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Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI.

ABSTRACT: Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm³ voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R_1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (T_max) measured in normal tissue was 3.2 ± 0.6 µmol/min/mL, the half saturation constant (K_t) was 8.8 ± 2.2 mM, the metabolic rate of glucose consumption (MR_glc) was 0.21 ± 0.13 µmol/min/mL, and the cerebral blood volume (v_b) was 0.006 ± 0.005 mL/mL. Values in tumour were: T_max = 7.1 ± 2.7 µmol/min/mL, K_t = 14 ± 1.7 mM, MR_glc = 0.22 ± 0.09 µmol/min/mL, v_b = 0.030 ± 0.035 mL/mL. T_max and K_t were significantly higher in tumour tissue than normal tissue (p = 0.006 and p = 0.011, respectively). When assuming glucose uptake also occurs via free diffusion, the free diffusion rate (k_d) was 0.061 ± 0.017 mL/min/mL in normal tissue and 0.12 ± 0.042 mL/min/mL in tumour. These parameter estimates agree well with literature values obtained using other approaches (e.g. NMR spectroscopy).

SUBMITTER: Dickie BR

PROVIDER: S-EPMC9580170 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI.

Dickie Ben R BR Jin Tao T Wang Ping P Hinz Rainer R Harris William W Boutin Hervé H Parker Geoff Jm GJ Parkes Laura M LM Matthews Julian C JC

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20220623 11

Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm3 voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (Tmax) measured in normal tissue was 3.2 ± 0. ...[more]

PMID: 35748031

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Project description:Purpose: To spatially correlate the pattern of glucose uptake to glucose transporter distributions in cultured lenses and map glucose metabolism in different lens regions. Methods: Ex vivo bovine lenses were incubated in artificial aqueous humour containing normoglycaemic stable isotopically-labelled (SIL) glucose (5 mM) for 5 min-20 h. Following incubations, lenses were frozen for subsequent matrix-assisted laser desorption/ionisation (MALDI) imaging mass spectrometry (IMS) analysis using high resolution mass spectrometry. Manually dissected, SIL-incubated lenses were subjected to gas chromatography-mass spectrometry (GC-MS) to verify the identity of metabolites detected by MALDI-IMS. Normal, unincubated lenses were manually dissected into epithelium flat mounts and fibre cell fractions and then subjected to either gel-based proteomic analysis (Gel-LC/MS) to detect facilitative glucose transporters (GLUTs) by liquid chromatography tandem mass spectrometry (LC-MS/MS). Indirect immunofluorescence and confocal microscopy of axial lens sections from unincubated fixed lenses labelled with primary antibodies specific for GLUT 1 or GLUT 3 were utilised for protein localisation. Results: SIL glucose uptake at 5 min was concentrated in the equatorial region of the lens. At later timepoints, glucose gradually distributed throughout the epithelium and the cortical lens fibres, and eventually the deeper lens nucleus. SIL glucose metabolites found in glycolysis, the sorbitol pathway, the pentose phosphate pathway, and UDP-glucose formation were mapped to specific lens regions, with distinct regional signal changes up to 20 h of incubation. Spatial proteomic analysis of the lens epithelium detected GLUT1 and GLUT3. GLUT3 was in higher abundance than GLUT1 throughout the epithelium, while GLUT1 was more abundant in lens fibre cells. Immunohistochemical mapping localised GLUT1 to epithelial and cortical fibre cell membranes. Conclusion: The major uptake site of glucose in the bovine lens has been mapped to the lens equator. SIL glucose is rapidly metabolised in epithelial and fibre cells to many metabolites, which are most abundant in the metabolically more active cortical fibre cells in comparison to central fibres, with low levels of metabolic activity observed in the nucleus.

Dataset Information

Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI.

Publications

Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI.

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