title: Corpus callosum diffusion tensor imaging and volume measures are associated with disease severity in pediatric Niemann-Pick disease type C1.
abstract: BACKGROUND
  Niemann-Pick disease type C1 is a neurodegenerative lysosomal storage disorder. Without a highly effective treatment, biomarkers of severity would be beneficial for prognostication and testing new interventions. Diffusion tensor imaging has shown microstructural abnormalities in adults with Niemann-Pick disease type C1. This is the first study to apply diffusion tensor imaging and volume analysis to evaluate the corpus callosum in a pediatric and adolescent population of patients with Niemann-Pick disease type C1. We hypothesized that the callosal fractional anisotropy, volume, and cross-sectional area will negatively correlate with NPC severity score.
  
  
  METHODS
  Thirty-nine individuals with Niemann-Pick disease type C1 aged 1-21.9 years (mean = 11.1; S.D. = 6.1), and each received one magnetic resonance imaging examination. Severity score were obtained by examination and clinical observation. An atlas-based automated approach was used to measure fractional anisotropy, cross-sectional area, and volume. For comparative analysis and validation of this atlas-based approach, one midsagittal image was chosen and the corpus callosum manually traced to obtain cross-sectional area. Statistical analyses were applied to study the relationships between imaging and clinical severity.
  
  
  RESULTS
  For patients with Niemann-Pick disease type C1, lower corpus callosum fractional anisotropy, volume, and cross-sectional area significantly correlate with higher severity score. Severity subdomain analysis revealed ambulation, speech, seizures, and incontinence have the strongest relationships with callosal measures. Comparison of atlas-based processing and manual tracing techniques demonstrated validity for the automated method.
  
  
  CONCLUSIONS
  For individuals with Niemann-Pick disease type C1, the corpus callosum measures correlate with clinical severity. These findings reveal promise for the discovery of new imaging biomarkers for this disorder.
authors.affiliation: Department of Neurology, Shriners Hospitals for Children-Honolulu, Honolulu, Hawaii; Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii. Electronic address: rylee@shrinenet.org.
authors.forename: Ryan
authors.initials: R
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Kalyna
authors.initials: K
authors.lastname: Apkarian
authors.affiliation: Department of Psychiatry, Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Eun Sol
authors.initials: ES
authors.lastname: Jung
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Yanjanin
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Shoko
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.affiliation: School of Medicine, New York University, New York, New York.
authors.forename: Jina
authors.initials: J
authors.lastname: Park
authors.affiliation: Division of Neurogenetics, Children's National Medical Center, Washington DC.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gropman
authors.affiliation: Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland.
authors.forename: Eva H
authors.initials: EH
authors.lastname: Baker
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D008297:Male; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D055815:Young Adult
keywords: DTI; NPC; Niemann-Pick; corpus callosum; diffusion tensor; severity; volume