Dataset Information

Longitudinal Assessment of Amyloid Pathology in Transgenic ArcA? Mice Using Multi-Parametric Magnetic Resonance Imaging.

ABSTRACT: Magnetic resonance imaging (MRI) can be used to monitor pathological changes in Alzheimer's disease (AD). The objective of this longitudinal study was to assess the effects of progressive amyloid-related pathology on multiple MRI parameters in transgenic arcA? mice, a mouse model of cerebral amyloidosis. Diffusion-weighted imaging (DWI), T1-mapping and quantitative susceptibility mapping (QSM), a novel MRI based technique, were applied to monitor structural alterations and changes in tissue composition imposed by the pathology over time. Vascular function and integrity was studied by assessing blood-brain barrier integrity with dynamic contrast-enhanced MRI and cerebral microbleed (CMB) load with susceptibility weighted imaging and QSM. A linear mixed effects model was built for each MRI parameter to incorporate effects within and between groups (i.e. genotype) and to account for changes unrelated to the disease pathology. Linear mixed effects modelling revealed a strong association of all investigated MRI parameters with age. DWI and QSM in addition revealed differences between arcA? and wt mice over time. CMBs became apparent in arcA? mice with 9 month of age; and the CMB load reflected disease stage. This study demonstrates the benefits of linear mixed effects modelling of longitudinal imaging data. Moreover, the diagnostic utility of QSM and assessment of CMB load should be exploited further in studies of AD.

SUBMITTER: Klohs J

PROVIDER: S-EPMC3686820 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Longitudinal Assessment of Amyloid Pathology in Transgenic ArcAβ Mice Using Multi-Parametric Magnetic Resonance Imaging.

Klohs Jan J Politano Igna Wojtyna IW Deistung Andreas A Grandjean Joanes J Drewek Anna A Dominietto Marco M Keist Ruth R Schweser Ferdinand F Reichenbach Jürgen R JR Nitsch Roger M RM Knuesel Irene I Rudin Markus M

PloS one 20130619 6

Magnetic resonance imaging (MRI) can be used to monitor pathological changes in Alzheimer's disease (AD). The objective of this longitudinal study was to assess the effects of progressive amyloid-related pathology on multiple MRI parameters in transgenic arcAβ mice, a mouse model of cerebral amyloidosis. Diffusion-weighted imaging (DWI), T1-mapping and quantitative susceptibility mapping (QSM), a novel MRI based technique, were applied to monitor structural alterations and changes in tissue comp ...[more]

PMID: 23840405

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Project description:ObjectiveThe aim of this study was to characterize response to photodynamic therapy (PDT) in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome.MethodsCT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of BALB/c mice. Therapy consisted of intravenous injection of the photosensitizer Bremachlorin, followed by 10 min laser illumination (200 mW/cm2) of the tumor 6 h post injection. MRI at 7 T was performed at baseline, directly after PDT, as well as at 24 h, and 72 h. Tumor relaxation time constants (T1 and T2) and apparent diffusion coefficient (ADC) were quantified at each time point. Additionally, Gd-DOTA dynamic contrast-enhanced (DCE) MRI was performed to estimate transfer constants (Ktrans) and volume fractions of the extravascular extracellular space (ve) using standard Tofts-Kermode tracer kinetic modeling. At the end of the experiment, tumor viability was characterized by histology using NADH-diaphorase staining.ResultsThe therapy induced extensive cell death in the tumor and resulted in significant reduction in tumor growth, as compared to untreated controls. Tumor T1 and T2 relaxation times remained unchanged up to 24 h, but decreased at 72 h after treatment. Tumor ADC values significantly increased at 24 h and 72 h. DCE-MRI derived tracer kinetic parameters displayed an early response to the treatment. Directly after PDT complete vascular shutdown was observed in large parts of the tumors and reduced uptake (decreased Ktrans) in remaining tumor tissue. At 24 h, contrast uptake in most tumors was essentially absent. Out of 5 animals that were monitored for 2 weeks after treatment, 3 had tumor recurrence, in locations that showed strong contrast uptake at 72 h.ConclusionDCE-MRI is an effective tool for visualization of vascular effects directly after PDT. Endogenous contrast parameters T1, T2, and ADC, measured at 24 to 72 h after PDT, are also potential biomarkers for evaluation of therapy outcome.

Project description:AimTo evaluate the ability of single heartbeat fast-strain encoded (SENC) cardiovascular magnetic resonance (CMR) derived myocardial strain to discriminate between different forms of left ventricular (LV) hypertrophy (LVH).Methods314 patients (228 with hypertensive heart disease (HHD), 45 with hypertrophic cardiomyopathy (HCM), 41 with amyloidosis, 22 competitive athletes, and 33 healthy controls) were systematically analysed. LV ejection fraction (LVEF), LV mass index and interventricular septal (IVS) thickness, T1 mapping and atypical late gadolinium enhancement (LGE) were assessed. In addition, the percentage of LV myocardial segments with strain ≤ - 17% (%normal myocardium) was determined.ResultsPatients with amyloidosis and HCM exhibited the highest IVS thickness (17.4 ± 3.3 mm and 17.4 ± 6 mm, respectively, p < 0.05 vs. all other groups), whereas patients with amyloidosis showed the highest LV mass index (95.1 ± 20.1 g/m2, p < 0.05 vs all others) and lower LVEF compared to controls (50.5 ± 9.8% vs 59.2 ± 5.5%, p < 0.05). Analysing subjects with mild to moderate hypertrophy (IVS 11-15 mm), %normal myocardium exhibited excellent and high precision, respectively for the differentiation between athletes vs. HCM (sensitivity and specificity = 100%, Area under the curve; AUC%normalmyocardium = 1.0, 95%CI = 0.85-1.0) and athletes vs. HHD (sensitivity = 83%, specificity = 75%, AUC%normalmyocardium = 0.85, 95%CI = 0.78-0.90). Combining %normal myocardial strain with atypical LGE provided high accuracy also for the differentiation of HHD vs. HCM (sensitivity = 82%, specificity = 100%, AUCcombination = 0.92, 95%CI = 0.88-0.95) and HCM vs. amyloidosis (sensitivity = 83%, specificity = 100%, AUCcombination = 0.83, 95%CI = 0.60-0.96).ConclusionFast-SENC derived myocardial strain is a valuable tool for differentiating between athletes vs. HCM and athletes vs. HHD. Combining strain and LGE data is useful for differentiating between HHD vs. HCM and HCM vs. cardiac amyloidosis.

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Project description:Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens. Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f, D*), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov, registration number NCT01902667). Results: Upper and lower 95% limits of agreement were 7.1 and -6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity (r = -0.42, p = 0.01, 95% confidence interval (CI) -0.22 to -0.59 for ADC; r = -0.45, p = 0.005, 95% CI -0.25 to -0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction (r = 0.79, p = 10-7, 95% CI 0.69-0.86). Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas.

Dataset Information

Longitudinal Assessment of Amyloid Pathology in Transgenic ArcA? Mice Using Multi-Parametric Magnetic Resonance Imaging.

Publications

Longitudinal Assessment of Amyloid Pathology in Transgenic ArcAβ Mice Using Multi-Parametric Magnetic Resonance Imaging.

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