David S. Fieno

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.

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

BackgroundMyocardial 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 ResultsThe 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). ConclusionsA 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 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.

Relationship of contractile function to transmural extent of infarction in patients with chronic coronary artery disease.

OBJECTIVES We sought to determine the relationship of contractile function to the transmural extent of infarction (TEI) in patients with chronic coronary artery disease. BACKGROUND In the setting of reperfused, chronic myocardial infarction (MI), the relationship of contractile function to the TEI has not been established. METHODS We studied function by cine magnetic resonance imaging (MRI) and the TEI by contrast-enhanced MRI in 31 patients with single-vessel disease 162 +/- 62 days after reperfused first MI. RESULTS Of all 516 segments with MI, blinded observers were unable to detect abnormal thickening in 193 (37%), and wall thickening measured quantitatively in these segments was 66 +/- 28%. Of the 193 segments, 163 (84%) were infarcts limited to the subendocardium. The average TEI reached 53% before half of the patients had abnormal contractile function. When patients with small MI (< or =5% of total left ventricular [LV] mass) were excluded, the average TEI reached 43% before half the patients had abnormal function. In subjects with small MI (< or =5% of total LV mass [n = 13]), even segments with TEI >75% had normal function (14 of 14) because they were surrounded by normally moving neighbor segments. CONCLUSIONS In the setting of reperfused chronic MI, the TEI approaches 50% before contractile dysfunction can be systematically identified. Contractile function cannot be used to rule out chronic MI.

TrueFISP: Assessment of accuracy for measurement of left ventricular mass in an animal model

To test the accuracy of a high performance true fast imaging with steady‐state precession (TrueFISP) pulse sequence for the assessment of left ventricular (LV) mass in a large animal model on 1.5‐T scanners.

Myocardial perfusion imaging based on the blood oxygen level-dependent effect using T2-prepared steady-state free-precession magnetic resonance imaging

Background—The decision to perform coronary revascularization procedures may hinge on assessment of myocardial perfusion reserve. Blood oxygen level–dependent (BOLD) MRI is a potential method to detect the effects of regional variations in myocardial blood flow during vasodilation. Methods and Results—We imaged dogs (n=13) on a 1.5-T whole-body MRI scanner using a new T2-prepared steady-state free-precession (SSFP) MRI pulse sequence sensitive to BOLD contrast. Images (in-plane resolution ≈1 mm2) of 5 short-axis and 2 long-axis slices of the heart were acquired during graded levels of adenosine infusion via a surgically placed left circumflex (LCx) catheter (n=11) or via a right atrial catheter in animals with an LCx occluder (n=2). Relative myocardial perfusion was measured with the use of fluorescent microspheres. Signal intensity changes in myocardium subtended by the left anterior descending coronary artery were compared with those in the LCx region. Unprocessed T2-weighted images revealed changes in signal intensity corresponding to areas of regional vasodilation or reduced myocardial perfusion reserve during systemic vasodilation. At maximal vasodilation, the signal intensity ratio in the LCx versus left anterior descending territories increased by 33±4% compared with baseline, corresponding to a 3.8±0.3-fold increase in relative perfusion (P<0.01). MR intensity at progressive levels of vasodilation demonstrated good agreement with microsphere flow (R=0.80, P<0.01). Conclusions—T2-prepared SSFP BOLD imaging is a promising method to determine an index of myocardial perfusion reserve in this animal model.

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.

Improved left ventricular mass quantification with partial voxel interpolation: in vivo and necropsy validation of a novel cardiac MRI segmentation algorithm.

Background— Cardiac magnetic resonance (CMR) typically quantifies LV mass (LVM) by means of manual planimetry (MP), but this approach is time-consuming and does not account for partial voxel components— myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM. Methods and Results— LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared with LVM quantified on echocardiography (echo) and an ex vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time versus MP (0:21±0:04 versus 4:18±1:02 minutes; P <0.001). ASFV mass (136±35 g) was slightly lower than MP (139±35; Δ=3±9 g, P <0.001). Both methods yielded similar proportions of patients with LV remodeling ( P =0.73) and hypertrophy ( P =1.00). Regarding partial voxel segmentation, ASPV yielded higher LVM (159±38 g) than MP (Δ=20±10 g) and ASFV (Δ=23±6 g, both P <0.001), corresponding to relative increases of 14% and 17%. In multivariable analysis, magnitude of difference between ASPV and ASFV correlated with larger voxel size (partial r =0.37, P <0.001) even after controlling for LV chamber volume ( r =0.28, P =0.002) and total LVM ( r =0.19, P =0.03). Among patients, ASPV yielded better agreement with echo (Δ=20±25 g) than did ASFV (Δ=43±24 g) or MP (Δ=40±22 g, both P <0.001). Among laboratory animals, ASPV and ex vivo results were similar (Δ=1±3 g, P =0.3), whereas ASFV (6±3 g, P <0.001) and MP (4±5 g, P =0.02) yielded small but significant differences with LVM at necropsy. Conclusions— Automated segmentation of myocardial partial voxels yields a 14–17% increase in LVM versus full voxel segmentation, with increased differences correlated with lower spatial resolution. Partial voxel segmentation yields improved CMR agreement with echo and necropsy-verified LVM.Background— Cardiac magnetic resonance (CMR) typically quantifies LV mass (LVM) by means of manual planimetry (MP), but this approach is time-consuming and does not account for partial voxel components— myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM. Methods and Results— LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared with LVM quantified on echocardiography (echo) and an ex vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time versus MP (0:21±0:04 versus 4:18±1:02 minutes; P<0.001). ASFV mass (136±35 g) was slightly lower than MP (139±35; &Dgr;=3±9 g, P<0.001). Both methods yielded similar proportions of patients with LV remodeling (P=0.73) and hypertrophy (P=1.00). Regarding partial voxel segmentation, ASPV yielded higher LVM (159±38 g) than MP (&Dgr;=20±10 g) and ASFV (&Dgr;=23±6 g, both P<0.001), corresponding to relative increases of 14% and 17%. In multivariable analysis, magnitude of difference between ASPV and ASFV correlated with larger voxel size (partial r=0.37, P<0.001) even after controlling for LV chamber volume (r=0.28, P=0.002) and total LVM (r=0.19, P=0.03). Among patients, ASPV yielded better agreement with echo (&Dgr;=20±25 g) than did ASFV (&Dgr;=43±24 g) or MP (&Dgr;=40±22 g, both P<0.001). Among laboratory animals, ASPV and ex vivo results were similar (&Dgr;=1±3 g, P=0.3), whereas ASFV (6±3 g, P<0.001) and MP (4±5 g, P=0.02) yielded small but significant differences with LVM at necropsy. Conclusions— Automated segmentation of myocardial partial voxels yields a 14–17% increase in LVM versus full voxel segmentation, with increased differences correlated with lower spatial resolution. Partial voxel segmentation yields improved CMR agreement with echo and necropsy-verified LVM.

Geometry-Independent Inclusion of Basal Myocardium Yields Improved Cardiac Magnetic Resonance Agreement with Echocardiography and Necropsy Quantified Left Ventricular Mass

Objectives: Left-ventricular mass (LVM) is widely used to guide clinical decision-making. Cardiac magnetic resonance (CMR) quantifies LVM by planimetry of contiguous short-axis images, an approach dependent on reader-selection of images to be contoured. Established methods have applied different binary cut-offs using circumferential extent of left-ventricular myocardium to define the basal left ventricle (LV), omitting images containing lesser fractions of left-ventricular myocardium. This study tested impact of basal slice variability on LVM quantification. Methods: CMR was performed in patients and laboratory animals. LVM was quantified with full inclusion of left-ventricular myocardium, and by established methods that use different cut-offs to define the left-ventricular basal-most slice: 50% circumferential myocardium at end diastole alone (ED50), 50% circumferential myocardium throughout both end diastole and end systole (EDS50). Results: One hundred and fifty patients and 10 lab animals were studied. Among patients, fully inclusive LVM (172.6 ± 42.3 g) was higher vs. ED50 (167.2 ± 41.8 g) and EDS50 (150.6 ± 41.1 g; both P < 0.001). Methodological differences yielded discrepancies regarding proportion of patients meeting established criteria for left-ventricular hypertrophy and chamber dilation (P < 0.05). Fully inclusive LVM yielded smaller differences with echocardiography (&Dgr; = 11.0 ± 28.8 g) than did ED50 (&Dgr; = 16.4 ± 29.1 g) and EDS50 (&Dgr; = 33.2 ± 28.7 g; both P < 0.001). Among lab animals, ex-vivo left-ventricular weight (69.8 ± 13.2 g) was similar to LVM calculated using fully inclusive (70.1 ± 13.5 g, P = 0.67) and ED50 (69.4 ± 13.9 g; P = 0.70) methods, whereas EDS50 differed significantly (67.9 ± 14.9 g; P = 0.04). Conclusion: Established CMR methods that discordantly define the basal-most LV produce significant differences in calculated LVM. Fully inclusive quantification, rather than binary cut-offs that omit basal left-ventricular myocardium, yields smallest CMR discrepancy with echocardiography-measured LVM and non-significant differences with necropsy-measured left-ventricular weight.