{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:00:06Z","timestamp":1772802006147,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T00:00:00Z","timestamp":1534982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003524","name":"Ministry of Business, Innovation and Employment","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008414","name":"University of Canterbury","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of fatal neurodegenerative lysosomal storage diseases of children caused by various mutations in a range of genes. Forms associated with mutations in two of these, <jats:italic>CLN5 <\/jats:italic>and <jats:italic>CLN6, <\/jats:italic>are being investigated in well\u2010established sheep models. Brain atrophy leading to psychomotor degeneration is among the defining features, as is regional progressive ossification of the inner cranium. Ongoing viral\u2010mediated gene therapy trials in these sheep are yielding encouraging results. In vivo assessment of brain atrophy is integral to the longitudinal monitoring of individual animals and provides robust data for translation to treatments for humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Computed tomography (CT)\u2010based three\u2010dimensional reconstruction of the intracranial volume (ICV) over time reflects the progression of cortical brain atrophy, verifying the use of ICV measurements as a surrogate measure for brain size in ovine NCL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ICVs of NCL\u2010affected sheep increase for the first few months, but then decline progressively between 5 and 13\u00a0months in <jats:italic>CLN5<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> sheep and 11\u201315\u00a0months in <jats:italic>CLN6<jats:sup>\u2212\/\u2212<\/jats:sup> <\/jats:italic>sheep. Cerebral ventricular volumes are also increased in affected animals. To facilitate ICV measures, the radiodensities of ovine brain tissue and cerebrospinal fluid were identified. Ovine brain tissue exhibited a Hounsfield unit (HU) range of (24; 56) and cerebrospinal fluid a HU range of (\u221212; 23).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Computed tomography scanning and reconstruction verify that brain atrophy ovine CLN5 NCL originates in the occipital lobes with subsequent propagation throughout the whole cortex and these regional differences are reflected in the ICV loss.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1096","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T10:04:33Z","timestamp":1535018673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Computed tomography provides enhanced techniques for longitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses"],"prefix":"10.1002","volume":"8","author":[{"given":"Katharina N.","family":"Russell","sequence":"first","affiliation":[{"name":"Faculty of Agriculture and Life Sciences Lincoln University Lincoln New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Sciences Lincoln University Lincoln New Zealand"},{"name":"Department of Radiology University of Otago Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel G.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Otago Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig R.","family":"Bunt","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Sciences Lincoln University Lincoln New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin P.","family":"Wellby","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Sciences Lincoln University Lincoln New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy R.","family":"Melzer","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"},{"name":"New Zealand Brain Research Institute Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham K.","family":"Barrell","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Sciences Lincoln University Lincoln New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9703-5351","authenticated-orcid":false,"given":"David N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Sciences Lincoln University Lincoln New Zealand"},{"name":"Department of Radiology University of Otago Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004728-197710000-00009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(83)90006-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.2002.tb10847.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.216.3.r00au37672"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(94)90130-9"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4669"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00522811"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.2.272"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24079"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2015.09.001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2012.05.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.09.006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00395247"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.06.010"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6997993"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.08.008"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00079"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00480169.2002.36311"},{"key":"e_1_2_7_20_1","first-page":"218","volume-title":"Ceroid\u2010Lipofuscinosis (Batten\u2019s Disease)","author":"Jolly R. 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