Kirsi Lauerma

Identification of myocardial reperfusion with echo planar magnetic resonance imaging. Discrimination between occlusive and reperfused infarctions.

BackgroundThe current treatment of many cases of acute myocardial infarction involves the use of thrombolytic agents. Evaluation of this therapy requires determination of the success of reperfusion and assessment of the presence and extent of infarction in the reperfused territory. The present study was designed to simulate in rat models several possible outcomes of reperfusion therapy: (1) successful reperfusion and absence of myocardial infarction, (2) successful reperfu-sion and presence of myocardial infarction, and (3) unsuccess-ful reperfusion. The usefulness of contrast-enhanced fast magnetic resonance (MR) imaging in defining the success of reperfusion was investigated. The dynamic effects were examined of low and high doses of gadolinium-BOPTA/dimeglu-mine (Gd-BOPTA/dimeg) on myocardial signal using MR inversion recovery echo planar imaging (IR-EPI) and gradient recalled echo planar imaging (GR-EPI), respectively. Methods and ResultsRats were subjected to one of the following regimens: reperfused reversible myocardial injury (n=9), reperfused irreversible myocardial injury (n=9), and occlusive infarction (n=9). MR echo planar images were acquired every 1 or 2 seconds before, during, and after administration of Gd-BOPTA/dimeg. In all groups, normal myocardial signal was sharply increased on IR-EPI and decreased on GR-EPI at the peak of the bolus, followed by a gradual decline to baseline. In animals subjected to reperfused reversible myocardial injury, normal and previously ischemic regions were indistinguishable during and after the passage of Gd-BOPTA/dimeg. On the other hand, enhancement of reperfused irreversibly injured myocardium was delayed but increased steadily to a higher level than normal myocardium on IR-EPI. The reperfused irreversibly injured myocardium was identified on IR-EPI as a zone of high signal (hot spot). On GR-EPI, signal loss in reperfused irreversibly injured myocardium was significantly less compared with normally perfused myocardium. In animals with occlusive infarctions, there was no change in signal intensity over the ischemic region on either IR-EPI or GR-EPI. Occlusive infarction was identified as zones of either low (cold spot) or high (hot spot) signal compared with normal myocardium, depending on MR pulse sequence and dose of the contrast medium. ConclusionsThe transit of Gd-BOPTA/dimeg monitored by fast MR imaging techniques can be used to distinguish between reperfused reversibly and reperfused irreversibly injured myocardium and between occlusive and reperfused infarctions.

Alterations in T1 of normal and reperfused infarcted myocardium after Gd‐BOPTA versus GD‐DTPA on inversion recovery EPI

This study tested whether Gd‐BOPTA/Dimeg or Gd‐DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd‐BOPTA is increased by weak binding to serum albumin. Thirty‐six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). ΔR1 was repeatedly measured over 30 min. Gd‐BOPTA caused greater ΔR1 for blood and myocardium than did Gd‐DTPA clearance of both agents from normal and infarcted myocardium was similar to blood clearance; plots of ΔR1myocardium/ΔR1blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd‐DTPA and Gd‐BOPTA, respectively, in reperfused infarction. The high value for Gd‐BOPTA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd‐BOPTA/Dimeg causes a greater ΔR1 than Gd‐DTPA in regions which contain serum albumin.

Identification of Myocardial Cell Death in Reperfused Myocardial Injury Using Dual Mechanisms of Contrast-Enhanced Magnetic Resonance Imaging

Rationale and Objectives. Because the magnitude of dysprosium-induced signal loss depends on the microheterogeneity of its distribution (exclusion from intracellular space), we proposed that loss of myocardial cell integrity would be reflected by decreased potency of dysprosium in the injured compared with normal myocardium. We measured the effect of dysprosium on magnetic resonance (MR) imaging signal intensity of reperfused infarcted and nonischemic myocardium and related it to tissue concentration of the contrast media. Methods. Rats were subjected to 1 hr coronary artery occlusion followed by 1 hr reperfusion. After 45 min of reflow, group 1 ( n = 9) received 1.0 and 0.2 mmol/kg dysprosium diethylenetriamine pentaacetic acid-bismethylamide (Dy-DTPA-BMA) and gadodiamide (GdDTPA-BMA), respectively. Group 2 ( n = 7) received no contrast agents. Excised hearts were imaged with spinecho T1- and T2-weighted sequences. After imaging, hearts were stained (triphenyltetrazolium chloride) to define the injured zones. Concentrations of Dy-DTPA-BMA and Gd-DPTA-BMA in regional myocardial tissue were determined by induction coupled plasma-atomic emission spectrometry. Separate groups received one or the other contrast medium alone to control for potential error from the mixed effects of the two agents. Results. Gd-DTPA-BMA delineated reperfused infarcted myocardium as a bright zone on T1-weighted images, thus indicating delivery of the agent and reperfusion at the tissue level. Dy-DTPA-BMA delineated the reperfused infarction as a bright region by decreasing the signal intensity of nonischemic myocardium significantly more than that of injured myocardium, despite being present in greater concentration (by 2.46-fold) in the injured myocardium. Conclusion. These findings are consistent with the hypothesis that the failure of myocardial cells to exclude the dysprosium compound is responsible for the diminished potency of dysprosium to cause MR imaging signal intensity loss in reperfused myocardial infarction. The combination of the two contrast media may define reperfusion of the myocardium at the tissue level (Gadolinium distribution) and the presence and extent of myocardial necrosis (diminished dysprosium effect) in reperfused myocardial infarctions.

The use of contrast-enhanced magnetic resonance imaging to define ischemic injury after reperfusion. Comparison in normal and hypertrophied hearts.

Lauerma K, Saeed M, Wendland MF, Derugin N, Yu KK, Higgins CB. The use of contrast-enhanced magnetic resonance imaging to define ischemic injury after reperfusion: comparison in normal and hypertrophied hearts. Invest Radiol 1994; 29:527-535. RATIONALE AND OBJECTIVES.Magnetic resonance imaging (MRI) was used to demonstrate the infarction size in reperfused ischemic myocardium of normal and hypertrophied hearts, and to test the hypothesis that hypertrophied hearts manifest greater susceptibility to ischemia. METHODS.Normal rats (n=11) and rats subjected to left ventricular hypertrophy (LVH) by aortic banding (n=13) were studied. After 7 weeks, the left coronary artery was occluded for 25 minutes and reperfused for 1 hour before MRI. Electrocardiogram-gated spin-echo images were acquired before and after administration of 0.3 mmol/kg gadoteridol. To quantify the hyperintense area demarcated by gadoteridol, 3 transaxial images were acquired at different levels. Jeopardy and infarcted areas were measured in the same three slices postmortem using blue dye and triphenyltetrazolium chloride (TTC) stain, respectively. RESULTS.Before administration, there was no significant difference in signal intensity between nonischemic (0.42 ± 0.03 arbitrary units) and ischemic (0.41 ± 0.03) myocardium in either group. After gadoteridol injection, signal intensity of the reperfused injured region was higher than that of nonischemic myocardium (1.48 ± 0.16 vs. 0.72 ± 0.06, P < .05). Magnetic resonance delineation of the hyperintense area persisted for at least 30 minutes. The size of the hyperintense area was larger in LVH than in control hearts (25 ± 5% vs. 7 ± 3% of LV surface area, P < .05) and did relate closely to the area of myocardial infarction (r=.97), but not with the jeopardy area (r=.42). On TTC staining, the infarction size also was significantly greater in LVH than in normal group (18 ± 5% vs. 5 ± 2% of LV surface area, P < .05). The jeopardy areas of normal and LVH hearts showed no significant difference (46 ± 2% vs. 47 ± 3%). CONCLUSION.Magnetic resonance imaging confirms the concept that reperfused myocardial injury is larger in LVH than normal hearts after brief coronary occlusion. Contrast-enhanced MRI can define the size of reperfused myocardial injury. Thus, MRI is a suitable technique to assess conditions accentuating ischemic injury.

Verapamil reduces the size of reperfused ischemically injured myocardium in hypertrophied rat hearts as assessed by magnetic resonance imaging

Contrast-enhanced magnetic resonance (MR) imaging was used to detect and quantify the extent of myocardial injury after a brief coronary occlusion and reperfusion in response to verapamil treatment in a rat model of left ventricular hypertrophy (LVH). Two groups of rats were prepared by banding the abdominal aorta for 7 to 8 weeks to produce LVH. Group 1 (n = 13) received oral verapamil for 3 days, whereas group 2 (n = 13) received no therapy. Before MR examination was performed, each rat was subjected to 25 min of coronary artery occlusion followed by 1 hour of reperfusion. T1-weighted spin echo images were acquired before and after 0.3 mmol/kg gadoteridol was injected. Three images were acquired at contiguous levels of the LV and used to estimate the size of the myocardial injury. The size of the infarcted region was demarcated at postmortem examination by using triphenyltetrazolium chloride dye (TTC). Before contrast medium was administered, no significant difference in signal intensity was seen between nonischemic and reperfused ischemically injured myocardium. After gadoteridol was injected, a hyperintense zone indicative of myocardial injury was observed in 8 of 13 rats treated with verapamil and in all untreated animals. The size of the injury was significantly larger in untreated hearts than in hearts treated with verapamil as defined on MR images (25% +/- 5% vs 18% +/- 5%, p < 0.05) and TTC staining (12% +/- 4% and 4% +/- 1%, p < 0.05). Good correlation (r = 0.91) was found between the two measurements. No significant difference in the size of jeopardy area was seen between the two groups as (defined by blue dye infusion). In conclusion, contrast-enhanced MR imaging is a suitable technique to evaluate the effects of therapies applied to reduce myocardial injury. Verapamil can cause reduction in the extent of ischemic injury after reperfusion of hypertrophied myocardium.

Novel electrocardiographic features in carriers of hypertrophic cardiomyopathy causing sarcomeric mutations

OBJECTIVES The sensitivity and specificity of the conventional 12-lead ECG to identify carriers of hypertrophic cardiomyopathy (HCM) - causing mutations without left ventricular hypertrophy (LVH) has been limited. We assessed the ability of novel electrocardiographic parameters to improve the detection of HCM mutation carriers. METHODS We studied 140 carriers (G+) of the TPM1-Asp175Asn or MYBPC3-Gln1061X pathogenic variants for HCM: The G+/LVH+ group (n = 98) consisted of mutation carriers with LVH and the G+/LVH- group (n = 42) without LVH. The control group consisted of 30 subjects. The standard 12-lead ECG was comprehensively analyzed and two novel ECG variables were introduced: RV1RV3 and septal remodeling. A subset of 65 individuals underwent cardiac magnetic resonance imaging and 2D strain echocardiography. RESULTS Conventional major ECG criteria were sensitive (90%) and specific (97%) in identifying G+/LVH+ subjects. RV1RV3 and septal remodeling were more prevalent in the G+/LVH- subjects compared to the control group (33% vs 3%, p = 0.005 and 45% vs 3%, p < 0.001, respectively). The combination of RV1RV3 and Q waves and repolarization abnormalities (QR) differentiated between the G+/LVH- subjects and the control group with a sensitivity of 52% and specificity of 97%. The combination of septal remodeling and QR differentiated between G+/LVH- subjects and the control group with a sensitivity of 64% and specificity of 97%. CONCLUSIONS The novel ECG-parameters RV1RV3 and septal remodeling were effective in identifying G+/LVH- subjects and could be useful in the diagnostics of new suspected HCM patients and in the screening and follow-up of HCM families.

2069 Assessment of genetic dilated cardiomyopathy in LMNA-mutation carriers by cardiac MRI

Introduction DCM is characterized by enlargement and impaired contraction of left or both ventricles. With an estimated prevalence of 36/100 000 in adults in the United States, DCM is a significant cause of morbidity and mortality. One third to one half of the causes are familial and the most important risk gene for cardiomyopathy is lamin A/C gene. Thus, we wanted to look for other methods than conventional echocardiography, to recognize this type of serious cardiomyopathy early. We wanted to characterize more precisely the cardiac findings of the Finnish LMNA patients using magnetic resonance imiging (MRI)