Progressive supranuclear palsy: High-field-strength MR microscopy in the human substantia nigra and globus pallidus

Parastou Foroutan, Melissa E Murray, Shinsuke Fujioka, Katherine J. Schweitzer, Dennis W Dickson, Zbigniew K Wszolek, Samuel C. Grant

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Materials and 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 (261%; P = .018), and entire basal ganglia section (263%; P = .016). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)280-288
Number of pages9
JournalRadiology
Volume266
Issue number1
DOIs
StatePublished - Jan 2013

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Progressive Supranuclear Palsy
Globus Pallidus
Substantia Nigra
Microscopy
Magnetic Resonance Spectroscopy
Iron
Ferritins
Putamen
Brain
Microglia
Basal Ganglia
Red Nucleus
Health Insurance Portability and Accountability Act
Hemosiderin
Research Ethics Committees
Mesencephalon
Informed Consent
Color
Biomarkers
Regression Analysis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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Progressive supranuclear palsy : High-field-strength MR microscopy in the human substantia nigra and globus pallidus. / Foroutan, Parastou; Murray, Melissa E; Fujioka, Shinsuke; Schweitzer, Katherine J.; Dickson, Dennis W; Wszolek, Zbigniew K; Grant, Samuel C.

In: Radiology, Vol. 266, No. 1, 01.2013, p. 280-288.

Research output: Contribution to journalArticle

Foroutan, Parastou ; Murray, Melissa E ; Fujioka, Shinsuke ; Schweitzer, Katherine J. ; Dickson, Dennis W ; Wszolek, Zbigniew K ; Grant, Samuel C. / Progressive supranuclear palsy : High-field-strength MR microscopy in the human substantia nigra and globus pallidus. In: Radiology. 2013 ; Vol. 266, No. 1. pp. 280-288.
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AU - Schweitzer, Katherine J.

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AU - Wszolek, Zbigniew K

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N2 - Purpose: 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. Materials and 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 (261%; P = .018), and entire basal ganglia section (263%; P = .016). Conclusion: 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.

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