Nuclei-specific deposits of iron and calcium in the rat thalamus after status epilepticus revealed with quantitative susceptibility mapping (QSM)

Manisha Aggarwal, Xu Li, Olli Gröhn, Alejandra Sierra

Research output: Research - peer-reviewArticle

Abstract

Purpose: To investigate pathological changes in the rat brain after pilocarpine-induced status epilepticus using quantitative susceptibility mapping (QSM). Materials and Methods: 3D multiecho gradient-echo (GRE) data were acquired from ex vivo brains of pilocarpine-injected and age-matched control rats at 11.7T. Maps of R2* and quantitative susceptibility were calculated from the acquired 3D GRE magnitude and phase data, respectively. QSM and R2* maps were compared with Perls' (iron) and Alizarin-red-S (calcium) stainings in the same brains to investigate the pathophysiological basis of susceptibility contrast. Results: Bilaterally symmetric lesions were detected in reproducible thalamic regions of pilocarpine-treated rats, characterized by hyperintensity in R2* maps. In comparison, quantitative susceptibility maps demonstrated heterogeneous contrast within the lesions, with distinct hyperintense (paramagnetic) and hypointense (diamagnetic) areas. Comparison with histological assessment revealed localized deposits of iron- and calcium-positive granules in thalamic nuclei corresponding to paramagnetic and diamagnetic areas delineated in the susceptibility maps, respectively. Pronounced differences were observed in the lesions between background-corrected phase images and reconstructed susceptibility maps, indicating unreliable differentiation of iron and calcium deposits in phase maps. Multiple linear regression showed a significant association between susceptibility values and measured optical densities (ODs) of iron and calcium in the lesions (R2=0.42, P < 0.001), with a positive dependence on OD of iron and negative dependence on OD of calcium. Conclusion: QSM can detect and differentiate pathological iron and calcium deposits with high sensitivity and improved spatial accuracy compared to R2* or GRE phase images, rendering it a promising technique for diagnosing thalamic lesions after status epilepticus.

LanguageEnglish (US)
JournalJournal of Magnetic Resonance Imaging
DOIs
StateAccepted/In press - 2017

Fingerprint

Status Epilepticus
Thalamus
Iron
Calcium
Pilocarpine
Brain
Thalamic Nuclei
Linear Models
Staining and Labeling
Alizarin Red S

Keywords

  • Brain
  • Calcification
  • Epilepsy
  • Iron
  • Lesions
  • Quantitative susceptibility mapping
  • R2

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{98788f42d25e4a7b9786ea6b0b74401f,
title = "Nuclei-specific deposits of iron and calcium in the rat thalamus after status epilepticus revealed with quantitative susceptibility mapping (QSM)",
abstract = "Purpose: To investigate pathological changes in the rat brain after pilocarpine-induced status epilepticus using quantitative susceptibility mapping (QSM). Materials and Methods: 3D multiecho gradient-echo (GRE) data were acquired from ex vivo brains of pilocarpine-injected and age-matched control rats at 11.7T. Maps of R2* and quantitative susceptibility were calculated from the acquired 3D GRE magnitude and phase data, respectively. QSM and R2* maps were compared with Perls' (iron) and Alizarin-red-S (calcium) stainings in the same brains to investigate the pathophysiological basis of susceptibility contrast. Results: Bilaterally symmetric lesions were detected in reproducible thalamic regions of pilocarpine-treated rats, characterized by hyperintensity in R2* maps. In comparison, quantitative susceptibility maps demonstrated heterogeneous contrast within the lesions, with distinct hyperintense (paramagnetic) and hypointense (diamagnetic) areas. Comparison with histological assessment revealed localized deposits of iron- and calcium-positive granules in thalamic nuclei corresponding to paramagnetic and diamagnetic areas delineated in the susceptibility maps, respectively. Pronounced differences were observed in the lesions between background-corrected phase images and reconstructed susceptibility maps, indicating unreliable differentiation of iron and calcium deposits in phase maps. Multiple linear regression showed a significant association between susceptibility values and measured optical densities (ODs) of iron and calcium in the lesions (R2=0.42, P < 0.001), with a positive dependence on OD of iron and negative dependence on OD of calcium. Conclusion: QSM can detect and differentiate pathological iron and calcium deposits with high sensitivity and improved spatial accuracy compared to R2* or GRE phase images, rendering it a promising technique for diagnosing thalamic lesions after status epilepticus.",
keywords = "Brain, Calcification, Epilepsy, Iron, Lesions, Quantitative susceptibility mapping, R2",
author = "Manisha Aggarwal and Xu Li and Olli Gröhn and Alejandra Sierra",
year = "2017",
doi = "10.1002/jmri.25777",
journal = "Journal of Magnetic Resonance Imaging",
issn = "1053-1807",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Nuclei-specific deposits of iron and calcium in the rat thalamus after status epilepticus revealed with quantitative susceptibility mapping (QSM)

AU - Aggarwal,Manisha

AU - Li,Xu

AU - Gröhn,Olli

AU - Sierra,Alejandra

PY - 2017

Y1 - 2017

N2 - Purpose: To investigate pathological changes in the rat brain after pilocarpine-induced status epilepticus using quantitative susceptibility mapping (QSM). Materials and Methods: 3D multiecho gradient-echo (GRE) data were acquired from ex vivo brains of pilocarpine-injected and age-matched control rats at 11.7T. Maps of R2* and quantitative susceptibility were calculated from the acquired 3D GRE magnitude and phase data, respectively. QSM and R2* maps were compared with Perls' (iron) and Alizarin-red-S (calcium) stainings in the same brains to investigate the pathophysiological basis of susceptibility contrast. Results: Bilaterally symmetric lesions were detected in reproducible thalamic regions of pilocarpine-treated rats, characterized by hyperintensity in R2* maps. In comparison, quantitative susceptibility maps demonstrated heterogeneous contrast within the lesions, with distinct hyperintense (paramagnetic) and hypointense (diamagnetic) areas. Comparison with histological assessment revealed localized deposits of iron- and calcium-positive granules in thalamic nuclei corresponding to paramagnetic and diamagnetic areas delineated in the susceptibility maps, respectively. Pronounced differences were observed in the lesions between background-corrected phase images and reconstructed susceptibility maps, indicating unreliable differentiation of iron and calcium deposits in phase maps. Multiple linear regression showed a significant association between susceptibility values and measured optical densities (ODs) of iron and calcium in the lesions (R2=0.42, P < 0.001), with a positive dependence on OD of iron and negative dependence on OD of calcium. Conclusion: QSM can detect and differentiate pathological iron and calcium deposits with high sensitivity and improved spatial accuracy compared to R2* or GRE phase images, rendering it a promising technique for diagnosing thalamic lesions after status epilepticus.

AB - Purpose: To investigate pathological changes in the rat brain after pilocarpine-induced status epilepticus using quantitative susceptibility mapping (QSM). Materials and Methods: 3D multiecho gradient-echo (GRE) data were acquired from ex vivo brains of pilocarpine-injected and age-matched control rats at 11.7T. Maps of R2* and quantitative susceptibility were calculated from the acquired 3D GRE magnitude and phase data, respectively. QSM and R2* maps were compared with Perls' (iron) and Alizarin-red-S (calcium) stainings in the same brains to investigate the pathophysiological basis of susceptibility contrast. Results: Bilaterally symmetric lesions were detected in reproducible thalamic regions of pilocarpine-treated rats, characterized by hyperintensity in R2* maps. In comparison, quantitative susceptibility maps demonstrated heterogeneous contrast within the lesions, with distinct hyperintense (paramagnetic) and hypointense (diamagnetic) areas. Comparison with histological assessment revealed localized deposits of iron- and calcium-positive granules in thalamic nuclei corresponding to paramagnetic and diamagnetic areas delineated in the susceptibility maps, respectively. Pronounced differences were observed in the lesions between background-corrected phase images and reconstructed susceptibility maps, indicating unreliable differentiation of iron and calcium deposits in phase maps. Multiple linear regression showed a significant association between susceptibility values and measured optical densities (ODs) of iron and calcium in the lesions (R2=0.42, P < 0.001), with a positive dependence on OD of iron and negative dependence on OD of calcium. Conclusion: QSM can detect and differentiate pathological iron and calcium deposits with high sensitivity and improved spatial accuracy compared to R2* or GRE phase images, rendering it a promising technique for diagnosing thalamic lesions after status epilepticus.

KW - Brain

KW - Calcification

KW - Epilepsy

KW - Iron

KW - Lesions

KW - Quantitative susceptibility mapping

KW - R2

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JO - Journal of Magnetic Resonance Imaging

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