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¹H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice.

Hekmatyar SK, Wilson M, Jerome N, Salek RM, Griffin JL, Peet A, Kauppinen RA - Br. J. Cancer (2010)

Bottom Line: These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice.Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas.The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Biomedical NMR Research Center, Dartmouth College, 706 Vail, Hanover, NH 03755, USA.

ABSTRACT

Background: Human medulloblastomas exhibit diverse molecular pathology. Aberrant hedgehog signalling is found in 20-30% of human medulloblastomas with largely unknown metabolic consequences.

Methods: Transgenic mice over-expressing smoothened (SMO) receptor in granule cell precursors with high incidence of exophytic medulloblastomas were sequentially followed up by magnetic resonance imaging (MRI) and characterised for metabolite phenotypes by ¹H MR spectroscopy (MRS) in vivo and ex vivo using high-resolution magic angle spinning (HR-MAS) ¹H MRS.

Results: Medulloblastomas in the SMO mice presented as T₂ hyperintense tumours in MRI. These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice. In contrast, ¹H MRS metabolite concentrations in normal appearing cerebellum of the SMO mice were not different from those in the WT mice. Macromolecule and lipid ¹H MRS signals in SMO medulloblastomas were not different from those detected in the cerebellum of WT mice. The HR-MAS analysis of SMO medulloblastomas confirmed the in vivo ¹H MRS metabolite profiles, and additionally revealed that phosphocholine was strongly elevated in medulloblastomas accounting for the high in vivo CCM.

Conclusions: These metabolite profiles closely mirror those reported from human medulloblastomas confirming that SMO mice provide a realistic model for investigating metabolic aspects of this disease. Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas. The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours.

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A plot between the cerebellum-to-forebrain length ratio and the volume of the fourth ventricle from WT and SMO mice with and without T2 MRI abnormality.
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fig3: A plot between the cerebellum-to-forebrain length ratio and the volume of the fourth ventricle from WT and SMO mice with and without T2 MRI abnormality.

Mentions: A typical macroscopic brain phenotype of SMO mice is displayed (Figure 2A), where the cerebellum is grossly enlarged approaching the size of the forebrain. This mouse showed widespread T2 hyperintensity in the cerebellum with hydrocephalus. A plot between cerebellum-to-forebrain length ratio and the volume of fourth ventricle shows that in a large number of SMO mice both the ratio and the fourth ventricle were higher than in WT mice (Figure 3). Histological sections for focal (Figure 2B) and uniform (Figure 2C and D) medulloblastomas are displayed. The histological slices showed high cell density in the external granular layer in the cerebellum. Small dark and dense cells that are stained strongly with hematoxylin, with disappearance of foliage pattern in MRI images are the microscopic hallmarks indicative of medulloblastomas.


¹H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice.

Hekmatyar SK, Wilson M, Jerome N, Salek RM, Griffin JL, Peet A, Kauppinen RA - Br. J. Cancer (2010)

A plot between the cerebellum-to-forebrain length ratio and the volume of the fourth ventricle from WT and SMO mice with and without T2 MRI abnormality.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967063&req=5

fig3: A plot between the cerebellum-to-forebrain length ratio and the volume of the fourth ventricle from WT and SMO mice with and without T2 MRI abnormality.
Mentions: A typical macroscopic brain phenotype of SMO mice is displayed (Figure 2A), where the cerebellum is grossly enlarged approaching the size of the forebrain. This mouse showed widespread T2 hyperintensity in the cerebellum with hydrocephalus. A plot between cerebellum-to-forebrain length ratio and the volume of fourth ventricle shows that in a large number of SMO mice both the ratio and the fourth ventricle were higher than in WT mice (Figure 3). Histological sections for focal (Figure 2B) and uniform (Figure 2C and D) medulloblastomas are displayed. The histological slices showed high cell density in the external granular layer in the cerebellum. Small dark and dense cells that are stained strongly with hematoxylin, with disappearance of foliage pattern in MRI images are the microscopic hallmarks indicative of medulloblastomas.

Bottom Line: These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice.Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas.The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Biomedical NMR Research Center, Dartmouth College, 706 Vail, Hanover, NH 03755, USA.

ABSTRACT

Background: Human medulloblastomas exhibit diverse molecular pathology. Aberrant hedgehog signalling is found in 20-30% of human medulloblastomas with largely unknown metabolic consequences.

Methods: Transgenic mice over-expressing smoothened (SMO) receptor in granule cell precursors with high incidence of exophytic medulloblastomas were sequentially followed up by magnetic resonance imaging (MRI) and characterised for metabolite phenotypes by ¹H MR spectroscopy (MRS) in vivo and ex vivo using high-resolution magic angle spinning (HR-MAS) ¹H MRS.

Results: Medulloblastomas in the SMO mice presented as T₂ hyperintense tumours in MRI. These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice. In contrast, ¹H MRS metabolite concentrations in normal appearing cerebellum of the SMO mice were not different from those in the WT mice. Macromolecule and lipid ¹H MRS signals in SMO medulloblastomas were not different from those detected in the cerebellum of WT mice. The HR-MAS analysis of SMO medulloblastomas confirmed the in vivo ¹H MRS metabolite profiles, and additionally revealed that phosphocholine was strongly elevated in medulloblastomas accounting for the high in vivo CCM.

Conclusions: These metabolite profiles closely mirror those reported from human medulloblastomas confirming that SMO mice provide a realistic model for investigating metabolic aspects of this disease. Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas. The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours.

Show MeSH
Related in: MedlinePlus