Spectroscopic Assessment of Alterations in Macromolecule and Small-Molecule Metabolites in Human Brain After Stroke

Background and Purpose— We sought to measure the temporal evolution and spatial distribution of lesion macromolecules and small molecules (lactate, N-acetyl compounds, creatine, and choline) in stroke patients by using short echo time in vivo proton MR spectroscopy. Methods— Single-voxel spectra with TE=22 ms were obtained with and without inversion recovery suppression of small-molecule resonances from 30 examinations of 24 patients 3 to 214 days after stroke. Subtraction of the suppressed from the unsuppressed spectra yielded metabolite spectra without overlap from macromolecules. Two-dimensional spectroscopic images were acquired with macromolecule and small-molecule suppression from 5 additional patients. Results— Macromolecule signals were elevated in lesions relative to normal brain and tended to increase in the subacute period, even as lactate peaks declined. Regions of increased lactate, increased macromolecule signal at 1.3 ppm, and decreased N-acetyl compounds were closely correlated in the 2D spectroscopic images. Conclusions— Short echo time spectra can be acquired in vivo in a manner that improves signal-to-noise ratio over long echo experiments and resolves overlapping macromolecule and small-molecule signals. The prominent macromolecule signals seen in the subacute period in association with persistently elevated lactate may represent mobile lipids in macrophages or other cells.

[1]  J. Garcìa,et al.  CEREBRAL INFARCTION: EVOLUTION OF HISTOPATHOLOGICAL CHANGES AFTER OCCLUSION OF A MIDDLE CEREBRAL ARTERY IN PRIMATES , 1974 .

[2]  J. Garcìa The neuropathology of stroke. , 1975, Human pathology.

[3]  S. Gordon,et al.  Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. , 1987, The Biochemical journal.

[4]  P. V. van Rijen,et al.  Cerebral lactate detected by regional proton magnetic resonance spectroscopy in a patient with cerebral infarction. , 1988, Stroke.

[5]  C. Mountford,et al.  Comparison of human polymorphonuclear leukocytes from peripheral blood and purulent exudates by high resolution 1H MRS , 1991, Magnetic resonance in medicine.

[6]  A. Howseman,et al.  Localized proton NMR observation of [3‐13C] lactate in stroke after [1‐13C] glucose infusion , 1991, Magnetic resonance in medicine.

[7]  R G Shulman,et al.  Proton Magnetic Resonance Spectroscopy of Cerebral Lactate and Other Metabolites in Stroke Patients , 1992, Stroke.

[8]  A. Blamire,et al.  Spectroscopic imaging of stroke in humans , 1992, Neurology.

[9]  George Fein,et al.  Proton magnetic resonance spectroscopy of human brain: Applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities , 1992, Magnetic resonance in medicine.

[10]  M. Weiner,et al.  Elevated Lactate and Alkalosis in Chronic Human Brain Infarction Observed by 1H and 31P MR Spectroscopic Imaging , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  K. Brindle,et al.  The appearance of neutral lipid signals in the 1H NMR spectra of a myeloma cell line correlates with the induced formation of cytoplasmic lipid droplets , 1993, Magnetic resonance in medicine.

[12]  A. Blamire,et al.  Early Temporal Variation of Cerebral Metabolites After Human Stroke: A Proton Magnetic Resonance Spectroscopy Study , 1993, Stroke.

[13]  T. Olsen,et al.  Long‐term Follow‐up of Cerebral Infarction Patients With Proton Magnetic Resonance Spectroscopy , 1994, Stroke.

[14]  A. Blamire,et al.  Clinical correlates of proton magnetic resonance spectroscopy findings after acute cerebral infarction. , 1995, Stroke.

[15]  R. Lenkinski,et al.  Lactate production by human monocytes/macrophages determined by proton mr spectroscopy , 1995, Magnetic resonance in medicine.

[16]  K. Behar,et al.  Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain , 1996, Magnetic resonance in medicine.

[17]  D. Saunders,et al.  Discrimination of Metabolite from Lipid and Macromolecule Resonances in Cerebral Infarction in Humans Using Short Echo Proton Spectroscopy , 1997, Journal of magnetic resonance imaging : JMRI.

[18]  A Moreno,et al.  Evidence that mobile lipids detected in rat brain glioma by 1H nuclear magnetic resonance correspond to lipid droplets. , 1997, Cancer research.

[19]  Gottfried Schlaug,et al.  Ischemic lesion volumes in acute stroke by diffusion‐weighted magnetic resonance imaging correlate with clinical outcome , 1997, Annals of neurology.

[20]  C. Gasparovic,et al.  Ca2+‐ and Mg2+‐Modulated Lipolysis in Neonatal Rat Brain Slices Observed by One‐ and Two‐Dimensional NMR , 1998, Journal of neurochemistry.

[21]  S. Warach,et al.  Magnetic Resonance Imaging of Acute Stroke , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  C. Gasparovic,et al.  Mobile lipids in rat brain slices observed by gradient‐enhanced NMR , 1999, Magnetic resonance in medicine.

[23]  P. Barber,et al.  Combined 1H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome , 2000, Neurology.

[24]  A. Pastuszyn,et al.  Magnetic resonance lipid signals in rat brain after experimental stroke correlate with neutral lipid accumulation , 2001, Neuroscience Letters.