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      A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging

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          Highlights

          • A finite element model of myocardial MR perfusion imaging is proposed.

          • A parameter space study is performed for models of both healthy and diseased tissue.

          • Clinical metrics non-monotonic with respect to changes in extra-vascular diffusivity.

          • Signal upslope a more robust clinical metric than peak signal value.

          Abstract

          Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number ( Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters, instead the contrast agents should be tailored to the specific imaging protocol and post-processing method to be used.

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          Most cited references55

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          Quantification of myocardial perfusion by cardiovascular magnetic resonance

          The potential of contrast-enhanced cardiovascular magnetic resonance (CMR) for a quantitative assessment of myocardial perfusion has been explored for more than a decade now, with encouraging results from comparisons with accepted "gold standards", such as microspheres used in the physiology laboratory. This has generated an increasing interest in the requirements and methodological approaches for the non-invasive quantification of myocardial blood flow by CMR. This review provides a synopsis of the current status of the field, and introduces the reader to the technical aspects of perfusion quantification by CMR. The field has reached a stage, where quantification of myocardial perfusion is no longer a claim exclusive to nuclear imaging techniques. CMR may in fact offer important advantages like the absence of ionizing radiation, high spatial resolution, and an unmatched versatility to combine the interrogation of the perfusion status with a comprehensive tissue characterization. Further progress will depend on successful dissemination of the techniques for perfusion quantification among the CMR community.
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            Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution.

            The myocardial perfusion reserve, defined as the ratio of hyperemic and basal myocardial blood flow, is a useful indicator of the functional significance of a coronary artery lesion. Rapid magnetic resonance (MR) imaging for the noninvasive detection of a bolus-injected contrast agent as a MR tracer is applied to the measurement of regional tissue perfusion during rest and hyperemia, in patients with microvascular dysfunction. A Fermi function model for the distribution of tracer residence times in the myocardium is used to fit the MR signal curves. The myocardial perfusion reserve is calculated from the impulse response amplitudes for rest and hyperemia. The assumptions of the model are tested with Monte Carlo simulations, using a multiple path, axially distributed mathematical model of blood tissue exchange, which allows for systematic variation of blood flow, vascular volume, and capillary permeability. For a contrast-to-noise ratio of 6:1, and over a range of flows from 0.5 to 4.0 ml/min per g of tissue, the ratio of the impulse response amplitudes for hyperemic and basal flows is linearly proportional to the ratio of model blood flows, if the mean transit time of the input function is shorter than approximately 9 s. The uncertainty in the blood flow reserve estimates grows both at low ( 3-4 ml/min/g) flows. The predictions of the Monte Carlo simulations agree with the results of MR first pass studies in patients without significant coronary artery lesions and microvascular dysfunction, where the perfusion reserve in the territory of the left anterior descending coronary artery (LAD) correlates linearly with the intracoronary Doppler ultrasound flow reserve in the LAD (r = 0.84), in agreement with previous PET studies.
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              Development of a universal dual-bolus injection scheme for the quantitative assessment of myocardial perfusion cardiovascular magnetic resonance

              Background The dual-bolus protocol enables accurate quantification of myocardial blood flow (MBF) by first-pass perfusion cardiovascular magnetic resonance (CMR). However, despite the advantages and increasing demand for the dual-bolus method for accurate quantification of MBF, thus far, it has not been widely used in the field of quantitative perfusion CMR. The main reasons for this are that the setup for the dual-bolus method is complex and requires a state-of-the-art injector and there is also a lack of post processing software. As a solution to one of these problems, we have devised a universal dual-bolus injection scheme for use in a clinical setting. The purpose of this study is to show the setup and feasibility of the universal dual-bolus injection scheme. Methods The universal dual-bolus injection scheme was tested using multiple combinations of different contrast agents, contrast agent dose, power injectors, perfusion sequences, and CMR scanners. This included 3 different contrast agents (Gd-DO3A-butrol, Gd-DTPA and Gd-DOTA), 4 different doses (0.025 mmol/kg, 0.05 mmol/kg, 0.075 mmol/kg and 0.1 mmol/kg), 2 different types of injectors (with and without "pause" function), 5 different sequences (turbo field echo (TFE), balanced TFE, k-space and time (k-t) accelerated TFE, k-t accelerated balanced TFE, turbo fast low-angle shot) and 3 different CMR scanners from 2 different manufacturers. The relation between the time width of dilute contrast agent bolus curve and cardiac output was obtained to determine the optimal predefined pause duration between dilute and neat contrast agent injection. Results 161 dual-bolus perfusion scans were performed. Three non-injector-related technical errors were observed (1.9%). No injector-related errors were observed. The dual-bolus scheme worked well in all the combinations of parameters if the optimal predefined pause was used. Linear regression analysis showed that the optimal duration for the predefined pause is 25s to separate the dilute and neat contrast agent bolus curves if 0.1 mmol/kg dose of Gd-DO3A-butrol is used. Conclusion The universal dual-bolus injection scheme does not require sophisticated double-head power injector function and is a feasible technique to obtain reasonable arterial input function curves for absolute MBF quantification.
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                Author and article information

                Contributors
                Journal
                Med Image Anal
                Med Image Anal
                Medical Image Analysis
                Elsevier
                1361-8415
                1361-8423
                1 October 2014
                October 2014
                : 18
                : 7
                : 1200-1216
                Affiliations
                [a ]Department of Biomedical Engineering, Division of Imaging Sciences & Biomedical Engineering, St. Thomas’ Hospital, King’s College London, London SE1 7EH, UK
                [b ]Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK
                Author notes
                [* ]Corresponding author. np.smith@ 123456auckland.ac.nz
                Article
                S1361-8415(14)00109-1
                10.1016/j.media.2014.07.002
                4156310
                25103922
                b293cfb7-53cf-4c30-8def-233a755bd3b0
                © 2014 The Authors
                History
                : 21 November 2013
                : 7 July 2014
                : 8 July 2014
                Categories
                Article

                Radiology & Imaging
                magnetic resonance imaging,myocardial perfusion,contrast agent,finite element method,idealised modelling

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