Clinical proton MR spectroscopy in central nervous system disorders

Abstract

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

RSNA, 2014

Figures

Figure 1:

1H MR spectrum acquired at 3.0 T from a volume of interest in occipital lobe (20 × 20 × 20 mm3, T1-weighted axial image) of healthy subject with the STEAM sequence (repetition time msec/echo time [TE] msec = 5000/8; 128 repetitions).tNAA = total N-acetylaspartate (NAA),tCr = total creatine (Cr), tCho = total choline,Glu = glutamate, Gln = glutamine,mIns = myo-inositol, MM = macromolecules.

Figure 2a:

MR spectroscopy of astrocytomas. Average (solid line) and standard deviation (shaded area) 1H MR spectra (1.5 T, STEAM or PRESS, 2000/30, 128–256 repetitions per spectrum included in average) in World Health Organization (a) grade II (n = 14) and (b) grade IV (n = 42) astrocytomas. Characteristically elevated tCho/tCr ratio and absence of tNAA is apparent in both tumor spectra compared with that from normal brain (see Fig 1). Lac in low-grade tumor may be the result of hypoxia and/or a metabolic shift toward glycolysis, as is commonplace in cancer. In high-grade tumor, large macromolecule (MM) and lipid (Lip) signals (at chemical shifts 2.0, 1.3, and 0.9 ppm) are associated with necrosis. Glx = combination of Glu and Gln. (Reprinted, with permission, from reference 49.)

Figure 2b:

MR spectroscopy of astrocytomas. Average (solid line) and standard deviation (shaded area) 1H MR spectra (1.5 T, STEAM or PRESS, 2000/30, 128–256 repetitions per spectrum included in average) in World Health Organization (a) grade II (n = 14) and (b) grade IV (n = 42) astrocytomas. Characteristically elevated tCho/tCr ratio and absence of tNAA is apparent in both tumor spectra compared with that from normal brain (see Fig 1). Lac in low-grade tumor may be the result of hypoxia and/or a metabolic shift toward glycolysis, as is commonplace in cancer. In high-grade tumor, large macromolecule (MM) and lipid (Lip) signals (at chemical shifts 2.0, 1.3, and 0.9 ppm) are associated with necrosis. Glx = combination of Glu and Gln. (Reprinted, with permission, from reference 49.)

Figure 3a:

1H MR spectroscopy in glioblastomas. Contrast-enhanced T1-weighted MR images and MR spectroscopy grid (3.0 T, PRESS, 1700/30, three repetitions, section thickness = 20 mm, matrix size = 16 × 16, total acquisition time = 6 minutes 46 seconds) are shown together with representative spectra from voxels in contrast-enhancing areas. (a) Image and spectrum from patient with recurrent gliobastoma multiforme exhibits elevated tCho/tCr ratio as well as elevated lipid (Lip) and Lac levels. (b) Image and spectrum from histologically proven case of postradiation injury exhibits markedly elevated lipid (Lip) and Lac levels along with normal-appearing tCho/tCr ratio.

Figure 3b:

1H MR spectroscopy in glioblastomas. Contrast-enhanced T1-weighted MR images and MR spectroscopy grid (3.0 T, PRESS, 1700/30, three repetitions, section thickness = 20 mm, matrix size = 16 × 16, total acquisition time = 6 minutes 46 seconds) are shown together with representative spectra from voxels in contrast-enhancing areas. (a) Image and spectrum from patient with recurrent gliobastoma multiforme exhibits elevated tCho/tCr ratio as well as elevated lipid (Lip) and Lac levels. (b) Image and spectrum from histologically proven case of postradiation injury exhibits markedly elevated lipid (Lip) and Lac levels along with normal-appearing tCho/tCr ratio.

Figure 4a:

1H MR spectroscopy in early assessment of perinatal hypoxia-ischemia in the newborn. MR imaging was performed (a–c) 12 hours and (d, e) 10 days after perinatal asphyxia. (a) Axial T2-weighted image shows no signal abnormalities, whereas (b) spectrum (1.5 T, PRESS, 1500/288, 192 repetitions) obtained from the right basal ganglia shows markedly increased Lac resonance with preserved tNAA, tCr, and tCho resonances.(c) Diffusion-weighted image (echo-planar imaging; 30 directions; b value, 700 sec/mm2) with axial apparent diffusion coefficient map shows no diffusion abnormalities. (d) Axial T2-weighted images show areas of high (white arrows) and low (black arrows) signal intensity in putamen and thalamus, representing clear ischemohemorrhagic lesions. (e) Axial proton density images demonstrate prominent detection of lesion’s extension. (Reprinted, with permission, from reference 76.)

Figure 4b:

1H MR spectroscopy in early assessment of perinatal hypoxia-ischemia in the newborn. MR imaging was performed (a–c) 12 hours and (d, e) 10 days after perinatal asphyxia. (a) Axial T2-weighted image shows no signal abnormalities, whereas (b) spectrum (1.5 T, PRESS, 1500/288, 192 repetitions) obtained from the right basal ganglia shows markedly increased Lac resonance with preserved tNAA, tCr, and tCho resonances.(c) Diffusion-weighted image (echo-planar imaging; 30 directions; b value, 700 sec/mm2) with axial apparent diffusion coefficient map shows no diffusion abnormalities. (d) Axial T2-weighted images show areas of high (white arrows) and low (black arrows) signal intensity in putamen and thalamus, representing clear ischemohemorrhagic lesions. (e) Axial proton density images demonstrate prominent detection of lesion’s extension. (Reprinted, with permission, from reference 76.)

Figure 4c:

1H MR spectroscopy in early assessment of perinatal hypoxia-ischemia in the newborn. MR imaging was performed (a–c) 12 hours and (d, e) 10 days after perinatal asphyxia. (a) Axial T2-weighted image shows no signal abnormalities, whereas (b) spectrum (1.5 T, PRESS, 1500/288, 192 repetitions) obtained from the right basal ganglia shows markedly increased Lac resonance with preserved tNAA, tCr, and tCho resonances.(c) Diffusion-weighted image (echo-planar imaging; 30 directions; b value, 700 sec/mm2) with axial apparent diffusion coefficient map shows no diffusion abnormalities. (d) Axial T2-weighted images show areas of high (white arrows) and low (black arrows) signal intensity in putamen and thalamus, representing clear ischemohemorrhagic lesions. (e) Axial proton density images demonstrate prominent detection of lesion’s extension. (Reprinted, with permission, from reference 76.)

Figure 4d:

1H MR spectroscopy in early assessment of perinatal hypoxia-ischemia in the newborn. MR imaging was performed (a–c) 12 hours and (d, e) 10 days after perinatal asphyxia. (a) Axial T2-weighted image shows no signal abnormalities, whereas (b) spectrum (1.5 T, PRESS, 1500/288, 192 repetitions) obtained from the right basal ganglia shows markedly increased Lac resonance with preserved tNAA, tCr, and tCho resonances.(c) Diffusion-weighted image (echo-planar imaging; 30 directions; b value, 700 sec/mm2) with axial apparent diffusion coefficient map shows no diffusion abnormalities. (d) Axial T2-weighted images show areas of high (white arrows) and low (black arrows) signal intensity in putamen and thalamus, representing clear ischemohemorrhagic lesions. (e) Axial proton density images demonstrate prominent detection of lesion’s extension. (Reprinted, with permission, from reference 76.)

Figure 4e:

1H MR spectroscopy in early assessment of perinatal hypoxia-ischemia in the newborn. MR imaging was performed (a–c) 12 hours and (d, e) 10 days after perinatal asphyxia. (a) Axial T2-weighted image shows no signal abnormalities, whereas (b) spectrum (1.5 T, PRESS, 1500/288, 192 repetitions) obtained from the right basal ganglia shows markedly increased Lac resonance with preserved tNAA, tCr, and tCho resonances.(c) Diffusion-weighted image (echo-planar imaging; 30 directions; b value, 700 sec/mm2) with axial apparent diffusion coefficient map shows no diffusion abnormalities. (d) Axial T2-weighted images show areas of high (white arrows) and low (black arrows) signal intensity in putamen and thalamus, representing clear ischemohemorrhagic lesions. (e) Axial proton density images demonstrate prominent detection of lesion’s extension. (Reprinted, with permission, from reference 76.)

Figure 5a:

1H MR spectroscopy of neurometabolic disorder. (a, b) White matter spectra (1.5 T, PRESS MR spectroscopic imaging, 3000/30, six weighted averages, nominal voxel size = 10 × 10 × 15 mm3) in girl with guanidinoacetate methyltransferase deficiency before treatment at age 3 years 2 months (a) and after 3.5 months of treatment with oral creatine supplementation (b). Resonance from creatine-containing metabolites (tCr) returned to normal in this region as well as in other investigated brain areas.

Figure 5b:

1H MR spectroscopy of neurometabolic disorder. (a, b) White matter spectra (1.5 T, PRESS MR spectroscopic imaging, 3000/30, six weighted averages, nominal voxel size = 10 × 10 × 15 mm3) in girl with guanidinoacetate methyltransferase deficiency before treatment at age 3 years 2 months (a) and after 3.5 months of treatment with oral creatine supplementation (b). Resonance from creatine-containing metabolites (tCr) returned to normal in this region as well as in other investigated brain areas.

Figure 6:

Single-voxel 1H MR spectroscopy shows progression of disease in boy with X-linked adrenoleukodystrophy. At baseline, T2-weighted signal abnormalities on conventional MR image are seen only in posterior third of centrum semiovale, and spectrum (4.0 T, STEAM, 4500/5, 64 repetitions) is normal. One year later, MR image shows progression of T2 signal abnormalities in middle third of centrum semiovale. Spectrum in anterior third of centrum semiovale already shows increased choline (tCho) and mIns in association with tNAA signal loss. As predicted with the spectrum at 1 year, MR image obtained 2 years later shows further progression of signal changes, with spectrum showing further mIns signal increase and tNAA loss. Also note progressive changes in Glu/Gln ratio and accumulation of mobile lipids (Lip) plus Lac at 1- and 2-year follow-up.

Figure 7a:

1H MR spectroscopy of pyogenic abscess in cerebellum. (a)Axial T2-weighted image shows well-defined hyperintense lesion with hypointense wall.(b) Axial T1-weighted image shows hypointense lesion with isointense wall. (c) Diffusion-weighted image shows restricted diffusion in lesion.(d) Postcontrast T1-weighted image shows ring enhancement.(e) In vivo 1H-MR spectrum (3.0 T, PRESS, 3000/144, 128 repetitions) from center of lesion shows resonances of amino acids (AA, 0.9 ppm), lipid (Lip) and Lac (1.3 ppm), alanine (Ala, 1.5 ppm), acetate (Ac, 1.9 ppm), and succinate (Suc, 2.4 ppm). The resonances from alanine, Lac, and amino acids are inverted at the TE used owing to J evolution.

Figure 7b:

1H MR spectroscopy of pyogenic abscess in cerebellum. (a)Axial T2-weighted image shows well-defined hyperintense lesion with hypointense wall.(b) Axial T1-weighted image shows hypointense lesion with isointense wall. (c) Diffusion-weighted image shows restricted diffusion in lesion.(d) Postcontrast T1-weighted image shows ring enhancement.(e) In vivo 1H-MR spectrum (3.0 T, PRESS, 3000/144, 128 repetitions) from center of lesion shows resonances of amino acids (AA, 0.9 ppm), lipid (Lip) and Lac (1.3 ppm), alanine (Ala, 1.5 ppm), acetate (Ac, 1.9 ppm), and succinate (Suc, 2.4 ppm). The resonances from alanine, Lac, and amino acids are inverted at the TE used owing to J evolution.

Figure 7c:

1H MR spectroscopy of pyogenic abscess in cerebellum. (a)Axial T2-weighted image shows well-defined hyperintense lesion with hypointense wall.(b) Axial T1-weighted image shows hypointense lesion with isointense wall. (c) Diffusion-weighted image shows restricted diffusion in lesion.(d) Postcontrast T1-weighted image shows ring enhancement.(e) In vivo 1H-MR spectrum (3.0 T, PRESS, 3000/144, 128 repetitions) from center of lesion shows resonances of amino acids (AA, 0.9 ppm), lipid (Lip) and Lac (1.3 ppm), alanine (Ala, 1.5 ppm), acetate (Ac, 1.9 ppm), and succinate (Suc, 2.4 ppm). The resonances from alanine, Lac, and amino acids are inverted at the TE used owing to J evolution.

Figure 7d:

1H MR spectroscopy of pyogenic abscess in cerebellum. (a)Axial T2-weighted image shows well-defined hyperintense lesion with hypointense wall.(b) Axial T1-weighted image shows hypointense lesion with isointense wall. (c) Diffusion-weighted image shows restricted diffusion in lesion.(d) Postcontrast T1-weighted image shows ring enhancement.(e) In vivo 1H-MR spectrum (3.0 T, PRESS, 3000/144, 128 repetitions) from center of lesion shows resonances of amino acids (AA, 0.9 ppm), lipid (Lip) and Lac (1.3 ppm), alanine (Ala, 1.5 ppm), acetate (Ac, 1.9 ppm), and succinate (Suc, 2.4 ppm). The resonances from alanine, Lac, and amino acids are inverted at the TE used owing to J evolution.

Figure 7e:

1H MR spectroscopy of pyogenic abscess in cerebellum. (a)Axial T2-weighted image shows well-defined hyperintense lesion with hypointense wall.(b) Axial T1-weighted image shows hypointense lesion with isointense wall. (c) Diffusion-weighted image shows restricted diffusion in lesion.(d) Postcontrast T1-weighted image shows ring enhancement.(e) In vivo 1H-MR spectrum (3.0 T, PRESS, 3000/144, 128 repetitions) from center of lesion shows resonances of amino acids (AA, 0.9 ppm), lipid (Lip) and Lac (1.3 ppm), alanine (Ala, 1.5 ppm), acetate (Ac, 1.9 ppm), and succinate (Suc, 2.4 ppm). The resonances from alanine, Lac, and amino acids are inverted at the TE used owing to J evolution.

Figure 8:

1H MR spectroscopic findings at different pathologic and clinical stages of Alzheimer disease. Top panel: Antemortem 1H MR spectroscopic findings in posterior cingulate gyrus voxel (T1-weighted midsagittal image) are associated with postmortem pathologic diagnosis of Alzheimer disease (low, intermediate, and high likelihood). For each pathologic diagnosis, plot shows individual values, a box plot of the distribution, and estimated mean and 95% confidence interval for the mean. A strong association is observed with tNAA/mIns ratio (R2 = 0.40; P < .001). (Reprinted, with permission, from reference 33.) Bottom panel: Examples of 1H MR spectra (1.5 T, PRESS, 2000/30, 128 repetitions) in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are compared with that from a cognitively normal subject (control). mIns is elevated as an early marker of subsequent neurodegenerative changes in patient with mild cognitive impairment. tNAA is decreased and mIns is further elevated in patient with Alzheimer disease.

Figure 9:

Minimum technical requirements to ensure that a 1H MR spectrum is clinically interpretable. SNR is calculated from a nonapodized spectrum by using maximum height of largest signal (typically tNAA) divided by standard deviation of noise. Note that these SNR limits are given only for visual assessment of spectra for ratio changes in major metabolites or for presence or absence of metabolites such as Lac. Higher SNR levels are necessary for reliable quantification of metabolites.FWHM = full width at half maximum.

Figure 10:

Comparison of MR spectral quality at multiple sites. 1H MR spectra were acquired at three different sites from cerebellar volume of interest (10 × 25 × 25 mm3, as shown on T1-weighted midsagittal image) in three healthy individuals. Spectra were obtained with 3.0-T MR unit (Tim Trio; Siemens Healthcare, Erlangen, Germany) with same acquisition protocol (fast automatic shimming technique by mapping along projections, or FASTMAP, semi-LASER [localization by adiabatic selective refocusing] [175], 5000/28, 64 repetitions). (Spectrum from Hôpital de la Salpêtrière courtesy of Fanny Mochel, MD, PhD.) MGH = Massachusetts General Hospital.