Limits of detection of regional differences in vasodilated flow in viable myocardium by first-pass magnetic resonance perfusion imaging.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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%.

An improved MR imaging technique for the visualization of myocardial infarction.

PURPOSE: To design a segmented inversion-recovery turbo fast low-angle shot (turboFLASH) magnetic resonance (MR) imaging pulse sequence for the visualization of myocardial infarction, compare this technique with other MR imaging approaches in a canine model of ischemic injury, and evaluate its utility in patients with coronary artery disease. MATERIALS AND METHODS: Six dogs and 18 patients were examined. In dogs, infarction was produced and images were acquired by using 10 different pulse sequences. In patients, the segmented turboFLASH technique was used to acquire contrast material-enhanced images 19 days +/- 7 (SD) after myocardial infarction. RESULTS: Myocardial regions of increased signal intensity were observed in all animals and patients at imaging. With the postcontrast segmented turboFLASH sequence, the signal intensity of the infarcted myocardium was 1,080% +/- 214 higher than that of the normal myocardium in dogs-nearly twice that of the next best sequence tested and approximately 10-fold greater than that in previous reports. All 18 patients with myocardial infarction demonstrated high signal intensity at imaging. On average, the signal intensity of the high-signal-intensity regions in patients was 485% +/- 43 higher than that of the normal myocardium. CONCLUSION: The segmented inversion-recovery turboFLASH sequence produced the greatest differences in regional myocardial signal intensity in animals. Application of this technique in patients with infarction substantially improved differentiation between injured and normal regions.

Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing.

OBJECTIVES: We sought to determine the relationship of delayed hyperenhancement by contrast magnetic resonance imaging (MRI) to viable and nonviable myocardium within the region at risk throughout infarct healing. BACKGROUND: The relationship of delayed MRI contrast enhancement patterns to injured but viable myocardium within the ischemic bed at risk has not been established. METHODS: We compared in vivo and ex vivo MRI contrast enhancement to histopathologic tissue sections encompassing the entire left ventricle in dogs (n = 24) subjected to infarction with (n = 12) and without (n = 12) reperfusion at 4 h, 1 day, 3 days, 10 days, 4 weeks and 8 weeks. In vivo MR imaging was performed 30 min after contrast injection. RESULTS: The sizes and shapes of in vivo myocardial regions of elevated image intensity (828+/-132% of remote) were the same as those observed ex vivo (241 slices, r = 0.99, bias = 0.05+/-1.6% of left ventricle [LV]). Comparison of ex vivo MRI to triphenyltetrazolim chloride-stained sections demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent ofinfarction at every stage of healing (510 slices, lowest r = 0.95, largest bias = 1.7+/-2.9% of LV). Conversely, hyperenhanced regions were smaller than the ischemic bed at risk defined by fluorescent microparticles at every stage of healing (239 slices, 35+/-24% of risk region, p<0.001). Image intensities of viable myocardium within the risk region were the same as those of remote, normal myocardium (102+/-9% of remote, p = NS). CONCLUSIONS: Delayed contrast enhancement by MRI distinguishes between viable and nonviable regions within the myocardium at risk throughout infarct healing.

Early assessment of myocardial salvage by contrast-enhanced magnetic resonance imaging.

BACKGROUND: Myocardial salvage after acute myocardial infarction is defined clinically by early restoration of flow and long-term improvement in contractile function. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI), performed early after myocardial infarction, indexes myocardial salvage. We studied the relationship between the transmural extent of hyperenhancement by contrast-enhanced MRI, restoration of flow, and recovery of function. METHODS AND RESULTS: The left anterior descending coronary artery was occluded in dogs (n=15) for either 45 minutes, 90 minutes, or permanently. Cine and contrast-enhanced MRI were performed 3 days after the procedure; cine MRI was also done 10 and 28 days after the procedure. The transmural extent of hyperenhancement and wall thickening were determined using a 60-segment model. The mean transmural extent of hyperenhancement for the 45-minute occlusion group was 22% of the 90-minute group and 18% of the permanent occlusion group (P:<0.05 for both). The transmural extent of hyperenhancement on day 3 was related to future improvement in both wall thickening score and absolute wall thickening at 10 and 28 days (P:<0.0001 for each). For example, of the 415 segments on day 3 that were dysfunctional and had <25% transmural hyperenhancement, 362 (87%) improved by day 28. Conversely, no segments (0 of 9) with 100% hyperenhancement improved. The transmural extent of hyperenhancement on day 3 was a better predictor of improvement in contractile function than occlusion time (P:<0.0001). CONCLUSIONS: A reduction in the transmural extent of hyperenhancement by contrast-enhanced MRI early after myocardial infarction is associated with an early restoration of flow and future improvement in contractile function.

Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function.

BACKGROUND: Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction. METHODS AND RESULTS: In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001). CONCLUSIONS: In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.

Relationship of elevated 23Na magnetic resonance image intensity to infarct size after acute reperfused myocardial infarction.

BACKGROUND: Elevated 23Na MR image intensity after acute myocardial infarction has previously been shown to correspond to high tissue [Na+] and loss of myocardial viability. In this study, we explored the potential of in vivo 23Na MRI to assess infarct size and investigated possible mechanisms for elevated 23Na image intensity. METHODS AND RESULTS: Thirteen dogs and 8 rabbits underwent in situ coronary artery occlusion and reperfusion and were imaged by 23Na MRI. For anatomically matched left ventricular short-axis cross sections (n=46), infarct size measured by in vivo 23Na MRI correlated well with triphenyltetrazolium chloride staining (r=0.87, y=0.92x+3.37, P<0.001). Elevated 23Na image intensity was observed in infarcted myocardium (206+/-37% of remote in dogs, P<0.001; 215+/-58% in rabbits, P<0.002) but was not observed after severe but reversible ischemic injury (101+/-11% of baseline, P=NS). High-resolution ex vivo imaging revealed that regions of elevated 23Na image intensity appeared to be identical to those of infarcted regions (r=0.97, y=0.92x+1.52, P<0.001). In infarcted regions, total tissue [Na+] was elevated (89+/-12 versus 37+/-9 mmol/L in control tissue, 156+/-60% increase, P<0.001) and was associated with increased intracellular sodium (254+/-68% of control, P<0.005) and an increased intracellular sodium/potassium ratio (868+/-512% of control, P<0.002). Morphometric analysis demonstrated only a minor increase in extracellular volume (17+/-8% versus 14+/-5%, P<0.05) in the infarcted territory. CONCLUSIONS: Elevated 23Na MR image intensity in vivo measures infarct size after reperfused infarction in both a large and a small animal model. The mechanism of elevated 23Na image intensity is probably intracellular sodium accumulation secondary to loss of myocyte ionic homeostasis.

Physiological basis for potassium (39K) magnetic resonance imaging of the heart.

The potassium cation (K+) is fundamentally involved in myocyte metabolism. To explore the potential utility of direct MRI of the most abundant natural isotope of potassium, 39K, we compared 39K magnetic resonance (MR) image intensity with regional myocardial K+ concentrations after irreversible injury. Rabbits were subjected either to 40 minutes of in situ coronary artery occlusion and 1 hour of reperfusion (n=26) or to 24 hours of permanent occlusion (n=4). The hearts were then isolated and imaged by 39K MRI (n=10), or tissue samples were analyzed for regional 39K content by MR spectroscopy (n=9), K+ and Na+ concentrations by atomic emission spectroscopy (inductively coupled plasma atomic emission spectroscopy; n=5), or intracellular K+ content by electron probe x-ray microanalysis (n=6). Three-dimensional 39K MR images of the isolated hearts were acquired in 44 minutes with 3 x 3 x 3-mm resolution. 39K MR image intensity was reduced in infarcted regions (51.7+/-4. 8% of remote; P<0.001). The circumferential extent and location of regions of reduced 39K image intensity were correlated with those of infarcted regions defined histologically (r=0.97 and r=0.98, respectively). Compared with remote regions, tissue analysis revealed that infarcted regions had reduced 39K concentration (by MR spectroscopy, 40.5+/-9.3% of remote; P<0.001), reduced potassium-to-sodium ratio (by inductively coupled plasma atomic emission spectroscopy, 20.7+/-2.1% of remote; P<0.01), and reduced intracellular potassium (by electron probe x-ray microanalysis, K+ peak-to-background ratio 0.95+/-0.32 versus 2.86+/-1.10, respectively; P<0.01). We acquired the first 39K MR images of hearts subjected to infarction. In the pathophysiologies examined, potassium (39K) MR image intensity primarily reflects regional intracellular K+ concentrations.

Theoretical basis for sodium and potassium MRI of the human heart at 1.5 T.

Knowledge of the extent and location of viable tissue is important to clinical diagnosis. In principle, sodium (23Na) and potassium (39K) MRI could noninvasively provide information about tissue viability. In practice, imaging of these nuclei is difficult because, compared with water protons (1H), 23Na and 39K have lower MR sensitivities (9.2 and 0.051%, respectively), and lower in vivo concentrations (ca. 1000-fold). On the other hand, the relatively short T1 relaxation times of 23Na and 39K (ca. 30 and 10 ms, respectively) suggest that optimized imaging pulse sequences may in part alleviate the weak signal of these nuclei. In this study, numerical simulations of high-speed imaging sequences were developed and used to maximize 23Na and 39K image signal-to-noise ratio (SNR) per unit time within the constraints of existing gradient hardware. The simulation demonstrated that decreasing receiver bandwidth at the expense of echo time (TE) results in a substantial increase in 23Na and 39K image SNR/time despite the short T2 and T2* of these nuclei. Referenced to the available 1H signal on existing 1.5 T scanners, the simulation suggested that it should be possible to acquire three-dimensional 23Na images of the human heart with 7 x 7 x 7 mm resolution and 39K images with 26 x 26 x 26 mm resolution in 30 min. Experimentally in humans at 1.5 T, three-dimensional 23Na images of the heart were acquired in 15 min with 6 x 6 x 12 mm resolution and signal-to-noise ratios of 11 and 7 in the left ventricular cavity and myocardium, respectively, which is very similar to the predicted result. The results demonstrate that by choosing imaging pulse sequence parameters that fully exploit the short relaxation times of 23Na and 39K, potassium MRI is improved but remains impractical, whereas sodium MRI improves to the point where 23Na imaging of the human heart may be clinically feasible on existing 1.5 T scanners.