Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI.

OBJECTIVE: To determine 1) the reproducibility of metabolite measurements by (1)H MRS in the motor cortex; 2) the extent to which (1)H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. METHODS: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice (1)H MRSI. (1)H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. RESULTS: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. CONCLUSION: Metabolite changes measured by (1)H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.

Reanalysis of multislice (1)H MRSI in amyotrophic lateral sclerosis.

The goal of this work was to reexamine previously published (1) brain spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis (ALS). Toward this goal, (1)H MR spectroscopic imaging data from 10 ALS and nine control subjects were reanalyzed using improved data analysis techniques, including automated curve fitting and tissue-volume correction. In the motor cortex of ALS, N-acetyl aspartate (NAA) was 23% (P = 0.004) lower than in controls, and in the posterior internal capsule of ALS choline compounds (Cho) were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in the posterior internal capsule (not expected). Magn Reson Med 45:513-516, 2001.

Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS.

The primary objectives of this study were to test whether 1) N-acetylaspartate (NAA), a neuronal marker, is reduced in motor cortex and corticospinal-tract (CST) brain regions of ALS patients; and 2) motor cortex NAA correlates to a clinical measurement of upper motor neuron function in ALS patients. Ten probable or definite ALS patients and nine neurologically normal control subjects were studied. Three axial planes of two-dimensional 1H MRSI data were collected, using a single spin-echo multislice sequence (TE140/TR2000). Two of the 1H MRSI planes were positioned superior to the lateral ventricles, and one plane was positioned at the level of the internal capsule. Spectroscopy voxels were selected from motor cortex, frontal cortex, parietal cortex, medial gray matter, centrum semiovale white matter, anterior internal capsule, and posterior internal capsule. Peak integrals were obtained for the three major 1H MRSI singlet resonances, NAA, creatine and phosphocreatine (Cr), and cholines (Cho). Maximum finger-tap rate was used as a clinical measurement of upper motor neuron function. In ALS, brain NAA/(Cho+Cr) was reduced 19% (p=0.024) in the motor cortex and 16% (p=0.021) in the CST (centrum semiovale and posterior internal capsule) regions. NAA/ (Cho+Cr) was not reduced in frontal cortex, parietal cortex, medial gray matter, or anterior internal capsule. There was a significant relation between ALS motor cortex NAA/(Cho+Cr) and maximum finger-tap rate (r=0.80; p=0.014). NAA/(Cho+Cr) was reduced in motor cortex and CST regions and unchanged in other brain regions of ALS patients when compared with controls. These findings are consistent with the known distribution of neuronal loss in ALS. The positive correlation between motor cortex NAA/(Cho+Cr) and maximum finger-tap rate suggests that reduced NAA/(Cho+Cr) is a surrogate marker of motor cortex neuron loss in ALS. These findings support the study of 1H MRSI NAA measurement as an objective and quantitative measurement of upper motor neuron dysfunction in ALS.

Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging.

The goals of the current study were threefold: first, to confirm previous single volume proton (1H) magnetic resonance spectroscopy results of reduced N-acetyl aspartate (NAA, a putative marker of neurons) in multiple sclerosis (MS) white matter lesions using multiple volume 1H magnetic resonance spectroscopic imaging (MRSI); second, to measure the phospholipid metabolites phosphomonoesters and phosphodiesters in such lesions using phosphorus (31P) MRSI; and third, to test the hypothesis that biochemical changes occur in the normal-appearing (on spin echo T2-weighted magnetic resonance images) white matter in patients with MS. Thirteen subjects with clinically definite MS were studied with both 1H and 31P MRSI, and 19 controls were studied with either 1H MRSI, 31P MRSI, or both. MS lesion, MS normal-appearing white matter, and region-matched control spectra from the centrum semiovale were analyzed. The major findings of this study were that in both white matter lesions and normal-appearing white matter in patients with MS, the metabolite ratio NAA/creatine and the total 31P peak integrals were significantly reduced compared with controls. In addition, in MS lesions NAA/choline and phosphodiesters/total 31P were significantly reduced compared with controls, and in MS normal-appearing white matter there was a trend for NAA/choline to be reduced compared with controls. In normal-appearing white matter in patients with MS, total creatine and phosphocreatine were significantly increased compared to controls, as detected with both 1H (total creatine peak integrals) and 31P (phosphocreatine/total 31P) MRSI techniques. These results suggest reduced neuronal density and altered phospholipid metabolites in white matter lesions in patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced phase encoding in spectroscopic imaging.

The effect of different spatial-encoding (k-space) sampling distributions are evaluated for magnetic resonance spectroscopic imaging (MRSI) using Fourier reconstruction. Previously, most MRSI studies have used square or cubic k-space functions, symmetrically distributed. These studies examine the conventional k-space distribution with spherical distribution, and 1/2 k-space acquisition, using computer simulation studies of the MRSI acquisition for three spatial dimensions and experimental results. Results compare the spatial response function, Gibbs ringing effects, and signal contamination for different spatial-encoding distribution functions. Results indicate that spherical encoding, in comparison with cubic encoding, results in a modest improvement of the response function with approximately equivalent spatial resolution for the same acquisition time. For spin-echo acquired data, reduced acquisition times can readily be obtained using 1/2 k-space methods, with a concomitant reduction in signal to noise ratio.

Quantitation of in vivo phosphorus metabolites in human brain with magnetic resonance spectroscopic imaging (MRSI).

A method for quantitation of in vivo 31P metabolite concentrations in human brain with 31P magnetic resonance spectroscopic imaging (MRSI) is described. The method relies on comparison of brain and calibration phantom measurements, with corrections for coil loading and metabolite magnetic relaxation. Estimated metabolite concentrations for the centrum semiovale in 11 normal adults (mean +/- SD) were: phosphomonoesters = 3.0 +/- 0.7 mM, inorganic phosphate = 0.7 +/- 0.2 mM, phosphodiesters = 10.9 +/- 1.8 mM, phosphocreatine = 2.7 +/- 0.5 mM, and adenosine triphosphate = 2.9 +/- 0.3 mM. These values are similar to previous results obtained from single-volume localized spectroscopy.

Lateralization of human focal epilepsy by 31P magnetic resonance spectroscopic imaging.

We attempted to lateralize the epileptogenic focus (seven temporal lobe hippocampal foci, one frontal lobe focus) in medically refractory unilateral complex partial seizures, using noninvasive 31P magnetic resonance spectroscopic imaging (MRSI) blindly and interictally to compare hippocampal or frontal regions. The seizure foci were more alkaline (intracellular pH = 7.17 +/- 0.03) compared with the contralateral region (7.06 +/- 0.02, p < 0.01) in all eight cases; the inorganic phosphate was relatively increased (240 +/- 50% of contralateral, seven of eight cases, p < 0.01); and phosphomonoesters were relatively reduced (68 +/- 9% of contralateral, seven of eight cases, p < 0.01). Other phosphorus metabolites were symmetric (+/- 10%). 31P MRSI correctly lateralized the seizure focus in all eight cases. By comparison, imaging correctly lateralized four cases and SPECT, two cases. In conclusion, 31P MRSI is a useful tool for the noninvasive clinical assessment of focal epilepsy and can accurately lateralize the epileptogenic focus.

Elevated lactate and alkalosis in chronic human brain infarction observed by 1H and 31P MR spectroscopic imaging.

The goal of this study was to investigate lactate and pH distributions in subacutely and chronically infarcted human brains. Magnetic resonance spectroscopic imaging (MRSI) was used to map spatial distributions of 1H and 31P metabolites in 11 nonhemorrhagic subacute to chronic cerebral infarction patients and 11 controls. All six infarcts containing lactate were alkalotic (pHi = 7.20 +/- 0.04 vs. 7.05 +/- 0.01 contralateral, p less than 0.01). This finding of elevated lactate and alkalosis in chronic infarctions does not support the presence of chronic ischemia; however, it is consistent with the presence of phagocytic cells, gliosis, altered buffering mechanisms, and/or luxury perfusion. Total 1H and 31P metabolites were markedly reduced (about 50% on average) in subacute and chronic brain infarctions (p less than 0.01), and N-acetyl aspartate (NAA) was reduced more (approximately 75%) than other metabolites (p less than 0.01). Because NAA is localized in neurons, selective NAA reduction is consistent with pathological findings of a greater loss of neurons than glial cells in chronic infarctions.

Spin echo 31P spectroscopic imaging in the human brain.

Spectroscopic imaging of phosphorus metabolites in the human brain has been carried out with two data acquisition methods: by observation of the free induction decay (FID) signal and by a short spin echo sequence. The resultant spectral images and spatially resolved spectra are compared. Spin echo observation is found to provide spectra of superior quality, and by suitably selecting the sequence timing, no significant increase in T2 losses, as compared with the FID method, is encountered. 31P images with approximately 3.5 cm spatial resolution are obtained within times of 37 min at 2.0 T field strength.

In vivo MR spectroscopic imaging with P-31. Work in progress.

Magnetic resonance imaging techniques were applied to in vivo spectroscopic analysis of spatially resolved phosphorus spectra in the cat brain to determine whether changes associated with stroke could be detected. Two-dimensional images of separate phosphorus-containing compounds, as well as spectra arising from spatially localized points, demonstrated that metabolism within tissue could be monitored in this manner. Preliminary results of phosphorus imaging of the human body in vivo are reported.