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SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy.

ABSTRACT: OBJECTIVE:Brain calcifications are associated with several neurodegenerative diseases. Here, we describe the occurrence of intracranial calcifications as a new phenotype in transgenic P301L mice overexpressing four repeat tau, a model of human tauopathy. MATERIALS AND METHODS:Thirty-six P301L mice (Thy1.2) and ten age-matched non-transgenic littermates of different ages were assessed. Gradient echo data were acquired in vivo and ex vivo at 7 T and 9.4 T for susceptibility-weighted imaging (SWI) and phase imaging. In addition, ex vivo micro-computed tomography (?CT) was performed. Histochemistry and immunohistochemistry were used to investigate the nature of the imaging lesions. RESULTS:SW images revealed regional hypointensities in the hippocampus, cortex, caudate nucleus, and thalamus of P301L mice, which in corresponding phase images indicated diamagnetic lesions. Concomitantly, µCT detected hyperdense lesions, though fewer lesions were observed compared to MRI. Diamagnetic susceptibility lesions in the hippocampus increased with age. The immunochemical staining of brain sections revealed osteocalcin-positive deposits. Furthermore, intra-neuronal and vessel-associated osteocalcin-containing nodules co-localized with phosphorylated-tau (AT8 and AT100) in the hippocampus, while vascular osteocalcin-containing nodules were detected in the thalamus in the absence of phosphorylated-tau deposition. DISCUSSION:SWI and phase imaging sensitively detected intracranial calcifications in the P301L mouse model of human tauopathy.

SUBMITTER: Ni R

PROVIDER: S-EPMC7669813 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy.

Ni Ruiqing R Zarb Yvette Y Kuhn Gisela A GA Müller Ralph R Yundung Yankey Y Nitsch Roger M RM Kulic Luka L Keller Annika A Klohs Jan J

Magma (New York, N.Y.) 20200528 6

<h4>Objective</h4>Brain calcifications are associated with several neurodegenerative diseases. Here, we describe the occurrence of intracranial calcifications as a new phenotype in transgenic P301L mice overexpressing four repeat tau, a model of human tauopathy.<h4>Materials and methods</h4>Thirty-six P301L mice (Thy1.2) and ten age-matched non-transgenic littermates of different ages were assessed. Gradient echo data were acquired in vivo and ex vivo at 7 T and 9.4 T for susceptibility-weighted ...[more]

PMID: 32468149

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Project description:PurposeTo compare gradient-echo (GRE) phase magnetic resonance (MR) imaging and quantitative susceptibility mapping (QSM) in the detection of intracranial calcifications and hemorrhages.Materials and methodsThis retrospective study was approved by the institutional review board. Thirty-eight patients (24 male, 14 female; mean age, 33 years ± 16 [standard deviation]) with intracranial calcifications and/or hemorrhages diagnosed on the basis of computed tomography (CT), MR imaging (interval between examinations, 1.78 days ± 1.31), and clinical information were selected. GRE and QSM images were reconstructed from the same GRE data. Two experienced neuroradiologists independently identified the calcifications and hemorrhages on the QSM and GRE phase images in two randomized sessions. Sensitivity, specificity, and interobserver agreement were computed and compared with the McNemar test and k coefficients. Calcification loads and volumes were measured to gauge intermodality correlations with CT.ResultsA total of 156 lesions were detected: 62 hemorrhages, 89 calcifications, and five mixed lesions containing both hemorrhage and calcification. Most of these lesions (146 of 151 lesions, 96.7%) had a dominant sign on QSM images suggestive of a specific diagnosis of hemorrhage or calcium, whereas half of these lesions (76 of 151, 50.3%) were heterogeneous on GRE phase images and thus were difficult to characterize. Averaged over the two independent observers for detecting hemorrhages, QSM achieved a sensitivity of 89.5% and a specificity of 94.5%, which were significantly higher than those at GRE phase imaging (71% and 80%, respectively; P < .05 for both readers). In the identification of calcifications, QSM achieved a sensitivity of 80.5%, which was marginally higher than that with GRE phase imaging (71%; P = .08 and .10 for the two readers), and a specificity of 93.5%, which was significantly higher than that with GRE phase imaging (76.5%; P < .05 for both readers). QSM achieved significantly better interobserver agreements than GRE phase imaging in the differentiation of hemorrhage from calcification (?: 0.91 vs 0.55, respectively; P < .05).ConclusionQSM is superior to GRE phase imaging in the differentiation of intracranial calcifications from hemorrhages and with regard to the sensitivity and specificity of detecting hemorrhages and the specificity of detecting calcifications.

Dataset Information

SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy.

Publications

SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy.

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