Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy - PubMed (original) (raw)
Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy
L L Cheng et al. Proc Natl Acad Sci U S A. 1997.
Abstract
We describe a method that directly relates tissue neuropathological analysis to medical imaging. Presently, only indirect and often tenuous relationships are made between imaging (such as MRI or x-ray computed tomography) and neuropathology. We present a biochemistry-based, quantitative neuropathological method that can help to precisely quantify information provided by in vivo proton magnetic resonance spectroscopy (1HMRS), an emerging medical imaging technique. This method, high resolution magic angle spinning (HRMAS) 1HMRS, is rapid and requires only small amounts of unprocessed samples. Unlike chemical extraction or other forms of tissue processing, this method analyzes tissue directly, thus minimizing artifacts. We demonstrate the utility of this method by assessing neuronal damage using multiple tissue samples from differently affected brain regions in a case of Pick disease, a human neurodegenerative disorder. Among different regions, we found an excellent correlation between neuronal loss shown by traditional neurohistopathology and decrease of the neuronal marker N-acetylaspartate measured by HRMAS 1HMRS. This result demonstrates for the first time, to our knowledge, a direct, quantitative link between a decrease in N-acetylaspartate and neuronal loss in a human neurodegenerative disease. As a quantitative method, HRMAS 1HMRS has potential applications in experimental and clinical neuropathologic investigations. It should also provide a rational basis for the interpretation of in vivo 1HMRS studies of human neurological disorders.
Figures
Figure 1
Proton MR spectra (400 MHz) of monkey brain tissue at 20°C. Spectrum a, static; spectrum b, HRMAS at 2.5 kHz.
Figure 2
Proton MR spectra (400 MHz) of human brain tissue collected from superior temporal gyrus histologically determined to be mildly affected with Pick disease. Spectrum a, intact tissue T2-weighted HRMAS at 2.5 kHz, at 2°C; spectrum b, tissue extraction solution at 20°C. Selected metabolite resonances were labeled on spectrum a (Lac:, lactate; GABA: γ-aminobutyric acid; Acet, acetate; Cre, creatine; Chol, choline; PCh, phosphorylcholine; Tau, taurine; Inos, inositol; alcohol conta: alcohol contamination). The resonances at 1.18 ppm (triplet) and 3.65 ppm (quartet) were only seen in the tissue spectrum, and were due to contamination with small amount of alcohol sprayed on the surface of the postmortem brain before tissue freezing (9).
Figure 3
(a) Photomicrograph taken from superficial occipital visual cortex, showing normal population of neurons and unremarkable neuropil. (×100.) (b) Photomicrograph taken from superficial cortex (layers 1 and 2) of the rostral inferior temporal gyrus, showing marked neuronal loss and severe astrogliosis. (×100.)
Figure 4
Comparison of HRMAS 1HMR spectra of brain tissue from primary visual cortex region, relatively unaffected by Pick disease (spectrum a), and the severely affected rostral inferior temporal gyrus region (spectrum b) at 2°C. Spectra were scaled according to the concentration of creatine (3.03 ppm, 8.48 μmol/g for spectrum a and 4.96 μmol/g for spectrum b) for better visualization.
Figure 5
The correlation between the population of surviving cortical neurons and the [NAA + Acet] (•) and [NAA] (○) concentrations measured in different Pick brain regions. The concentrations are corrected according to their measured T2 values. See text for details.
Figure 6
Degradation of normal human brain tissue at 20°C measured at 2.5 kHz spinning. The concentrations of NAA (○) and Acet (•) are normalized by the total spectral intensity in the region of 0.5–4.5 ppm.
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