Spectroscopic imaging of stroke in humans: Histopathology correlates of spectral changes

Previous studies of human stroke by ¹H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by ¹H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. ¹H spectra from voxels including the infarcts showed increased lactate and decreased N-acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm² near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm². Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages—which begin to appear 3 days after infarction and gradually disappear over several months—could be a major source of elevated lactate signals that persist for months after stroke.