Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model.

Autor: Knoernschild K; Department of Radiology, University of Iowa, 200 Hawkins Drive cc704 GH, Iowa City, IA, 52242, USA.; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA., Johnson HJ; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Schroeder KE; Department of Radiology, University of Iowa, 200 Hawkins Drive cc704 GH, Iowa City, IA, 52242, USA., Swier VJ; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA., White KA; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA., Sato TS; Department of Radiology, University of Iowa, 200 Hawkins Drive cc704 GH, Iowa City, IA, 52242, USA., Rogers CS; Precigen Exemplar, Coralville, IA, USA., Weimer JM; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA., Sieren JC; Department of Radiology, University of Iowa, 200 Hawkins Drive cc704 GH, Iowa City, IA, 52242, USA. jessica-sieren@uiowa.edu.; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA. jessica-sieren@uiowa.edu.; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. jessica-sieren@uiowa.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Mar 29; Vol. 13 (1), pp. 5146. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1038/s41598-023-32071-z
Abstrakt: Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2 R208X/R208X miniswine and wild type controls were evaluated at 12- and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1- and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (- 9.06 cm 3 ), gray matter (- 4.37% 95 CI - 7.41; - 1.83), caudate (- 0.16%, 95 CI - 0.24; - 0.08) and putamen (- 0.11% 95 CI - 0.23; - 0.02) were all notably smaller in CLN2 R208X/R208X miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (- 8.27%, 95 CI - 10.1; - 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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