In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging

Anu E. Meerwaldt; Milou Straathof; Wija Oosterveld; Caroline L. van Heijningen; Mandy M.T. van Leent; Yohana C. Toner; Jazz Munitz; Abraham J.P. Teunissen; Charlotte C. Daemen; Annette van der Toorn; Gerard van Vliet; Geralda A.F. van Tilborg; Henk M. De Feyter; Robin A. de Graaf; Elly M. Hol; Willem J.M. Mulder; Rick M. Dijkhuizen

doi:10.1177/0271678X221148970

In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging

Anu E. Meerwaldt, Milou Straathof, Wija Oosterveld, Caroline L. van Heijningen, Mandy M.T. van Leent, Yohana C. Toner, Jazz Munitz, Abraham J.P. Teunissen, Charlotte C. Daemen, Annette van der Toorn, Gerard van Vliet, Geralda A.F. van Tilborg, Henk M. De Feyter, Robin A. de Graaf, Elly M. Hol, Willem J.M. Mulder, Rick M. Dijkhuizen (Corresponding author)

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Abstract

Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (²H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue.

Original language	English
Pages (from-to)	778-790
Number of pages	13
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	43
Issue number	5
DOIs	https://doi.org/10.1177/0271678X221148970
Publication status	Published - May 2023

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by grants from the Netherlands Organisation for Scientific Research (NWO, Graduate Program NCU: 022.006.001). Acknowledgements

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by grants from the Netherlands Organisation for Scientific Research (NWO, Graduate Program NCU: 022.006.001). Acknowledgements

Funders	Funder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	022.006.001
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

Cerebral glucose metabolism
deuterium metabolic imaging
ischemic stroke
magnetic resonance imaging/spectroscopy
positron emission tomography
Stroke
Mice, Inbred C57BL
Positron-Emission Tomography
Deuterium/metabolism
Brain/blood supply
Pilot Projects
Animals
Infarction, Middle Cerebral Artery/pathology
Ischemic Stroke/pathology
Fluorodeoxyglucose F18/metabolism
Glucose/metabolism
Mice

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Meerwaldt, A. E., Straathof, M., Oosterveld, W., van Heijningen, C. L., van Leent, M. M. T., Toner, Y. C., Munitz, J., Teunissen, A. J. P., Daemen, C. C., van der Toorn, A., van Vliet, G., van Tilborg, G. A. F., De Feyter, H. M., de Graaf, R. A., Hol, E. M., Mulder, W. J. M., & Dijkhuizen, R. M. (2023). In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging. Journal of Cerebral Blood Flow and Metabolism, 43(5), 778-790. https://doi.org/10.1177/0271678X221148970

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title = "In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging",

abstract = "Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (2H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue.",

keywords = "Cerebral glucose metabolism, deuterium metabolic imaging, ischemic stroke, magnetic resonance imaging/spectroscopy, positron emission tomography, Stroke, Mice, Inbred C57BL, Positron-Emission Tomography, Deuterium/metabolism, Brain/blood supply, Pilot Projects, Animals, Infarction, Middle Cerebral Artery/pathology, Ischemic Stroke/pathology, Fluorodeoxyglucose F18/metabolism, Glucose/metabolism, Mice",

author = "Meerwaldt, {Anu E.} and Milou Straathof and Wija Oosterveld and {van Heijningen}, {Caroline L.} and {van Leent}, {Mandy M.T.} and Toner, {Yohana C.} and Jazz Munitz and Teunissen, {Abraham J.P.} and Daemen, {Charlotte C.} and {van der Toorn}, Annette and {van Vliet}, Gerard and {van Tilborg}, {Geralda A.F.} and {De Feyter}, {Henk M.} and {de Graaf}, {Robin A.} and Hol, {Elly M.} and Mulder, {Willem J.M.} and Dijkhuizen, {Rick M.}",

note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by grants from the Netherlands Organisation for Scientific Research (NWO, Graduate Program NCU: 022.006.001). Acknowledgements ",

year = "2023",

month = may,

doi = "10.1177/0271678X221148970",

language = "English",

volume = "43",

pages = "778--790",

journal = "Journal of Cerebral Blood Flow and Metabolism",

issn = "0271-678X",

publisher = "SAGE Publications Ltd",

number = "5",

}

Meerwaldt, AE, Straathof, M, Oosterveld, W, van Heijningen, CL, van Leent, MMT, Toner, YC, Munitz, J, Teunissen, AJP, Daemen, CC, van der Toorn, A, van Vliet, G, van Tilborg, GAF, De Feyter, HM, de Graaf, RA, Hol, EM, Mulder, WJM & Dijkhuizen, RM 2023, 'In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging', Journal of Cerebral Blood Flow and Metabolism, vol. 43, no. 5, pp. 778-790. https://doi.org/10.1177/0271678X221148970

In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging. / Meerwaldt, Anu E.; Straathof, Milou; Oosterveld, Wija et al.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 43, No. 5, 05.2023, p. 778-790.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging

AU - Meerwaldt, Anu E.

AU - Straathof, Milou

AU - Oosterveld, Wija

AU - van Heijningen, Caroline L.

AU - van Leent, Mandy M.T.

AU - Toner, Yohana C.

AU - Munitz, Jazz

AU - Teunissen, Abraham J.P.

AU - Daemen, Charlotte C.

AU - van der Toorn, Annette

AU - van Vliet, Gerard

AU - van Tilborg, Geralda A.F.

AU - De Feyter, Henk M.

AU - de Graaf, Robin A.

AU - Hol, Elly M.

AU - Mulder, Willem J.M.

AU - Dijkhuizen, Rick M.

N1 - Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by grants from the Netherlands Organisation for Scientific Research (NWO, Graduate Program NCU: 022.006.001). Acknowledgements

PY - 2023/5

Y1 - 2023/5

N2 - Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (2H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue.

AB - Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (2H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue.

KW - Cerebral glucose metabolism

KW - deuterium metabolic imaging

KW - ischemic stroke

KW - magnetic resonance imaging/spectroscopy

KW - positron emission tomography

KW - Stroke

KW - Mice, Inbred C57BL

KW - Positron-Emission Tomography

KW - Deuterium/metabolism

KW - Brain/blood supply

KW - Pilot Projects

KW - Animals

KW - Infarction, Middle Cerebral Artery/pathology

KW - Ischemic Stroke/pathology

KW - Fluorodeoxyglucose F18/metabolism

KW - Glucose/metabolism

KW - Mice

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U2 - 10.1177/0271678X221148970

DO - 10.1177/0271678X221148970

M3 - Article

C2 - 36606595

AN - SCOPUS:85146074399

SN - 0271-678X

VL - 43

SP - 778

EP - 790

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 5

ER -

In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging

Abstract

Bibliographical note

Funding

Keywords

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