Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria
Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder causing developmental delay, intellectual disability, and eventual death. A distinct feature in AGU is iron accumulation within the thalamus. Our aim is to demonstrate that susceptibility-weighted images (SWI) could be used as an MRI...
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doaj-c31a32f22ad44189bb5a6efc7a8478492020-11-25T02:49:32ZengMDPI AGBrain Sciences2076-34252020-09-011067767710.3390/brainsci10100677Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with AspartylglucosaminuriaViljami Sairanen0Anna Tokola1Ritva Tikkanen2Minna Laine3Taina Autti4HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, FinlandHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, FinlandInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, GermanyHelsinki University Central Hospital, Child Neurology, 00029 Helsinki, FinlandHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, FinlandAspartylglucosaminuria (AGU) is a rare lysosomal storage disorder causing developmental delay, intellectual disability, and eventual death. A distinct feature in AGU is iron accumulation within the thalamus. Our aim is to demonstrate that susceptibility-weighted images (SWI) could be used as an MRI biomarker to evaluate the response within the AGU population to newly evolving treatments. SWI from 16 patients with AGU and 16 age-matched controls were used in the analysis. Thalamic volume with an iron accumulation was identified using a permutation test. Group differences were investigated for both the complete thalamus and the iron accumulation regions. Group-wise age correlation within these volumes were assessed with analysis of variance and multivariate regression. We found a statistically significant and large difference (<i>p</i>-value = 0.01, Cohen’s D = 0.97) for the whole thalamus comparison and an even greater difference in the iron accumulation regions (<i>p</i>-value < 0.01, Cohen’s D = 3.52). Furthermore, we found strong evidence for iron accumulation as a linear function of age with R<sup>2</sup> = 0.65 only for AGU. The statistical analysis of SWI provides tools for assessing the degree of iron accumulation. This method could be used to study the response to treatments, in that a successful treatment would be expected to result in a decline in iron accumulation.https://www.mdpi.com/2076-3425/10/10/677aspartylglucosaminuriaaspartylglucosaminidasemagnetic resonance imagingsusceptibility-weighted imagingmedical image analysisgene therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Viljami Sairanen Anna Tokola Ritva Tikkanen Minna Laine Taina Autti |
spellingShingle |
Viljami Sairanen Anna Tokola Ritva Tikkanen Minna Laine Taina Autti Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria Brain Sciences aspartylglucosaminuria aspartylglucosaminidase magnetic resonance imaging susceptibility-weighted imaging medical image analysis gene therapy |
author_facet |
Viljami Sairanen Anna Tokola Ritva Tikkanen Minna Laine Taina Autti |
author_sort |
Viljami Sairanen |
title |
Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria |
title_short |
Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria |
title_full |
Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria |
title_fullStr |
Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria |
title_full_unstemmed |
Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria |
title_sort |
statistical permutation test reveals progressive and region-specific iron accumulation in the thalami of children with aspartylglucosaminuria |
publisher |
MDPI AG |
series |
Brain Sciences |
issn |
2076-3425 |
publishDate |
2020-09-01 |
description |
Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder causing developmental delay, intellectual disability, and eventual death. A distinct feature in AGU is iron accumulation within the thalamus. Our aim is to demonstrate that susceptibility-weighted images (SWI) could be used as an MRI biomarker to evaluate the response within the AGU population to newly evolving treatments. SWI from 16 patients with AGU and 16 age-matched controls were used in the analysis. Thalamic volume with an iron accumulation was identified using a permutation test. Group differences were investigated for both the complete thalamus and the iron accumulation regions. Group-wise age correlation within these volumes were assessed with analysis of variance and multivariate regression. We found a statistically significant and large difference (<i>p</i>-value = 0.01, Cohen’s D = 0.97) for the whole thalamus comparison and an even greater difference in the iron accumulation regions (<i>p</i>-value < 0.01, Cohen’s D = 3.52). Furthermore, we found strong evidence for iron accumulation as a linear function of age with R<sup>2</sup> = 0.65 only for AGU. The statistical analysis of SWI provides tools for assessing the degree of iron accumulation. This method could be used to study the response to treatments, in that a successful treatment would be expected to result in a decline in iron accumulation. |
topic |
aspartylglucosaminuria aspartylglucosaminidase magnetic resonance imaging susceptibility-weighted imaging medical image analysis gene therapy |
url |
https://www.mdpi.com/2076-3425/10/10/677 |
work_keys_str_mv |
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