Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI.

INTRODUCTION: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. METHODS: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere. RESULTS: Partial Spearman correlation of phosphorylated tau and cortical thickness with TAR DNA-binding protein 43 (TDP-43) and α-synuclein scores, age, sex, and postmortem interval as covariates showed significant relationships in entorhinal and primary visual cortices, temporal pole, and insular and posterior cingulate gyri. Linear models including Braak stages, TDP-43 and α-synuclein scores, age, sex, and postmortem interval showed significant correlation between Braak stage and thickness in the parahippocampal gyrus, entorhinal cortex, and Broadman area 35. CONCLUSION: We demonstrated an association of measures of AD pathology with tissue loss in several AD regions despite a limited range of pathology in these cases. HIGHLIGHTS: Neurodegenerative disorders are associated with co-occurring pathologies that cannot be measured specifically with in vivo methods. Identification of the topographic patterns of these pathologies in structural magnetic resonance imaging (MRI) may provide probabilistic biomarkers. We demonstrated the correlation of the specific patterns of tissue loss from ex vivo brain MRI with underlying pathologies detected in postmortem brain hemispheres in patients with Alzheimer's disease (AD) spectrum disorders. The results provide insight into the interpretation of in vivo structural MRI studies in patients with AD spectrum disorders.

A perfusion phantom for ASL MRI based on impinging jets.

PURPOSE: We present a novel perfusion phantom for validation of arterial spin labeled (ASL) perfusion MRI methods and protocols. METHODS: Impinging jets, driven by a peristaltic pump, were used to achieve perfusion-like mixing of magnetically labeled inflowing fluid within a perfusion compartment. The phantom was validated by varying pump rates and obtaining ASL-MRI data at multiple postlabeling delays using a pseudo-continuous ASL sequence with a 3D stack-of-spirals readout. An additional data set was acquired using a pseudo-continuous ASL sequence with a 2D EPI readout. Phantom sensitivity to pseudo-continuous ASL labeling efficiency was also tested. RESULTS: Fluid dynamics simulations predicted that maximum mixing would occur near the central axis of the perfusion compartment. Experimentally observed signal changes within this region were reproducible and well fit by the standard Buxton general kinetic model. Simulations and experimental data showed no label outflow from the perfusion chamber and calculated perfusion rates, averaged over the entire phantom volume, agreed with the expected volumetric flow rates provided by the flow pump. Phantom sensitivity to pseudo-continuous ASL labeling parameters was also demonstrated. CONCLUSION: Perfusion-like signal can be simulated using impinging jets to create a well-mixed compartment. Observed perfusion and transit time values were reproducible and within the physiological range for brain perfusion. This phantom design has a broad range of potential applications in both basic and clinical research involving ASL MRI.