{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T05:07:17Z","timestamp":1783832837937,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The neuronal ceroid lipofuscinoses are the most common group of human paediatric genetic neurodegenerative disorders and have also been reported in multiple animal species. This study explores sheep with the CLN6 disease subtype, which occurs in humans either as a late-infantile or as an adult-onset disease. This study characterised morphometric changes that occur in the brains of 15-month-old Merino sheep with CLN6 disease compared to healthy, adult Merino control brains using ultra-high field magnetic resonance imaging (MRI). The formalin-fixed brains of seven affected and three wild-type control sheep were scanned in a 9.4 T Bruker MRI scanner with a T1-weighted gradient echo. Bioimaging technology \u2018Amira-Avizo\u2019 was used to segment each region of interest to create a 3D reconstruction of each ovine brain. Volumetric and statistical analysis of each region of interest found that the thalamus, corpus callosum, occipital cortex, hippocampal region and striatum of affected sheep all experienced a significant loss of volume; 80%, 77%, 73%, 50%, 46% respectively, compared to the control brains. The left side of the affected brain showed a significant reduction of 44%, while the volume of the lateral ventricle non-significantly increased by 43%. However, the cerebellum and arbour vitae of affected sheep lost 15% and 8% of their volume, respectively, which was not significant. These findings are overall consistent with previous gross pathology, histopathology and traditional in vivo MRI findings of ovine CLN6 disease models, but suggest that postmortem ultra-high field MRI of formalin-fixed brains can be a complementary approach to in vivo studies. Volumetric analysis of affected brain regions, including the corpus callosum, thalamus, occipital cortex, striatum, and hippocampal region, can provide valuable biomarkers for assessing the effectiveness of therapeutic interventions in NCL.<\/jats:p>","DOI":"10.3390\/biology15141114","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:46:47Z","timestamp":1783676807000},"page":"1114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Morphometric Brain Changes in a Merino Sheep (Ovis aries) CLN6 Neuronal Ceroid Lipofuscinosis Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Amelia","family":"Nanni","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Elcombe","sequence":"additional","affiliation":[{"name":"Ingham Institute of Applied Medical Research, Liverpool, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maverick Ho Ming","family":"Cheung","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-8202","authenticated-orcid":false,"given":"Timothy","family":"Stait-Gardner","sequence":"additional","affiliation":[{"name":"Nanoscale Organisation and Dynamics Group, School of Science, Western Sydney University, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Sydney School of Veterinary Science, The University of Sydney, Camden, NSW 2570, Australia"},{"name":"Elizabeth Macarthur Agricultural Institute, Department of Primary Industries and Regional Development, Menangle, NSW 2568, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5520-6597","authenticated-orcid":false,"given":"Imke","family":"Tammen","sequence":"additional","affiliation":[{"name":"Sydney School of Veterinary Science, The University of Sydney, Camden, NSW 2570, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne D.","family":"Keller","sequence":"additional","affiliation":[{"name":"Sydney School of Veterinary Science, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Noebels, J.L., Avoli, M., Rogawski, M.A., Vezzani, A., and Delgado-Escueta, A.V. (2024). The Neuronal Ceroid Lipofuscinoses. Jasper\u2019s Basic Mechanisms of the Epilepsies, Oxford University Press. Chapter 50.","DOI":"10.1093\/med\/9780197549469.001.0001"},{"key":"ref_2","unstructured":"OMIM (2025, October 31). Online Mendelian Inheritance in Man. MIM Number: 601780 and 204300. Available online: https:\/\/omim.org\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1177\/0883073813494813","article-title":"Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease)","volume":"28","author":"Adams","year":"2013","journal-title":"J. Child Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.ajhg.2011.04.004","article-title":"Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6","volume":"88","author":"Arsov","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.bbadis.2013.01.009","article-title":"Use of model organisms for the study of neuronal ceroid lipofuscinosis","volume":"1832","author":"Bond","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","unstructured":"Nicholas, F.W., Tammen, I., and Sydney Informatics Hub (2025, October 31). Online Mendelian Inheritance in Animals (OMIA). Available online: https:\/\/omia.org\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.bbadis.2006.09.004","article-title":"A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA","volume":"1762","author":"Tammen","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","unstructured":"Mohd Ismail, I.F. (2014). Identification of a Novel Mutation in the CLN6 Gene (CLN6) in South Hampshire Sheep Affected with Neuronal Ceroid Lipofuscinosis. [Ph.D. Thesis, The University of Sydney]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1093\/emboj\/19.12.2786","article-title":"A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration","volume":"19","author":"Sohar","year":"2000","journal-title":"EMBO J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.nbd.2007.09.006","article-title":"A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571+1G>A) leading to excision of exon 3","volume":"29","author":"Frugier","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Murray, S.J., and Mitchell, N.L. (2022). The translational benefits of sheep as large animal models of human neurological disorders. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.831838"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mitchell, N.L., Murray, S.J., Wellby, M.P., Barrell, G.K., Russell, K.N., Deane, A.R., Wynyard, J.R., Palmer, M.J., Pulickan, A., and Prendergast, P.M. (2023). Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1212228"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e70431","DOI":"10.1002\/brb3.70431","article-title":"Magnetic resonance imaging as a readout of CLN5 gene therapy efficacy in sheep","volume":"15","author":"Murray","year":"2025","journal-title":"Brain Behav."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Banstola, A., and Reynolds, J.N.J. (2022). The sheep as a large animal model for the investigation and treatment of human disorders. Biology, 11.","DOI":"10.3390\/biology11091251"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/jnr.25147","article-title":"Batten disease through different in vivo and in vitro models: A review","volume":"101","author":"Nittari","year":"2023","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"165681","DOI":"10.1016\/j.bbadis.2020.165681","article-title":"Future perspectives: What lies ahead for neuronal ceroid lipofuscinosis research?","volume":"1866","author":"Cooper","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/af\/vfz024","article-title":"The development of brain magnetic resonance approaches in large animal models for preclinical research","volume":"9","author":"Ella","year":"2019","journal-title":"Anim. Front."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1093\/jnen\/nlaa053","article-title":"Longitudinal magnetic resonance spectroscopy and diffusion tensor imaging in sheep (Ovis aries) with quinolinic acid lesions of the striatum: Time-dependent recovery of N-acetylaspartate and fractional anisotropy","volume":"79","author":"Kuchel","year":"2020","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1007\/s00429-019-01885-x","article-title":"The motor cortex of the sheep: Laminar organization, projections and diffusion tensor imaging of the intracranial pyramidal and extrapyramidal tracts","volume":"224","author":"Peruffo","year":"2019","journal-title":"Brain Struct. Funct."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/jnr.24079","article-title":"Large animal models of traumatic brain injury","volume":"96","author":"Vink","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.5625\/lar.2013.29.3.138","article-title":"Morphometrical dimensions of the sheep thoracolumbar vertebrae as seen on digitised CT images","volume":"29","author":"Mageed","year":"2013","journal-title":"Lab. Anim. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1080\/10790268.2016.1222475","article-title":"An ovine model of spinal cord injury","volume":"40","author":"Wilson","year":"2017","journal-title":"J. Spinal Cord Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/j.bbadis.2015.06.013","article-title":"Recent studies of ovine neuronal ceroid lipofuscinoses from BARN, the Batten Animal Research Network","volume":"1852","author":"Palmer","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/dneu.22918","article-title":"Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease)","volume":"83","author":"Mitchell","year":"2023","journal-title":"Dev. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"fcac339","DOI":"10.1093\/braincomms\/fcac339","article-title":"Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis","volume":"5","author":"Murray","year":"2023","journal-title":"Brain Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sawiak, S.J., Perumal, S.R., Rudiger, S.R., Matthews, L., Mitchell, N.L., McLaughlan, C.J., Bawden, C.S., Palmer, D.N., Kuchel, T., and Morton, A.J. (2015). Rapid and progressive regional brain atrophy in CLN6 Batten disease affected sheep measured with longitudinal magnetic resonance imaging. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132331"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.ijpsycho.2021.07.008","article-title":"Development and function of the corpus callosum","volume":"168","author":"Richards","year":"2021","journal-title":"Int. J. Psychophysiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Halassa, M.M. (2022). The Thalamus, Cambridge University Press.","DOI":"10.1017\/9781108674287"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.nbd.2005.01.025","article-title":"Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6)","volume":"20","author":"Oswald","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.tins.2017.12.004","article-title":"The hippocampus: From memory, to map, to memory map","volume":"41","author":"Jeffery","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.tins.2019.06.003","article-title":"Astrocyte\u2013neuron interactions in the striatum: Insights on identity, form, and function","volume":"42","author":"Khakh","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_32","unstructured":"Thermo Fisher Scientific (2018). Amira Software Segmentation User Guide, Konrad-Zuse-Zentrum fur Informationstechnik Berlin (ZIB)."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Goh, K.R.Q., Anthoniel, N.B., Stait-Gardner, T., Kurniawan, N.D., and Keller, M.D. (2026). Description of the koala (Phascolarctos cinereus) brain based on magnetic resonance images. Front Neurol., 17.","DOI":"10.3389\/fneur.2026.1733030"},{"key":"ref_34","unstructured":"Johnson, J., Sudheimer, K., Davis, K., Kerndt, G., and Winn, B. (2023). The Sheep Brain Atlas, Michigan State University Brain Biodiversity Bank."},{"key":"ref_35","unstructured":"Westbrook, C., and Roth, C.K. (2011). Artefacts and their compensation. MRI in Practice, John Wiley & Sons, Incorporated."},{"key":"ref_36","unstructured":"R Core Team (2013). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http:\/\/www.R-project.org\/."},{"key":"ref_37","unstructured":"Cheng, H.M., and Strijkers, G.J. (2023). Quantitative perfusion MRI: Techniques, applications and practical considerations. Quantitative MRI of the Brain, Elsevier."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pnmrs.2018.06.001","article-title":"Pros and cons of ultra-high-field MRI\/MRS for human application","volume":"109","author":"Ladd","year":"2018","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kalluvila, A., Patel, J.B., and Johnson, J.M. (2025). Ultra-high resolution 9.4T brain MRI segmentation via a newly engineered multi-scale residual nested U-Net with gated attention. Bioengineering, 12.","DOI":"10.3390\/bioengineering12101014"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.applanim.2015.11.012","article-title":"Manifestation of neuronal ceroid lipofuscinosis in Australian Merino sheep: Observations on altered behaviour and growth","volume":"175","author":"Cronin","year":"2016","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.pediatrneurol.2013.10.013","article-title":"Hippocampal volumes in juvenile neuronal ceroid lipofuscinosis: A longitudinal magnetic resonance imaging study","volume":"50","author":"Tokola","year":"2014","journal-title":"Pediatr. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s00234-022-02988-9","article-title":"Natural history of MRI brain volumes in patients with neuronal ceroid lipofuscinosis 3: A sensitive imaging biomarker","volume":"64","author":"Hochstein","year":"2022","journal-title":"Neuroradiology"},{"key":"ref_43","first-page":"198042","article-title":"A missense mutation in canine CLN6 in an Australian Shepherd with neuronal ceroid lipofuscinosis","volume":"2011","author":"Katz","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13023-021-02162-z","article-title":"Neuronal ceroid lipofuscinosis type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica\u2019s experience","volume":"17","author":"Weimer","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ymgme.2018.12.001","article-title":"Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients","volume":"126","author":"Chin","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1751-0813.2002.tb10847.x","article-title":"Neuronal ceroid lipofuscinosis in Merino sheep","volume":"80","author":"Cook","year":"2002","journal-title":"Aust. Vet. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41586-022-04554-y","article-title":"Brain charts for the human lifespan","volume":"604","author":"Bethlehem","year":"2022","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Clifford, K.P., Miles, A.E., Prevot, T.D., Misquitta, K.A., Ellegood, J., Lerch, J.P., Sibille, E., Nikolova, Y.S., and Banasr, M. (2023). Brain structure and working memory adaptations associated with maturation and aging in mice. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1195748"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gull, S., Gaser, C., Herrmann, K.H., Urbach, A., Boehme, M., Afzal, S., Reichenbach, J.R., Witte, O.W., and Schmidt, S. (2023). Brain macro-structural alterations in aging rats: A longitudinal lifetime approach. Cells, 12.","DOI":"10.3390\/cells12030432"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e2366232024","DOI":"10.1523\/JNEUROSCI.2366-23.2024","article-title":"Age-related brain atrophy and the positive effects of behavioral enrichment in middle-aged beagles","volume":"44","author":"Noche","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s11357-020-00190-4","article-title":"A short life on the farm: Aging and longevity in agricultural, large-bodied mammals","volume":"42","author":"Hoffman","year":"2020","journal-title":"Geroscience"},{"key":"ref_52","first-page":"qzaf020","article-title":"A developmental gene expression atlas reveals novel biological basis of complex phenotypes in sheep","volume":"23","author":"Zhao","year":"2025","journal-title":"GPB"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lerch, J.P., Gazdzinski, L., Germann, J., Sled, J.G., Henkelman, R.M., and Nieman, B.J. (2019). Wanted dead or alive? The tradeoff between in-vivo versus ex-vivo MR brain imaging in the mouse. Front. Neuroinform., 6.","DOI":"10.3389\/fninf.2012.00006"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bouckaert, C., Christiaen, E., Verhoeven, J., Descamps, B., De Meulenaere, V., Boon, P., Carrette, E., Vonck, K., Vanhove, C., and Raedt, R. (2021). Comparison of in vivo and ex vivo magnetic resonance imaging in a rat model for glioblastoma-associated epilepsy. Diagnostics, 11.","DOI":"10.3390\/diagnostics11081311"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2310\/7290.2009.00004","article-title":"Automated segmentation of in vivo and ex vivo mouse brain magnetic resonance images","volume":"8","author":"Scheenstra","year":"2009","journal-title":"Mol. Imaging"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"26901","DOI":"10.1038\/s41598-024-78246-0","article-title":"Relationship between regional volume changes and water diffusion in fixed marmoset brains: An in vivo and ex vivo comparison","volume":"14","author":"Yoshimaru","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_57","first-page":"5185","article-title":"Comparison of in vivo and ex vivo MRI of the human hippocampal formation in the same subjects","volume":"27","author":"Wisse","year":"2017","journal-title":"Cereb. Cortex"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ma, D., Holmes, H.E., Cardoso, M.J., Modat, M., Harrison, I.F., Powell, N.M., O\u2019Callaghan, J.M., Ismail, O., Johnson, R.A., and O\u2019Neill, M.J. (2019). Study the longitudinal in vivo and cross-sectional ex vivo brain volume difference for disease progression and treatment effect on mouse model of tauopathy using automated MRI structural parcellation. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00011"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Holmes, H.E., Powell, N.M., Ma, D., Ismail, O., Harrison, I.F., Wells, J.A., Colgan, N., O\u2019Callaghan, J.M., Johnson, R.A., and Murray, T.K. (2017). Comparison of in vivo and ex vivo MRI for the detection of structural abnormalities in a mouse model of tauopathy. Front. Neuroinform., 11.","DOI":"10.3389\/fninf.2017.00020"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.neuroimage.2011.08.025","article-title":"Asymmetric bias in user guided segmentations of brain structures","volume":"59","author":"Maltbie","year":"2012","journal-title":"NeuroImage"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1088\/0031-9155\/56\/14\/021","article-title":"Comparison of manual and automatic segmentation methods for brain structures in the presence of space-occupying lesions: A multi-expert study","volume":"56","author":"Deeley","year":"2011","journal-title":"Phys. Med. Biol."},{"key":"ref_62","first-page":"148","article-title":"A comparison of automated segmentation and manual tracing of magnetic resonance imaging to quantify lateral ventricle volumes","volume":"44","author":"Acer","year":"2022","journal-title":"Erciyes Med. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101574","DOI":"10.1016\/j.nicl.2018.10.012","article-title":"Automated and manual hippocampal segmentation techniques: Comparison of results, reproducibility and clinical applicability","volume":"21","author":"Hurtz","year":"2019","journal-title":"NeuroImage Clin."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s40478-019-0799-y","article-title":"Perfusion fixation in brain banking: A systematic review","volume":"7","author":"McFadden","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/0014-4827(57)90148-9","article-title":"Volume changes of tissues in physiological fluids during fixation in osmium tetroxide or formaldehyde and during subsequent treatment","volume":"12","author":"Bahr","year":"1957","journal-title":"Exp. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Del Signore, F., Arribarat, G., Della Salda, L., Mogicato, G., Deviers, A., Cartiaux, B., Vignoli, M., Peran, P., and de Pasquale, F. (2022). Volumetric assessment and longitudinal changes of subcortical structures in formalinized Beagle brains. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0261484"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1684\/epd.2016.0844","article-title":"Neuronal ceroid lipofuscinoses","volume":"18","author":"Nita","year":"2016","journal-title":"Epileptic Disord."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/14\/1114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T04:15:19Z","timestamp":1783829719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/14\/1114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":67,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["biology15141114"],"URL":"https:\/\/doi.org\/10.3390\/biology15141114","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]}}}