoma. Clin Nucl Med 36:672–677CrossRefPubMedGoogle Scholar
  22. 22.
    Kneisl JS, Patt JC, Johnson JC, Zuger JH (2006) Is PET useful in detecting occult nonpulmonary metastases in pediatric bone sarcomas? Clin Orthop Relat Res 450:101–104CrossRefPubMedGoogle Scholar
  23. 23.
    Klenk C, Gawande R, Uslu L et al (2014) Ionising radiation-free whole-body MRI versus 18F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study. Lancet Oncol 15:275–285CrossRefPubMedGoogle Scholar
  24. 24.
    Mattsson S, Johansson L, Leide Svegborn S et al (2015) Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. Ann ICRP 44:7–321CrossRefPubMedGoogle Scholar
  25. 25.
    Deak PD, Smal Y, Kalender WA (2010) Multisection CT protocols: sex- and age-specific conversion factors used to determine effective dose from dose-length product. Radiology 257:158–166CrossRefPubMedGoogle Scholar
  26. 26.
    Cipriano C, Brockman L, Romancik J et al (2015) The clinical significance of initial pulmonary micronodules in young sarcoma patients. J Pediatr Hematol Oncol 37:548–553CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ciet P, Tiddens HA, Wielopolski PA et al (2015) Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging. Pediatr Radiol 45:1901–1915CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    von Schulthess GK, Veit-Haibach P (2014) Workflow considerations in PET/MR imaging. J Nucl Med 55:19S–24SCrossRefGoogle Scholar
  29. 29.
    Martinez-Moller A, Eiber M, Nekolla SG et al (2012) Workflow and scan protocol considerations for integrated whole-body PET/MRI in oncology. J Nucl Med 53:1415–1426CrossRefPubMedGoogle Scholar
  30. 30.
    Vanderby SA, Babyn PS, Carter MW, Jewell SM, McKeever PD (2010) Effect of anesthesia and sedation on pediatric MR imaging patient flow. Radiology 256:229–237CrossRefPubMedGoogle Scholar
  31. 31.
    Aghighi M, Pisani LJ, Sun Z et al (2016) Speeding up PET/MR for cancer staging of children and young adults. Eur Radiol 26:4239–4248CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Eiber M, Martinez-Moller A, Souvatzoglou M et al (2011) Value of a Dixon-based MR/PET attenuation correction sequence for the localization and evaluation of PET-positive lesions. Eur J Nucl Med Mol Imaging 38:1691–1701CrossRefPubMedGoogle Scholar
  33. 33.
    Klenk C, Gawande R, Tran VT et al (2016) Progressing toward a cohesive pediatric 18F-FDG PET/MR protocol: is Administration of Gadolinium Chelates Necessary? J Nucl Med 57:70–77CrossRefPubMedGoogle Scholar
  34. 34.
    Daldrup-Link HE, Rummeny EJ, Ihssen B et al (2002) Iron-oxide-enhanced MR imaging of bone marrow in patients with non-Hodgkin’s lymphoma: differentiation between tumor infiltration and hypercellular bone marrow. Eur Radiol 12:1557–1566CrossRefPubMedGoogle Scholar
  35. 35.
    Li YW, Chen ZG, Wang JC, Zhang ZM (2015) Superparamagnetic iron oxide-enhanced magnetic resonance imaging for focal hepatic lesions: systematic review and meta-analysis. World J Gastroenterol 21:4334–4344CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ferrucci JT, Stark DD (1990) Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years. AJR Am J Roentgenol 155:943–950CrossRefPubMedGoogle Scholar
  37. 37.
    Perazella MA (2009) Current status of gadolinium toxicity in patients with kidney disease. Clin J Am Soc Nephrol 4:461–469CrossRefPubMedGoogle Scholar
  38. 38.
    Varallyay CG, Nesbit E, Fu R et al (2013) High-resolution steady-state cerebral blood volume maps in patients with central nervous system neoplasms using ferumoxytol, a superparamagnetic iron oxide nanoparticle. J Cereb Blood Flow Metab 33:780–786CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lu M, Cohen MH, Rieves D, Pazdur R (2010) FDA report: ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease. Am J Hematol 85:315–319PubMedGoogle Scholar
  40. 40.
    Muehe AM, Feng D, von Eyben R et al (2016) Safety report of Ferumoxytol for magnetic resonance imaging in children and young adults. Investig Radiol 51:221–227CrossRefGoogle Scholar
  41. 41.
    Fakhran S, Alhilali L, Kale H, Kanal E (2015) Assessment of rates of acute adverse reactions to gadobenate dimeglumine: review of more than 130,000 administrations in 7.5 years. Am J Roentgenol 204:703–706CrossRefGoogle Scholar
  42. 42.
    Pearce MS, Salotti JA, Little MP et al (2012) Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 380:499–505CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Brenner DJ, Doll R, Goodhead DT et al (2003) Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Nat Acad Scie (USA) 100:13761–13766CrossRefGoogle Scholar
  44. 44.
    Minamimoto R, Levin C, Jamali M et al (2016) Improvements in PET image quality in time of flight (TOF) simultaneous PET/MRI. Mol Imaging Biol 18:776–781CrossRefPubMedGoogle Scholar
  45. 45.
    Grant AM, Deller TW, Khalighi MM, Maramraju SH, Delso G, Levin CS (2016) NEMA NU 2-2012 performance studies for the SiPM-based ToF-PET component of the GE SIGNA PET/MR system. Med Phys 43:2334CrossRefPubMedGoogle Scholar
  46. 46.
    Ward E, DeSantis C, Robbins A, Kohler B, Jemal A (2014) Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64:83–103CrossRefPubMedGoogle Scholar
  47. 47.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30CrossRefPubMedGoogle Scholar
  48. 48.
    Borra RJ, Cho HS, Bowen SL et al (2015) Effects of ferumoxytol on quantitative PET measurements in simultaneous PET/MR whole-body imaging: a pilot study in a baboon model. Eur J Nucl Med Mol Imaging Phys 2:6. doi: 10.1186/s40658-015-0109-0 Google Scholar
  49. 49.
    Meignan M, Gallamini A, Meignan M et al (2009) Report on the first international workshop on interim-PET-scan in lymphoma. Leuk Lymph 50:1257–1260CrossRefGoogle Scholar

Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • Anne M. Muehe
    • 1
  • Ashok J. Theruvath
    • 1
    • 2
  • Lillian Lai
    • 1
  • Maryam Aghighi
    • 1
  • Andrew Quon
    • 1
  • Samantha J. Holdsworth
    • 1
  • Jia Wang
    • 3
  • Sandra Luna-Fineman
    • 4
  • Neyssa Marina
    • 4
  • Ranjana Advani
    • 5
  • Jarrett Rosenberg
    • 1
  • Heike E. Daldrup-Link
    • 1
    • 4
  1. 1.Department of Radiology, Pediatric Radiology, Lucile Packard Children’s HospitalStanford UniversityStanfordUSA
  2. 2.Department of Diagnostic and Interventional RadiologyUniversity Medical Center MainzMainzGermany
  3. 3.Environmental Health and SafetyStanford UniversityStanfordUSA
  4. 4.Department of Pediatrics, Pediatric Hematology/Oncology, Lucile Packard Children’s HospitalStanford UniversityStanfordUSA
  5. 5.Department of Medicine, Hematology/Oncology, Stanford HospitalStanford UniversityStanfordUSA

Personalised recommendations