In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent

Clifford R. Jack, Michael Garwood, Thomas M. Wengenack, Bret Borowski, Geoffrey L. Curran, Joseph Lin, Gregor Adriany, Olli H J Gröhn, Roger Grimm, Joseph F. Poduslo

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop "human-like" plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques noninvasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content, not plaque size. In vivo MRI-ex vivo MRI-in vitro histologic correlations are provided. Histologically verified plaques as small as 50 μm in diameter were visualized in living animals. To our knowledge this work represents the first demonstration of noninvasive in vivo visualization of individual AD plaques without the use of a contrast agent.

Original languageEnglish (US)
Pages (from-to)1263-1271
Number of pages9
JournalMagnetic resonance in medicine
Volume52
Issue number6
DOIs
StatePublished - Dec 1 2004

Fingerprint

Amyloid Plaques
Contrast Media
Transgenic Mice
Alzheimer Disease
Magnetic Resonance Imaging
Iron
Genes

Keywords

  • Alzheimer's disease
  • MR microscopy
  • Magnetic resonance imaging
  • Transgenic mice

Cite this

In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent. / Jack, Clifford R.; Garwood, Michael; Wengenack, Thomas M.; Borowski, Bret; Curran, Geoffrey L.; Lin, Joseph; Adriany, Gregor; Gröhn, Olli H J; Grimm, Roger; Poduslo, Joseph F.

In: Magnetic resonance in medicine, Vol. 52, No. 6, 01.12.2004, p. 1263-1271.

Research output: Contribution to journalArticle

Jack, Clifford R. ; Garwood, Michael ; Wengenack, Thomas M. ; Borowski, Bret ; Curran, Geoffrey L. ; Lin, Joseph ; Adriany, Gregor ; Gröhn, Olli H J ; Grimm, Roger ; Poduslo, Joseph F. / In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent. In: Magnetic resonance in medicine. 2004 ; Vol. 52, No. 6. pp. 1263-1271.
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