title: Cerebral Involvement in Stargardt's Disease: A VBM and TBSS Study.
abstract: OBJECTIVE
  To assess whether and to what extent macro- and/or microstructural modifications are present in the brain of patients with selective central visual loss due to a juvenile macular degeneration, Stargardt's disease (STGD), taking advantage of the complementary information provided by voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).
  
  
  METHODS
  Eighteen patients with clinical and molecular diagnosis of STGD related to ABCA4 mutations and 23 normally sighted volunteers of comparable age and sex were enrolled. Structural T1-weighted (T1w) volumes, for brain tissue volume assessment by segmentation, and DTI, for the investigation of diffusivity parameters via a tract-based spatial statistics (TBSS) procedure, were acquired at 3 Tesla in all subjects. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), biomicroscopy, ophthalmoscopy, electroretinography (ERG), microperimetry, and optical coherence tomography (OCT). Correlations between imaging data and clinical measures were tested.
  
  
  RESULTS
  Stargardt's disease patients showed a significant gray matter (GM) loss bilaterally in the occipital cortices, extending into the right precuneus, and in the fronto-orbital cortices. At TBSS, significant reductions in fractional anisotropy were detected throughout large regions in the supratentorial white matter (WM), more pronounced in the posterior areas. Gray matter volume correlated directly with mean visual sensitivity in the right middle frontal and left calcarine gyri, and inversely with retinal thickness in the left supramarginal gyrus.
  
  
  CONCLUSIONS
  In STGD, widespread microstructural WM alterations are present, suggestive of minor fiber loss coupled with GM loss, also in cortical regions not traditionally linked to visual pathways, at least partly related to the retinal damage.
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II," Naples, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Olivo
authors.forename: Olivo
authors.initials: O
authors.lastname: Gaia
authors.affiliation: Multidisciplinary Department of Medical, Surgical, and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Melillo
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II," Naples, Italy.
authors.forename: Sirio
authors.initials: S
authors.lastname: Cocozza
authors.forename: Cocozza
authors.initials: C
authors.lastname: Sirio
authors.affiliation: Multidisciplinary Department of Medical, Surgical, and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy.
authors.forename: Francesco Maria
authors.initials: FM
authors.lastname: D'Alterio
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Prinster
authors.affiliation: Multidisciplinary Department of Medical, Surgical, and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Testa
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II," Naples, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Brunetti
authors.affiliation: Multidisciplinary Department of Medical, Surgical, and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Quarantelli
mesh_terms: D000293:Adolescent; D000328:Adult; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D015203:Reproducibility of Results; D012160:Retina / Q000473:pathology*; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence / Q000379:methods; D066127:White Matter / Q000473:pathology*; D055815:Young Adult