Multiple sclerosis: Pathogenesis and MR imaging features of T1 hypointensities in murine model

Istvan Pirko, Tifany K. Nolan, Scott K. Holland, Aaron J. Johnson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: To prospectively determine how T1 hypointensities (T1 black holes) on brain magnetic resonance (MR) images are generated by the immune system by using a Theiler murine encephalitis virus-induced model of multiple sclerosis and high-field-strength MR imaging. Materials and Methods: All animal protocols and experiments were approved by the institutional animal care and use committee. Volumetric MR imaging studies were conducted at 7 T in six C57BL/6 mice and in immune differentiation marker (recombination activation gene [RAG]-1)-, immune cell (CD4, CD8)-, and immune effector molecule (Fas ligand, perforin)-deficient mice (six mice in each group) to determine which immune cell types and effector molecules lead to T1 hypointensities. The main outcome measure was the total T1 black hole volume per animal, as determined with volumetric analysis, and was analyzed statistically by using software. Results: Compared with C57BL/6 mice, RAG-1-deficient mice showed a significant (P = .003) decrease in total T1 black hole volume, suggesting a clear role for the adaptive immune system. While CD4-deficient mice did not show a significant decrease in T1 black hole volume (P - .33), CD8-deficient mice did (P = .003). Perforin-deficient mice showed a significant reduction of T1 black hole volume (P = .002), whereas Fas ligand-deficient mice did not (P = .77). Conclusion: The data suggest that CD8 T cells utilizing perforin effector molecules are responsible for T1 black hole formation.

Original languageEnglish (US)
Pages (from-to)790-795
Number of pages6
JournalRadiology
Volume246
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

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Multiple Sclerosis
Magnetic Resonance Imaging
Fas Ligand Protein
Inbred C57BL Mouse
Transcriptional Activation
Genetic Recombination
Immune System
Encephalitis Viruses
Animal Care Committees
Perforin
Differentiation Antigens
Magnetic Resonance Spectroscopy
Software
Biomarkers
Outcome Assessment (Health Care)
T-Lymphocytes
Brain
mouse perforin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Multiple sclerosis : Pathogenesis and MR imaging features of T1 hypointensities in murine model. / Pirko, Istvan; Nolan, Tifany K.; Holland, Scott K.; Johnson, Aaron J.

In: Radiology, Vol. 246, No. 3, 03.2008, p. 790-795.

Research output: Contribution to journalArticle

Pirko, Istvan ; Nolan, Tifany K. ; Holland, Scott K. ; Johnson, Aaron J. / Multiple sclerosis : Pathogenesis and MR imaging features of T1 hypointensities in murine model. In: Radiology. 2008 ; Vol. 246, No. 3. pp. 790-795.
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