Advertisement

A Protocol for Sedation Free MRI and PET Imaging in Adults with Autism Spectrum Disorder

Abstract

Imaging technologies such as positron emission tomography (PET) and magnetic resonance imaging (MRI) present unparalleled opportunities to investigate the neural basis of autism spectrum disorder (ASD). However, challenges such as deficits in social interaction, anxiety around new experiences, impaired language abilities, and hypersensitivity to sensory stimuli make participating in neuroimaging studies challenging for individuals with ASD. In this commentary, we describe the existent training protocols for preparing individuals with ASD for PET/MRI scans and our own experience developing a training protocol to facilitate the inclusion of low-functioning adults with ASD in PET-MRI studies. We hope to raise awareness of the need for more information exchange between research groups about lessons learned in this context in order to include the entire disease spectrum in neuroimaging studies.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Association.

  2. Barnea-Goraly, N., Frazier, T. W., Piacenza, L., Minshew, N. J., Keshavan, M. S., Reiss, A. L., et al. (2014). A preliminary longitudinal volumetric MRI study of amygdala and hippocampal volumes in autism. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 48, 124–128.

  3. Biederman, G. B., Stepaniuk, S., Davey, V. A., Raven, K., & Ahn, D. (1999). Observational learning in children with Down syndrome and developmental delays: The effect of presentation speed in videotaped modelling. Down Syndrome Research and Practice, 6(1), 12–18.

  4. Black, K. R., Stevenson, R. A., Segers, M., Ncube, B. L., Sun, S. Z., Philipp-Muller, A., et al. (2017). Linking anxiety and insistence on sameness in autistic children: The role of sensory hypersensitivity. Journal of Autism and Developmental Disorders, 47(8), 2459–2470.

  5. Bonhomme, V., Boveroux, P., Brichant, J. F., Laureys, S., & Boly, M. (2012). Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI). Archives Italiennes de Biologie, 2–3, 155–163.

  6. CDC. (2014). Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network 11 sites, United States, 2010 Morbidity and mortality weekly report. Surveillance Summaries, 63(Suppl. 2), 1–21.

  7. Chakrabarti, B. (2017). Commentary: Critical considerations for studying low-functioning autism. Journal of Child Psychology and Psychiatry, 58(4), 436–438.

  8. Charlop-Christy, M. H., Le, L., & Freeman, K. A. (2000). A comparison of video modeling with in vivo modeling for teaching children with autism. Journal of Autism and Developmental Disorders, 30(6), 537–552.

  9. de Bie, H. M., Boersma, M., Wattjes, M. P., Adriaanse, S., Vermeulen, R. J., Oostrom, K. J., et al. (2010). Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans. European Journal of Pediatrics, 169(9), 1079–1085.

  10. Duvekot, J., van der Ende, J., Verhulst, F. C., & Greaves-Lord, K. (2016). Examining bidirectional effects between the autism spectrum disorder (ASD) core symptom domains and anxiety in children with ASD. Journal of Child Psychology and Psychiatry, 59(3), 277–284.

  11. Goh, S., & Peterson, B. S. (2012). Imaging evidence for disturbances in multiple learning and memory systems in persons with autism spectrum disorders. Developmental Medicine and Child Neurology, 54(3), 208–213.

  12. Greene, D. J., Black, K. J., & Schlaggar, B. L. (2016). Considerations for MRI study design and implementation in pediatric and clinical populations. Developmental Cognitive Neuroscience, 18, 101–112.

  13. Hallowell, L. M., Stewart, S. E., de Amorim, E., Silva, C. T., & Ditchfield, M. R. (2008). Reviewing the process of preparing children for MRI. Pediatric Radiology, 38(3), 271–279.

  14. Harned, R. K., II, & Strain, J. D. (2001). MRI-compatible audio/visual system: Impact on pediatric sedation. Pediatric Radiology, 31(4), 247–250.

  15. Hull, J. V., Jacokes, Z. J., Torgerson, C. M., Irimia, A., & Van Horn, J. D. (2017). Resting-state functional connectivity in autism spectrum disorders: A review. Frontiers in Psychiatry, 4, 7–205.

  16. Izquierdo-Garcia, D., Izquierdo-Garcia, D., Hansen, A. E., Förster, S., Benoit, D., Schachoff, S., et al. (2014). An SPM8-based approach for attenuation correction combining segmentation and nonrigid template formation: Application to simultaneous PET/MR brain imaging. Journal of nuclear medicine: official publication, Society of Nuclear Medicine, 55(11), 1825–1830.

  17. Jack, A., & Pelphrey, K. A. (2017). Annual research review: Understudied populations with autism spectrum—current trends and future directions in neuroimaging research. Journal of Child Psychology and Psychiatry, 58(4), 411–435.

  18. Jaimes, C., & Gee, M. S. (2016). Strategies to minimize sedation in pediatric body magnetic resonance imaging. Pediatric Radiology, 46(6), 916–927.

  19. Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage, 17(2), 825–841.

  20. Kolb, A., Wehrl, H. F., Hofmann, M., Judenhofer, M. S., Eriksson, L., Ladebeck, R., et al. (2012). Technical performance evaluation of a human brain PET/MRI system. European Radiology, 22(8), 1776–1788.

  21. Lai, G., Pantazatos, S. P., Schneider, H., & Hirsch, J. (2012). Neural systems for speech and song in autism. Brain, 135(Pt 3), 961–975.

  22. Li, D., Karnath, H. O., & Xu, X. (2017). Candidate biomarkers in children with autism spectrum disorder: A review of MRI studies. Neuroscience Bulletin, 33, 219–237.

  23. Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24(5), 659–685.

  24. Lord, C., Rutter, M., & Le Couteur, A. (2012). Autism diagnostic observation schedule, second edition (ADOS-2). Los Angeles: Western Psychological Services.

  25. Nordahl, C. W., Mello, M., Shen, A. M., Shen, M. D., Vismara, L. A., Li, D., et al. (2016). Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation. Journal of Neurodevelopmental Disorders, 8, 20.

  26. Nordahl, C. W., Simon, T. J., Zierhut, C., Solomon, M., Rogers, S. J., & Amaral, D. G. (2008). Brief report: Methods for acquiring structural MRI data in very young children with autism without the use of sedation. Journal of Autism and Developmental Disorders, 38(8), 1581–1590.

  27. Ozsivadjian, A., Knott, F., & Magiati, I. (2012). Parent and child perspectives on the nature of anxiety in children and young people with autism spectrum disorders: A focus group study. Autism., 16(2), 107–121.

  28. Pressdee, D., May, L., Eastman, E., & Grier, D. (1997). The use of play therapy in the preparation of children undergoing MR imaging. Clinical Radiology, 52(12), 945–947.

  29. Rappaport, B. A., et al. (2015). Anesthetic neurotoxicity—clinical implications of animal models. New England Journal of Medicine, 372(9), 796–797.

  30. Raschle, N. M., Lee, M., Buechler, R., Christodoulou, J. A., Chang, M., Vakil, M., et al. (2009). Making MR imaging child’s play—pediatric neuroimaging protocol, guidelines and procedure. Journal of Visualized Experiments, 29, 1309.

  31. Roid, G. (2003). Stanford-Binet intelligence scales (5th ed.). Itasca: Riverside Publishing.

  32. Rutter, M., Le Couteur, A., & Lord, C. (2003). Autism diagnostic interview-revised. Los Angeles, CA: Western Psychological Services.

  33. Sandbank, M., & Cascio, C. (2018). Using a motion-tracking device to facilitate motion control in children with ASD for neuroimaging. Developmental Neurorehabilitation, 6, 1–11.

  34. Shearrer, G. E., House, B. T., Gallas, M. C., Luci, J. J., & Davis, J. N. (2016). Fat imaging via magnetic resonance imaging (MRI) in young children (Ages 1-4 Years) without sedation. PLoS ONE, 11(2), e0149744.

  35. Slifer, K. J., Cataldo, M. F., Cataldo, M. D., Llorente, A. M., & Gerson, A. C. (1993). Behavior analysis of motion control for pediatric neuroimaging. Journal of Applied Behavior Analysis, 26(4), 469–470.

  36. Tisdall, M. D., Reuter, M., Qureshi, A., Buckner, R. L., Fischl, B., & van der Kouwe, A. J. W. (2016). Prospective motion correction with volumetric navigators (vNavs) reduces the bias and variance in brain morphometry induced by subject motion. Neuroimage, 127, 11–22.

  37. Zurcher, N. R., Bhanot, A., McDougle, C. J., & Hooker, J. M. (2015). A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: Current state and future research opportunities. Neuroscience and Biobehavioral Reviews, 52, 56–73.

  38. Zwart, F. S., Vissers, C. T. W. M., Kessels, R. P. C., & Maes, J. H. R. (2017). Procedural learning across the lifespan: A systematic review with implications for atypical development. Journal of Neuropsychology, 45, 78–89.

Download references

Acknowledgments

We wish to thank Gregory Hren (Greg Hren Photography Inc.) for producing all the videos and DVDs, Regan Butterfield for helpful discussions, coordinating the video recordings and for radiotracer injection, Dr. Michael Placzek and Shirley Hsu for participating in the videos, as well as Jonathan Kent for working on an earlier version of this manuscript. We would like to thank Dr. Chieh-En (Jane) Tseng and Thomas Morin for assistance with motion estimation, Dr. Ciprian Catana, Dr. Daniel Chonde and Dr. David Izquierdo-Garcia for assistance with PET data reconstruction, Dr. Marco Loggia and Dr. Hsiao-Ying Wey for assistance with PET data analysis, and Dr. Nouchine Hadjikhani, Christine Wu, Baileigh Hightower, Lauren Richey and Anjali Parmar for help with data acquisition. We thank the physicians Dr. Christopher Keary and Dr. Michelle Palumbo for obtaining informed consent, Dr. Lisa Nowinski for neuropsychological assessments, the nurse practitioners Marlene Wentworth, Amy Kendall and Natacha Nortelus for medical coverage and nuclear medicine technologists Shirley Hsu and Grae Arabasz for radiotracer injection and assistance with PET-MRI scans, as well as Judit Sore and the radiopharmacy team for radioligand production.

Funding

Funding for this study was provided by the Robert E. and Donna Landreth Fund for the Study of Neuroinflammation in Autism, the Nancy Lurie Marks Family Foundation, and the Meixner Translational Postdoctoral Fellowship # 9258 from Autism Speaks awarded to Nicole R. Zürcher as well as the Transatlantic Research Scholar awarded to Nicole R. Zürcher.

Author information

CJS, AB, and EN performed literature search; EN, JEM, CJM, NRZ, and JMH designed and developed the training protocol; AB, JEM, and NRZ implemented the training protocol and acquired data; NRZ analyzed data; CJS, SDB, CJM, NRZ, and JMH conceived of the commentary; CJS and NRZ wrote the manuscript. All authors edited the manuscript.

Correspondence to J. M. Hooker.

Ethics declarations

Conflict of interest

Author J. M. Hooker is a co-founder of Eikonizo Therapeutics and serves on the scientific advisory board of Psy Therapeutics. Within the past 12 months, J.M.H. has consulted for Psy Therapeutics, Rodin Therapeutics, Evelo Biosciences, Denali Therapeutics and Vertex and has received honoraria for grant review or speaking from Alzheimer’s Drug Discovery Foundation, Lawrence Berkeley National Lab, and Cure Alzheimer’s Fund. Authors C. J. Smith, A. Bhanot, E. Norman, J. E. Mullett, S. D. Bilbo, C. J. McDougle and N. R. Zürcher have no conflicts of interest to declare.

Ethical Approval

This study referenced in this commentary was approved by the Institutional Review Board (IRB) of Partners Healthcare and the radioactive drug research committee (RDRC) at Massachusetts General Hospital.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (MP4 225346 kb)

Supplementary material 2 (MP4 23124 kb)

Supplementary material 3 (MP4 46738 kb)

Supplementary material 4 (MP4 44344 kb)

Supplementary material 5 (MP4 62733 kb)

Supplementary material 6 (MP4 131800 kb)

Supplementary material 1 (MP4 225346 kb)

Supplementary material 2 (MP4 23124 kb)

Supplementary material 3 (MP4 46738 kb)

Supplementary material 4 (MP4 44344 kb)

Supplementary material 5 (MP4 62733 kb)

Supplementary material 6 (MP4 131800 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Smith, C.J., Bhanot, A., Norman, E. et al. A Protocol for Sedation Free MRI and PET Imaging in Adults with Autism Spectrum Disorder. J Autism Dev Disord 49, 3036–3044 (2019) doi:10.1007/s10803-019-04010-3

Download citation

Keywords

  • Autism spectrum disorder
  • Neuroimaging
  • Positron emission tomography
  • Magnetic resonance imaging
  • Training protocols