Whole-brain N-Acetylaspartate concentration is preserved during mild hypercapnia challenge

S. Chawla, Y. Ge, H. Lu, O. Marshall, M. S. Davitz, G. Fatterpekar, B. J. Soher, O. Gonen

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND PURPOSE: Although NAA is often used as a marker of neuronal health and integrity in neurologic disorders, its normal response to physiologic challenge is not well-established and its changes are almost always attributed exclusively to brain pathology. The purpose of this study was to test the hypothesis that the neuronal cell marker NAA, often used to assess neuronal health and integrity in neurologic disorders, is not confounded by (possibly transient) physiologic changes. Therefore, its decline, when observed by using 1H-MR spectroscopy, can almost always be attributed exclusively to brain pathology. MATERIALS AND METHODS: Twelve healthy young male adults underwent a transient hypercapnia challenge (breathing 5% CO2 air mixture), a potent vasodilator known to cause a substantial increase in CBF and venous oxygenation. We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy, venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with pseudo-continuous arterial spin-labeling, and the cerebral metabolic rate of oxygen, during normocapnia (breathing room air) and hypercapnia. RESULTS: There was insignificant whole-brain NAA change (P = .88) from normocapnia to hypercapnia and back to normocapnia in this cohort, as opposed to highly significant increases: 28.0 ± 10.3% in venous oxygenation and 49.7 ± 16.6% in global CBF (P <10-4); and a 6.4 ± 10.9% decrease in the global cerebral metabolic rate of oxygen (P = .04). CONCLUSIONS: Stable whole-brain NAA during normocapnia and hypercapnia, despite significant global CBF and cerebral metabolic rate of oxygen changes, supports the hypothesis that global NAA changes are insensitive to transient physiology. Therefore, when observed, they most likely reflect underlying pathology resulting from neuronal cell integrity/viability changes, instead of a response to physiologic changes.

Original languageEnglish (US)
Pages (from-to)2055-2061
Number of pages7
JournalAmerican Journal of Neuroradiology
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2015

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Hypercapnia
Brain
Pathology
Oxygen
Nervous System Diseases
Respiration
Magnetic Resonance Spectroscopy
Air
Health
Vasodilator Agents
Protons
Young Adult
Cell Survival
N-acetylaspartate

ASJC Scopus subject areas

  • Clinical Neurology
  • Radiology Nuclear Medicine and imaging

Cite this

Chawla, S., Ge, Y., Lu, H., Marshall, O., Davitz, M. S., Fatterpekar, G., ... Gonen, O. (2015). Whole-brain N-Acetylaspartate concentration is preserved during mild hypercapnia challenge. American Journal of Neuroradiology, 36(11), 2055-2061. https://doi.org/10.3174/ajnr.A4424

Whole-brain N-Acetylaspartate concentration is preserved during mild hypercapnia challenge. / Chawla, S.; Ge, Y.; Lu, H.; Marshall, O.; Davitz, M. S.; Fatterpekar, G.; Soher, B. J.; Gonen, O.

In: American Journal of Neuroradiology, Vol. 36, No. 11, 01.11.2015, p. 2055-2061.

Research output: Contribution to journalArticle

Chawla, S, Ge, Y, Lu, H, Marshall, O, Davitz, MS, Fatterpekar, G, Soher, BJ & Gonen, O 2015, 'Whole-brain N-Acetylaspartate concentration is preserved during mild hypercapnia challenge', American Journal of Neuroradiology, vol. 36, no. 11, pp. 2055-2061. https://doi.org/10.3174/ajnr.A4424
Chawla, S. ; Ge, Y. ; Lu, H. ; Marshall, O. ; Davitz, M. S. ; Fatterpekar, G. ; Soher, B. J. ; Gonen, O. / Whole-brain N-Acetylaspartate concentration is preserved during mild hypercapnia challenge. In: American Journal of Neuroradiology. 2015 ; Vol. 36, No. 11. pp. 2055-2061.
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abstract = "BACKGROUND AND PURPOSE: Although NAA is often used as a marker of neuronal health and integrity in neurologic disorders, its normal response to physiologic challenge is not well-established and its changes are almost always attributed exclusively to brain pathology. The purpose of this study was to test the hypothesis that the neuronal cell marker NAA, often used to assess neuronal health and integrity in neurologic disorders, is not confounded by (possibly transient) physiologic changes. Therefore, its decline, when observed by using 1H-MR spectroscopy, can almost always be attributed exclusively to brain pathology. MATERIALS AND METHODS: Twelve healthy young male adults underwent a transient hypercapnia challenge (breathing 5{\%} CO2 air mixture), a potent vasodilator known to cause a substantial increase in CBF and venous oxygenation. We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy, venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with pseudo-continuous arterial spin-labeling, and the cerebral metabolic rate of oxygen, during normocapnia (breathing room air) and hypercapnia. RESULTS: There was insignificant whole-brain NAA change (P = .88) from normocapnia to hypercapnia and back to normocapnia in this cohort, as opposed to highly significant increases: 28.0 ± 10.3{\%} in venous oxygenation and 49.7 ± 16.6{\%} in global CBF (P <10-4); and a 6.4 ± 10.9{\%} decrease in the global cerebral metabolic rate of oxygen (P = .04). CONCLUSIONS: Stable whole-brain NAA during normocapnia and hypercapnia, despite significant global CBF and cerebral metabolic rate of oxygen changes, supports the hypothesis that global NAA changes are insensitive to transient physiology. Therefore, when observed, they most likely reflect underlying pathology resulting from neuronal cell integrity/viability changes, instead of a response to physiologic changes.",
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AU - Soher, B. J.

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