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

Seidemo, Anina; Knutsson, Linda; Yadav, Nirbhay N; Sundgren, Pia C; Wirestam, Ronnie; van Zijl, Peter Cm

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

Mark

Seidemo, Anina ^LU

; Knutsson, Linda ^LU

; Yadav, Nirbhay N ; Sundgren, Pia C ^LU

; Wirestam, Ronnie ^LU

and van Zijl, Peter Cm (2025) In Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism p.1-24

Abstract: 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... (More); 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.

(Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/7f4ee66f-6023-46fe-b192-66094cefd0cd

author

Seidemo, Anina ^LU

; Knutsson, Linda ^LU

; Yadav, Nirbhay N ; Sundgren, Pia C ^LU

; Wirestam, Ronnie ^LU

and van Zijl, Peter Cm

organization

publishing date

2025-08-25

type

Contribution to journal

publication status

epub

subject

in

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

pages

1 - 24

publisher

Nature Publishing Group

external identifiers

scopus:105014397849
pmid:40854155

ISSN

1559-7016

DOI

10.1177/0271678X251366074

language

English

LU publication?

yes

id

7f4ee66f-6023-46fe-b192-66094cefd0cd

date added to LUP

2025-08-27 18:29:30

date last changed

2025-10-14 09:37:18

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  abstract     = {{<p>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 (<br>
 <br>
 <br>
 <br>
 K<br>
 <br>
 <br>
 T<br>
 <br>
 <br>
 ) and maximum rates for transport<br>
 <br>
 <br>
 <br>
 <br>
 (<br>
 T<br>
 <br>
 <br>
 max<br>
 <br>
 <br>
 )<br>
 <br>
 over the BBB and the cell membrane (CMB). These transport parameters and the maximum rate for hexokinase-catalyzed metabolism ( <br>
 <br>
 <br>
 <br>
 V<br>
 <br>
 <br>
 max<br>
 <br>
 <br>
 H<br>
 K<br>
 <br>
 <br>
 ) 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 (<br>
 <br>
 <br>
 <br>
 R<br>
 <br>
 <br>
 A<br>
 /<br>
 L<br>
 <br>
 <br>
 ) of GLUT1 receptors on abluminal and luminal membranes. Four-compartment fitting with<br>
 <br>
 <br>
 <br>
 <br>
 R<br>
 <br>
 <br>
 A<br>
 /<br>
 L<br>
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 <br>
 =<br>
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 resulted in<br>
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 T<br>
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 <br>
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 <br>
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 <br>
 <br>
 =<br>
 0.804<br>
 ±<br>
 0.131<br>
  <br>
 µmol/g/min,<br>
 <br>
 <br>
 <br>
 <br>
 K<br>
 <br>
 <br>
 T<br>
 <br>
 <br>
 BBB<br>
 <br>
 <br>
 =<br>
 6.20<br>
 ±<br>
 1.53<br>
  <br>
 mM,<br>
 <br>
 <br>
 <br>
 <br>
 T<br>
 <br>
 <br>
 max<br>
 <br>
 <br>
 CMB<br>
 <br>
 <br>
 =<br>
 1.04<br>
 ±<br>
 0.25<br>
  <br>
 µmol/g/min,<br>
 <br>
 <br>
 <br>
 <br>
 K<br>
 <br>
 <br>
 T<br>
 <br>
 <br>
 CMB<br>
 <br>
 <br>
 =<br>
 3.10<br>
 ±<br>
 0.70<br>
  <br>
 mM and<br>
 <br>
 <br>
 <br>
 <br>
 V<br>
 <br>
 <br>
 max<br>
 <br>
 <br>
 H<br>
 K<br>
 <br>
 <br>
 =<br>
 0.260<br>
 ±<br>
 0.039<br>
  <br>
 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.<br>
 </p>}},
  author       = {{Seidemo, Anina and Knutsson, Linda and Yadav, Nirbhay N and Sundgren, Pia C and Wirestam, Ronnie and van Zijl, Peter Cm}},
  issn         = {{1559-7016}},
  language     = {{eng}},
  month        = {{08}},
  pages        = {{1--24}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}},
  title        = {{Cerebral glucose delivery, transport and metabolism : Theory and modeling using four, three, and two tissue compartments}},
  url          = {{http://dx.doi.org/10.1177/0271678X251366074}},
  doi          = {{10.1177/0271678X251366074}},
  year         = {{2025}},
}

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