Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

RATIONALE: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. OBJECTIVES: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. METHODS: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. MEASUREMENTS AND MAIN RESULTS: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. CONCLUSIONS: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic resonance imaging and their relationships to global lung perfusion and lung diffusing capacity: the multiethnic study of atherosclerosis chronic obstructive pulmonary disease study.

OBJECTIVES: The aim of this study was to evaluate the quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO). MATERIALS AND METHODS: A total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined. RESULTS: Quantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements. CONCLUSION: Regional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging-derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.

In hypertrophic cardiomyopathy reduction of relative resting myocardial blood flow is related to late enhancement, T2-signal and LV wall thickness.

OBJECTIVES: To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract obstruction and age. MATERIALS AND METHODS: Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal), LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher's exact test. RESULTS: 804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (p = 0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p = 0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (p = 0.026) and T2 dark signal (p = 0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion. CONCLUSION: In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease.

Right and left ventricular myocardial perfusion reserves correlate with right ventricular function and pulmonary hemodynamics in patients with pulmonary arterial hypertension.

PURPOSE: To evaluate the relationships of right ventricular (RV) and left ventricular (LV) myocardial perfusion reserves with ventricular function and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) by using adenosine stress perfusion cardiac magnetic resonance (MR) imaging. MATERIALS AND METHODS: This HIPAA-compliant study was institutional review board approved. Twenty-five patients known or suspected to have PAH underwent right heart catheterization and adenosine stress MR imaging on the same day. Sixteen matched healthy control subjects underwent cardiac MR imaging only. RV and LV perfusion values at rest and at adenosine-induced stress were calculated by using the Fermi function model. The MR imaging-derived RV and LV functional data were calculated by using dedicated software. Statistical testing included Kruskal-Wallis tests for continuous data, Spearman rank correlation tests, and multiple linear regression analyses. RESULTS: Seventeen of the 25 patients had PAH: 11 with scleroderma-associated PAH, and six with idiopathic PAH. The remaining eight patients had scleroderma without PAH. The myocardial perfusion reserve indexes (MPRIs) in the PAH group (median RV MPRI, 1.7 [25th-75th percentile range, 1.3-2.0]; median LV MPRI, 1.8 [25th-75th percentile range, 1.6-2.1]) were significantly lower than those in the scleroderma non-PAH (median RV MPRI, 2.5 [25th-75th percentile range, 1.8-3.9] [P = .03]; median LV MPRI, 4.1 [25th-75th percentile range, 2.6-4.8] [P = .0003]) and control (median RV MPRI, 2.9 [25th-75th percentile range, 2.6-3.6] [P < .01]; median LV MPRI, 3.6 [25th-75th percentile range, 2.7-4.1] [P < .01]) groups. There were significant correlations between biventricular MPRI and both mean pulmonary arterial pressure (mPAP) (RV MPRI: ρ = -0.59, Bonferroni P = .036; LV MPRI: ρ = -0.79, Bonferroni P < .002) and RV stroke work index (RV MPRI: ρ = -0.63, Bonferroni P = .01; LV MPRI: ρ = -0.75, Bonferroni P < .002). In linear regression analysis, mPAP and RV ejection fraction were independent predictors of RV MPRI. mPAP was an independent predictor of LV MPRI. CONCLUSION: Biventricular vasoreactivity is significantly reduced with PAH and inversely correlated with RV workload and ejection fraction, suggesting that reduced myocardial perfusion reserve may contribute to RV dysfunction in patients with PAH.

Improvement of hyperemic myocardial oxygen extraction fraction estimation by a diffusion-prepared sequence.

Myocardial oxygen extraction fraction (OEF) during hyperemia can be estimated using a double-inversion-recovery-prepared T(2)-weighted black-blood sequence. Severe irregular electrocardiogram (ECG) triggering due to elevated heart rate and/or arrhythmias may render it difficult to adequately suppress the flowing left ventricle blood signal and thus potentially cause errors in the estimates of myocardial OEF. Thus, the goal of this study was to evaluate another black-blood technique, a diffusion-weighted-prepared turbo spin echo sequence for its ability to determine regional myocardial OEF during hyperemia. Control dogs and dogs with acute coronary artery stenosis were imaged with both the double-inversion-recovery- and diffusion-weighted-prepared turbo spin echo sequences at rest and during either dipyridamole or dobutamine hyperemia. Validation of MRI OEF estimates was performed using blood sampling from the artery and coronary sinus in control dogs. The two methods showed comparable correlations with blood sampling results (R(2) = 0.9). Similar OEF estimations for all dogs were observed, except for the group of dogs with severe coronary stenosis during dobutamine stress. In these dogs, the diffusion-weighted method provided more physiologically reasonable OEF (hyperemic OEF = 0.75 +/- 0.08 versus resting OEF of 0.6) than the double-inversion-recovery method (hyperemic OEF = 0.56 +/- 0.10). Diffusion-weighted preparation may be a valuable alternative for more accurate oxygenation measurements during irregular ECG-triggering.

Roles of myocardial blood volume and flow in coronary artery disease: an experimental MRI study at rest and during hyperemia.

OBJECTIVE: To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. METHODS: A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and (99m)Tc-labeled red blood cells were injected to obtain respective gold standards. RESULTS: Microsphere-measured MBF and (99m)Tc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. CONCLUSIONS: MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion.

Quantification of regional myocardial oxygenation by magnetic resonance imaging: validation with positron emission tomography.

BACKGROUND: A comprehensive evaluation of myocardial ischemia requires measures of both oxygen supply and demand. Positron emission tomography (PET) is currently the gold standard for such evaluations, but its use is limited because of its ionizing radiation, limited availability, and high cost. A cardiac MRI method was developed for assessing myocardial oxygenation. The purpose of this study was to evaluate and validate this technique compared with PET during pharmacological stress in a canine model of coronary artery stenosis. METHODS AND RESULTS: Twenty-one beagles and small mongrel dogs without coronary artery stenosis (controls) or with moderate to severe acute coronary artery stenosis underwent MRI and PET imaging at rest and during dipyridamole vasodilation or dobutamine stress to induce a wide range of changes in cardiac perfusion and oxygenation. MRI first-pass perfusion imaging was performed to quantify myocardial blood flow and volume. The MRI blood oxygen level-dependent technique was used to determine the myocardial oxygen extraction fraction during pharmacological hyperemia. Myocardial oxygen consumption was determined by the Fick law. In the same dogs, (15)O-water and (11)C-acetate were used to measure myocardial blood flow and myocardial oxygen consumption, respectively, by PET. Regional assessments were performed for both MR and PET. MRI data correlated nicely with PET values for myocardial blood flow (R(2)=0.79, P<0.001), myocardial oxygen consumption (R(2)=0.74, P<0.001), and oxygen extraction fraction (R(2)=0.66, P<0.01). CONCLUSIONS: Cardiac MRI methods may provide an alternative to radionuclide imaging in settings of myocardial ischemia. Our newly developed quantitative MRI oxygenation imaging technique may be a valuable noninvasive tool to directly evaluate myocardial energetics and efficiency.

Myocardial blood volume is associated with myocardial oxygen consumption: an experimental study with cardiac magnetic resonance in a canine model.

Understanding the oxygen consumption of the left ventricular myocardium provides important insight into the relationship between myocardial oxygen supply and demand. In other territories, cardiac magnetic resonance has been utilized to measure myocardial oxygen consumption with a blood level oxygen dependent (BOLD) technique. The BOLD technology requires repetitive sampling of stationary tissues and is frequently implemented in areas such as the brain. A limitation to utilizing BOLD cardiac magnetic resonance techniques in the heart has been cardiac motion. In this study, we document a methodology for acquiring BOLD images in the heart and demonstrate the utility of the technique for identifying associations between myocardial oxygen consumption and blood flow.

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.

Quantification of myocardial blood volume during dipyridamole and doubtamine stress: a perfusion CMR study.

PURPOSE: Myocardial blood volume (MBV) may provide complementary information about myocardial oxygen needs and viability. The aim of this study is to examine a Cardiovascular Magnetic Resonance (CMR) perfusion method to quantify the changes in MBV, in comparison with the radiolabeled 99mTc-Red-Blood-Cell (RBC) method. METHODS: Normal mongrel dogs (n=12) were used in this study. Eight dogs were injected intravenously with dipyridamole, and 4 dogs were given dobutamine during the MR scans. CMR first-pass perfusion imaging was performed at rest and during the pharmacological stress. An intravascular contrast agent, Gadomer (Schering AG, Berlin, Germany), was injected (0.015 mmol/kg) as a bolus during the scans. A perfusion quantification method was applied to obtain MBV maps. Radiolabeled-RBCs were injected at the end of the study to measure reference MBV at rest (n=4), during dipyridamole vasodilation (n=4), and during dobutamine stress (n=4). RESULTS: Myocardial blood flow (MBF) increased approximately 3-fold with both dipyridamole and dobutamine injections. Transmural MBV values measured by CMR were closely correlated with those measured by 99mTc method (CMR:MBV=6.2+/-1.3, 7.2+/-0.8, and 8.3+/-0.5 mL/100 g, at rest, with dipyridamole, and with dobutamine, respectively. 99mTc-RBC: MBV=6.1+/-0.5, 7.0+/-0.9, and 8.6+/-0.7 mL/100 g). Dobutamine stress significantly increased MBV by CMR (33%) and 99mTc methods (35%). During dipyridamole induced vasodilation, MBV increased non-significantly by 14% with the 99mTc method and 1% with CMR method, which agreed well with other reports. CONCLUSION: First-pass perfusion CMR with the injection of intravascular contrast agents is a promising non-invasive approach for the assessment of MBV both at rest and pharmacologically induced stress.

Improvement of quantification of myocardial first-pass perfusion mapping: a temporal and spatial wavelet denoising method.

Mapping of myocardial blood flow (MBF) with first-pass perfusion imaging is becoming an important tool in the study of coronary artery disease. In this study a wavelet-based denoising method was developed to improve the accuracy of pixel-by-pixel MBF maps. We performed an in vivo study in five stenotic dogs with 70% stenosis in the left coronary arteries. First-pass perfusion imaging sessions were performed by administering the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Color microspheres (MS) were injected into the dogs to measure MBF at the same time. After denoising was performed, the signal-to-noise ratio (SNR) of the first-pass perfusion image improved by approximately 180%, whereas spatial variation of MBF maps decreased 38%. It was also found that the correlation of MBFs measured by MRI with the MS method indicates a significant improvement with the denoising method (R2 increased from 0.24 to 0.78, P < .001). This suggests that the wavelet denoising method may be an effective way to increase the accuracy of pixel-by-pixel MBF quantification and reduce spatial variation, and may be applicable to other forms of noise-sensitive image analysis.