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Background <p>The hypothalamus is considered a central hub in the pathophysiology of cluster headache (CH), yet its neurochemical profile remains poorly understood. Proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) offers a non-invasive tool for in vivo assessment of brain metabolites related to neuronal integrity and energy metabolism, but previous studies in CH have been restricted to conventional magnetic field scanner (≤ 3 T), which has resulted in limited metabolic information. Ultra-high field (7 T) MR scanners enhance <sup>1</sup>H-MRS with improved signal-to-noise ratio and separation of metabolite signals, providing more accurate and broader metabolic information, which may refine our understanding of hypothalamic dysfunction in chronic cluster headache (cCH). This study investigated whether patients with cCH exhibit altered hypothalamic metabolite concentrations compared with healthy volunteers (HVs). </p> Methods <p><sup>1</sup>H-MRS at 7 T was performed in 10 cCH patients and 11 HVs to measure the neurochemical profile of the hypothalamus. Spectra were quantified with LCModel, yielding ratios of 9 metabolites relative to total creatine (tCr). Welch’s unpaired t-tests were performed as a first-level exploratory analysis to compare metabolites between the two groups. Then, group differences in metabolite ratios were examined using analysis of covariance, with age and sex included as covariates to control for potential demographic effects.</p> Results <p>Compared with HVs, cCH patients showed significantly reduced glutamate (Glu)/tCr (∼17%; <i>p</i> &lt; 0.001) and N-acetyleaspartate (NAA)/tCr (∼10%; <i>p</i> = 0.048), with no other metabolite differences. After adjusting for covariates, a significant group effect was still observed for Glu/tCr (<i>p</i> = 0.0045), whereas no group difference was found for NAA/tCr (<i>p</i> = 0.079). Tissue composition within the voxel did not differ between groups, indicating that the observed metabolic differences were unlikely to be driven by partial-volume effects.</p> Conclusions <p>This is the first study to characterize hypothalamic metabolism in cCH at 7 T. The observed reductions in Glu, together with a statistically less robust decrease in NAA, indicates hypothalamic neuronal involvement, possibly reflecting mitochondrial and energetic dysfunction. This ultrahigh-field finding extends previous results at conventional magnetic field intensities, offering more specific neurochemical evidence for hypothalamic involvement in cCH.</p>

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Altered hypothalamic metabolism in chronic cluster headache patients measured with 1H-MRS at ultra-high magnetic field

  • 期刊论文

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  • 发表日期：

    2026年7月4日

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  • Avneesh Jain,
  • Anna Xiu Rørnes,
  • Anne Farestveit,
  • Maria Tunset Grinde,
  • Axel Karl Gottfrid Nyman,
  • Beathe Sitter,
  • Tore Wergeland,
  • Erling Tronvik,
  • Guglielmo Genovese

摘要

Background

The hypothalamus is considered a central hub in the pathophysiology of cluster headache (CH), yet its neurochemical profile remains poorly understood. Proton magnetic resonance spectroscopy (1H-MRS) offers a non-invasive tool for in vivo assessment of brain metabolites related to neuronal integrity and energy metabolism, but previous studies in CH have been restricted to conventional magnetic field scanner (≤ 3 T), which has resulted in limited metabolic information. Ultra-high field (7 T) MR scanners enhance 1H-MRS with improved signal-to-noise ratio and separation of metabolite signals, providing more accurate and broader metabolic information, which may refine our understanding of hypothalamic dysfunction in chronic cluster headache (cCH). This study investigated whether patients with cCH exhibit altered hypothalamic metabolite concentrations compared with healthy volunteers (HVs).

Methods

1H-MRS at 7 T was performed in 10 cCH patients and 11 HVs to measure the neurochemical profile of the hypothalamus. Spectra were quantified with LCModel, yielding ratios of 9 metabolites relative to total creatine (tCr). Welch’s unpaired t-tests were performed as a first-level exploratory analysis to compare metabolites between the two groups. Then, group differences in metabolite ratios were examined using analysis of covariance, with age and sex included as covariates to control for potential demographic effects.

Results

Compared with HVs, cCH patients showed significantly reduced glutamate (Glu)/tCr (∼17%; p < 0.001) and N-acetyleaspartate (NAA)/tCr (∼10%; p = 0.048), with no other metabolite differences. After adjusting for covariates, a significant group effect was still observed for Glu/tCr (p = 0.0045), whereas no group difference was found for NAA/tCr (p = 0.079). Tissue composition within the voxel did not differ between groups, indicating that the observed metabolic differences were unlikely to be driven by partial-volume effects.

Conclusions

This is the first study to characterize hypothalamic metabolism in cCH at 7 T. The observed reductions in Glu, together with a statistically less robust decrease in NAA, indicates hypothalamic neuronal involvement, possibly reflecting mitochondrial and energetic dysfunction. This ultrahigh-field finding extends previous results at conventional magnetic field intensities, offering more specific neurochemical evidence for hypothalamic involvement in cCH.