Skip to main content
Advertisement

Main menu

  • Home
  • Content
    • Current Issue
    • Accepted Manuscripts
    • Article Preview
    • Past Issue Archive
    • Video Articles
    • AJNR Case Collection
    • Case of the Week Archive
    • Case of the Month Archive
    • Classic Case Archive
  • Special Collections
    • AJNR Awards
    • Low-Field MRI
    • Alzheimer Disease
    • ASNR Foundation Special Collection
    • Photon-Counting CT
    • View All
  • Multimedia
    • AJNR Podcasts
    • AJNR SCANtastic
    • Trainee Corner
    • MRI Safety Corner
    • Imaging Protocols
  • For Authors
    • Submit a Manuscript
    • Submit a Video Article
    • Submit an eLetter to the Editor/Response
    • Manuscript Submission Guidelines
    • Statistical Tips
    • Fast Publishing of Accepted Manuscripts
    • Graphical Abstract Preparation
    • Imaging Protocol Submission
    • Author Policies
  • About Us
    • About AJNR
    • Editorial Board
    • Editorial Board Alumni
  • More
    • Become a Reviewer/Academy of Reviewers
    • Subscribers
    • Permissions
    • Alerts
    • Feedback
    • Advertisers
    • ASNR Home

User menu

  • Alerts
  • Log in

Search

  • Advanced search
American Journal of Neuroradiology
American Journal of Neuroradiology

American Journal of Neuroradiology

ASHNR American Society of Functional Neuroradiology ASHNR American Society of Pediatric Neuroradiology ASSR
  • Alerts
  • Log in

Advanced Search

  • Home
  • Content
    • Current Issue
    • Accepted Manuscripts
    • Article Preview
    • Past Issue Archive
    • Video Articles
    • AJNR Case Collection
    • Case of the Week Archive
    • Case of the Month Archive
    • Classic Case Archive
  • Special Collections
    • AJNR Awards
    • Low-Field MRI
    • Alzheimer Disease
    • ASNR Foundation Special Collection
    • Photon-Counting CT
    • View All
  • Multimedia
    • AJNR Podcasts
    • AJNR SCANtastic
    • Trainee Corner
    • MRI Safety Corner
    • Imaging Protocols
  • For Authors
    • Submit a Manuscript
    • Submit a Video Article
    • Submit an eLetter to the Editor/Response
    • Manuscript Submission Guidelines
    • Statistical Tips
    • Fast Publishing of Accepted Manuscripts
    • Graphical Abstract Preparation
    • Imaging Protocol Submission
    • Author Policies
  • About Us
    • About AJNR
    • Editorial Board
    • Editorial Board Alumni
  • More
    • Become a Reviewer/Academy of Reviewers
    • Subscribers
    • Permissions
    • Alerts
    • Feedback
    • Advertisers
    • ASNR Home
  • Follow AJNR on Twitter
  • Visit AJNR on Facebook
  • Follow AJNR on Instagram
  • Join AJNR on LinkedIn
  • RSS Feeds

AJNR Awards, New Junior Editors, and more. Read the latest AJNR updates

Brief ReportCLINICAL REPORT

Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities

Kevin Ferenchak, Julie B. Guerin, Asra Nayab, Gesina F. Keating, Madeline Q. Lopour, Lauren A. Dalvin, Lisa A. Schimmenti, Brittni A. Scruggs and V. Michelle Silvera
American Journal of Neuroradiology February 2025, ajnr.A8707; DOI: https://doi.org/10.3174/ajnr.A8707
Kevin Ferenchak
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julie B. Guerin
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Asra Nayab
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.B.B.S.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gesina F. Keating
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Madeline Q. Lopour
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.S.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lauren A. Dalvin
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa A. Schimmenti
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brittni A. Scruggs
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D, Ph. D
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. Michelle Silvera
From the Department of Ophthalmology (K.F, L.A.D., B.A.S) Mayo Clinic, Rochester, MN, USA; Department of Radiology (J.B.G., A.N., V.M.S.) Mayo Clinic, Rochester, MN, USA; Department of Clinical Genomics (L.A.S., M.Q.L) Mayo Clinic, Rochester, MN, USA; Department of Neurology (G.F.K.) Mayo Clinic, Rochester, MN, USA.
M.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • Responses
  • PDF
Loading
Submit a Response to This Article
Compose eLetter

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. [email protected]
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Statement of Competing Interests

Vertical Tabs

Jump to comment:

  • Low ADC in the Cerebellum of Infants: A Normal Developmental Phenomenon
    Thibault Agripnidis and Jean-François Hak
    Published on: 20 April 2025
  • Published on: (20 April 2025)
    Page navigation anchor for Low ADC in the Cerebellum of Infants: A Normal Developmental Phenomenon
    Low ADC in the Cerebellum of Infants: A Normal Developmental Phenomenon
    • Thibault Agripnidis, Neuroradiologist, Department of Neuroradiology, Timone Hospital, Marseille, France
    • Other Contributors:
      • Jean-François Hak, Neuroradiologist

    I would like to thank the authors for these new data on Norrie disease. However, we believe an important point deserves further discussion: the quantitative evidence of low ADC in the neonatal cerebellum in infants under 6 months, ADC values in the cerebellum can physiologically fall around 0.6–0.7 × 10⁻³ mm²/s due to normal maturation processes. Data from Özkan et al. (2019)(1) show that the mean ADC in the cerebellar cortex reaches as low as 0.75, with standard deviations allowing lower bounds down to 0.63. Similarly, the middle cerebellar peduncle shows values dropping to 0.78 with normal variability reaching 0.66. These findings confirm that ADC values near 0.6–0.7 are part of normal cerebellar development, not pathological restriction. (Table 1)
    These lower values typically occur during the first few weeks to months after birth and reflect rapid maturation processes rather than diffusion restriction due to injury.
    There are several mechanisms behind physiological ADC reduction.
    First, early myelination: the cerebellar white matter and peduncles myelinate early, often from birth to 3 months of age on T1-weighted imaging(2). Myelination reduces extracellular water, restricts water diffusion, and lowers ADC.
    Second, high cellular density: The cerebellum has a persisting external granular layer in the early postnatal period. This temporary, densely packed layer leads to reduced interstitial space and further restricts diffusion physiologically....

    Show More

    I would like to thank the authors for these new data on Norrie disease. However, we believe an important point deserves further discussion: the quantitative evidence of low ADC in the neonatal cerebellum in infants under 6 months, ADC values in the cerebellum can physiologically fall around 0.6–0.7 × 10⁻³ mm²/s due to normal maturation processes. Data from Özkan et al. (2019)(1) show that the mean ADC in the cerebellar cortex reaches as low as 0.75, with standard deviations allowing lower bounds down to 0.63. Similarly, the middle cerebellar peduncle shows values dropping to 0.78 with normal variability reaching 0.66. These findings confirm that ADC values near 0.6–0.7 are part of normal cerebellar development, not pathological restriction. (Table 1)
    These lower values typically occur during the first few weeks to months after birth and reflect rapid maturation processes rather than diffusion restriction due to injury.
    There are several mechanisms behind physiological ADC reduction.
    First, early myelination: the cerebellar white matter and peduncles myelinate early, often from birth to 3 months of age on T1-weighted imaging(2). Myelination reduces extracellular water, restricts water diffusion, and lowers ADC.
    Second, high cellular density: The cerebellum has a persisting external granular layer in the early postnatal period. This temporary, densely packed layer leads to reduced interstitial space and further restricts diffusion physiologically.
    Third, microstructural complexity: As highlighted by Hüppi & Dubois (2006)(3), axon packing, oligodendrocyte proliferation, and early organization of white matter tracts all contribute to lowering diffusivity even before overt myelin is seen on conventional MRI.
    Fourth, normal maturation pattern: Mukherjee et al. (2001)(4) show that ADC decreases follow a biphasic exponential decline with age. The steepest decline is in the first 6 months, and the cerebellum is no exception, as its maturation is advanced compared to supratentorial regions.
    An ADC around 0.7 × 10⁻³ mm²/s in the cerebellum of infants under 6 months is typically symmetrical and homogeneous, consistent with normal development. It should not be misinterpreted as pathological, such as in cases of hypoxic-ischemic injury or cerebellitis. Crucially, such a pattern lacks associated DWI hyperintensity, T2 signal changes, or cortical swelling, which are hallmarks of true diffusion restriction.
    We urge clinicians and radiologists to interpret ADC values in the context of age-specific normative data, anatomical symmetry, and clinical presentation. Similarly, when considering contrast enhancement, the absence of spontaneous T1 hyperintensity on non-contrast sequences must be demonstrated — which, in this case, was not shown by the authors for the cerebellum enhancement.
    We trust that these observations will support the ongoing refinement of diffusion imaging interpretation in early infancy and underscore the importance of age-specific reference values.

    REFERENCES:
    1. Özkan M, Taşkent İ, Teke M. Evaluation of changes in myelination in the brain during infancy and childhood using ADC maps. Journal of Surgery and Medicine [Internet]. 4 nov 2019 [cité 19 avr 2025]; Disponible sur: https://ojs.selsistem.com.tr/doi/10.28982/josam.633584
    2. Barkovich AJ, Kjos BO, Jackson DE, Norman D. Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T. Radiology. janv 1988;166(1 Pt 1):173‑80.
    3. Hüppi PS, Dubois J. Diffusion tensor imaging of brain development. Seminars in Fetal and Neonatal Medicine. 1 déc 2006;11(6):489‑97.
    4. Mukherjee P, Miller JH, Shimony JS, Conturo TE, Lee BC, Almli CR, et al. Normal brain maturation during childhood: developmental trends characterized with diffusion-tensor MR imaging. Radiology. nov 2001;221(2):349‑58.

    TABLE 1:
    Cerebellar ADC Values in Infants <6 Months (Özkan et al., 2019)
    Middle Cerebellar Peduncle (White Matter)
    Age Group Region Mean ADC (×10⁻³ mm²/s) SD Lower Bound (Mean - 2SD)
    0–3 months Right MCP 0.93 0.05 0.83
    0–3 months Left MCP 0.91 0.07 0.77
    3–6 months Right MCP 0.80 0.05 0.70
    3–6 months Left MCP 0.78 0.06 0.66

    Cerebellar Cortex (Gray Matter)
    Age Group Region Mean ADC (×10⁻³ mm²/s) SD Lower Bound (Mean - 2SD)
    0–3 months Right Cortex 0.87 0.12 0.63
    0–3 months Left Cortex 0.88 0.14 0.60
    3–6 months Right Cortex 0.75 0.07 0.61
    3–6 months Left Cortex 0.76 0.09 0.58

    Show Less
    Competing Interests: None declared.
PreviousNext
Back to top
Advertisement
Download PDF
Email Article

Thank you for your interest in spreading the word on American Journal of Neuroradiology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities
(Your Name) has sent you a message from American Journal of Neuroradiology
(Your Name) thought you would like to see the American Journal of Neuroradiology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Cite this article
Accepted Manuscript
Kevin Ferenchak, Julie B. Guerin, Asra Nayab, Gesina F. Keating, Madeline Q. Lopour, Lauren A. Dalvin, Lisa A. Schimmenti, Brittni A. Scruggs, V. Michelle Silvera
Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities
American Journal of Neuroradiology Feb 2025, ajnr.A8707; DOI: 10.3174/ajnr.A8707

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
1 Responses
Respond to this article
Share
Bookmark this article
Accepted Manuscript
Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities
Kevin Ferenchak, Julie B. Guerin, Asra Nayab, Gesina F. Keating, Madeline Q. Lopour, Lauren A. Dalvin, Lisa A. Schimmenti, Brittni A. Scruggs, V. Michelle Silvera
American Journal of Neuroradiology Feb 2025, ajnr.A8707; DOI: 10.3174/ajnr.A8707
del.icio.us logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Purchase

Jump to section

  • Article
  • Info & Metrics
  • Responses
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Crossref
  • Google Scholar

This article has not yet been cited by articles in journals that are participating in Crossref Cited-by Linking.

More in this TOC Section

  • Revisiting a Rare Anomaly Described 25 Years Ago in the AJNR: A Journey from Pediatric Hemifacial Microsomia and Middle Cranial Fossa Aplasia to CSF-Lymphatic Fistula and Spontaneous Intracranial Hypotension as an Adult
  • World’s first real-time artificial intelligence-assisted mechanical thrombectomy for acute ischemic stroke
Show more Clinical Report

Similar Articles

Advertisement

Indexed Content

  • Current Issue
  • Accepted Manuscripts
  • Article Preview
  • Past Issues
  • Editorials
  • Editor's Choice
  • Fellows' Journal Club
  • Letters to the Editor
  • Video Articles

Cases

  • Case Collection
  • Archive - Case of the Week
  • Archive - Case of the Month
  • Archive - Classic Case

More from AJNR

  • Trainee Corner
  • Imaging Protocols
  • MRI Safety Corner

Multimedia

  • AJNR Podcasts
  • AJNR Scantastics

Resources

  • Turnaround Time
  • Submit a Manuscript
  • Submit a Video Article
  • Submit an eLetter to the Editor/Response
  • Manuscript Submission Guidelines
  • Statistical Tips
  • Fast Publishing of Accepted Manuscripts
  • Graphical Abstract Preparation
  • Imaging Protocol Submission
  • Evidence-Based Medicine Level Guide
  • Publishing Checklists
  • Author Policies
  • Become a Reviewer/Academy of Reviewers
  • News and Updates

About Us

  • About AJNR
  • Editorial Board
  • Editorial Board Alumni
  • Alerts
  • Permissions
  • Not an AJNR Subscriber? Join Now
  • Advertise with Us
  • Librarian Resources
  • Feedback
  • Terms and Conditions
  • AJNR Editorial Board Alumni

American Society of Neuroradiology

  • Not an ASNR Member? Join Now

© 2025 by the American Society of Neuroradiology All rights, including for text and data mining, AI training, and similar technologies, are reserved.
Print ISSN: 0195-6108 Online ISSN: 1936-959X

Powered by HighWire