Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced first-pass MRI technique in humans

PURPOSE: To compare fully quantitative and semiquantitative analysis of rest and stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using a dual-bolus first-pass perfusion MRI method in humans. MATERIALS AND METHODS: Rest and dipyridamole stress perfusion imaging was performed on 10 healthy humans by administering gadolinium contrast using a dual-bolus protocol. Ventricular and myocardial time-signal intensity curves were generated from a series of T1-weighted images and adjusted for surface-coil intensity variations. Corrected signal intensity curves were then fitted using fully quantitative model constrained deconvolution (MCD) to quantify MBF (mL/min/g) and MPR. The results were compared with semiquantitative contrast enhancement ratio (CER) and upslope index (SLP) measurements. RESULTS: MBF (mL/min/g) estimated with MCD averaged 1.02 +/- 0.22 at rest and 3.39 +/- 0.59 for stress with no overlap in measures. MPR was 3.43 +/- 0.71, 1.91 +/- 0.65, and 1.16 +/- 0.19 using MCD, SLP, and CER. Both semiquantitative parameters (SLP and CER) significantly underestimated MPR (P < 0.001) and failed to completely discriminate rest and stress perfusion. CONCLUSION: Rest and stress MBF (mL/min/g) and MPR estimated by dual-bolus perfusion MRI fit within published ranges. Semiquantitative methods (SLP and CER) significantly underestimated MPR.     

Fast mapping of myocardial blood flow with MR first-pass perfusion imaging.

Accurate and fast quantification of myocardial blood flow (MBF) with MR first-pass perfusion imaging techniques on a pixel-by-pixel basis remains difficult due to relatively long calculation times and noise-sensitive algorithms. In this study, Zierler's central volume principle was used to develop an algorithm for the calculation of MBF with few assumptions on the shapes of residue curves. Simulation was performed to evaluate the accuracy of this algorithm in the determination of MBF. To examine our algorithm in vivo, studies were performed in nine normal dogs. Two first-pass perfusion imaging sessions were performed with the administration of the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Radiolabeled microspheres were injected to measure MBF at the same time. MBF measurements in dogs using MR methods correlated well with the microsphere measurements (R2=0.96, slope=0.9), demonstrating a fair accuracy in the perfusion measurements at rest and during the vasodilation stress. In addition to its accuracy, this method can also be optimized to run relatively fast, providing potential for fast and accurate myocardial perfusion mapping in a clinical setting.     

Noninvasive determination of regional myocardial perfusion with first-pass magnetic resonance (MR) imaging

RATIONALE AND OBJECTIVES: To develop a method to provide absolute values of regional myocardial perfusion by means of color maps, and to determine myocardial perfusion reserve using magnetic resonance imaging during the first pass of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). MATERIALS AND METHODS: The study population consisted of five patients with hypertrophic cardiomyopathy, two with dilated cardiomyopathy, four with coronary artery disease, and one with normal coronary arteries who presented with mildly abnormal electrocardiogram findings. For each heartbeat, six continuous slices were acquired during the first pass of Gd-DTPA (0.05 mmol/kg body weight) before and during adenosine triphosphate (ATP) **stress using an electrocardiogram-triggered fast low-angle shot (FLASH) sequence on a 1.5-T magnetic resonance unit. Myocardial perfusion images were created and displayed by means of a color scale. The parameters were calculated pixel by pixel, using the upslope method. Myocardial perfusion reserve was then calculated, as the quotient of myocardial perfusion during ATP stress and perfusion before ATP stress. RESULTS: Myocardial perfusion during ATP stress in patients with normal coronary arteries (n = 1) or after successful percutaneous coronary intervention (n = 2) was increased compared with that before ATP stress. However, the patients with coronary artery disease (n = 2) failed to show increased myocardial perfusion. The patients with hypertrophic cardiomyopathy showed increased myocardial perfusion during ATP stress, although two with dilated cardiomyopathy did not. CONCLUSION: Our new technique can provide absolute values of regional myocardial perfusion by means of color maps, and has potential for widespread use for evaluation of ischemic and other types of heart disease.     

Nonlinear myocardial signal intensity correction improves quantification of contrast-enhanced first-pass MR perfusion in humans

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.     

PET心肌灌注显像测定心肌血流量及冠状动脉血流储备的研究进展

PET心肌灌注显像可绝对定量测定局部心肌血流量（MBF）和冠状动脉血流储备（CFR）。由于显像剂半衰期短,允许在短时间内重复进行PET心肌灌注显像,获得静息态、冷加压试验和药物负荷试验等不同状态下的MBF,进而评价冠状动脉血管内皮依赖性和非依赖性的CFR功能。在早期诊断冠心病,准确诊断冠状动脉多支病变,评价微血管病变,早期检测冠状动脉内皮细胞功能异常及CFR功能的异常,估测预后,帮助临床治疗方案的制定以及检测疗效等方面,PET心肌灌注显像有重要的临床价值。该文将介绍PET心肌灌注显像相关知识及其在心血管领域的主要应用。     

Quantification of myocardial blood flow using model based analysis of first‐pass perfusion MRI: Extraction fraction of Gd‐DTPA varies with myocardial blood flow in human myocardium

For the absolute quantification of myocardial blood flow (MBF), Patlak plot‐derived K1 need to be converted to MBF by using the relation between the extraction fraction of gadolinium contrast agent and MBF. This study was conducted to determine the relation between extraction fraction of Gd‐DTPA and MBF in human heart at rest and during stress. Thirty‐four patients (19 men, mean age of 66.5 ± 11.0 years) with normal coronary arteries and no myocardial infarction were retrospectively evaluated. First‐pass myocardial perfusion MRI during adenosine triphosphate stress and at rest was performed using a dual bolus approach to correct for saturation of the blood signal. Myocardial K1 was quantified by Patlak plot method. Mean MBF was determined from coronary sinus flow measured by phase contrast cine MRI and left ventricle mass measured by cine MRI. The extraction fraction of Gd‐DTPA was calculated as the K1 divided by the mean MBF. The extraction fraction of Gd‐DTPA was 0.46 ± 0.22 at rest and 0.32 ± 0.13 during stress (P < 0.001). The relationship between extraction fraction (E) and MBF in human myocardium can be approximated as E = 1 ? exp(?(0.14 × MBF + 0.56)/MBF). The current results indicate that MBF can be accurately quantified by Patlak plot method of first‐pass myocardial perfusion MRI by performing a correction of extraction fraction. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Mapping myocardial perfusion with an intravascular MR contrast agent: robustness of deconvolution methods at various blood flows.

Evaluation of quantitative parameters such as regional myocardial blood flow (rMBF), blood volume (rMBV), and mean transit time (rMTT) by MRI is gaining acceptance for clinical applications, but still lacks robust postprocessing methods for map generation. Moreover, robustness should be preserved over the full range of myocardial flows and volumes. Using experimental data from an isolated pig heart preparation, synthetic MR kinetics were generated and four deconvolution approaches were evaluated. These methods were then applied to the first-pass T(1) images of the isolated pig heart using an intravascular contrast agent and rMBF, rMBV and rMTT maps were generated. In both synthetic and experimental data, the fit between calculated and original data reached equally good results with the four techniques. rMBV was the only parameter estimated correctly in numerical experiments. Moreover, using the algebraic method ARMA, abnormal regions were well delineated on rMBV maps. At high flows, rMBF was underestimated at the experimental noise level. Finally, rMTT maps appeared noisy and highly unreliable, especially at high flows. In conclusion, over the myocardial flow range, i.e., 0-400 ml/min/100g, rMBF identification was biased in presence of noise, whereas rMBV was correctly identified. Thus, rMBV mapping could be a fast and robust way to detect abnormal myocardial regions.     

Single- or dual-bolus approach for the assessment of myocardial perfusion reserve in quantitative MR perfusion imaging.

A dual-bolus protocol can overcome limitations due to T1-induced MR signal attenuation and hence enables more accurate quantification of myocardial blood flow (MBF) by contrast enhanced MR perfusion imaging. The study explores potential benefits of the dual-bolus technique for the assessment of myocardial perfusion reserve (MPR) over a standard single-bolus protocol. Nineteen patients without obstructive coronary artery disease as assessed by cardiac catheterization underwent a stress-rest MR perfusion study using a dual-bolus protocol. Gd-DTPA dosages of 0.005 and 0.05 mmol/kg of bodyweight were delivered as pre- and main-bolus. For comparison arterial input curves where extracted from left ventricular cavity passage including both, pre-bolus and main-bolus data. Global and segmental MPR were determined from semiquantitative and from full quantitative measures of MBF. As a result good agreement between dual- and single-bolus technique was found with relative differences of maximally 10% in global MPR estimates. For the dual bolus approach a significant relative decrease of 30% (P<0.001) was found for the coefficient of segmental MPR variation, which may allow a more reliable detection of hypoperfused segments in clinical studies.     

Quantitative analysis of first‐pass contrast‐enhanced myocardial perfusion MRI using a patlak plot method and blood saturation correction

The objectives of this study were to develop a method for quantifying myocardial K₁ and blood flow (MBF) with minimal operator interaction by using a Patlak plot method and to compare the MBF obtained by perfusion MRI with that from coronary sinus blood flow in the resting state. A method that can correct for the nonlinearity of the blood time–signal intensity curve on perfusion MR images was developed. Myocardial perfusion MR images were acquired with a saturation‐recovery balanced turbo field‐echo sequence in 10 patients. Coronary sinus blood flow was determined by phase‐contrast cine MRI, and the average MBF was calculated as coronary sinus blood flow divided by left ventricular (LV) mass obtained by cine MRI. Patlak plot analysis was performed using the saturation‐corrected blood time–signal intensity curve as an input function and the regional myocardial time–signal intensity curve as an output function. The mean MBF obtained by perfusion MRI was 86 ± 25 ml/min/100 g, showing good agreement with MBF calculated from coronary sinus blood flow (89 ± 30 ml/min/100 g, r = 0.74). The mean coefficient of variation for measuring regional MBF in 16 LV myocardial segments was 0.11. The current method using Patlak plot permits quantification of MBF with operator interaction limited to tracing the LV wall contours, registration, and time delays. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Absolute blood contrast concentration and blood signal saturation on myocardial perfusion MRI: Estimation from CT data

Purpose

To determine the optimal contrast injection rate and absolute blood gadolinium concentration for optimal first‐pass imaging.

Materials and Methods

The concentration of contrast medium in left ventricle (LV) was estimated from dynamic computed tomography (CT) by administering iodinated contrast medium of volume (0.2 mL/kg) equivalent to 0.1 mmol/kg of gadolinium injection in 50 subjects. A blood sample study was performed to determine the relationship between blood signal and gadolinium concentration on perfusion MRI.

Results

The mean peak gadolinium concentration in LV increased as the injection rate increased from 1 mL/sec (3.7 ± 1.2 mM), to 4 mL/sec (6.9 ± 2.7 mM) (P < 0.01). However, no significant improvement was found with an increase in the injection rate from 4 mL/sec to 5 mL/sec (6.8 ± 1.5 mM, P = 0.86). In a blood sample study the linear relationship between blood signal and gadolinium concentration was maintained in the range of ≤0.67 mM (r = 0.992), which corresponds to a peak blood concentration following a 0.01 mmol/kg gadolinium injection.

Conclusion

The optimal contrast injection rate for myocardial perfusion magnetic resonance imaging (MRI) appears to be 4 mL/sec. Saturation of arterial input signal is inevitable if the dose of gadolinium contrast medium exceeds 0.01 mmol/kg. These findings are essential for accurate quantification of myocardial blood flow from perfusion MRI. J. Magn. Reson. Imaging 2009;29:205–210. © 2008 Wiley‐Liss, Inc.     

Steady-state free precession sequences in myocardial first-pass perfusion MR imaging: comparison with TurboFLASH imaging

The aim of this study was to compare the image quality of a saturation-recovery gradient-recalled echo (GRE; TurboFLASH) and a saturation-recovery SSFP (SR-TrueFISP) sequence for myocardial first-pass perfusion MRI. Eight patients with chronic myocardial infarction and 8 volunteers were examined with a TurboFLASH (TR 2.1 ms, TE 1 ms, FA 8°) and a SR-TrueFISP sequence (TR 2.1 ms, TE 0.9 ms, FA, 50°) on a 1.5 T scanner. During injection of 0.05 mmol/kg BW Gd-DTPA at 4 ml/s, three short axis slices (8 mm) of the left ventricle (LV) were simultaneously scanned during breath-hold. Maximum signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) between infarcted and normal myocardium, and percentage signal intensity change (PSIC) were measured within the LV lumen and in four regions of the LV myocardium for the three slices separately. For the LV lumen, SR-TrueFISP was superior in SNR and PSIC (factor 3.2 and 1.6, respectively). Mean maximum SNR, PSIC, and CNR during peak enhancement in the LV myocardium were higher for SR-TrueFISP compared with TurboFLASH (factor 2.4, 1.25, and 1.24, respectively). The SNR was higher in the septal portion of the ventricle than in anterior/posterior and lateral regions. The SR-TrueFISP provides higher SNR and improves image quality compared with TurboFLASH in first-pass myocardial perfusion MRI.     

Multislice MR first-pass myocardial perfusion imaging: impact of the receiver coil array

PURPOSE: To compare a new 12-element body phased-array coil with a conventional four-element surface receiver coil array to provide increased signal-to-noise ratios (SNRs) for cardiac steady state free precession (SSFP) perfusion imaging. MATERIALS AND METHODS: Thirteen consecutive patients were included in the study. Patients were examined both with a four-element surface coil array and a 12-element body coil array. First-pass myocardial perfusion imaging using saturation recovery SSFP was acquired during antecubital injection of Gd-DTPA. Imaging parameters: TR 2.8 msec/TE 1.3 msec, flip angle 50 degrees , bandwidth 960 Hz/pixel and half-Fourier acquisition. SNR was calculated using six regions of interest (ROI) for the myocardial perfusion scans. Calculations of corresponding ROIs using the two different coil setups were compared using analysis of variance (ANOVA). Semiquantitative perfusion parameters were calculated for both groups. RESULTS: The mean SNR in myocardial perfusion imaging increased by 21% using the 12-element coil setup (P < 0.001) when compared to the four-element coil. ROI comparisons revealed an increased signal inhomogeneity with the 12-element coil when compared to four-element coil experiments. Absolute normal range values of semiquantitative perfusion parameters were consistently higher using the 12-element coil setup (P < 0.001). CONCLUSION: The 12-element coil array provides higher SNR, but these improvements come with trade-offs in image homogeneity. Increased SNR translates into higher semiquantitative perfusion values and offers the potential for improved detection of perfusion defects.     

BASE imaging: A new spin labeling technique for measuring absolute perfusion changes

A new technique for magnetic resonance imaging of absolute perfusion changes that uses magnetically labeled tissue water proton spins as a freely diffusible tracer is described. It consists of unprepared basis (BA) images that serve as a reference and selective (SE) inversion prepared images that are sensitive to perfusion changes. In the present study, the BASE technique was applied to functional neuroimaging. BA and SE images were alternatingly and repeatedly acquired during periods of visual stimulation and control. Visual stimulation was achieved with an alternating black/white checkerboard operating at a frequency of 8 Hz. Maps of the absolute cerebral blood flow changes (ACBF) were calculated from the image intensities of the corresponding BA and SE images. The individual mean values of ACBF measured in five healthy volunteers ranged from 69 ± 18 to 99 ± 26 ml/min/100 g. Since the BASE technique does not require nonselective spin inversion, it can be used with small transmit/receive head coils (e.g., surface coils). In addition, the BASE technique is robust against a mismatch of the inversion and detection slice profiles.     

Reproducibility of first‐pass cardiovascular magnetic resonance myocardial perfusion

Purpose:

To assess the reproducibility of semiquantitative and quantitative analysis of first‐pass myocardial perfusion cardiovascular magnetic resonance (CMR) in healthy volunteers.

Materials and Methods:

Eleven volunteers underwent myocardial perfusion CMR during adenosine stress and rest on 2 separate days. Perfusion data were acquired in a single mid‐ventricular section in two cardiac phases to permit cardiac phase reproducibility comparisons. Semiquantitative analysis was performed to derive normalized upslopes of myocardial signal intensity profiles (myocardial perfusion index, MPI). The quantitative analysis estimated absolute myocardial blood flow (MBF) using Fermi‐constrained deconvolution. The perfusion reserve index was calculated by dividing stress by rest data. Two observers performed all the measurements independently. One observer repeated all first scan measurements 4 weeks later.

Results:

The reproducibility of perfusion CMR was highest for semiquantitative analysis with an intraobserver coefficient of variability (CoV) of 3%–7% and interobserver CoV of 4%–10%. Semiquantitative interstudy comparison was less reproducible (CoV of 13%–27%). Quantitative intraobserver CoV of 10%–18%, interobserver CoV of 8%–15% and interstudy CoV of 20%–41%. Reproducibility of systolic and diastolic phases and the endocardial and epicardial myocardial layer showed similar reproducibility on both semiquantitative and quantitative analysis.

Conclusion:

The reproducibility of CMR myocardial perfusion estimates is good, but varies between intraobserver, interobserver, and interstudy comparisons. In this study semiquantitative analysis was more reproducible than quantitative analysis. J. Magn. Reson. Imaging 2013;37:865–874. © 2013 Wiley Periodicals, Inc.     

Multislice first-pass cardiac perfusion MRI: validation in a model of myocardial infarction.

The purpose of this study was to validate a first-pass MRI method for imaging myocardial perfusion with multislice coverage and relatively small analyzable regions of interest (ROIs). A fast gradient-echo (FGRE) sequence with an echo-train (ET) readout was used to achieve multislice coverage, and a high dose of a contrast agent (CA) was used to achieve a high signal-to-noise ratio (SNR). Dogs (N = 6) were studied 1 day after reperfused myocardial infarction, and fluorescent microspheres were used as a standard for perfusion. First-pass MRI correlated well vs. microsphere flow, achieving mean R values of 0.87 (range = 0.82-0.93), 0.71 (range = 0.46-0.85), and 0.72 (range = 0.49-0.95) for subendocardial ROIs, transmural ROIs, and the endocardial-epicardial ratio, respectively. Additionally, analysis of myocardial time-intensity curves (TICs) indicated that 15.8 +/- 6 sectors, corresponding to 260 microl of endocardium, can be analyzed (R(2) > 0.95).