Whole-Brain N-Acetylaspartate as a Surrogate Marker of Neuronal Damage in Diffuse Neurologic Disorders

Abstract

SUMMARY: Proton MR spectroscopy ( 1 H-MR spectroscopy) is a quantitative MR imaging technique often used to complement the sensitivity of conventional MR imaging with specific metabolic information. A key metabolite is the amino acid derivative N-acetylaspartate (NAA), which is almost exclusive to neurons and their processes and is, therefore, an accepted marker of their health and attenuation. Unfortunately, most 1 H-MR spectroscopy studies only account for small 1-to 200-cm volumes of interest (VOI), representing less than 20% of the total brain volume. These VOIs have at least 5 additional restrictions: 1) To avoid contamination from subcutaneous and bone marrow lipids, they must be placed away from the skull, thereby missing most of the cortex. 2) They must be image-guided onto MR imaging-visible pathology, subjecting them to the implicit assumption that metabolic changes occur only there. 3) They encounter misregistration errors in serial studies. 4) The time needed to accumulate sufficient signal-intensity quality is often restrictive, and 5) they incur (unknown) T1-and T2-weighting. All these issues are avoided (at the cost of specific localization) by measuring the nonlocalized average NAA concentration over the entire brain. Indeed, whole-brain NAA quantification has been applied to several diffuse neurodegenerative diseases (where specific localization is less important than the total load of the pathology), and the results are presented in this review.

Decrease in N-Acetylaspartate Following Concussion May Be Coupled to Decrease in Creatine

“…8,10,11 Recently, particular attention has been given to compounds, noninvasively detectable in vivo by proton magnetic resonance (MR) spectroscopy ( 1 H MRS), that may be used as markers of brain metabolism following mTBI. 1 H MRS allows the routine measurement of NAA, creatine (Cr), and choline (Cho) in a single set of spectral acquisition, 16 although the low magnetic field currently used in the clinical setting (1.5 or 3 T) does not allow to resolve the N-acetylaspartatylglutamate signal in the NAA peak 17 or the creatine phosphate (CrP) signal in the Cr peak, 17 or to resolve about 10 different compounds containing the choline moiety in their molecule in the Cho peak. 17 NAA, Cr and Cho can be measured by 1 H MRS either by determining their absolute values 17 or by using the metabolite ratios.…”

“…1 H MRS allows the routine measurement of NAA, creatine (Cr), and choline (Cho) in a single set of spectral acquisition, 16 although the low magnetic field currently used in the clinical setting (1.5 or 3 T) does not allow to resolve the N-acetylaspartatylglutamate signal in the NAA peak 17 or the creatine phosphate (CrP) signal in the Cr peak, 17 or to resolve about 10 different compounds containing the choline moiety in their molecule in the Cho peak. 17 NAA, Cr and Cho can be measured by 1 H MRS either by determining their absolute values 17 or by using the metabolite ratios. 18 When referring to NAA and Cr, this is of limited relevance since, in the brain tissue, NAA and Cr are about 10 times more concentrated than their respective related compounds N-acetylaspartatylglutamate and CrP.…”

“…However, since these compounds are related to phospholipid metabolism, the Cho peak area is generally considered as a good indicator of the cell membrane turnover, 17,19 that of NAA is used as a marker of energy state and neuronal integrity, 8,10,11,17 and that of Cr is thought to be a marker of cellular energy. 17 Since the period of brain vulnerability following an mTBI is mainly characterized by evident biochemical, metabolic, and molecular changes, 3,5,6,20 it is questionable whether the tests currently adopted in the clinical practice to monitor mTBI patients (neuropsychological tests, balance tests, etc), because of their inability to evaluate cerebral biochemical changes, are of utility to determine the end of brain vulnerability. Although some of them (neuropsychological tests) are largely applied to assess the return of athletes with concussive head injury to play, [21][22][23] it has never been demonstrated that this type of normalization overlaps with the recovery of brain metabolism.…”

High field MRI in the diagnosis of multiple sclerosis: high field–high yield?

“…In MS, two major metabolites are of special interest: the first one, the N-acetyl moiety (tNAA), a maker of neuronal viability. The second metabolite, myo-inositol (mIns), is mostly located in astroglial cells and serves as a marker of glial cell activity [61][62][63][64].…”

Middle-aged rat hippocampus and some early changes accompanying aging

“…Recently attention has been given also to brain metabolites and changes of their content during aging. N-acetyl-aspartate (NAA) has been accepted as a marker of neuronal health or damage [14]. NAA and other key brain metabolites like creatine, choline, etc.…”