{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:49:18Z","timestamp":1774896558625,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The formation of concrements in human pineal gland (PG) is a physiological process and, according to many researchers, is associated with the involution of PG structures. The majority of scientific publications concern progressive calcification of PG, leaving out studies on the destruction of already formed calcified concrements. Our study fills the gap in knowledge about calcified zones destruction in PG in normal aging and neuropathological conditions, which has not been addressed until now.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Our objective is to gain insight into human PG tissue impairment in both normal aging and neurodegenerative conditions. X\u2010ray phase\u2010contrast tomography (XPCT) allowed us to study PG tissue degeneration at high spatial resolution and, for the first time, to examine the damaged PG concrements in detail. Our research finding could potentially enhance the understanding of the PG involvement in the process of aging as well as in Alzheimer's disease (AD) and vascular dementia (VD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The research was carried out on human PG autopsy material in normal aging, VD, and AD conditions. Laboratory\u2010based micro\u2010computed tomography (micro\u2010CT) was used to collect and evaluate samples of native, uncut, and unstained PG with different degrees of pineal calcification. The detailed high\u2010resolution 3D images of the selected PGs were produced using synchrotron\u2010based XPCT. Histology and immunohistochemistry of soft PG tissue confirmed XPCT results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We performed via micro\u2010CT the evaluation of the morphometric parameters of PG such as total sample volume, calcified concrements volume, and percentage of concrements in the total volume of the sample. XPCT imaging revealed high\u2010resolution details of age\u2010related PG alteration. In particular, we noted signs of moderate degradation of concrements in some PGs from elderly donors. In addition, our analysis revealed noticeable degenerative change in both concrements and soft tissue of PGs with neuropathology. In particular, we observed a hollow core and separated layers as well as deep ragged cracks in PG concrements of AD and VD samples. In parenchyma of some samples, we detected wide pinealocyte\u2010free fluid\u2010filled areas adjacent to the calcified zones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present work provides the basis for future scientific research focused on the dynamic nature of PG calcium deposits and PG soft tissue in normal aging and neurodegenerative diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.16080","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T19:38:00Z","timestamp":1667158680000},"page":"1601-1613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Micromorphology of pineal gland calcification in age\u2010related neurodegenerative diseases"],"prefix":"10.1002","volume":"50","author":[{"given":"Inna","family":"Bukreeva","sequence":"first","affiliation":[{"name":"Institute of Nanotechnology \u2013 CNR, Rome unit  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Junemann","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology \u2013 CNR, Rome unit  Rome Italy"},{"name":"Research Institute of Human Morphology  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Cedola","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology \u2013 CNR, Rome unit  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Brun","sequence":"additional","affiliation":[{"name":"Department of Engineering and Architecture University of Trieste  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Longo","sequence":"additional","affiliation":[{"name":"Elettra\u2010Sincrotrone Trieste S.C.p.A.  Basovizza Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana","family":"Tromba","sequence":"additional","affiliation":[{"name":"Elettra\u2010Sincrotrone Trieste S.C.p.A.  Basovizza Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Wilde","sequence":"additional","affiliation":[{"name":"Institute of Materials Physics, Helmholtz\u2010Zentrum Hereon  Geesthacht Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina V.","family":"Chukalina","sequence":"additional","affiliation":[{"name":"Federal Scientific Research Center \u201cCrystallography and Photonics\u201d RAS  Moscow Russian Federation"},{"name":"Smart Engines Service LLC  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri S.","family":"Krivonosov","sequence":"additional","affiliation":[{"name":"Federal Scientific Research Center \u201cCrystallography and Photonics\u201d RAS  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina G.","family":"Dyachkova","sequence":"additional","affiliation":[{"name":"Federal Scientific Research Center \u201cCrystallography and Photonics\u201d RAS  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey V.","family":"Buzmakov","sequence":"additional","affiliation":[{"name":"Federal Scientific Research Center \u201cCrystallography and Photonics\u201d RAS  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis A.","family":"Zolotov","sequence":"additional","affiliation":[{"name":"Federal Scientific Research Center \u201cCrystallography and Photonics\u201d RAS  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Palermo","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology \u2013 CNR, Rome unit  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Gigli","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology \u2013 CNR, c\/o Campus Ecotekne \u2013 Universit\u00e0 del Salento via Monteroni  Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry A.","family":"Otlyga","sequence":"additional","affiliation":[{"name":"Research Institute of Human Morphology  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Saveliev","sequence":"additional","affiliation":[{"name":"Research Institute of Human Morphology  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Fratini","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology \u2013 CNR, Rome unit  Rome Italy"},{"name":"Laboratory of Neurophysics and Neuroimaging (NaN) IRCCS Santa Lucia Foundation  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor E.","family":"Asadchikov","sequence":"additional","affiliation":[{"name":"Federal Scientific Research Center \u201cCrystallography and Photonics\u201d RAS  Moscow Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1985.63.3.0321"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0162\u20100134(93)80006\u2010U"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bem.10053"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00984"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23020301"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(87)90720\u20107"},{"issue":"9","key":"e_1_2_9_8_1","first-page":"121","article-title":"The problems of the central regulation of immune system biorhythms: the role of exogenous and endogenous melatonin","author":"Trufakin VA","year":"2006","journal-title":"Vestn Ross Akad Med Nauk"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2007.09.002"},{"issue":"4","key":"e_1_2_9_10_1","first-page":"276","article-title":"Association of mast cells with calcification in the human pineal gland","volume":"48","author":"Ma\u015bli\u0144ska D","year":"2010","journal-title":"Folia Neuropathol"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711080207"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092110414"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.12.3.305"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/908915"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00327294"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.10.003"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.027"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2002.tb04807.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2006.04.004"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH\u201013.851"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893\u2010133X(99)00069\u2010X"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2008.05.003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207459208994773"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079x.1992.tb00031.x"},{"issue":"2","key":"e_1_2_9_25_1","first-page":"269","article-title":"Calcium concrements in the pineal gland of the Arctic fox (Vulpes lagopus) and their relationship to pinealocytes, glial cells and type I and III collagen fibers","volume":"13","author":"Bulc M","year":"2010","journal-title":"Pol J Vet Sci"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH\u201024.407"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00222155"},{"issue":"5","key":"e_1_2_9_28_1","first-page":"20","article-title":"The morphogenesis and spatial organization of human epiphyseal concretions in Alzheimer's disease, schizophrenia, and alcoholism","volume":"68","author":"Fokin EI","year":"2006","journal-title":"Arkh Patol"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031\u20109155\/58\/1\/R1"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2020.107659"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1134\/S106377451806007XM4"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-30050-4_54-1"},{"key":"e_1_2_9_33_1","doi-asserted-by":"crossref","unstructured":"WildeF OgurreckM GrevingI et\u00a0al.Micro\u2010CT at the imaging beamline P05 at PETRA III.AIP Conference Proceedings.American Institute of Physics Inc.;2016:030035.https:\/\/doi.org\/10.1063\/1.4952858","DOI":"10.1063\/1.4952858"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1364\/OE.418448"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1109\/IEMBS.2011.6091531"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3103\/S1062873819020084"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40679\u2010016\u20100036\u20108"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultramic.2015.05.002"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.033"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1149043"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102818.2002.01010.x"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01262-9"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102818.1997.1340694.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.142.3.7063680"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0079\u20106123(08)63452\u20104"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079X.2004.00196.x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1017\/S104161029000028X"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079X.2004.00196.x"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294615"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.122.3.503"},{"issue":"4","key":"e_1_2_9_52_1","first-page":"310","article-title":"Pineal calcification","volume":"27","author":"Bhatti IH","year":"1977","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101819.1948.tb02770.x"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1159\/000122036"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1259\/0007\u20101285\u201049\u2010583\u2010594"},{"issue":"8","key":"e_1_2_9_56_1","first-page":"765","article-title":"Pineal calcification among black patients","volume":"75","author":"Fan KJ","year":"1983","journal-title":"J Natl Med Assoc"},{"key":"e_1_2_9_57_1","first-page":"13","article-title":"Human Epiphyseal concrements in schizophrenia","volume":"4","author":"Saveliev SV","year":"2004","journal-title":"Arkh Patol"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH\u201013.851"},{"key":"e_1_2_9_59_1","first-page":"41","article-title":"Pineal calcification: structural and functional aspects","volume":"3","author":"Welsh MG","year":"1985","journal-title":"Pineal Res Rev"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079x.1985.tb00625.x"},{"key":"e_1_2_9_61_1","first-page":"415","article-title":"Pineal calcification: its mechanism and significance","volume":"21","author":"Krsti\u0107 R","year":"1986","journal-title":"J Neural Transm Suppl"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070210306"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sab.2007.02.015"}],"container-title":["Medical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.16080","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mp.16080","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.16080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:38:24Z","timestamp":1692664704000},"score":1,"resource":{"primary":{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/10.1002\/mp.16080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,26]]},"references-count":62,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/mp.16080"],"URL":"https:\/\/doi.org\/10.1002\/mp.16080","archive":["Portico"],"relation":{},"ISSN":["0094-2405","2473-4209"],"issn-type":[{"value":"0094-2405","type":"print"},{"value":"2473-4209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,26]]},"assertion":[{"value":"2021-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}