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      Development of a universal dual-bolus injection scheme for the quantitative assessment of myocardial perfusion cardiovascular magnetic resonance

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          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.


          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.


          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.


          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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          Most cited references 12

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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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            Absolute myocardial perfusion in canines measured by using dual-bolus first-pass MR imaging.

            To compare fluorescent microsphere measurements of myocardial blood flow (MBF) with qualitative, semiquantitative, and fully quantitative measurements of first-pass perfusion at magnetic resonance (MR) imaging. Coronary artery occlusion or intracoronary adenosine infusion was successfully performed in 16 beagles; both procedures were performed simultaneously in one animal. MBF was assessed at microsphere analysis. First-pass myocardial perfusion MR imaging was performed during a dual-bolus administration of gadopentetate dimeglumine (0.0025 mmol/kg followed by 0.10 mmol/kg). The absolute myocardial perfusion at MR imaging was calculated by using Fermi function deconvolution methods. Qualitative, semiquantitative, and absolute myocardial perfusion MR imaging measurements were compared with microsphere MBF measurements by using paired t tests, linear correlation, and Bland-Altman analysis. Fully quantitative (ie, absolute) analysis of MBF at MR imaging correlated with microsphere MBF measurement (r = 0.95, P 5.0 mL/min/g). Similar close correlations were observed in endocardial and epicardial segments (representing approximately 0.85 g of the myocardium). With modest increases in MBF, qualitative measurements plateaued in the hyperemic zones. Semiquantitative measurements did not correlate with MBF as well (r = 0.69-0.89); they plateaued around 3.0 mL/min/g. Dual-bolus MR imaging enabled accurate measurement of absolute epicardial and endocardial perfusion across a wide range of blood flow rates (0 to >5.0 mL/min/g). Use of qualitative MR imaging measures such as the contrast enhancement ratio led to substantially underestimated hyperemic blood flow measurements. Copyright RSNA, 2004
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              Myocardial blood flow quantification with MRI by model-independent deconvolution.

              Magnetic resonance (MR) imaging during the first pass of an injected contrast agent has been used to assess myocardial perfusion, but the quantification of blood flow has been generally judged as too complex for its clinical application. This study demonstrates the feasibility of applying model-independent deconvolution to the measured tissue residue curves to quantify myocardial perfusion. Model-independent approaches only require minimal user interaction or expertise in modeling. Monte Carlo simulations were performed with contrast-to-noise ratios typical of MR myocardial perfusion studies to determine the accuracy of the resulting blood flow estimates. With a B-spline representation of the tissue impulse response and Tikhonov regularization, the bias of blood flow estimates obtained by model-independent deconvolution was less than 1% in all cases for peak contrast to noise ratios in the range from 15:1 to 20:1. The relative dispersion of blood flow estimates in Monte Carlo simulations was less than 7%. Comparison of MR blood flow estimates against measurements with radio-isotope labeled microspheres indicated excellent linear correlation (R2 = 0.995, slope: 0.96, intercept: 0.06). It can be concluded from these studies that the application of myocardial blood flow quantification with MRI can be performed with model-independent methods, and this should support a more widespread use of blood flow quantification in the clinical environment.

                Author and article information

                [1 ]King's College London BHF Centre of Excellence, NIHR Biomedical Research Centre and Welcome Trust and EPSRC Medical Engineering Centre at Guy's and St. Thomas' NHS Foundation Trust, Division of Imaging Sciences, The Rayne Institute, London, UK
                [2 ]Internal Medicine II, University of Ulm, Germany
                [3 ]Internal Medicine III, University of Heidelberg, Germany
                [4 ]Philips Healthcare, Hamburg, Germany
                [5 ]Kings College Hospital, London, UK
                [6 ]Academic Unit of Cardiovascular Medicine, University of Leeds, Leeds, UK
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central
                24 May 2011
                : 13
                : 1
                : 28
                Copyright ©2011 Ishida et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Technical Notes

                Cardiovascular Medicine


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