title: Progressive supranuclear palsy: high-field-strength MR microscopy in the human substantia nigra and globus pallidus.
abstract: OBJECTIVE
  To characterize changes in the magnetic resonance (MR) relaxation properties of progressive supranuclear palsy (PSP) and tissue from neurologically normal brains by using high-resolution (21.1-T, 900-MHz) MR microscopy of postmortem human midbrain and basal ganglia.
  
  
  METHODS
  This HIPAA-compliant study was approved by the institutional review board at the Mayo Clinic and informed consent was obtained. Postmortem tissue from age-matched PSP (n = 6) and control (n = 3) brains was imaged by using three-dimensional fast low-angle shot MR imaging with isotropic resolution of 50 μm. Relaxation times and parametric relaxation maps were generated from spin-echo and gradient-recalled-echo sequences. MR findings were correlated with histologic features by evaluating the presence of iron by using Prussian blue and ferritin and microglia burden as determined by a custom-designed color deconvolution algorithm. T2 and T2*, signal intensities, percent pixels (that could not be fitted in a pixel-by-pixel regression analysis due to severe hypointensity), and histologic data (total iron, ferritin, and microglia burden) were statistically analyzed by using independent sample t tests (P < .05).
  
  
  RESULTS
  PSP specimens showed higher iron burden in the cerebral peduncles and substantia nigra than did controls. However, only the putamen was significantly different, and it correlated with a decrease of T2* compared with controls (-48%; P = .043). Similarly, substantia nigra showed a significant decrease of T2* signal in PSP compared with controls (-57%; P = .028). Compared with controls, cerebral peduncles showed increased T2 (38%; P = .026) and T2* (34%; P = .014), as well as higher T2 signal intensity (57%; P = .049). Ferritin immunoreactivity was the opposite from iron burden and was significantly lower compared with controls in the putamen (-74%; P = .025), red nucleus (-61%; P = .018), and entire basal ganglia section (-63%; P = .016).
  
  
  CONCLUSIONS
  High-field-strength MR microscopy yielded pronounced differences in substantia nigra and globus pallidus of PSP compared with control brains. Histologic data also suggested that the predominant iron in PSP is hemosiderin, not ferritin. Iron in the brain is a contrast enhancer and potential biomarker for PSP.
authors.affiliation: Department of Chemical & Biomedical Engineering, Florida A&M University-Florida State University College of Engineering and National High Magnetic Field Laboratory, 1800 E Paul Dirac Dr, Tallahassee, FL 32310, USA. parastou.foroutan@moffitt.org
authors.forename: Parastou
authors.initials: P
authors.lastname: Foroutan
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Schweitzer
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Grant
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002102:Cadaver; D005260:Female; D005917:Globus Pallidus / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008853:Microscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000473:pathology*