Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients
Previous MRI studies consistently reported iron accumulation within the striatum of patients with Huntington’s disease (HD). However, the pattern and origin of iron accumulation is poorly understood. This study aimed to characterize the histopathological correlates of iron-sensitive ex vivo MRI cont...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | NeuroImage: Clinical |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158220303351 |
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| author | Marjolein Bulk Ingrid Hegeman-Kleinn Boyd Kenkhuis Ernst Suidgeest Willeke van Roon-Mom Jan Lewerenz Sjoerd van Duinen Itamar Ronen Louise van der Weerd |
| author_facet | Marjolein Bulk Ingrid Hegeman-Kleinn Boyd Kenkhuis Ernst Suidgeest Willeke van Roon-Mom Jan Lewerenz Sjoerd van Duinen Itamar Ronen Louise van der Weerd |
| author_sort | Marjolein Bulk |
| collection | DOAJ |
| description | Previous MRI studies consistently reported iron accumulation within the striatum of patients with Huntington’s disease (HD). However, the pattern and origin of iron accumulation is poorly understood. This study aimed to characterize the histopathological correlates of iron-sensitive ex vivo MRI contrast change in HD brains. To this end, T2*-weighted 7T MRI was performed on postmortem tissue of the striatum of three control subjects and 10 HD patients followed by histological examination. In addition, formalin-fixed paraffin-embedded material of three control subjects and 14 HD patients was selected for only histology to identify the cellular localization of iron using stainings for iron, myelin, microglia and astrocytes. As expected HD striata showed prominent atrophy. Compared to controls, the striatum of HD patients was in general more hypointense on T2*-weighted high-field MRI and showed a more intense histopathological staining for iron. In addition, T2*-weighted MRI identified large focal hypointensities within the striatum of HD patients. Upon histological examination, these large focal hypointensities frequently colocalized with enlarged perivascular spaces and iron was found within the vessel wall and reactive astrocytes. In conclusion, we show that the striatum of HD patients has a distinctive phenotype on T2*-weighted MRI compared to control subjects. On ex vivo MRI, these contrast changes are heavily biased by enlarged perivascular spaces from which it is currently unknown whether this is a fixation artefact or a disease specific observation. Clinically, the observation of iron within reactive astrocytes is of importance for the interpretation and understanding of the potential underlying mechanisms of T2*-weighted MRI results in HD patients. |
| first_indexed | 2024-12-23T04:21:09Z |
| format | Article |
| id | doaj.art-16f59392ae9d4403a65794b77d7eafb2 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-23T04:21:09Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-16f59392ae9d4403a65794b77d7eafb22022-12-21T18:00:15ZengElsevierNeuroImage: Clinical2213-15822020-01-0128102498Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patientsMarjolein Bulk0Ingrid Hegeman-Kleinn1Boyd Kenkhuis2Ernst Suidgeest3Willeke van Roon-Mom4Jan Lewerenz5Sjoerd van Duinen6Itamar Ronen7Louise van der Weerd8Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author at: Leiden University Medical Center Department of Radiology Leiden, The Netherlands.Department of Pathology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Ulm University Hospital, Ulm, GermanyDepartment of Pathology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the NetherlandsPrevious MRI studies consistently reported iron accumulation within the striatum of patients with Huntington’s disease (HD). However, the pattern and origin of iron accumulation is poorly understood. This study aimed to characterize the histopathological correlates of iron-sensitive ex vivo MRI contrast change in HD brains. To this end, T2*-weighted 7T MRI was performed on postmortem tissue of the striatum of three control subjects and 10 HD patients followed by histological examination. In addition, formalin-fixed paraffin-embedded material of three control subjects and 14 HD patients was selected for only histology to identify the cellular localization of iron using stainings for iron, myelin, microglia and astrocytes. As expected HD striata showed prominent atrophy. Compared to controls, the striatum of HD patients was in general more hypointense on T2*-weighted high-field MRI and showed a more intense histopathological staining for iron. In addition, T2*-weighted MRI identified large focal hypointensities within the striatum of HD patients. Upon histological examination, these large focal hypointensities frequently colocalized with enlarged perivascular spaces and iron was found within the vessel wall and reactive astrocytes. In conclusion, we show that the striatum of HD patients has a distinctive phenotype on T2*-weighted MRI compared to control subjects. On ex vivo MRI, these contrast changes are heavily biased by enlarged perivascular spaces from which it is currently unknown whether this is a fixation artefact or a disease specific observation. Clinically, the observation of iron within reactive astrocytes is of importance for the interpretation and understanding of the potential underlying mechanisms of T2*-weighted MRI results in HD patients.http://www.sciencedirect.com/science/article/pii/S2213158220303351MRIIronHuntington’s diseaseMicrogliaAstrocytesStriatum |
| spellingShingle | Marjolein Bulk Ingrid Hegeman-Kleinn Boyd Kenkhuis Ernst Suidgeest Willeke van Roon-Mom Jan Lewerenz Sjoerd van Duinen Itamar Ronen Louise van der Weerd Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients NeuroImage: Clinical MRI Iron Huntington’s disease Microglia Astrocytes Striatum |
| title | Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients |
| title_full | Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients |
| title_fullStr | Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients |
| title_full_unstemmed | Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients |
| title_short | Pathological characterization of T2*-weighted MRI contrast in the striatum of Huntington’s disease patients |
| title_sort | pathological characterization of t2 weighted mri contrast in the striatum of huntington s disease patients |
| topic | MRI Iron Huntington’s disease Microglia Astrocytes Striatum |
| url | http://www.sciencedirect.com/science/article/pii/S2213158220303351 |
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