Towards a representative reference for MRI-based human axon radius assessment using light microscopy

•A pipeline for automated estimation of ensemble mean axon radii at MRI voxel scale•Incorporation of 4 human white matter brain tissue samples for training and testing•Accurate mapping of the MRI-visible radius in the presence of staining heterogeneity•Includes 2 to 4 orders of magnitude more axons...

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Veröffentlicht in:NeuroImage (Orlando, Fla.) Jg. 249; S. 118906
Hauptverfasser: Mordhorst, Laurin, Morozova, Maria, Papazoglou, Sebastian, Fricke, Björn, Oeschger, Jan Malte, Tabarin, Thibault, Rusch, Henriette, Jäger, Carsten, Geyer, Stefan, Weiskopf, Nikolaus, Morawski, Markus, Mohammadi, Siawoosh
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Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.04.2022
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ISSN:1053-8119, 1095-9572, 1095-9572
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Abstract •A pipeline for automated estimation of ensemble mean axon radii at MRI voxel scale•Incorporation of 4 human white matter brain tissue samples for training and testing•Accurate mapping of the MRI-visible radius in the presence of staining heterogeneity•Includes 2 to 4 orders of magnitude more axons than the current gold standard (EM)•The pipeline enables validation of biophysical, MRI-based radius estimation models Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.
AbstractList Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (r ). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (r ) on small ensembles of axons, it is unsuited to estimate the tail-weighted r . We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for r . In a human corpus callosum, we assessed estimation accuracy and bias of r and r . Furthermore, we investigated whether mapping anatomy-related variation of r and r is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in r . Compared to r , r was estimated with higher accuracy (maximum normalized-root-mean-square-error of r : 8.5 %; r : 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of r : 4.8 %; r : 13.4 %). While r was confounded by variation of the image intensity, variation of r seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to r . In conclusion, the proposed method is a step towards representatively estimating r at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.
•A pipeline for automated estimation of ensemble mean axon radii at MRI voxel scale•Incorporation of 4 human white matter brain tissue samples for training and testing•Accurate mapping of the MRI-visible radius in the presence of staining heterogeneity•Includes 2 to 4 orders of magnitude more axons than the current gold standard (EM)•The pipeline enables validation of biophysical, MRI-based radius estimation models Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.
Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.
Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.
Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.
ArticleNumber 118906
Author Morozova, Maria
Fricke, Björn
Mordhorst, Laurin
Jäger, Carsten
Geyer, Stefan
Tabarin, Thibault
Morawski, Markus
Rusch, Henriette
Oeschger, Jan Malte
Weiskopf, Nikolaus
Papazoglou, Sebastian
Mohammadi, Siawoosh
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  givenname: Sebastian
  surname: Papazoglou
  fullname: Papazoglou, Sebastian
  organization: Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  surname: Mohammadi
  fullname: Mohammadi, Siawoosh
  organization: Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35032659$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1371_journal_pbio_3002906
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Keywords Deep learning
MRI-based axon radius
Neuroanatomy
Cross microscopy
Axon radii distribution
Language English
License This is an open access article under the CC BY license.
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Snippet •A pipeline for automated estimation of ensemble mean axon radii at MRI voxel scale•Incorporation of 4 human white matter brain tissue samples for training and...
Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal...
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StartPage 118906
SubjectTerms Aged
Aged, 80 and over
Anatomy
Axon radii distribution
Axons
Axons - ultrastructure
Brain
Brain architecture
Corpus callosum
Cross microscopy
Deep Learning
Estimates
Female
Histology
Humans
Light microscopy
Magnetic Resonance Imaging
Male
Microscopy
Microscopy - methods
Middle Aged
MRI-based axon radius
Nervous system
Neuroanatomy
Neuroimaging - methods
Segmentation
Variation
White Matter - diagnostic imaging
White Matter - ultrastructure
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