Establishment of normal ranges for N-acetyl aspartate, choline, creatine, myo-inositol, and lipids/lactate in healthy brain tissue using proton magnetic resonance spectroscopy (1H-MRS)

Introduction: This study aims to establish normal ranges for the metabolites N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mI), and lipids/lactate (Lip/Lac) in healthy brain tissue using proton magnetic resonance spectroscopy ( 1 H-MRS) with 1.5T MRI equipment. Objective: Determine the normal ranges of NAA, Cho, Cr, mI, and Lip/Lac in healthy brain parenchyma. These normal ranges are necessary for the training of Artificial intelligence or the implementation of machine learning approaches. Without these ranges, automatic classification based on NAA, Cho, and Cr is not feasible. Methodology: The analysis included 60 patients (24 females and 36 males) with a total of 150 spectra (some patients contributed more than one spectrum). All spectra were acquired from structurally normal brain regions with no signal abnormalities in any MRI sequence. Normal ranges were established for each metabolite concentration, and linear regressions were performed to assess age-related changes. ROC curves were constructed to evaluate diagnostic accuracy. Results: The normal ranges established were: [Cho]n: 42.8 ± 1.66, [Cr]n: 42.3 ± 1.22, [NAA]n: 78.9 ± 1.04, [Lip/Lac]n: 28.7 ± 3.16, [mI]n: 10.8 ± 0.80. No significant differences were observed in the metabolites in terms of gender or echo time (TE). Normalized concentrations of Cho, Lip/Lac, and mI increased linearly with age, whereas NAA decreased significantly with age, indicating a loss of neurons related to ageing. Based on the results, we propose the following equation to calculate the normal range of metabolite concentrations according to age: [M]a = β coefficient× age + [M]x, where [M]a represents the age-adjusted normalized concentration of the metabolite, and [M]x is the average concentration of the metabolite. Conclusions: 1 H-MRS is a non-invasive diagnostic technique that allows the establishment of normal ranges for cerebral metabolites in healthy brain parenchyma. These reference points aid in the clinical interpretation of spectroscopy studies in patients with brain pathologies.