{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:37:03Z","timestamp":1791265023890,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,6,10]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>in vivo<\/jats:italic>\n                    proton magnetic resonance spectroscopy (\n                    <jats:sup>1<\/jats:sup>\n                    HMRS), an emerging medical imaging technique. This method, high resolution magic angle spinning (HRMAS)\n                    <jats:sup>1<\/jats:sup>\n                    HMRS, 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                    <jats:italic>N<\/jats:italic>\n                    -acetylaspartate measured by HRMAS\n                    <jats:sup>1<\/jats:sup>\n                    HMRS. This result demonstrates for the first time, to our knowledge, a direct, quantitative link between a decrease in\n                    <jats:italic>N<\/jats:italic>\n                    -acetylaspartate and neuronal loss in a human neurodegenerative disease. As a quantitative method, HRMAS\n                    <jats:sup>1<\/jats:sup>\n                    HMRS has potential applications in experimental and clinical neuropathologic investigations. It should also provide a rational basis for the interpretation of\n                    <jats:italic>in vivo<\/jats:italic>\n                    <jats:sup>1<\/jats:sup>\n                    HMRS studies of human neurological disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.12.6408","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"6408-6413","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":295,"title":["Quantitative neuropathology by high resolution magic angle spinning proton magnetic\u2009resonance\u2009spectroscopy"],"prefix":"10.1073","volume":"94","author":[{"given":"L. L.","family":"Cheng","sequence":"first","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Ma","sequence":"additional","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Becerra","sequence":"additional","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Ptak","sequence":"additional","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Tracey","sequence":"additional","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lackner","sequence":"additional","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. G.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"NMR Center, Division of Neuroradiology, Department of Radiology, and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and Department of Comparative Pathology, New England Regional Primate Research Center and Harvard Medical School, One  Pine Hill Road, Southborough, MA 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,6,10]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"31","volume":"9","author":"Howe F A","year":"1993","unstructured":"F A Howe, R J Maxwell, D E Saunders, M M Brown, J R Griffiths Magn Reson Q 9, 31\u201359 (1993).","journal-title":"Magn Reson Q"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02033352"},{"key":"e_1_3_3_3_2","first-page":"1853","volume":"15","author":"Coetey A","year":"1994","unstructured":"A Coetey, J G Jarvik, R E Lenkinski, R I Grossman, I Frank, M Delivoria-Papadopoulos Am J Neuroradiol 15, 1853\u20131859 (1994).","journal-title":"Am J Neuroradiol"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.167.3.299"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(95)00062-K"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.195.1.7892497"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0396-323"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1988.tb04850.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00300-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1940070308"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910360502"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/1821659a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.2.285"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.437915"},{"key":"e_1_3_3_15_2","first-page":"361","volume":"44","author":"VanderHart D L","year":"1981","unstructured":"D L VanderHart, W L Earl, A N Garroway J Magn Reson 44, 361 (1981).","journal-title":"J Magn Reson"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00472a048"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00212a010"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf00085a016"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmrb.1995.1031"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(95)80062-7"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.163.1.100"},{"key":"e_1_3_3_22_2","first-page":"167","volume-title":"Alzheimer\u2019s Disease","author":"Hansen L A","year":"1994","unstructured":"L A Hansen Alzheimer\u2019s Disease, eds R D Terry, R Katzman, K L Bick (Raven, New York), pp. 167\u2013177 (1994)."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199501000-00006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)65789-8"},{"key":"e_1_3_3_25_2","first-page":"551","volume":"14","author":"Nadler J","year":"1972","unstructured":"J Nadler, J Cooper J Neurochem 14, 551\u2013554 (1972).","journal-title":"J Neurochem"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199103000-00005"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90101-S"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93383-K"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.7.1349"},{"key":"e_1_3_3_30_2","volume-title":"Mitochondria and Free Radicals in Neurodegenerative Diseases","author":"Jenkins B G","year":"1997","unstructured":"B G Jenkins, I Y Chen, B R Rosen Mitochondria and Free Radicals in Neurodegenerative Diseases, eds M F Beal, N Howell, I Bodis-Wolnet (Wiley\u2013Liss, New York, , in press. 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