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Radiation exposure of image-guided intrathecal administration of nusinersen to adult patients with spinal muscular atrophy

  • Spinal Neuroradiology
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Abstract

Purpose

To examine diagnostic reference levels (DRL) and achievable doses (AD) of image-guided and size-specific dose estimates (SSDE) and organ and effective doses of CT-guided intrathecal nusinersen administration to adult patients with spinal muscular atrophy (SMA).

Methods

This study involved a total of 60 image-guided intrathecal nusinersen treatments between August 2017 and June 2018. Patient cohort comprised 14 adult patients with the following SMA types: type 2 (n = 9) and type 3 (n = 5) with a mean age of 33.6 years (age range 25–57 years). DRL, AD, SSDE, organ, and effective doses were assessed with a dose-monitoring program based on the Monte Carlo simulation techniques.

Results

DRL and AD for computed tomography are summarised as follows: in terms of CT-dose index (CTDIvol), DRL 56.4 mGy and AD 36.7 mGy; in terms of dose-length product (DLP), DRL 233.1 mGy cm and AD 120.1 mGy cm. DRL and AD for fluoroscopic guidance were distributed as follows: in terms of dose-area product (DAP), DRL 239.1 μGy m2 and AD 135.2 mGy cm2. Mean SSDE was 9.2 mGy. Mean effective dose of the CT-guided injections was 2.5 mSv (median 2.0 mSv, IQR 1.3–3.2 mSv). Highest organ doses in the primary beam of radiation were the small intestine 12.9 mSv, large intestine 9.5 mSv, and ovaries 3.6 mSv.

Conclusion

Radiation exposure of SMA patients measured as DRLs is generally not higher compared with patients without SMA despite severe anatomical hazards. Dose monitoring data may allow clinicians to stratify radiation risk, identify organs at risk, and adopt measures for specific radiation dose reduction.

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Abbreviations

AD:

Achievable doses

CT:

Computed tomography

CTDIvol :

CT-dose index

ICRP:

International Commission on Radiological Protection

IQR:

Interquartile range

DAP:

Dose area product

DLP:

Dose length product

DRL:

Diagnostic reference levels

kV:

Kilovolt (tube voltage)

mAs:

Milliampere second (tube current–time product)

mSv:

Millisievert (effective dose)

SD:

Standard deviation

SMA:

Spinal muscular atrophy

SMN:

Survival motor neuron

SSDE:

Size-specific dose estimates

References

  1. Hodgson A (2008) Computer-assisted orthopedic surgery. In: Peters T, Cleary K (eds) Image-guided interventions: technology and applications. Springer, Berlin, pp 333–386

    Chapter  Google Scholar 

  2. Kassamali RH, Ladak B (2015) The role of robotics in interventional radiology: current status. Quant Imaging Med Surg 5:340–343

    PubMed  PubMed Central  Google Scholar 

  3. Thanou M (2018) Theranostics and image guided drug delivery. Royal Society of Chemistry, Croyden

    Book  Google Scholar 

  4. Lefebvre S, Bürglen L, Reboullet S et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80(1):155–165

    Article  CAS  PubMed  Google Scholar 

  5. Mercuri E, Bertini E, Iannaccone ST (2012) Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol 11(5):443–452

    Article  PubMed  Google Scholar 

  6. Bürglen L, Lefebvre S, Clermont O et al (1996) Structure and organization of the human survival motor neurone (SMN) gene. Genomics 32(3):479–482

    Article  PubMed  Google Scholar 

  7. Hua Y, Sahashi K, Hung G et al (2010) Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev 24(15):1634–1644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chiriboga CA, Swoboda KJ, Darras BT et al (2016) Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 86(10):890–897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. European Medicines Agency (EMA) in May 2017

  10. Finkel RS, Mercuri E, Darras BT et al (2017) Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med 377(18):1723–1732

    Article  CAS  PubMed  Google Scholar 

  11. Mercuri E, Darras BT, Chiriboga CA et al (2018) Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med 378(7):625–635

    Article  CAS  PubMed  Google Scholar 

  12. Geary RS, Yu RZ, Levin AA (2001) Pharmacokinetics of phosphorothioate antisense oligodeoxynucleotides. Curr Opin Investig Drugs 2(4):562–573

    CAS  PubMed  Google Scholar 

  13. Sugarman EA, Nagan N, Zhu H et al (2012) Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet 20:27–32

    Article  PubMed  Google Scholar 

  14. Little MP (2003) Risks associated with ionizing radiation environmental pollution and health. Br Med Bull 68:259–275

    Article  CAS  PubMed  Google Scholar 

  15. Rehani MM, Berry M (2000) Radiation doses in computed tomography. The increasing doses of radiation need to be controlled. Br Med J 320:593–594

    Article  CAS  Google Scholar 

  16. 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 380:499–505

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brenner DJ, Hall EJ (2007) Computed tomography—an increasing source of radiation exposure. N Engl J Med 357:2277–2284

    Article  CAS  PubMed  Google Scholar 

  18. NCRP Report No. 172 (2012) Reference levels and achievable doses in medical and dental imaging: recommendations for the United States. ISBN 978–0–9835450-2-6

  19. Shrimpton PC, Lewis MA, Dunn M (2005) Doses from computed tomography (CT) examinations in the UK- 2003 review. NRPB-W67. ISBN 0-85951-556-7

  20. American Association of Physicists in Medicine (AAPM) Size-specific dose estimates (SSDE) in pediatric and adult body CT examinations: the report of AAPM Task Group 204. AAPM website. http://www.aapm.org/pubs/reports/RPT_204.pdf . Accessed 02.08.2018

  21. ICRP (2007) The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103. Ann ICRP 37:2–4

    Google Scholar 

  22. Guberina N, Forsting M, Suntharalingam S, Nassenstein K, Theysohn J, Ringelstein A, Wetter A (2017) Radiation dose monitoring in the clinical routine. Rofo 189:356–360

    PubMed  Google Scholar 

  23. Wall BF, Haylock R, Jansen JTM et al (2011) Radiation risk from medical X-ray examinations as a function of the age and sex of the patient. HPA-CRCE-028. ISBN 978-0-85951-709-6

  24. Jumbo Java-based biometrical software tool; University Münster; Institute for Biometry and Clinical Research: http://jumbo.uni-muenster.de/fileadmin/jumbo/applets/falla.html. Accessed 02.08.2018

  25. Debnam JM, Schellingerhout D, Kumar AJ et al (2009) Multidetector CT-guided lumbar puncture in patients with Cancer. Interv Neuroradiol 15:61–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wagner AL (2004) Selective lumbar nerve root blocks with CT fluoroscopic guidance: technique, results, procedure time, and radiation dose. Am J Neuroradiol 25:1592–1594

    PubMed  Google Scholar 

  27. Gossner J (2014) Safety of CT-guided lumbar nerve root infiltrations: analysis of a two-year period. Interv Neuroradiol 20(5):533–537

    Article  PubMed  PubMed Central  Google Scholar 

  28. Brook AD, Burns J, Dauer E, Schoendfeld AH, Miller TS (2014) Comparison of CT and fluoroscopic guidance for lumbar puncture in an obese population with prior failed unguided attempt. J Neurointerv Surg 6:324–328

    Article  PubMed  Google Scholar 

  29. Guberina N, Forsting M, Ringelstein A, Suntharalingam S, Nassenstein K, Theysohn J, Wetter A (2018) Radiation exposure during CT-guided biopsies: recent CT machines provide markedly lower doses. Eur Radiol. https://doi.org/10.1007/s00330-018-5350-1

  30. Strauss KJ, Goske MJ, Frush DP, Butler PF, Morrison G (2009) Image gently vendor summit: working together for better estimates of pediatric radiation dose from CT. AJR Am J Roentgenol 192(5):1169–1175

    Article  PubMed  Google Scholar 

  31. (2002) Pediatr Radiol 32:221–316 (entire issue)

  32. Brenner DJ, Elliston CD, Hall EJ, Berdon WE (2001) Estimated risks of radiation-induced fatal cancer from pediatric CT. Am J Roentgenol 176:289–296

    Article  CAS  Google Scholar 

  33. Hintenlang KM, Williams JL, Hintenlang DE (2002) A survey of radiation dose associated with pediatric plain-film chest X-ray examination. Pediatr Radiol 32:771–777

    Article  PubMed  Google Scholar 

  34. Mettler FA, Wiest PW, Locken JA et al (2000) CT scanning: patterns of use and dose. J Radiol Prot 20:353–359

    Article  PubMed  Google Scholar 

  35. Andreassi MG, Picano E (2014) Reduction of radiation to children: our responsibility to change. Circulation 130:135–137

    Article  PubMed  Google Scholar 

  36. Guberina N, Suntharalingam S, Naßenstein K et al (2018) Verification of organ doses calculated by a dose monitoring software tool based on Monte Carlo simulation in thoracic CT protocols. Acta Radiol 59:322–326

    Article  PubMed  Google Scholar 

  37. Guberina N, Suntharalingam S, Naßenstein K et al (2016) Clinical evaluation of a dose monitoring software tool based on Monte Carlo simulation in assessment of eye lens doses for cranial CT scans. Neuroradiology 58:955–959

    Article  PubMed  Google Scholar 

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Funding

No funding was received for this study.

Author information

Authors and Affiliations

  1. Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany

    D. Oldenburg, N. Guberina, E. Stenzel, A. Radbruch, M. Forsting & C. Mönninghoff

  2. Department of Neurology, University Hospital Essen, Essen, Germany

    B. Stolte, K. Kizina, C. Kleinschnitz & T. Hagenacker

Authors
  1. D. Oldenburg
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  2. N. Guberina
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  3. B. Stolte
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  4. K. Kizina
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  5. E. Stenzel
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  6. A. Radbruch
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  7. C. Kleinschnitz
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  8. T. Hagenacker
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  9. M. Forsting
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  10. C. Mönninghoff
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Corresponding author

Correspondence to D. Oldenburg.

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Conflict of interest

B. Stolte received travel reimbursement from Biogen. C. Kleinschnitz acts as consultant, received travel reimbursement, speaker and Advisory Board honoraria from Biogen. T. Hagenacker acts as consultant, received travel reimbursement, speaker and advisory board honoraria from Biogen and speaker honoraria from Novartis and Biogen. C. Mönninghoff acts as consultant, received travel reimbursement, and advisory board honoraria from Biogen.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

For this type of study formal consent is not required.

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Informed consent was obtained from all individual participants included in the study.

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Oldenburg, D., Guberina, N., Stolte, B. et al. Radiation exposure of image-guided intrathecal administration of nusinersen to adult patients with spinal muscular atrophy. Neuroradiology 61, 565–574 (2019). https://doi.org/10.1007/s00234-019-02189-x

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  • DOI: https://doi.org/10.1007/s00234-019-02189-x

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