Skip to main content
Top
Published in: Neuroradiology 4/2016

01-04-2016 | Functional Neuroradiology

A comprehensive analysis of metabolic changes in the salvaged penumbra

Authors: Andrew Bivard, Nawaf Yassi, Venkatesh Krishnamurthy, Longting Lin, Christopher Levi, Neil J. Spratt, Ferdi Mittef, Stephen Davis, Mark Parsons

Published in: Neuroradiology | Issue 4/2016

Login to get access

Abstract

Introduction

We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery.

Methods

One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5 h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24 h after stroke onset, including single-voxel, short-echo-time (30 ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area.

Results

The concentrations of total creatine (5.39 vs 5.85 mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13 mM ± 1.57, p < 0.001) were reduced in peri-infarct tissue compared to the matching contralateral region. Baseline National Institutes of Health Stroke Score was correlated with glutamate concentration in the reperfused penumbra at 24 h (r 2 = 0.167, p = 0.017). Higher total creatine was associated with better neurological outcome at 24 h (r 2 = 0.242, p = 0.004). Lower peri-infarct glutamate was a stronger predictor of worse 3-month clinical outcome (area under the curve (AUC) 0.89, p < 0.001) than DWI volume (AUC = 0.79, p < 0.001).

Conclusion

Decreased glutamate, creatine, and NAA concentrations are associated with poor neurological outcome at 24 h and greater disability at 3 months. The significant metabolic variation in salvaged tissue may potentially explain some of the variability seen in stroke recovery despite apparently successful reperfusion.
Literature
1.
go back to reference Nagakane Y, Christensen S, Brekenfeld C, Ma H, Churilov L, Parsons MW, Levi CR, Butcher KS, Peeters A, Barber PA, Bladin CF, De Silva DA, Fink J, Kimber TE, Schultz DW, Muir KW, Tress BM, Desmond PM, Davis SM, Donnan GA, for the EPITHET Investigators (2011) EPITHET: positive result after reanalysis using baseline diffusion-weighted imaging/perfusion-weighted imaging co-registration. Stroke 42:59–64CrossRefPubMed Nagakane Y, Christensen S, Brekenfeld C, Ma H, Churilov L, Parsons MW, Levi CR, Butcher KS, Peeters A, Barber PA, Bladin CF, De Silva DA, Fink J, Kimber TE, Schultz DW, Muir KW, Tress BM, Desmond PM, Davis SM, Donnan GA, for the EPITHET Investigators (2011) EPITHET: positive result after reanalysis using baseline diffusion-weighted imaging/perfusion-weighted imaging co-registration. Stroke 42:59–64CrossRefPubMed
2.
go back to reference O’CollMI VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467–477CrossRef O’CollMI VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467–477CrossRef
3.
go back to reference Corbett D, Nguemeni C, Gomez-Smith M (2014) How can you mend a broken brain? Neurorestorative approaches to stroke recovery. Cerebrovasc Dis 38(4):233–239CrossRefPubMed Corbett D, Nguemeni C, Gomez-Smith M (2014) How can you mend a broken brain? Neurorestorative approaches to stroke recovery. Cerebrovasc Dis 38(4):233–239CrossRefPubMed
4.
go back to reference Saur D, Buchert R, Knab R, Weiller C, Röther J (2006) Iomazenil-single-photon emission computed tomography reveals selective neuronal loss in magnetic resonance-defined mismatch areas. Stroke 37(11):2713–2719CrossRefPubMed Saur D, Buchert R, Knab R, Weiller C, Röther J (2006) Iomazenil-single-photon emission computed tomography reveals selective neuronal loss in magnetic resonance-defined mismatch areas. Stroke 37(11):2713–2719CrossRefPubMed
5.
go back to reference Patel TB, Clark JB (1979) Synthesis of N-acetyl-L-aspartate by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport. Biochem J 184:539–546CrossRefPubMedPubMedCentral Patel TB, Clark JB (1979) Synthesis of N-acetyl-L-aspartate by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport. Biochem J 184:539–546CrossRefPubMedPubMedCentral
6.
go back to reference Baron JC, Yamauchi H, Fujioka M, Endres M (2014) Selective neuronal loss in ischemic stroke and cerebrovascular disease. J Cereb Blood Flow Metab 34:2–18CrossRefPubMedPubMedCentral Baron JC, Yamauchi H, Fujioka M, Endres M (2014) Selective neuronal loss in ischemic stroke and cerebrovascular disease. J Cereb Blood Flow Metab 34:2–18CrossRefPubMedPubMedCentral
7.
go back to reference Guadagno JV, Jones PS, Aigbirhio FI, Wang D, Fryer TD, Day DJ, Antoun N, Nimmo-Smith I, Warburton EA, Baron JC (2008) Selective neuronal loss in rescued penumbra relates to initial hypoperfusion. Brain 131:2666–267CrossRefPubMed Guadagno JV, Jones PS, Aigbirhio FI, Wang D, Fryer TD, Day DJ, Antoun N, Nimmo-Smith I, Warburton EA, Baron JC (2008) Selective neuronal loss in rescued penumbra relates to initial hypoperfusion. Brain 131:2666–267CrossRefPubMed
8.
go back to reference Parsons MW, Miteff F, Bateman GA, Spratt N, Loiselle A, Attia J et al (2009) Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window. Neurology 72:915–921CrossRefPubMed Parsons MW, Miteff F, Bateman GA, Spratt N, Loiselle A, Attia J et al (2009) Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window. Neurology 72:915–921CrossRefPubMed
9.
go back to reference Bivard A, Stanwell P, Levi CR, Parsons MW (2013) Arterial spin labeling identifies tissue salvage and good clinical recovery after acute ischemic stroke. J Neuroimaging 23:391–396CrossRefPubMed Bivard A, Stanwell P, Levi CR, Parsons MW (2013) Arterial spin labeling identifies tissue salvage and good clinical recovery after acute ischemic stroke. J Neuroimaging 23:391–396CrossRefPubMed
10.
go back to reference Parsons MW, Pepper EM, Bateman GA, Wang Y, Levi CR (2007) Identification of the penumbra and infarct core on hyperacute noncontrast and perfusion CT. Neurology 68:730–736CrossRefPubMed Parsons MW, Pepper EM, Bateman GA, Wang Y, Levi CR (2007) Identification of the penumbra and infarct core on hyperacute noncontrast and perfusion CT. Neurology 68:730–736CrossRefPubMed
11.
go back to reference Bivard A, Levi C, Spratt N, Parsons M (2013) Perfusion CT in acute stroke: a comprehensive analysis of infarct and penumbra. Radiology 267:543–550CrossRefPubMed Bivard A, Levi C, Spratt N, Parsons M (2013) Perfusion CT in acute stroke: a comprehensive analysis of infarct and penumbra. Radiology 267:543–550CrossRefPubMed
12.
go back to reference Bivard A, Stanwell P, Spratt N, Davis S, Krishnamurthy V, Levi C, Parsons M Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion. Neurad 447 Bivard A, Stanwell P, Spratt N, Davis S, Krishnamurthy V, Levi C, Parsons M Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion. Neurad 447
13.
go back to reference Bivard A, Levi C, Krishnamurthy V, Hislop-Jambrich J, Salazar P, Jackson B, Davis S, Parsons M (2014) Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion. J Neuroradiol 41(5):307–315CrossRefPubMed Bivard A, Levi C, Krishnamurthy V, Hislop-Jambrich J, Salazar P, Jackson B, Davis S, Parsons M (2014) Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion. J Neuroradiol 41(5):307–315CrossRefPubMed
14.
go back to reference Bivard A, Spratt N, Levi C, Parsons M (2011) Perfusion computer tomography: imaging and clinical validation in acute ischaemic stroke. Brain 134:3408–3416CrossRefPubMed Bivard A, Spratt N, Levi C, Parsons M (2011) Perfusion computer tomography: imaging and clinical validation in acute ischaemic stroke. Brain 134:3408–3416CrossRefPubMed
15.
go back to reference Provencher W (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679CrossRefPubMed Provencher W (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679CrossRefPubMed
16.
go back to reference Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM (2007) N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 81(2):89–131CrossRefPubMedPubMedCentral Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM (2007) N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 81(2):89–131CrossRefPubMedPubMedCentral
17.
go back to reference Hakim AM, Pokrupa RP, Villanueva J, Diksic M, Evans AC, Thompson CJ, Meyer E, Yamamoto YL, Feindel WH (1987) The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts. Ann Neurol 21(3):279–289CrossRefPubMed Hakim AM, Pokrupa RP, Villanueva J, Diksic M, Evans AC, Thompson CJ, Meyer E, Yamamoto YL, Feindel WH (1987) The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts. Ann Neurol 21(3):279–289CrossRefPubMed
18.
go back to reference Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G et al (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31:347–354CrossRefPubMed Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G et al (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31:347–354CrossRefPubMed
19.
go back to reference Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629CrossRefPubMedPubMedCentral Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629CrossRefPubMedPubMedCentral
20.
go back to reference Parsons MW, Li T, Barber PA, Yang Q, Darby DG, Desmond PM, Gerraty RP, Tress BM, Davis SM (2000) Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome. Neurology 55(4):498–505CrossRefPubMed Parsons MW, Li T, Barber PA, Yang Q, Darby DG, Desmond PM, Gerraty RP, Tress BM, Davis SM (2000) Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome. Neurology 55(4):498–505CrossRefPubMed
Metadata
Title
A comprehensive analysis of metabolic changes in the salvaged penumbra
Authors
Andrew Bivard
Nawaf Yassi
Venkatesh Krishnamurthy
Longting Lin
Christopher Levi
Neil J. Spratt
Ferdi Mittef
Stephen Davis
Mark Parsons
Publication date
01-04-2016
Publisher
Springer Berlin Heidelberg
Published in
Neuroradiology / Issue 4/2016
Print ISSN: 0028-3940
Electronic ISSN: 1432-1920
DOI
https://doi.org/10.1007/s00234-015-1638-x

Other articles of this Issue 4/2016

Neuroradiology 4/2016 Go to the issue