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Quantification of Myocardial Perfusion: MRI
Abstract
Rapid magnetic resonance imaging (MRI) of the heart, during the first pass of an injected contrast bolus is routinely used to detect hypoperfused myocardium, both at rest, and during vasodilator stress. Adapting this approach for quantitative perfusion imaging has been successfully tested and validated over more than 15 years in experimental models and clinical studies, yielding quantitative estimates of the perfusion reserve to detect epicardial stenoses and microvascular dysfunction, and to quantify absolute myocardial blood flow (in mL/minute/g of myocardial tissue). This review presents an overview of the most common approaches used in contrast-enhanced cardiac MRI for quantification of myocardial perfusion, and identifies some critical areas of current research. In its present state, cardiac MRI is a viable, diagnostically valuable alternative to other cardiac imaging modalities for the quantification of myocardial perfusion.
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.
Absolute quantification of perfusion with cardiovascular magnetic resonance has not previously been applied in patients with coronary artery bypass grafting (CABG). Owing to increased contrast bolus dispersion due to the greater distance of travel through a bypass graft, this approach may result in systematic underestimation of myocardial blood flow (MBF). As resting MBF remains normal in segments supplied by noncritical coronary stenosis (<85%), measurement of perfusion in such territories may be utilized to reveal systematic error in the quantification of MBF. The objective of this study was to test whether absolute quantification of perfusion with cardiovascular magnetic resonance systematically underestimates MBF in segments subtended by bypass grafts.
The study population comprised 28 patients undergoing elective CABG for treatment of multivessel coronary artery disease. Eligible patients had angiographic evidence of at least 1 myocardial segment subtended by a noncritically stenosed coronary artery (<85%). Subjects were studied at 1.5 T, with evaluation of resting MBF using model-independent deconvolution. Analyses were confined to myocardial segments subtended by native coronary arteries with <85% stenosis at baseline, and MBF was compared in grafted and ungrafted segments before and after revascularization. A total of 249 segments were subtended by coronary arteries with <85% stenosis at baseline. After revascularization, there was no significant difference in MBF in ungrafted (0.82±0.19 mL/min/g) versus grafted segments (0.82±0.15 mL/min/g, P=0.57). In the latter, MBF after revascularization did not change significantly from baseline (0.86±0.20 mL/min/g, P=0.82).
Model-independent deconvolution analysis does not systematically underestimate blood flow in graft-subtended territories, justifying the use of this methodology to evaluate myocardial perfusion in patients with CABG.
Accurate quantification of pharmacokinetic model parameters in tracer kinetic imaging experiments requires correspondingly accurate determination of the arterial input function (AIF). Despite significant effort expended on methods of directly measuring patient-specific AIFs in modalities as diverse as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), dynamic positron emission tomography (PET), and perfusion computed tomography (CT), fundamental and technical difficulties have made consistent and reliable achievement of that goal elusive. Here, we validate a new algorithm for AIF determination, the Monte Carlo blind estimation (MCBE) method (which is described in detail and characterized by extensive simulations in a companion paper), by comparing AIFs measured in DCE-MRI studies of eight brain tumor patients with results of blind estimation. Blind AIFs calculated with the MCBE method using a pool of concentration-time curves from a region of normal brain tissue were found to be quite similar to the measured AIFs, with statistically significant decreases in fit residuals observed in six of eight patients. Biases between the blind and measured pharmacokinetic parameters were the dominant source of error. Averaged over all eight patients, the mean biases were +7% in K(trans), 0% in k(ep), -11% in v(p) and +10% in v(e). Corresponding uncertainties (median absolute deviation from the best fit line) were 0.0043 min(-1) in K(trans), 0.0491 min(-1) in k(ep), 0.29% in v(p) and 0.45% in v(e). The use of a published population-averaged AIF resulted in larger mean biases in three of the four parameters (-23% in K(trans), -22% in k(ep), -63% in v(p)), with the bias in v(e) unchanged, and led to larger uncertainties in all four parameters (0.0083 min(-1) in K(trans), 0.1038 min(-1) in k(ep), 0.31% in v(p) and 0.95% in v(e)). When blind AIFs were calculated from a region of tumor tissue, statistically significant decreases in fit residuals were observed in all eight patients despite larger deviations of these blind AIFs from the measured AIFs. The observed decrease in root-mean-square fit residuals between the normal brain and tumor tissue blind AIFs suggests that the local blood supply in tumors is measurably different from that in normal brain tissue and that the proposed method is able to discriminate between the two. We have shown the feasibility of applying the MCBE algorithm to DCE-MRI data acquired in brain, finding generally good agreement with measured AIFs and decreased biases and uncertainties relative to the use of a population-averaged AIF. These results demonstrate that the MCBE algorithm is a useful alternative to direct AIF measurement in cases where acquisition of high-quality arterial input function data is difficult or impossible.
Widespread adoption of quantitative pharmacokinetic modeling methods in conjunction with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has led to increased recognition of the importance of obtaining accurate patient-specific arterial input function (AIF) measurements. Ideally, DCE-MRI studies use an AIF directly measured in an artery local to the tissue of interest, along with measured tissue concentration curves, to quantitatively determine pharmacokinetic parameters. However, the numerous technical and practical difficulties associated with AIF measurement have made the use of population-averaged AIF data a popular, if sub-optimal, alternative to AIF measurement. In this work, we present and characterize a new algorithm for determining the AIF solely from the measured tissue concentration curves. This Monte Carlo blind estimation (MCBE) algorithm estimates the AIF from the subsets of D concentration-time curves drawn from a larger pool of M candidate curves via nonlinear optimization, doing so for multiple (Q) subsets and statistically averaging these repeated estimates. The MCBE algorithm can be viewed as a generalization of previously published methods that employ clustering of concentration-time curves and only estimate the AIF once. Extensive computer simulations were performed over physiologically and experimentally realistic ranges of imaging and tissue parameters, and the impact of choosing different values of D and Q was investigated. We found the algorithm to be robust, computationally efficient and capable of accurately estimating the AIF even for relatively high noise levels, long sampling intervals and low diversity of tissue curves. With the incorporation of bootstrapping initialization, we further demonstrated the ability to blindly estimate AIFs that deviate substantially in shape from the population-averaged initial guess. Pharmacokinetic parameter estimates for K(trans), k(ep), v(p) and v(e) all showed relative biases and uncertainties of less than 10% for measurements having a temporal sampling rate of 4 s and a concentration measurement noise level of sigma = 0.04 mM. A companion paper discusses the application of the MCBE algorithm to DCE-MRI data acquired in eight patients with malignant brain tumors.
Quantitative estimates of myocardial perfusion generally require accurate measurement of the arterial input function (AIF). The saturation of signal intensity in the blood that occurs with most doses of contrast agent makes obtaining an accurate AIF challenging. This work seeks to evaluate the performance of a method that uses a radial k-space perfusion sequence and multiple saturation recovery times (SRT) to quantify myocardial perfusion with cardiovascular magnetic resonance (CMR).
Perfusion CMR was performed at 3 Tesla with a saturation recovery radial turboFLASH sequence with 72 rays. Fourteen subjects were given a low dose (0.004 mmol/kg) of dilute (1/5 concentration) contrast agent (Gd-BOPTA) and then a higher non-dilute dose of the same volume (0.02 mmol/kg). AIFs were calculated from the blood signal in three sub-images with differing effective saturation recovery times. The full and sub-images were reconstructed iteratively with a total variation constraint. The images from the full 72 ray data were processed to obtain six tissue enhancement curves in two slices of the left ventricle in each subject. A 2-compartment model was used to determine absolute flows
The proposed multi-SRT method resulted in AIFs that were similar to those obtained with the dual-bolus method. Myocardial blood flow (MBF) estimates from the dual-bolus and the multi-SRT methods were related by MBFmulti-SRT = 0.85MBFdual-bolus + 0.18 (r = 0.91).
The multi-SRT method, which uses a radial k-space perfusion sequence, can be used to obtain an accurate AIF and thus quantify myocardial perfusion for doses of contrast agent that result in a relatively saturated AIF.
Almost all x-ray-based techniques intended to assess regional myocardial perfusion from myocardial concentration-time curves following the administration of soluble contrast agents assume that these agents behave as intravascular indicators and can therefore provide measurements of intravascular transit time and intramyocardial blood volume.
We tested this assumption by comparing a conventional nonionic contrast agent (ioversol) to a particulate emulsion (ethiodol) that remained in the vascular space in closed-chest dogs during pharmacological vasodilation. Using fast computed tomography (CT), pairs of myocardial CT intensity-time curves were obtained following sequential bolus aortic administration of the two contrast agents. The emulsion (particle size less than 3 microns) was almost completely washed out of the myocardial region of interest within a few seconds, as would be anticipated for a vascular indicator. At the onset of recirculation, CT intensity for ethiodol fell to 5 +/- 1% (SEM) of peak values in normally perfused areas and to 10 +/- 4% of peak values in an area in which flow had been reduced by 50% by a chronically implanted coronary artery occluder (p = NS). In comparison, the diffusible nonionic contrast agent ioversol showed substantial intramyocardial retention at the onset of recirculation. At the time of recirculation, CT intensities for ioversol averaged 36 +/- 2% of peak values in normally perfused nonstenotic areas and 54 +/- 4% of peak values in stenotic areas (p less than 0.01). Using residue function analysis for a diffusible indicator, first-pass extractions of the conventional nonionic agent averaged 33 +/- 2% in normally perfused areas and 50 +/- 3% in stenotic areas (p less than 0.01). Because of the significant first-pass myocardial retention of ioversol, both mean myocardial appearance time and intramyocardial blood volume were consistently overestimated.
Soluble radiographic contrast agents, like other small molecules, enter the interstitial space to a degree, which is important because it affects estimates of myocardial perfusion based on transit time and intramyocardial blood volume. Indicator dilution models intended to quantify myocardial perfusion with conventional radiographic contrast agents need to account for this extravascular exchange.
The purpose of the present study was to determine the accuracy and the sources of error in estimating regional myocardial blood flow and vascular volume from experimental residue functions obtained by external imaging of an intravascular indicator. For the analysis, a spatially distributed mathematical model was used that describes transport through a multiple-pathway vascular system. Reliability of the parameter estimates was tested by using sensitivity function analysis and by analyzing "pseudodata": realistic model solutions to which random noise was added. Increased uncertainty in the estimates of flow in the pseudodata was observed when flow was near maximal physiological values, when dispersion of the vascular input was more than twice the dispersion of the microvascular system for an impulse input, and when the sampling frequency was < 2 samples/s. Estimates of regional blood volume were more reliable than estimates of flow. Failure to account for normal flow heterogeneity caused systematic underestimates of flow. To illustrate the method used for estimating regional flow, magnetic resonance imaging was used to obtain myocardial residue functions after left atrial injections of polylysine-Gd-diethylenetriaminepentaacetic acid, an intravascular contrast agent, in anesthetized chronically instrumental dogs. To test the increase in dispersion of the vascular input after central venous injections, magnetic resonance imaging data obtained in human subjects were compared with left ventricular blood pool curves obtained in dogs. It is concluded that if coronary flow is in the normal range, when the vascular input is a short bolus, and the heart is imaged at least once per cardiac cycle, then regional myocardial blood flow and vascular volume may be reliably estimated by analyzing residue functions of an intravascular indicator, providing a noninvasive approach with potential clinical application.
The dispersion and dilution of contrast medium through the myocardial vasculature is examined first with a serial model comprised of arterial, capillary, and venous components in series to determine their time-concentration curves (TCC) and the myocardial dilution curve (MDC). Analysis of general characteristics shows that the first moment of the MDC, adjusted for that of the aortic TCC and mean transit time (MTT) from the aorta to the first intramyocardial artery, is one-half the MTT of the myocardial vasculature and that the ratio of the area of the MDC and aortic TCC is the fractional myocardial blood volume (MBV). The use of known coronary vascular morphometry and a set of transport functions indicates that the temporal change in MDC is primarily controlled by the MTT. An analysis of several models with heterogeneous flow distributions justifies the procedures to calculate MTT and MBV from the measured MDC. Compared with previously described models, the present model is more general and provides a physical basis for the effects of flow dispersion and heterogeneity on the characteristics of the MDC.
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 <.001) across the full range of blood flow rates encountered (from 0 to >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.
Noninvasive assessment of absolute myocardial blood flow is important for evaluation of microvascular function and serial changes in perfusion. Absolute flow can be calculated from magnetic resonance (MR) perfusion studies, but a nonlinear relationship between signal intensity (SI) and gadolinium concentration ([Gd]) in the myocardium may cause underestimation. When the relationship between SI and [Gd] was mapped in chronically instrumented dogs, this was linear in the left ventricular (LV) bloodpool for a 0.005 mmol/kg Gd-DTPA minibolus but nonlinear in the myocardium for a 0.05 mmol/kg bolus. 14 dual-bolus MR first-pass perfusion studies were performed at rest and during vasodilation with variable degrees of left circumflex coronary artery stenosis. Absolute flow by Fermi function deconvolution of MR SI-time curves underestimated microsphere flow by nearly 50% (y = 0.52x + 0.07, r2 = 0.61). When the myocardial and LV SI-[Gd] relationships were used as calibration curves to convert SI values to [Gd], deconvolution of [Gd]-time curves yielded accurate myocardial flow values (y = 0.93x + 0.05, r2 = 0.68). As seen in the figure , absolute flow measured in endo-, mid-, and epicardial layers progressively decreased from epi- to endocardium in the stenotic zone, (p = 0.0004) while flow did not vary across the myocardial wall in the normal zone (p = 0.72). Correcting the curvilinear myocardial signal response to gadolinium improves the accuracy of absolute myocardial flow quantification by MR perfusion imaging. The high spatial resolution enables measurement of transmural flow differences caused by impaired vasodilator reserve.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
The value of ultrafast MRI for detection of myocardial perfusion abnormalities in patients with coronary artery disease (CAD) was assessed in 10 patients with stable angina pectoris and angiographically proven one-vessel CAD using double-level short-axis ultrafast MRI with bolus injection of gadolinium-DTPA and tomographic technetium-99m SestaMIBI imaging (SPECT) during dipyridamole-induced coronary hy-peremia. Abnormally perfused regions were assessed with SPECT and MRI in all (100%) patients. Agreement in localization between arteriography and SPECT was 80%; between arteriography and MR, 70%; and between SPECT and MR, 90%. The signal intensity increase after the bolus injection of gadolinium-DTPA using a linear fit, and the slope of gado-linium-DTPA wash-in using double exponential model fitting were significantly different between abnormally and normally perfused regions. These preliminary results demonstrate the potential of dipyridamole ultrafast MR to monitor stress-induced flow maldistribution in patients with single vessel CAD.
This study sought to determine whether arterial spin labeled (ASL) cardiac magnetic resonance (CMR) is capable of detecting clinically relevant increases in regional myocardial blood flow (MBF) with vasodilator stress testing in human myocardium.
Measurements of regional myocardial perfusion at rest and during vasodilatation are used to determine perfusion reserve, which indicates the presence and distribution of myocardial ischemia. ASL CMR is a perfusion imaging technique that does not require any contrast agents, and is therefore safe for use in patients with end-stage renal disease, and capable of repeated or continuous measurement.
Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine CMR adenosine induced vasodilator stress protocol and was performed in 29 patients. Patients who were suspected of having ischemic heart disease based on first-pass imaging also underwent x-ray angiography. Myocardial ASL was performed using double-gated flow-sensitive alternating inversion recovery tagging and balanced steady-state free precession imaging at 3-T.
Sixteen patients were found to be normal and 13 patients were found to have visible perfusion defect based on first-pass CMR using intravenous gadolinium chelate. In the normal subjects, there was a statistically significant difference between MBF measured by ASL during adenosine infusion (3.67 ± 1.36 ml/g/min), compared to at rest (0.97 ± 0.64 ml/g/min), with p < 0.0001. There was also a statistically significant difference in perfusion reserve (MBF(stress)/MBF(rest)) between normal myocardial segments (3.18 ± 1.54) and the most ischemic segments in the patients with coronary artery disease identified by x-ray angiography (1.44 ± 0.97), with p = 0.0011.
This study indicates that myocardial ASL is capable of detecting clinically relevant increases in MBF with vasodilatation and has the potential to identify myocardial ischemia.
The objective of this study was to compare visual and quantitative analysis of high spatial resolution cardiac magnetic resonance (CMR) perfusion at 3.0-T against invasively determined fractional flow reserve (FFR).
High spatial resolution CMR myocardial perfusion imaging for the detection of coronary artery disease (CAD) has recently been proposed but requires further clinical validation.
Forty-two patients (33 men, age 57.4 ± 9.6 years) with known or suspected CAD underwent rest and adenosine-stress k-space and time sensitivity encoding accelerated perfusion CMR at 3.0-T achieving in-plane spatial resolution of 1.2 × 1.2 mm(2). The FFR was measured in all vessels with >50% severity stenosis. Fractional flow reserve <0.75 was considered hemodynamically significant. Two blinded observers visually interpreted the CMR data. Separately, myocardial perfusion reserve (MPR) was estimated using Fermi-constrained deconvolution.
Of 126 coronary vessels, 52 underwent pressure wire assessment. Of these, 27 lesions had an FFR <0.75. Sensitivity and specificity of visual CMR analysis to detect stenoses at a threshold of FFR <0.75 were 0.82 and 0.94 (p < 0.0001), respectively, with an area under the receiver-operator characteristic curve of 0.92 (p < 0.0001). From quantitative analysis, the optimum MPR to detect such lesions was 1.58, with a sensitivity of 0.80, specificity of 0.89 (p < 0.0001), and area under the curve of 0.89 (p < 0.0001).
High-resolution CMR MPR at 3.0-T can be used to detect flow-limiting CAD as defined by FFR, using both visual and quantitative analyses.
The purpose of this paper was to compare quantitative cardiac magnetic resonance (CMR) first-pass contrast-enhanced perfusion imaging to qualitative interpretation for determining the presence and severity of coronary artery disease (CAD).
Adenosine CMR can detect CAD by measuring perfusion reserve (PR) or by qualitative interpretation (QI).
Forty-one patients with an abnormal nuclear stress scheduled for X-ray angiography underwent dual-bolus adenosine CMR. Segmental myocardial perfusion analyzed using both QI and PR by Fermi function deconvolution was compared to quantitative coronary angiography.
In the 30 patients with complete quantitative data, PR (mean +/- SD) decreased stepwise as coronary artery stenosis (CAS) severity increased: 2.42 +/- 0.94 for <50%, 2.14 +/- 0.87 for 50% to 70%, and 1.85 +/- 0.77 for >70% (p < 0.001). The PR and QI had similar diagnostic accuracies for detection of CAS >50% (83% vs. 80%), and CAS >70% (77% vs. 67%). Agreement between observers was higher for quantitative analysis than for qualitative analysis. Using PR, patients with triple-vessel CAD had a higher burden of detectable ischemia than patients with single-vessel CAD (60% vs. 25%; p = 0.02), whereas no difference was detected by QI (31% vs. 21%; p = 0.26). In segments with myocardial scar (n = 64), PR was 3.10 +/- 1.34 for patients with CAS <50% (n = 18) and 1.91 +/- 0.96 for CAS >50% (p < 0.0001).
Quantitative PR by CMR differentiates moderate from severe stenoses in patients with known or suspected CAD. The PR analysis differentiates triple- from single-vessel CAD, whereas QI does not, and determines the severity of CAS subtending myocardial scar. This has important implications for assessment of prognosis and therapeutic decision making.
To test whether image normalization using either a separate 3D proton-density (PD)-weighted prescan, or 2D PD-weighted images prior to the perfusion series, improves correction of differences in spatial sensitivity induced by radiofrequency (RF) surface receiver coils. Originally, this correction was applied using the baseline signal in the myocardium before arrival of the contrast agent. This is of importance, as quantitative analysis of magnetic resonance (MR) myocardial perfusion using deconvolution with the arterial input assumes equal signal sensitivity over the heart.
First-pass myocardial perfusion measurements were obtained in 13 patients without known coronary artery disease. Absolute perfusion values were assessed for 18 myocardial segments without any normalization and using the three different normalization methods.
Using 2D or 3D PD-weighted normalization, similar mean perfusion values were found, but with reduced spatial variance over the 18 segments. The relative dispersion of perfusion at rest was 23% and 35% for the 3D prescan normalization and the baseline normalization, respectively. With 2D and 3D PD-weighted prescan normalization the relative dispersion was closer to the expected physiological heterogeneity.
PD-weighted prescan normalization proved to be a valuable addition to quantitative analysis of myocardial perfusion, and better than baseline-based normalization.
The aim of this study was to determine the accuracy of cardiac magnetic resonance (CMR) first pass (FP) perfusion measures of absolute myocardial blood flow (MBF) with a 3.0-T magnet and compare these measures with FP perfusion at 1.5-T with absolute MBF by labeled microspheres as the gold standard.
First-pass magnetic resonance (MR) myocardial perfusion imaging can quantify MBF, but images are of low signal at conventional magnetic field strength due to the need for rapid acquisition.
A pig model was used to alter MBF in a coronary artery during FP CMR (intracoronary adenosine followed by ischemia). This produces an active zone with a range of MBF and a control zone. Microspheres were injected into the left atrium with concurrent reference sampling. FP MR perfusion imaging was performed at 1.5-T (n = 9) or 3.0-T (n = 8) with a saturation-recovery gradient echo sequence in short-axis slices during a bolus injection of 0.025 mmol/kg gadolinium-diethylenetriamine pentaacetic acid. Fermi function deconvolution was performed on active and control region of interest from short-axis slices with an arterial input function derived from the left ventricular cavity. These MR values of MBF were matched to microsphere values obtained from short-axis slices at pathology.
Occlusion MBF was 0.21 +/- 0.26 ml/min/g, adenosine MBF was 2.28 +/- 0.99 ml/min/g, and control zone MBF was 0.70 +/- 0.22 ml/min/g. The correlation of MR FP CMR with microsphere was close for both field strengths: 3.0-T, r = 0.98, p < 0.0001 and 1.5-T, r = 0.95, p < 0.0001. The 95% confidence limits of agreement were slightly narrower at 3.0-T (3.0-T = 0.49 ml/min/g, 1.5-T = 0.68 ml/min/g, p < 0.05). The FP CMR image characteristics were better at 3.0-T (noise and contrast enhancement were both superior at 3.0-T). In myocardial zones where MBF <0.50 ml/min/g, the correlation with microspheres was closer at 3.0-T (r = 0.55 at 1.5-T, r = 0.85 at 3.0-T).
Absolute MBF by FP perfusion imaging is accurate at both 1.5- and 3.0-T. Signal quality is better at 3.0-T, which might confer a benefit for estimating MBF in ischemic zones.
Quantification of myocardial blood flow (MBF) by means of T1-weighted first-pass magnetic resonance imaging (MRI) requires knowledge of the arterial input function (AIF), which is usually estimated from the left ventricle (LV). Dispersion of the contrast agent bolus may occur between the LV and the tissue of interest, which leads to systematic underestimation of the MBF. The aim of this study was to simulate the dispersion along a simplified coronary artery with different stenoses. To analyze the dispersion in vessels with typical dimensions of coronary arteries, simulations were performed using the computational fluid dynamics approach. Simulations were accomplished on straight vessels with integrated stenoses of different degrees of area reduction and length as well as two different shapes-an axial symmetric and an asymmetric. Two boundary conditions were used representing myocardial blood flow at rest and under hyperemic conditions. The results under steady boundary conditions show that the dispersion is more pronounced in resting condition than during hyperemia yielding an underestimation of the MBF around 15% in the resting state and around 8% under stress conditions. At the outlet of the vessel an axial symmetric stenosis results in increased dispersion whereas an asymmetric stenosis yields a reduction. Due to the more severe dispersion, resting MBF may be more underestimated in quantitative myocardial perfusion MRI studies compared with MBF under stress conditions. In consequence the myocardial perfusion reserve may be overestimated. The amount of systematic error depends in a complex way on the shape and degree of stenoses.
Arterial spin labeling (ASL) is a powerful tool for the quantitative measurement of tissue blood flow, and has been extensively applied to the brain, lungs, and kidneys. ASL has been recently applied to myocardial blood flow (MBF) measurement in small animals; however, its use in humans is limited by inadequate signal-to-noise ratio (SNR) efficiency and timing restrictions related to cardiac motion. We present preliminary results demonstrating MBF measurement in humans, using cardiac-gated flow-sensitive alternating inversion recovery (FAIR) tagging and balanced steady-state free precession (SSFP) imaging at 3T, and present an analysis of thermal and physiological noise and their impact on MBF measurement error. Measured MBF values in healthy volunteers were 1.36 +/- 0.40 ml/ml/min at rest, matching the published literature based on quantitative (13)N-ammonia positron emission tomography (PET), and increased by 30% and 29% with passive leg elevation and isometric handgrip stress, respectively. With thermal noise alone, MBF can be quantified to within +/- 0.1 ml/ml/min with 85.5% confidence, for 3.09 cm(3) regions averaged over 6 breath-holds. This study demonstrates the feasibility of quantitative assessment of myocardial blood flow in humans using ASL, and identifies SNR improvement and the reduction of physiological noise as key areas for future development.
By serially imaging the myocardium during the initial transit of gadolinium contrast, magnetic resonance perfusion imaging can accurately assess relative reductions in regional myocardial blood flow and identify hemodynamically significant coronary artery disease. Models can be used to quantify myocardial blood flow (in milliliters/minute/gram) on the basis of dynamic signal changes within the myocardium and left ventricular cavity. Although the mathematical modeling involved in this type of analysis adds complexity, the benefits of absolute blood flow quantification might improve clinical diagnosis and have important implications for cardiovascular research.
To improve myocardial perfusion magnetic resonance imaging (MRI) by reconstructing undersampled radial data with a spatiotemporal constrained reconstruction method (STCR).
The STCR method jointly reconstructs all of the time-frames for each slice. In 7 subjects at rest, on a 3-T scanner, the method was compared with a conventional (GRAPPA) Cartesian approach.
Increased slice coverage was obtained, as compared with Cartesian acquisitions. On average, 10 slices were obtained per heartbeat for radial acquisitions (8 of which are suitable for visual analysis with the remaining 2 slices, in theory, usable for quantitative purposes), whereas 4 slices were obtained for the conventional Cartesian acquisitions. The new method was robust to interframe motion, unlike using Cartesian undersampling and STCR. STCR produced images with an image quality rating (1 for best and 5 for worst) of 1.7 +/- 0.5; the Cartesian images were rated 2.6 +/- 0.4 (P = 0.0006). A mean improvement of 44 (+/-17) in signal-to-noise (SNR) ratio and 46 (+22) in contrast-to-noise ratio (CNR) was observed for STCR.
The new radial data acquisition and reconstruction scheme for dynamic myocardial perfusion imaging is a promising approach for obtaining significantly higher coverage and improved SNR ratios. Further testing of this approach is warranted during vasodilation in patients with coronary artery disease.
Ultrafast magnetic resonance imaging (MRI) and first pass observation of an interstitial contrast agent are currently being used to study myocardial perfusion. Image intensity, however, is a function of several parameters, including the delivery of the contrast agent to the interstitium (coronary flow rate and diffusion into the interstitium) and the relaxation properties of the tissue (contrast agent concentration, proton exchange rates, and relative intra- and extracellular volume fractions). In this study, image intensity during gadopentetate dimeglumine (Gd-DTPA) administration with T1-weighted ultrafast MR imaging was assessed in an isolated heart preparation. With increasing Gd-DTPA concentration, the steady-state myocardial image intensity increased but the time to reach steady state remained unchanged, resulting in an increased slope of image intensity change. A range of physiologic perfusion pressures (and resulting coronary flow rates) had insignificant effects on kinetics of Gd-DTPA wash-in or steady-state image intensity, suggesting that diffusion of Gd-DTPA into the interstitium is the rate limiting step in image intensity change with this preparation. Following global ischemia and reperfusion, transmural differences in the slope of image intensity change were apparent. However, the altered steady-state image intensity (due to postischemic edema) makes interpretation of this finding difficult. The studies described here demonstrate that although Gd-DTPA administration combined with ultrafast imaging may be a sensitive indicator of perfusion abnormalities, factors other than perfusion will affect image intensity. Extensive studies will be required before image intensity with this protocol is fully understood.
Contrast-enhanced magnetic resonance (MR) imaging can define myocardial perfusion defects due to acute coronary occlusion. However, since most clinically important diagnostic examinations involve coronary arteries with subtotal stenoses, we investigated the ability of MR imaging with a manganese contrast agent to detect perfusion abnormalities in a canine model of partial coronary artery stenosis. The contrast agent was administered after the creation of a partial coronary artery stenosis with the addition of the coronary vasodilator dipyridamole in six of 12 animals. The hearts were imaged ex situ using gradient reversal and spin-echo sequences, and images were analyzed to determine differences in signal intensity between hypoperfused and normally perfused myocardium. Comparison of MR images with regional blood flow and thallium-201 measurements showed good concordance of hypoperfused segments in those animals given dipyridamole, with 75% of the abnormal segments correctly identified. In those animals not given dipyridamole, 48% of segments were correctly identified. Thus, ex vivo MR imaging with a paramagnetic contrast enhancement can be used to detect acute regional myocardial perfusion abnormalities due to severe partial coronary artery stenoses.
The authors studied cardiac perfusion by administering gadolinium diethylenetriaminepentaacetic acid (DTPA) in conjunction with an ultrafast imaging technique that produces strongly T1-weighted images. The method consisted of a 180 degrees inversion pulse, followed by a gradient-echo acquisition with a very short repetition time (less than 4 msec). Each image was acquired throughout a small fraction of the cardiac cycle. The method was applied in an isolated perfused rat heart model (acquisition time = 116 msec) and in human subjects without known cardiac disease (acquisition time = 125 msec). Fast, high-resolution images (128 X 128 matrix) were created by combining sequentially acquired small matrixes. After bolus administration of Gd-DTPA in the perfused rat heart model, contrast was pronounced between the nonperfused myocardium and perfused normal myocardium. First-pass wash-in and washout phases of the contrast material were observed in the perfused rat heart model and in human subjects. Results demonstrated the clinical feasibility of first-pass perfusion studies of the heart. The studies can be performed on a conventional whole-body imaging system with standard hardware.
In animal hearts, the magnitude of integrated ultrasonic backscatter is increased in fibrotic myocardium. Our purpose in this study was to quantitate the relationship between ultrasonic backscatter and collagen deposition in 10 excised human hearts with old infarcts. A 2.25 MHz, 50% fractional bandwidth transducer was positioned at the transducer focal distance from the epicardium of each specimen. The radio frequency backscatter signal was digitized, squared, and integrated to yield the integrated ultrasonic backscatter, which was referenced to the backscatter from a water/steel interface. The interrogated myocardium was then excised and divided into two portions. One portion was assayed for hydroxyproline, a marker for collagen. A second portion was sectioned, stained with Masson's trichrome, and studied with the use of a computer-assisted image analysis system. There was a linear correlation between the magnitude of integrated backscatter and myocardial collagen content estimated by hydroxyproline assay (r = .78). Quantitative histologic analysis revealed a variable relationship between the transmural distribution of collagen and the corresponding transmural pattern of the backscatter signal. In two specimens exhibiting a discrete layer of subendocardial fibrosis, the backscatter amplitude was also increased in the subendocardial region. In specimens with other patterns of fibrosis, the local backscatter amplitude did not correspond to the transmural pattern of collagen distribution. We conclude that the quantitative analysis of ultrasonic backscatter shows promise for the noninvasive evaluation of myocardial fibrosis after infarction.
In order to calculate the mean transit time of tissue, such as brain, from dynamic computed tomography performed after a bolus injection of intravenous contrast material, the time dependence of the input of contrast material to the tissue must be "deconvolved" from the observed time course of the tissue contrast enhancement. If the approximate shape of the curve of the response of the tissue to an instantaneous injection of contrast material is assumed, the width of this curve that gives the best fit to the observed tissue response can be used to find a value for the tissue mean transit time. Applying this technique to dynamic CT scans of two normal volunteers yielded values comparable to those in the literature by other techniques. The method has the advantages of being simple to implement, relatively insensitive to noise and the details of the assumed curve shape, and not requiring any curve fitting to correct for recirculation.
The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.
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 (< 1.0 ml/min/g) and high (> 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.
A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.
Myocardial perfusion reserve can be noninvasively assessed with cardiovascular MR. In this study, the diagnostic accuracy of this technique for the detection of significant coronary artery stenosis was evaluated.
In 15 patients with single-vessel coronary artery disease and 5 patients without significant coronary artery disease, the signal intensity-time curves of the first pass of a gadolinium-DTPA bolus injected through a central vein catheter were evaluated before and after dipyridamole infusion to validate the technique. A linear fit was used to determine the upslope, and a cutoff value for the differentiation between the myocardium supplied by stenotic and nonstenotic coronary arteries was defined. The diagnostic accuracy was then examined prospectively in 34 patients with coronary artery disease and was compared with coronary angiography. A significant difference in myocardial perfusion reserve between ischemic and normal myocardial segments (1.08+/-0.23 and 2.33+/-0.41; P<0.001) was found that resulted in a cutoff value of 1.5 (mean minus 2 SD of normal segments). In the prospective analysis, sensitivity, specificity, and diagnostic accuracy for the detection of coronary artery stenosis (> or =75%) were 90%, 83%, and 87%, respectively. Interobserver and intraobserver variabilities for the linear fit were low (r=0.96 and 0.99).
MR first-pass perfusion measurements yielded a high diagnostic accuracy for the detection of coronary artery disease. Myocardial perfusion reserve can be easily and reproducibly determined by a linear fit of the upslope of the signal intensity-time curves.
The purpose of this study was to determine the potential value of magnetic resonance myocardial perfusion in the follow-up of patients after coronary intervention.
In some patients a residual impairment of myocardial perfusion reserve (MPR) early after successful coronary intervention has been observed. In this study we evaluated an MPR index before and after intervention with magnetic resonance.
Thirty-five patients with single- and multivessel coronary artery disease were studied before and 24 h after intervention. The signal intensity time curves of the first pass of a gadolinium-diethylene triamine pentacetic acid bolus injected via a central vein catheter were evaluated before and after dipyridamole infusion. The upslope was determined using a linear fit. Myocardial perfusion reserve index was estimated from the alterations of the upslope.
The MPR index in segments perfused by the stenotic artery was significantly lower than in the control segments (1.07 +/- 0.24 vs. 2.18 +/- 0.35, p < 0.001) and improved significantly after intervention (1.89 +/- 0.39, p < 0.001) but did not normalize completely (p < 0.01). After intervention the MPR index remained significantly lower in the balloon percutaneous transluminal coronary angioplasty group (1.72 +/- 0.38; n = 13) in comparison with the stent group (1.99 +/- 0.36, n = 18, p < 0.05). In the stent group a complete normalization of the MPR index was found 24 h after stenting.
Magnetic resonance perfusion measurements allow a reliable assessment of MPR index. An improvement of MPR index can be observed after coronary intervention, which is more pronounced after stenting. Magnetic resonance perfusion measurements allow the assessment and may be useful for the follow-up of patients with coronary artery disease after coronary intervention.
Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction.
Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences (y=0.96 x+/-0.07, P<0.0001, r(2)=0.87). The 95% confidence limits for individual MRI measurements were +/-35%. Regional differences of >/=2-fold were consistently apparent in unprocessed MR images.
Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of >/=70%.
The study compared flow reserve indices by magnetic resonance imaging (MRI) with quantitative measures of coronary angiography and positron emission tomography (PET).
The noninvasive evaluation of myocardial flow by MRI has recently been introduced. However, a comparison to quantitative flow measurement as assessed by PET has not been reported in patients with coronary artery disease (CAD).
Two groups of healthy volunteers and 25 patients with angiographically documented CAD were examined by MRI and PET at rest and during adenosine stress. Dynamic MRI was performed using a multi-slice ultra-fast hybrid sequence and a rapid gadolinium-diethylenetriaminepenta-acetic acid bolus injection (0.05 mmol/l). Upslope and peak-intensity indices were regionally determined from first-pass signal intensity curves and compared to N-13 ammonia PET flow reserve measurements.
In healthy volunteers, the upslope analysis showed a stress/rest index of 2.1 plus minus 0.6, which was higher than peak intensity (1.5 plus minus 0.3), but lower than flow reserve by PET (3.9 plus minus 1.1). Localization of coronary artery stenoses (> 75%, MRI < 1.2), based on the upslope index, yielded sensitivity, specificity and diagnostic accuracy of 69%, 89% and 79%, respectively. Upslope index correlated with PET flow reserve (r = 0.70). A reduced coronary flow reserve (PET < 2.0, MRI < 1.3) was detected by the upslope index with sensitivity, specificity and diagnostic accuracy of 86%, 84% and 85%, respectively.
Magnetic resonance imaging first-pass perfusion measurements underestimate flow reserve values, but may represent a promising semi-quantitative technique for detection and severity assessment of regional CAD.
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.
It is controversial whether transmyocardial laser revascularization (TMLR) improves myocardial perfusion. Therefore, we assessed myocardial perfusion before and after TMLR with quantitative magnetic resonance perfusion imaging (MRPI) in an animal study.
One week after partial occlusion of the left circumflex artery (LCx) in 12 pigs, resting perfusion (ml/g/min), perfusion reserve (PR) with adenosine, regional wall thickening (RWT), cardiac output (CO) were quantified with MRI in the LCx (lateral) and LAD (septal) dependent myocardium. Subsequently, six animals were treated with TMLR of the lateral left ventricle (LV). Six animals were left untreated. A final MR was performed 8 weeks later. MRPI data were compared to microsphere-derived blood flow and % LV necrosis (TTC). 'Normal' myocardial perfusion was assessed with MRPI in 12 non-instrumented animals.
Resting perfusion prior to TMLR (0.7-0.9+/-0.3) in the LV-lateral myocardium was preserved after TMLR (1.0+/-0.3) and decreased without TMLR (0.3+/-0.1, P<0.05). There was a significant difference (P<0.01) between the TMLR treated and untreated group. Compared to 'normals' (1.2+/-0.2) perfusion of the LV-lateral wall was not different after TMLR but reduced (P<0.02) without TMLR. PR was not different between TMLR-treated (1.4+/-0.9) and untreated (1.9+/-0.6) group but was reduced (P<0.04) compared to PR of 'normals' (2.7+/-0.8). MRPI data and microsphere-derived perfusion were significantly correlated (P<0.01). RWT in the LCx-dependent myocardium improved (P<0.02) after TMLR. CO decreased (P<0.02) and TTC-staining indicated more LV-necrosis without TMLR (6.6+/-1.6 vs. 3.7+/-1.5, P<0.01).
TMLR preserves regional myocardial perfusion and improves function as shown with MRPI.
To determine with an intravascular contrast agent the relation between the rate of myocardial signal enhancement during the first pass (upslope) and myocardial blood flow (MBF), and to derive and validate a corrected perfusion reserve (PR) index from the upslope parameter.
Measurements of the upslope parameter for myocardial contrast enhancement with an intravascular contrast agent (MS-325) were performed in a porcine model with ameroid coronary constrictor. MBF was estimated with MRI and was validated against separate invasive measurements with labeled microspheres. PR indices were calculated from the upslope of the tissue curves. A new PR index was corrected by the time delay between appearance of the tracer and the upslope maximum.
MBFs determined by MRI vs. MBFs measured with microspheres were in agreement within the 95% confidence intervals (CIs) for the identity relation. The new PR index slightly overestimated the MBF reserve by an average +1.4% (95% CI = -44% to +46%). The uncorrected PR index underestimated the MBF reserve by -33% (95% CI = -92% to +25%).
A perfusion index derived from the maximum upslope of myocardial contrast enhancement produces accurate estimates of the PR if corrected by the time-to-maximum upslope.
To develop a method for accurate measurement of the arterial input function (AIF) during high-dose, single-injection, quantitative T1-weighted myocardial perfusion cardiovascular magnetic resonance (CMR).
Fast injection of high-dose gadolinium with highly T1 sensitive myocardial perfusion imaging is normally incompatible with quantitative perfusion modeling because of distortion of the peak of the AIF caused by full recovery of the blood magnetization. We describe a new method that for each cardiac cycle uses a low-resolution short-axis (SA) image with a short saturation-recovery time immediately after the R-wave in order to measure the left ventricular (LV) blood pool signal, which is followed by a single SA high-resolution image with a long saturation-recovery time in order to measure the myocardial signal with high sensitivity. Fifteen subjects were studied. Using the new method, we compared the myocardial perfusion reserve (MPR) with that obtained from the dual-bolus technique (a low-dose bolus to measure the blood pool signal and a high-dose bolus to measure the myocardial signal).
A small significant difference was found between MPRs calculated using the new method and the MPRs calculated using the dual-bolus method.
This new method for measuring the AIF introduced no major error, while removing the practical difficulties of the dual-bolus approach. This suggests that quantification of the MPR can be achieved using the simple high-dose single-bolus technique, which could also image multiple myocardial slices.
The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 x 469 mum and a slice thickness of 2 mm. The T(1) imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions. The group average myocardial perfusion at baseline was determined to be 701 +/- 53 mL (100 g . min)(-1) for anesthesia with isoflurane (N = 11) at a mean heart rate (HR) of 455 +/- 10 beats per minute (bpm). This value is in good agreement with perfusion values determined by invasive microspheres examinations. For i.v. administration of the anesthetic Propofol, the baseline perfusion decreased to 383 +/- 40 mL (100 g . min)(-1) (N = 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 +/- 13 bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial infarction were studied under isoflurane anesthesia (HR 397 +/- 7 bpm). The perfusion maps showed a clear decrease of the perfusion in the infarcted area. The perfusion in the remote myocardium decreased significantly to 476 +/- 81 mL (100 g . min)(-1) (P < 0.05 versus sham). Regarding the regional blood volume, a mean value of 11.8 +/- 0.8 vol % was determined for healthy murine myocardium under anesthesia with Propofol (N = 4, HR 233 +/- 17 bpm). In total, the presented techniques provide noninvasive in vivo assessment of the perfusion and the regional blood volume in the murine myocardium for the first time and seem to be promising tools for the characterization of mouse models in cardiovascular research.
The aim of the study is to develop a theory-based signal calibration approach to be used for the conversion of signal-time curves to absolute contrast concentration-time curves for first-pass contrast-enhanced quantitative myocardial perfusion studies.
A normalization procedure was used to obtain a theoretical relationship between image signal and T1 and perform rapid single-point T1 measurements. T1 measurements were compared with reference T1 measurements. The method also was used in preliminary in vivo contrast-enhanced first-pass perfusion studies, and its applicability for dual-delay-time acquisitions was shown. A theory-based error sensitivity analysis was used to characterize the robustness of the method.
The normalization procedure was implemented with minimal noise enhancement and insensitivity to small misregistrations through postprocessing techniques. The rapid T1 measurements are in excellent agreement with the reference measurements (R = 0.99, slope = 1.05, bias = -5.96 milliseconds). For in vivo studies, it is possible to simultaneously calibrate the arterial input function and myocardial enhancement curves acquired with different effective trigger delays through appropriate use of the theory-based signal calibration model. With this method, errors of in vivo baseline T1 estimates are large, but the effect of these large errors on the accuracy of contrast agent concentration estimates is limited.
This theory-based signal calibration approach can be used to perform rapid T1 mapping and provides flexibility for in vivo calibration of signal-time curves resulting from dual-delay-time first-pass contrast-enhanced acquisitions.
Coronary artery disease (CAD), a leading cause of death in the US and worldwide, can be effectively diagnosed and assessed using non-invasive myocardial perfusion MRI. Tracer kinetic models play a crucial role in the analysis and quantification of perfusion. In this work, we evaluate the performance of 3 different kinetic models used to analyze perfusion: (a) a modified 2-compartment model (b) the Johnson-Wilson (JW) model and (c) a modified JW model. We hypothesized that three different models would give statistically different results and that the modified JW model would be better than the other two because it would most closely model the underlying physiological processes. Results indicate that the models are statistically different from each other but the 2-compartment model is more stable than both models (b) and (c) and that the modified JW model is the most sensitive to ischemia as compared to the others.
Counterexamples are used to motivate the revision of the established theory of tracer transport. Then dynamic contrast enhanced magnetic resonance imaging in particular is conceptualized in terms of a fully distributed convection-diffusion model from which a widely used convolution model is derived using, alternatively, compartmental discretizations or semigroup theory. On this basis, applications and limitations of the convolution model are identified. For instance, it is proved that perfusion and tissue exchange states cannot be identified on the basis of a single convolution equation alone. Yet under certain assumptions, particularly that flux is purely convective at the boundary of a tissue region, physiological parameters such as mean transit time, effective volume fraction, and volumetric flow rate per unit tissue volume can be deduced from the kernel.
To study the nonlinearity of myocardial signal intensity and gadolinium contrast concentration during first-pass perfusion MRI, and to compare quantitative perfusion estimates using nonlinear myocardial signal intensity correction.
The nonlinearity of signal intensity and contrast concentration was simulated by magnetization modeling and evaluated in phantom measurements. A total of 10 healthy volunteers underwent rest and stress dual-bolus perfusion studies using an echo-planar imaging sequence at both short and long saturation-recovery delay times (TD70 and TD150). Perfusion estimates were compared before and after the correction.
The phantom data showed a linear relationship (R(2) = 1.00 and 0.99) of corrected signal intensity vs. contrast concentrations. Peak myocardial contrast concentration averaged 0.64 +/- 0.10 mmol x L(-1) at rest and 0.91 +/- 0.21 mmol x L(-1) during stress for TD70 and were similar for TD150 (P = not significant [NS]). The corrections were larger for stress than rest perfusion and larger for TD150 than TD70 studies (both P < 0.01). Perfusion estimates of TD70 and TD150 stress studies were significantly different before the correction (P < 0.01) but equivalent after the correction (P = NS).
The nonlinearity between signal intensity and myocardial contrast concentration in perfusion MRI can be corrected through magnetization modeling. A nonlinear correction of myocardial signal intensity is feasible and improves quantitative perfusion analysis.
To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF).
Dogs had local hyperemia of MBF in the left anterior descending (LAD) coronary artery (intracoronary adenosine). Animals (n = 6) had sequential single- and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROI).
Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROI was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion.
Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results.
Dynamic perfusion studies by ultrafast MR imaging: initial clinical results from cardiology
- N Wilke
- T Maching
- G Engels
Blind system identification. Paper presented at: Proceedings of the IEEE
- K Abed-Merain
- W Qui
- Y Hua