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Cerebral glucose delivery, transport and metabolism: Theory and modeling using four, three, and two tissue compartments

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  • معلومة اضافية
    • Contributors:
      Lund University, Faculty of Science, Medical Radiation Physics, Lund, MR Physics, Lunds universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik, Lund, MR Physics, Originator; Lund University, Profile areas and other strong research environments, Lund University Profile areas, LU Profile Area: Light and Materials, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Lunds universitets profilområden, LU profilområde: Ljus och material, Originator; Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), MultiPark: Multidisciplinary research focused on Parkinson's disease, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), MultiPark: Multidisciplinary research focused on Parkinson's disease, Originator; Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator; Lund University, Faculty of Medicine, Lund University Bioimaging Center, Lunds universitet, Medicinska fakulteten, Lund University Bioimaging Center, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section V, Diagnostic Radiology, (Lund), Neuroradiology, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion V, Diagnostisk radiologi, Lund, Neuroradiologi, Originator
    • نبذة مختصرة :
      Flux equations describing brain D-glucose uptake are presented for up to four tissue compartments: blood, endothelial intracellular space in the blood-brain barrier (BBB), extravascular-extracellular space (EES), and intracellular space. Transport rates are described by Michaelis-Menten kinetics, including half-saturation constants ( K T ) and maximum rates for transport ( T max ) over the BBB and the cell membrane (CMB). These transport parameters and the maximum rate for hexokinase-catalyzed metabolism ( V max H K ) were determined by numerical fitting of the models to both steady-state and dynamic D-glucose uptake data in human gray matter from MRS. Two-, three-, and four-compartment results are compared, including effects of incorporating an endothelial compartment with unequal ratios ( R A / L ) of GLUT1 receptors on abluminal and luminal membranes. Four-compartment fitting with R A / L = 2.0 resulted in T max BBB = 0.804 ± 0.131   µmol/g/min, K T BBB = 6.20 ± 1.53   mM, T max CMB = 1.04 ± 0.25   µmol/g/min, K T CMB = 3.10 ± 0.70   mM and V max H K = 0.260 ± 0.039   µmol/g/min, comparing well with the simpler models. A model with at least three tissue compartments (blood, EES, cell) is essential for quantification and interpretation of dynamic glucose-enhanced (DGE) MRI data in brain tumors, where signal intensities depend on compartmental pH in addition to concentration, and where the signal contribution from the EES is dominant. It should also be relevant to PET and MR(S) studies of pathologies where the BBB is compromised.