{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:31:38Z","timestamp":1760711498223,"version":"3.44.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Office of the Principal Scientific Adviser, Government of India"},{"name":"The Pratiksha Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Holoprosencephaly (HPE) is a well-described forebrain patterning disorder in mid-late gestation fetuses and infants. Here, we used a novel, whole-brain multimodal approach (ultrasonography, magnetic resonance imaging, and histology with 3-dimensional [3D] reconstructions with cell mapping) in earlier-gestation specimens than previously reported. In one 13- and two 22-gestational week fetuses and age-matched controls, we elucidated heretofore underappreciated HPE findings of (1) abnormal clustering of immature (doublecortin-immunoreactive) cells in the midline and paramedian forebrain, (2) linear arrays of cells in the intermediate zone of the cerebral mantle (reminiscent of subcortical band heterotopia, but possibly transient), (3) \u201creactive\u201d-appearing glial fibrillary acidic protein-immunoreactive cortical cells, and (4) apparent \u201cmidline fusion\u201d of rostral ganglionic eminences. We observed disorganization of orbitofrontal cortices and midline structures, rostral subarachnoid (marginal zone) heterotopia, and lateral displacement of the hippocampal formations utilizing multiscale multimodal 3D analytics. These findings shed light on the temporal evolution of HPE at earlier gestational ages. Moreover, this approach is scalable to include the wide range of phenotypes of HPE and is applicable to other neurologic disorders, including developmental as well as adult vascular, infectious, neoplastic, and degenerative conditions for which spatial analyses permit a fuller understanding of their pathologic spectrum.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf057","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T11:39:21Z","timestamp":1748086761000},"page":"807-818","source":"Crossref","is-referenced-by-count":1,"title":["Insights into holoprosencephaly using multimodal high-resolution imaging and 3D histology"],"prefix":"10.1093","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8925-723X","authenticated-orcid":false,"given":"Jaikishan","family":"Jayakumar","sequence":"first","affiliation":[{"name":"Sudha Gopalakrishnan Brain Centre, Indian Institute of Technology Madras , Chennai, Tamil Nadu,","place":["India"]},{"name":"Center for Computational Brain Research, Indian Institute of Technology Madras , Chennai, Tamil Nadu,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jivitha Jyothi","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Sudha Gopalakrishnan Brain Centre, Indian Institute of Technology Madras , Chennai, Tamil Nadu,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca D","family":"Folkerth","sequence":"additional","affiliation":[{"name":"Brain Injury Research Center, Department of Rehabilitation and Human Potential, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Latha","sequence":"additional","affiliation":[{"name":"MediScan Systems , Chennai, Tamil Nadu,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harish","family":"Kumar","sequence":"additional","affiliation":[{"name":"MediScan Systems , Chennai, Tamil Nadu,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Suresh","sequence":"additional","affiliation":[{"name":"MediScan Systems , Chennai, Tamil Nadu,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chitra","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saveetha Medical College , Chennai, Tamil Nadu,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayaraman","family":"Kumutha","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Saveetha Medical College , Chennai, Tamil 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