Assessment of ferritin content in multiple sclerosis brains using temperature‐induced R*<sub>2</sub> changes

Birkl, Christoph; Carassiti, Daniele; Hussain, Fariha; Langkammer, Christian; Enzinger, Christian; Fazekas, Franz; Schmierer, Klaus; Ropele, Stefan

doi:10.1002/mrm.26780

Cited by 13 publications

(9 citation statements)

References 34 publications

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“…In addition, the region of U-fibers has long medullary arterioles and venules in a gyriform distribution. 24 The other important question to address is the cause of iron deposition in PML. In 1981, Konijn et al 25 had already suggested that ferritin accumulation could be a nonspecific, acute-phase reactant in response to inflammation.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

Thurnher

Boban

Rieger³

et al. 2019

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) represents a life-threatening demyelinating disorder of the brain caused by reactivation of a rare opportunistic infection with JC Polyomavirus. The aims of this study were to describe the incidence of a susceptibility-weighted imaging hypointense rim in patients with multifocal leukoencephalopathy and to explore the histologic correlates and prognostic value of the rim with regard to the clinical outcome. MATERIALS AND METHODS: This retrospective study included 18 patients with a definite diagnosis of progressive multifocal leukoencephalopathy. Ten patients were HIV-positive, 3 patients had natalizumab-associated progressive multifocal leukoencephalopathy, 1 patient had multiple myeloma, 3 patients had a history of lymphoma, and 1 was diagnosed with acute myeloid leukemia. Patients were divided into short-(up to 12 months) and long-term (Ͼ12 months) survivors. A total of 93 initial and follow-up MR imaging examinations were reviewed. On SWI, the presence and development of a hypointense rim at the periphery of the progressive multifocal leukoencephalopathy lesions were noted. A postmortem histologic examination was performed in 2 patients: A rim formed in one, and in one, there was no rim. RESULTS: A total of 73 progressive multifocal leukoencephalopathy lesions were observed. In 13 (72.2%) patients, a well-defined thin, linear, hypointense rim at the periphery of the lesion toward the cortical side was present, while in 5 (27.8%) patients, it was completely absent. All 11 long-term survivors and 2 short-term survivors presented with a prominent SWI-hypointense rim, while 5/7 short-term survivors did not have this rim. CONCLUSIONS: The thin, uniformly linear, gyriform SWI-hypointense rim in the paralesional U-fibers in patients with definite progressive multifocal leukoencephalopathy might represent an end-point stage of the neuroinflammatory process in long-term survivors.

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Section: Discussionmentioning

confidence: 99%

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

Thurnher

Boban

Rieger³

et al. 2019

AJNR Am J Neuroradiol

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“…Temperature is another important source of variability between in vivo and post mortem scanning [ 59 ], making our results not directly transferable to in vivo imaging. According to Curie’s Law, the paramagnetic part of the magnetic susceptibility is inversely proportional to temperature.…”

Section: Discussionmentioning

confidence: 99%

Untangling the R2* contrast in multiple sclerosis: A combined MRI-histology study at 7.0 Tesla

et al. 2018

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T2*-weighted multi-echo gradient-echo magnetic resonance imaging and its reciprocal R2* are used in brain imaging due to their sensitivity to iron content. In patients with multiple sclerosis who display pathological alterations in iron and myelin contents, the use of R2* may offer a unique way to untangle mechanisms of disease. Coronal slices from 8 brains of deceased multiple sclerosis patients were imaged using a whole-body 7.0 Tesla MRI scanner. The scanning protocol included three-dimensional (3D) T2*-w multi-echo gradient-echo and 2D T2-w turbo spin echo (TSE) sequences. Histopathological analyses of myelin and iron content were done using Luxol fast blue and proteolipid myelin staining and 3,3′-diaminobenzidine tetrahydrochloride enhanced Turnbull blue staining. Quantification of R2*, myelin and iron intensity were obtained. Variations in R2* were found to be affected differently by myelin and iron content in different regions of multiple sclerosis brains. The data shall inform clinical investigators in addressing the role of T2*/R2* variations as a biomarker of tissue integrity in brains of MS patients, in vivo.

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“…Both can cause an increase in susceptibility, which generates the need to develop a method to separate the two sources. Birkl et al addressed the confounding effect of myelin on iron quantification in MS tissue by exploiting the temperature dependency of the susceptibility of paramagnetic iron, which decreases with temperature, while the susceptibility of the diamagnetic myelin remains constant ( 109 ). While this technique is well suited for ex vivo research, it cannot be applied to patients.…”

Section: Qsm In Msmentioning

confidence: 99%

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

et al. 2018

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Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i.e., the rim and normal adjacent white matter of chronic active lesions. In chronic active lesions, microglia and macrophages may contain high amounts of iron, express markers of proinflammatory polarization, are activated for an extended period of time (years), and drive chronic tissue damage. Iron-positive myeloid cells can be visualized and quantified with quantitative susceptibility mapping (QSM), a magnetic resonance imaging technique. Thus, QSM has potential as an in vivo biomarker for chronic inflammatory activity in established white matter MS lesions. Reducing chronic inflammation associated with iron accumulation using existing or novel MS therapies may impact disease severity and progression.

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Assessment of ferritin content in multiple sclerosis brains using temperature‐induced R*₂ changes

Cited by 13 publications

References 34 publications

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

Untangling the R2* contrast in multiple sclerosis: A combined MRI-histology study at 7.0 Tesla

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

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Assessment of ferritin content in multiple sclerosis brains using temperature‐induced R*2 changes

Cited by 13 publications

References 34 publications

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

Untangling the R2* contrast in multiple sclerosis: A combined MRI-histology study at 7.0 Tesla

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

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Assessment of ferritin content in multiple sclerosis brains using temperature‐induced R*₂ changes