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Purpose: Vessel wall MRI (VW-MRI) can be used to evaluate the nature of intracranial atherosclerosis (ICAS) plaque in vivo. Phosphodiesterase 4D (PDE4D) participates in stroke development. This study aims to explore the value of VW-MRI findings and the PDE4D gene variant in predicting stroke recurrence in patients with ICAS. Methods: We prospectively recruited 324 symptomatic ICAS patients. VW-MRI was performed to determine luminal and wall changes. PDE4D gene single-nucleotide polymorphisms (SNPs)—namely, SNP32, SNP83, and SNP87—were determined by direct sequencing. The risk factors of stroke recurrence were analyzed using the multivariate Cox proportional hazards model. Results: Of the 324 subjects, 97 (29.9%) experienced recurrent ischemic stroke during the follow-up period. A total of 254 patients (78.4%) showed plaque enhancement; 87 of these patients experienced stroke recurrence. The CT/CC genotype frequencies of PDE4D83 were significantly higher in participants with recurrent stroke than in patients without stroke recurrence (p = 0.019 and p < 0.001, respectively). However, the PDE4D32 and PDE4D87 variants were not correlated with recurrent stroke. Multivariate analysis showed that plaque enhancement from VW-MRI (HR 4.52, 95% CI 2.35–8.73, p < 0.001) and the PDE4D83 variant (HR 7.43, 95% CI 1.75–31.87, p = 0.005) were independently correlated with stroke recurrence. Kaplan–Meier curves showed significant differences in stroke recurrence rates between the plaque-enhanced group and the non-enhanced group (p < 0.001) and between the PDE4D83 variant carriers and noncarriers (p = 0.002). Conclusion: Plaque enhancement on VW-MRI and the presence of the PDE4D83 variant are associated with ischemic stroke recurrence in subjects with symptomatic ICAS. [ABSTRACT FROM AUTHOR]

Purpose: Probe-based dynamic (4-D) imaging modalities capture breast intratumor heterogeneity both spatially and kinetically. Characterizing heterogeneity through tumor sub-populations with distinct functional behavior may elucidate tumor biology to improve targeted therapy specificity and enable precision clinical decision making. Methods: We propose an unsupervised clustering algorithm for 4-D imaging that integrates Markov-Random Field (MRF) image segmentation with time-series analysis to characterize kinetic intratumor heterogeneity. We applied this to dynamic FDG PET scans by identifying distinct time-activity curve (TAC) profiles with spatial proximity constraints. We first evaluated algorithm performance using simulated dynamic data. We then applied our algorithm to a dataset of 50 women with locally advanced breast cancer imaged by dynamic FDG PET prior to treatment and followed to monitor for disease recurrence. A functional tumor heterogeneity (FTH) signature was then extracted from functionally distinct sub-regions within each tumor. Cross-validated time-to-event analysis was performed to assess the prognostic value of FTH signatures compared to established histopathological and kinetic prognostic markers. Results: Adding FTH signatures to a baseline model of known predictors of disease recurrence and established FDG PET uptake and kinetic markers improved the concordance statistic (C-statistic) from 0.59 to 0.74 (p = 0.005). Unsupervised hierarchical clustering of the FTH signatures identified two significant (p < 0.001) phenotypes of tumor heterogeneity corresponding to high and low FTH. Distributions of FDG flux, or Ki, were significantly different (p = 0.04) across the two phenotypes. Conclusions: Our findings suggest that imaging markers of FTH add independent value beyond standard PET imaging metrics in predicting recurrence-free survival in breast cancer and thus merit further study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between plaque enhancement and stroke recurrence in subjects with intracranial atherosclerosis. Methods: Ischemic stroke patients with symptomatic intracranial atherosclerosis were prospectively included and followed in a comprehensive stroke center. Pre- and post-contrast vessel wall images were used to evaluate plaque enhancement. Other established suggestive imaging markers were also acquired simultaneously. Univariate- and multivariate-adjusted Cox proportional hazard regression models were used to determine the association between plaque enhancement and stroke recurrence. Finally, receiver operating characteristic (ROC) curves were used to demonstrate the predictive value of different imaging markers. Results: Of the 60 subjects included, 12 (20.0%) patients presented with ipsilateral stroke recurrence during the median 12-month follow-up. Cox proportional hazard regression models indicated that plaque enhancement was an independent risk factor associated with stroke recurrence after adjusted covariates, with a hazard ratio (HR) of 14.24 and 95% confidence interval (95% CI) (1.21, 168.11), p = 0.04. In addition, border zone infarction was also statistically significant in predicting stroke recurrence in multi-variable regression (HR = 3.80; 95% CI = 1.04, 13.80; p = 0.04). Collateral status was in marginal significance (HR = 0.25; 95% CI = 0.06, 1.08; p = 0.06). ROC analysis indicated that the area under the curve and 95% CI to identify stroke recurrence are 0.67 (0.51, 0.82) for plaque enhancement and 0.71 (0.54, 0.88) for infarction pattern and collateral status and may increase to 0.82 (0.70, 0.93) by combining the three markers above. Conclusion: Plaque enhancement is independently associated with stroke recurrence in subjects with intracranial atherosclerosis and has added value to hemodynamic indicators in predicting stroke recurrence. [ABSTRACT FROM AUTHOR]

The clinical relevance of gray/white matter contrast ratio (GWR) in mild cognitive impairment (MCI) remains unknown. This study examined baseline GWR and 3-year follow-up diagnostic status in MCI. Alzheimer's Disease Neuroimaging Initiative MCI participants with baseline 1.5 T MRI and 3-year follow-up clinical data were included. Participants were categorized into two groups based on 3-year follow-up diagnoses: 1) non-converters ( n = 69, 75 ± 7, 26 % female), and 2) converters (i.e., dementia at follow-up; n = 69, 75 ± 7, 30 % female) who were matched on baseline age and Mini-Mental State Examination scores. Groups were compared on FreeSurfer generated baseline GWR from structural images in which higher values represent greater tissue contrast. A general linear model, adjusting for APOE-status, scanner type, hippocampal volume, and cortical thickness, revealed that converters evidenced lower GWR values than non-converters (i.e., more degradation in tissue contrast; p = 0.03). Individuals with MCI who convert to dementia have lower baseline GWR values than individuals who remain diagnostically stable over a 3-year period, statistically independent of cortical thickness or hippocampal volume. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms and the time and spatial evolution of penumbra following an ischemic stroke is crucially important for developing therapeutics aimed at preventing this area from evolving towards infarction. To help in integrating the available data, we decided to build a formal model. We first collected and categorised the major available evidence from animal models and human observations and summarized this knowledge in a flow-chart with the potential key components of an evolving stroke. Components were grouped in ten sub-models that could be modelled and tested independently: the sub-models of tissue reactions, ionic movements, oedema development, glutamate excitotoxicity, spreading depression, NO synthesis, inflammation, necrosis, apoptosis, and reperfusion. Then, we figured out markers, identified mediators and chose the level of complexity to model these sub-models. We first applied this integrative approach to build a model based on cytotoxic oedema development following a stroke. Although this model includes only three sub-models and would need to integrate more mechanisms in each of these sub-models, the characteristics and the time and spatial evolution of penumbra obtained by simulation are qualitatively and, to some extent, quantitatively consistent with those observed using medical imaging after a permanent occlusion or after an occlusion followed by a reperfusion. [ABSTRACT FROM AUTHOR]