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Cardiac Imaging |
1 From the Departments of Radiology (J.J.W.S., T.P., M.B., C.L., K.B., F.B., W.K., D.H.) and Internal Medicine (K.H., W.V.), University of Würzburg, Klinikstrasse 8, D-97070 Würzburg, Germany; and Department of Cardiovascular Medicine, Oxford University, England (S.N.). Received September 21, 2000; revision requested November 22; revision received January 31, 2001; accepted February 26. Supported by a grant from the Bundesministerium für Bildung und Forschung, IZKF Würzburg (01 KS 9603). Address correspondence to J.J.W.S. (e-mail: joern.sandstede@mail.uni-wuerzburg.de).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Thirty patients underwent MR imaging 8 days ± 4 (subacute, n = 15) or more than 6 months (chronic, n = 15) after myocardial infarction by using a 23Na surface coil with a double angulated electrocardiogram-triggered three-dimensional gradient-echo sequence at 1.5 T. In addition, cine, inversion-recovery gradient-echo, and, in the subacute group, T2-weighted images (n = 9) were obtained. Myocardial infarction mass was depicted as elevated signal intensity or wall motion abnormalities and expressed as a percentage of total left ventricular mass for all modalities. Correlations were tested with correlation coefficients.
RESULTS: All patients after subacute infarction and 12 of 15 patients with chronic infarction had an area of elevated 23Na signal intensity that significantly correlated with wall motion abnormalities (subacute; r = 0.96, P < .001, and chronic; r = 0.9, P < .001); three patients had no wall motion abnormalities or elevated 23Na signal intensity. Only 10 patients in the subacute and nine in the chronic group revealed late enhancement; significant correlation with 23Na MR imaging occurred only in subacute group (r = 0.68, P < .05). Myocardial edema in subacute infarction correlated (r = 0.71, P < .05) with areas of elevated 23Na signal intensity but was extensively larger.
CONCLUSION: 23Na MR imaging demonstrates dysfunctional myocardium caused by subacute and chronic myocardial infarction.
Index terms: Myocardium, infarction, 511.771 • Myocardium, MR, 511.12147 • Magnetic resonance (MR), sodium studies, 511.121412, 511.12147
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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All patients but one underwent left ventriculography and coronary angiography; in one patient in the subacute group, no invasive procedure was performed due to patient’s age of 88 years. In the subacute group, seven of 15 patients had undergone early revascularization at percutaneous transluminal coronary angioplasty of the infarct-related coronary artery during the acute phase of infarction, six underwent thrombolytic therapy, two patients did not undergo early revascularization. All examinations and interventions were performed by using standard procedures. Diagnosis and localization of myocardial infarction for all patients were performed by means of clinical history, plasma creatine kinase levels (elevated to more than twice the normal level with an MB fraction >5%), electrocardiographic signs, and, except for the one patient in the subacute group showing typical enzymes, angiographic depiction of the infarct-related artery.
MR Image Acquisition
MR imaging was performed with a 1.5-T imager (Magnetom VISION; Siemens, Erlangen, Germany) with 25 mT/m maximum gradient strength. For sodium imaging, patients were examined in the prone position by using a 23Na surface coil (RAPID Biomedical, Wuerzburg, Germany) with a size of 286 x 174 mm2 and using the broadband spectroscopy option. No further special imager hardware was needed. Double angulated short axis images of the heart were imaged with a specially written electrocardiogram-triggered three-dimensional spoiled gradient-echo (fast low-angle shot) sequence (23). By using a non–section-selective radio-frequency pulse and an asymmetric gradient echo, an echo time of 3.1 msec was achieved. The repetition time was 21 msec; bandwidth, 65 Hz/pixel; and flip angle, 70°. A field of view of 450 mm and a matrix of 64 x 128 x 20 (two-dimensional phase direction x read direction x three-dimensional phase direction) resulted in an in-plane resolution of 3.5 x 7 mm2; section thickness was 16 mm. Therefore, on average, six sections covered the entire heart, and four to five sections covered the left ventricle. The acquisition window for each heart beat was 420 msec, independent of heart rate, and was placed in diastole. For the reduction of respiratory artifacts, 32 acquisitions were averaged. Total acquisition time was 29 minutes ± 8, depending on heart rate.
For the evaluation of wall motion abnormalities (WMAs), contrast enhancement, and myocardial edema, patients were examined in the supine position by using a phased-array body coil. Short-axis MR imaging of the left ventricle from base to apex was performed with a section thickness of 8 mm without an intersection gap during electrocardiogram triggering and breath holding for each imaging method, the number of sections acquired ranged from nine to 11. For cine MR imaging, the pulse sequence was a segmented two-dimensional fast low-angle shot sequence (field of view, 240 x 320 mm2; matrix, 126 x 256; 9.9/4.8 [repetition time msec/echo time msec]; flip angle, 30°). The acquisition window for one cardiac phase was 80–100 msec, which resulted in a temporal resolution of 40–50 msec due to echo sharing; the number of cardiac phases imaged depended on heart rate. Late-enhancement MR imaging was performed 10–15 minutes after the injection of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany; 0.2 mmol per kilogram of body weight) by using a nonselective inversion recovery–prepared segmented two-dimensional turbo fast low-angle shot acquisition (field of view, 240 x 320 mm2; matrix, 165 x 256; 7.5/3.4; inversion time, 170 msec; flip angle, 25°; acquisition window, 250 msec placed in diastole). T2-weighted images were acquired with a turbo spin-echo sequence with dark blood preparation (field of view, 240 x 320 mm2; matrix, 138 x 256; repetition time = R-R - interval, 10%; TE, 57 msec; flip angle, 140°). Total examination time ranged from 80 to 90 minutes.
Data Analysis
For the assessment of myocardial infarct size as indicated by the MR imaging methods, cine, T2-weighted, late enhancement, and 23Na MR images were analyzed together for areas of WMAs or elevated signal intensity (SI) by two experienced radiologists (J.J.W.S., W.K.) in consensus. Due to the various section thicknesses, two hydrogen 1 (1H) sections were compared to one 23Na section. Viewing of the 1H images was used for wall delineation on the 23Na images. After visual determination of these areas, all MR images were evaluated quantitatively. All endo- and epicardial borders and the borders of the infarcted areas were traced manually by one radiologist (J.J.W.S.) by using computer software (ARGUS, version VB31B; Siemens). The mass of the infarcted area was obtained by summing the infarct volume for each section and was expressed as percentage of total left ventricular muscle mass (8). For the purposes of comparison with cine and 23Na MR imaging that did not allow transmural differentiation of the infarct, elevated SI of T2-weighted images and late enhancement was regarded as being transmural for the evaluation of the percentage of infarcted left ventricular mass. In addition, quantification of the transmural extent of elevated SI was possible with late enhancement and with T2-weighted images by expressing the areas of elevated SI as a percentage of the entire left ventricular wall. For 23Na MR imaging, SIs of the infarcted area and of the entire circumference of the noninfarcted myocardium on the same section were measured and expressed as percentage of elevation of 23Na SI of infarcted myocardium over noninfarcted myocardium.
All data are presented as mean plus or minus the SD. The correlation between the percentage of infarct size determined by using 23Na MR imaging and by using cine MR imaging, late enhancement, or T2-weighted imaging was determined with correlation coefficients. The Mann-Whitney U test was used to identify differences between elevation of 23Na SI in subacute and chronic myocardial infarction. A P value of less than .05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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All patients in the subacute group showed an area of elevated 23Na SI that well correlated with the areas of WMA. The percentage of left ventricular mass representing infarcted myocardium determined by using 23Na and cine MR imaging was 17.0% ± 13.7 and 13.4% ± 11.2, respectively, and showed a high correlation, although the areas of elevated 23Na were slightly but frequently larger than the areas of WMA (r = 0.96, P < .001; Table). Ten patients showed late enhancement and five did not. Average sizes of the areas with elevated SI for these 10 patients showing late enhancement determined with 23Na MR imaging and late enhancement were 22.0% ± 14.3 and 26.2% ± 14.6, respectively. There was also a correlation between both methods, but 23Na MR imaging frequently underestimated the areas of late enhancement (r = 0.68, P < .05) (Fig 1a). With all patients (five with and four without late enhancement) examined by using T2-weighted imaging, the area of myocardial edema was larger than the area of elevated SI at 23Na MR imaging (15.9% ± 11.1 vs 41.8% ± 18.2 for 23Na and T2-weighted MR imaging, respectively), but there was also a correlation between both imaging methods (r = 0.71, P < .05). (Figs 1b, 2). Two patients showed a mismatch between elevated SI on T2-weighted images and WMAs; that is, an additional edema was detected in the septum and in the anterior wall, respectively. Percentage of transmural extent of elevated SI on late enhancement and T2-weighted images was 65.4% ± 17.3 and 62.7% ± 17.7, respectively, without significant correlation for the five patients examined with T2-weighted imaging showing late enhancement (P > .05). 23Na SI in infarcted and noninfarcted myocardium was 64.2 ± 18.6 and 40.5 ± 14.5, respectively, with an increase of 23Na SI in infarcted myocardium of 67% ± 50 over noninfarcted myocardium.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Cine MR imaging allows for detection of regional WMAs after myocardial infarction, but these abnormalities can be due to nonviable, scarred, or viable, hibernating or stunned myocardium and may be reversible after revascularization (6,7). Therefore, cine MR imaging detects not only irreversibly but also reversibly injured myocardium. The closest estimation of the areas of irreversibly injured myocardium is achievable by late enhancement 10–15 minutes after contrast material injection. In animal models, this has been shown to be feasible for both acute and chronic myocardial infarction (9,11). Histologic examination revealed high correlation between areas of late enhancement and postmortem 2,3,5-triphenyltetrazolium chloride–negative areas, with only a slight overestimation by 9%–12% of the late-enhancement–determined infarct size (9,12). Thus, this method is suitable for measuring infarct size and has been applied in experimental studies (12,13). Furthermore, the absence of late enhancement has also been shown to be a predictor of myocardial viability in humans (14,15). Therefore, we postulate that late enhancement is a suitable reference method for measurement of the size of irreversibly injured myocardium for comparison with 23Na MR imaging in humans.
Irreversible ischemic myocyte injury leads to the Na-K-ATPase inhibition and, subsequently, to the loss of cell membrane integrity and of intracellular-extracellular ion homeostasis. For this reason, irreversible ischemic injury leads to an increase of sodium compared to noninfarcted myocardial tissue (24). In addition, muscle necrosis is associated with interstitial edema, which also contributes to an increased sodium content in the infarcted area. In chronically infarcted hearts, higher sodium concentration in the infarcted area also affords contrast between scarred and normal tissue. In contrast to subacute infarction, this effect is most likely due to a chronic increase of extracellular-intracellular volume relation. The acute phase of myocardial injury is followed by subsequent leucocyte infiltration and penetration of blood capillaries and connective tissue. Up until the 3rd week, muscle fibers are removed and then replaced by collagen fibers leading to an enlarged extracellular space in following weeks (25). All these processes lead to elevated sodium concentration in the infarcted area that correlates with the extent of the ischemic injury in the subacute as well as in the chronic state of disease (19,24,26).
23Na MR imaging has previously been shown to be feasible in humans (21). In an animal model, measurement of infarct size and assessment of myocardial viability is possible (16–19). Kim et al (16) demonstrated at 4.7 T that a regional increase of 23Na SI is associated with nonviable myocardium. Additional spectroscopic analysis showed that this elevated 23Na SI is due to increased tissue sodium content. Further study showed that areas of myocardial infarction measured by in vivo 23Na MR imaging were identical to histologically determined areas. Intracellular sodium content was elevated, whereas extracellular volume was only slightly increased (17). Thus, the major cause of elevated total sodium content in acute myocardial infarction appears to be the elevated intracellular sodium content, whereas an increase of the extracellular volume plays only a minor role.
In the current study, all patients with subacute myocardial infarction showed an area of elevated 23Na SI with matching areas of WMAs of the clinically determined infarct localization, whereas in chronic myocardial infarction only the patients with WMAs also had areas of elevated 23Na SI. Determination of infarct size with cine and 23Na MR imaging demonstrated a strong correlation between both methods, and myocardial masses determined by using both methods were similar. This high correlation indicates that the patients with the smallest infarct sizes as measured by using 23Na MR imaging also have the smallest sizes as measured by using cine MR imaging; this is also true for the midrange and the largest values. However, the areas of elevated 23Na SI were in most cases larger than the areas with regional WMAs. One explanation for this observation was the lower spatial resolution of 23Na MR imaging, which leads to less accurate delineation of the infarct borders. Another possibility is the presence of a border zone with either injured cells or enlarged extracellular space that still shows normal contractility.
In all patients who underwent T2-weighted imaging in the subacute group, areas of elevated SI were detectable in the infarcted areas indicated at cine, 23Na MR imaging, and, if present, late-enhancement imaging. However, there were also zones of elevated T2 that did not match with the infarct area, and the infarct size determined from the presence of myocardial edema was in each case larger than the infarct size assessed by using the other imaging modalities. This can be ascribed to the well-known overestimation of infarct size by T2-weighted images (1). Nevertheless, this observation indicates that 23Na MR imaging not only images changes of the extracellular space but depicts intracellular changes caused by the loss of cell membrane integrity rather than the surrounding areas of myocardial edema that were not detected.
Concerning late enhancement, with our study there was weak or no correlation between the areas with elevated 23Na SI and late enhancement, which indicates that infarct size values are not in the same general quantity by using the two different methods. This cannot only be due to the lower spatial resolution of 23Na MR imaging not allowing for a transmural differentiation of 23Na SI because five of 15 subacute-group patients and three of 12 chronic-group patients showed areas with WMAs and elevated 23Na SI but no late enhancement. With regards to late enhancement after administration of gadopentetate dimeglumine as an indicator of irreversibly injured myocardium, it has to be concluded that these patients had only reversible myocardial injury—that is, stunned or hibernating myocardium—demonstrated by the presence of WMAs combined with the absence of late enhancement. Therefore, it seems that 23Na MR imaging performed with the presented technique not only images irreversibly injured myocardium but offers different information on dysfunctional myocardium than late enhancement does, possibly also depicting stunned myocardium in subacute myocardial infarction or hibernating areas in chronic myocardial infarction. This has to be evaluated with further study, including follow-up examinations after revascularization therapy for the exact determination of viable and nonviable myocardium in humans.
A general limitation of in vivo studies, which aims at the assessment of myocardial infarct size, is the lack of an independent accepted standard. Therefore, in our study, MR imaging approaches were used for correlation with 23Na imaging, but none of these methods can be considered for showing the true infarct size as is possible with 2,3,5-triphenyltetrazolium chloride staining in experimental studies. Further limitations are due to the 23Na MR imaging technique itself. One methodological limitation is the lack of differentiation between intra- and extracellular sodium content, which is possible only by using 23Na MR spectroscopy with a shift reagent currently unavailable for use in humans (16). Thus, the relationship between intracellular sodium accumulation and enlarged extracellular volume leading to an increased total sodium content cannot be depicted by using global 23Na MR imaging. However, since the changes of total sodium content are mainly caused by increased intracellular sodium content in acute myocardial infarction and by the enlarged extracellular volume in chronic myocardial infarction, such a differentiation may not be essential.
A further limitation of the presented 23Na MR imaging technique is that it does not allow quantification of total 23Na content. Although, in this study, 23Na SI of subacute and chronic myocardial infarction was provided for purposes of comparison, this 23Na SI does not represent the absolute sodium content. This is due to the SI profile of the surface coil used leading to lower SI in the posterior parts of the heart. Since no "unenhanced" image is available, the determination of relative SI is also impossible, and the comparison with adjacent myocardium is not a valuable technique for absolute quantification due to coil profile. Possible approaches for quantification of the elevated 23Na SI and, thus, of absolute 23Na content may either be the use of a birdcage coil with a homogeneous excitation profile or the use of B1 mapping with an external standard. Furthermore, determination of the T2 time representing 23Na content might offer a solution (23,27). However, since 23Na is known to have a long and a short T2 component, T2 time determination in the human heart would require sequences with shorter echo time as were presented for absolute quantification of brain and muscle (28,29). Another technical limitation is the low spatial resolution of current 23Na imaging. This does not allow differentiation of transmurally and nontransmurally partial elevated SI as it is possible for late enhancement. Although spatial resolution is much higher with 1H imaging and allows a differentiation of the transmural extent of SI, elevated SI on T2-weighted and late-enhancement images was regarded as being transmural for purposes of comparison with 23Na images. This might contribute to the only fair correlation between the infarct sizes measured with the various techniques. In the future, an improvement of spatial resolution combined with quantification of sodium content might allow detection of myocardial viability at 23Na MR imaging.
In summary, elevated 23Na SI on MR images demonstrates dysfunctional myocardium following subacute and chronic myocardial infarction in humans. Technical improvements and further studies are necessary to evaluate the relationship of 23Na SI and irreversible or reversible ischemic myocardial injury. These studies will reveal whether 23Na MR imaging is suitable for detection of myocardial viability.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, J.J.W.S., D.H.; study concepts, J.J.W.S., T.P.; study design, J.J.W.S., S.N.; literature research, J.J.W.S., C.L.; clinical studies, C.L., K.H., W.V.; data acquisition, J.J.W.S., M.B., C.L., F.B.; data analysis/interpretation, J.J.W.S., K.B., W.K.; statistical analysis, J.J.W.S.; manuscript preparation and definition of intellectual content, J.J.W.S.; manuscript revision/review, T.P., M.B., S.N.; manuscript editing and final version approval, J.J.W.S., S.N.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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