Extraction of a vascular function for a fully automated dynamic contrast-enhanced magnetic resonance brain image processing pipeline.

PURPOSE: To develop a deep-learning model that leverages the spatial and temporal information from dynamic contrast-enhanced magnetic resonance (DCE MR) brain imaging in order to automatically estimate a vascular function (VF) for quantitative pharmacokinetic (PK) modeling. METHODS: Patients with glioblastoma multiforme were scanned post-resection approximately every 2 months using a high spatial and temporal resolution DCE MR imaging sequence ( ≈5 s and ≈2 cm3 ). A region over the transverse sinus was manually drawn in the dynamic T1-weighted images to provide a ground truth VF. The manual regions and their resulting VF curves were used to train a deep-learning model based on a 3D U-net architecture. The model concurrently utilized the spatial and temporal information in DCE MR images to predict the VF. In order to analyze the contribution of the spatial and temporal terms, different weighted combinations were examined. The manual and deep-learning predicted regions and VF curves were compared. RESULTS: Forty-three patients were enrolled in this study and 155 DCE MR scans were processed. The 3D U-net was trained using a loss function that combined the spatial and temporal information with different weightings. The best VF curves were obtained when both spatial and temporal information were considered. The predicted VF curve was similar to the manual ground truth VF curves. CONCLUSION: The use of spatial and temporal information improved VF curve prediction relative to when only the spatial information is used. The method generalized well for unseen data and can be used to automatically estimate a VF curve suitable for quantitative PK modeling. This method allows for a more efficient clinical pipeline and may improve automation of permeability mapping.

Calgary Normative Study: design of a prospective longitudinal study to characterise potential quantitative MR biomarkers of neurodegeneration over the adult lifespan.

INTRODUCTION: A number of MRI methods have been proposed to be useful, quantitative biomarkers of neurodegeneration in ageing. The Calgary Normative Study (CNS) is an ongoing single-centre, prospective, longitudinal study that seeks to develop, test and assess quantitative magnetic resonance (MR) methods as potential biomarkers of neurodegeneration. The CNS has three objectives: first and foremost, to evaluate and characterise the dependence of the selected quantitative neuroimaging biomarkers on age over the adult lifespan; second, to evaluate the precision, variability and repeatability of quantitative neuroimaging biomarkers as part of biomarker validation providing proof-of-concept and proof-of-principle; and third, provide a shared repository of normative data for comparison to various disease cohorts. METHODS AND ANALYSIS: Quantitative MR mapping of the brain including longitudinal relaxation time (T1), transverse relaxation time (T2), T2*, magnetic susceptibility (QSM), diffusion and perfusion measurements, as well as morphological assessments are performed. The Montreal Cognitive Assessment (MoCA) and a brief, self-report medical history will be collected. Mixed regression models will be used to characterise changes in quantitative MR biomarker measures over the adult lifespan. In this report, we describe the study design, strategies to recruit and perform changes to the acquisition protocol from inception to 31 December 2018, planned statistical approach and data sharing procedures for the study. ETHICS AND DISSEMINATION: Participants provide signed informed consent. Changes in quantitative MR biomarkers measured over the adult lifespan as well as estimates of measurement variance and repeatability will be disseminated through peer-reviewed scientific publication.

Accelerated passive MR catheter tracking into the carotid artery of canines.

BACKGROUND: Using magnetic resonance (MR) imaging for navigating catheters has several advantages when compared with the current "gold standard" modality of X-ray imaging. A significant drawback to interventional MR is inferior temporal and spatial resolutions, as high spatial resolution images cannot be collected and displayed at rates equal to X-ray imaging. In particular, passive MR catheter tracking experiments that use positive contrast mechanisms have poor temporal imaging rates and signal-to-noise ratio. As a result, with passive methods, it is often difficult to reconstruct motion artifact-free tracking images from areas with motion, such as the thoracic cavity. METHODS: In this study, several accelerated MR acquisition strategies, including parallel imaging and compressed sensing (CS), were evaluated to determine which method is most effective at improving the frame rate and passive detection of catheters in regions of physiological motion. Device navigation was performed both in vitro, through the aortic arch of an anthropomorphic chest phantom, and in vivo from the femoral artery, up the descending aorta into the supra-aortic branching vessels in canines. RESULTS AND DISCUSSION: The different parallel imaging methods produced images of low quality. CS with a two-fold acceleration was found to be the most effective method for generating tracking images, improving the image frame rate to 5.2 Hz, while maintaining a relatively high in-plane resolution. Using CS, motion artifact was decreased and the catheters were visualized with good conspicuity near the heart. CONCLUSIONS: The improvement in the imaging frame rate by image acceleration was sufficient to overcome motion artifacts and to better visualize catheters in the thoracic cavity with passive tracking. CS preformed best at tracking. Navigation with passive MR catheter tracking was demonstrated from the femoral artery to the carotid artery in canines.

A human cell model for dynamic testing of MR contrast agents.

To determine the initial feasibility of using magnetic resonance (MR) imaging to detect early atherosclerosis, we investigated inflammatory cells labeled with a positive contrast agent in an endothelial cell-based testing system. The human monocytic cell line THP-1 was labeled by overnight incubation with a gadolinium colloid (Gado CELLTrack) prior to determination of the in vitro release profile from T1-weighted MR images. Next, MR signals arising from both a synthetic model of THP-1/human umbilical vein endothelial cell (HUVEC) accumulation and the dynamic adhesion of THP-1 cells to activated HUVECs under flow were obtained. THP-1 cells were found to be successfully--but not optimally--labeled with gadolinium colloid, and MR images demonstrated increased signal from labeled cells in both the synthetic and dynamic THP-1/HUVEC models. The observed THP-1 contrast release profile was rapid, suggesting the need for an agent that is optimized for retention in the target cells for use in further studies. Detection of labeled THP-1 cells was accomplished with no signal enhancement from unlabeled cells. These achievements demonstrate the feasibility of targeting early atherosclerosis with MR imaging, and suggest that using an in vitro system like the one described provides a rapid, efficient, and cost-effective way to support the development and evaluation of novel MR contrast agents.

Evolution of hyperacute stroke over 6 hours using serial MR perfusion and diffusion maps.

PURPOSE: To develop an appropriate method to evaluate the time-course of diffusion and perfusion changes in a clinically relevant animal model of ischemic stroke and to examine lesion progression on MR images. An exploration of acute stroke infarct expansion was performed in this study by using a new methodology for developing time-to-infarct maps based on the time at which each voxel becomes infarcted. This enabled definition of homogeneous regions from the heterogeneous stroke infarct. MATERIALS AND METHODS: Time-to-infarct maps were developed based on apparent diffusion coefficient (ADC) changes. These maps were validated and then applied to blood flow and time-to-peak maps to examine perfusion changes. RESULTS: ADC stroke infarct showed different evolution patterns depending on the time at which that region of tissue infarcted. Applying the time-to-infarct maps to the perfusion maps showed localized perfusion evolution characteristics. In some regions, perfusion was immediately affected and showed little change over the experiment; however, in some regions perfusion changes were more dynamic. CONCLUSION: Results were consistent with the diffusion-perfusion mismatch hypothesis. In addition, characteristics of collateral recruitment were identified, which has interesting stroke pathophysiology and treatment implications.

MRI of ischemic stroke in canines: applications for monitoring intraarterial thrombolysis.

PURPOSE: To describe a canine embolic stroke model that is appropriate for endovascular procedure evaluations and develop local cerebral blood flow (CBF) maps to monitor the progression of stroke and thrombolysis. In the future, MR may displace X-ray imaging in some endovascular procedures, such as intraarterial (IA) thrombolysis for stroke therapy, due to increased monitoring capabilities. For MR to attain its full potential in endovascular therapy, the development of appropriate disease models and monitoring techniques is essential. MATERIALS AND METHODS: The canine stroke model uses an injection of autologous clot to produce ischemic and infarcted tissue and produces a range of stroke severities within the anterior cerebral circulation. Local CBF maps were formed by using the catheter that would be in place to deliver the thrombolytic agent for treatment to deliver the gadolinium-based contrast agent for perfusion imaging. RESULTS: After the injection of clot, changes on imaging were consistent with the progression of ischemic stroke. Local CBF maps showed perfusion changes with stroke progression and treatment. CONCLUSION: We successfully demonstrate the progression of ischemic stroke in the canine to mimic the progression of human stroke. CBF maps to show local perfusion characteristics show great potential in the evaluation of stroke therapy.