Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with integrated backscatter

We have shown recently that tissue characterization of myocardium with ultrasound reflects changes associated with contractile function throughout the cardiac cycle. To determine whether ultrasonic tissue characterization can sensitively detect the impact of ischemic injury and reperfusion on contractile properties of the heart, we studied the time course of change of backscatter after 5, 20, and 60 min of coronary occlusion followed by reperfusion in 15 dogs. The time-averaged integrated backscatter (IB) and the amplitude and phase of cyclic variation of IB (phase relative to the left ventricular pressure waveform) were measured. A novel ultrasonic index of acute injury was identified, the phase-weighted amplitude of cyclic variation, and calculated by weighting the amplitude of cyclic variation of IB with respect to the phase. We hypothesized that backscatter variables would change dramatically after occlusion and that their restitution after reperfusion would sensitively reflect the extent and time course of reversibility of ischemic injury. After coronary occlusion, segmental wall thickening decreased from approximately 55% to 5% regardless of the duration of ischemia. Changes in backscatter associated with this decrease included an increase in time-averaged IB of approximately 5 dB, a 5 dB decrease in cyclic variation, an 80 degree phase shift, and a 7 dB decrease in phase-weighted amplitude. Wall thickening after reperfusion immediately after the 5, 20, or 60 min occlusions recovered to 45%, 27%, and 12% of baseline values, respectively. Within 3 hr it recovered to 53%, 44%, and 22%. Time-averaged IB recovered initially by 89%, 61%, and 44% (all p less than .05) and continued to recover subsequently although more slowly. Ultimate recovery was virtually complete. In contrast to the rapid recovery of time-averaged IB, phase-weighted amplitude recovered initially to only 72%, 41%, and -7% of baseline (all p less than .05) and manifested slower and incomplete recovery when ischemia had been present for 20 or 60 min. After reperfusion, the time course of both cyclic variation and phase were reflected by changes in the phase-weighted amplitude. The backscatter variables assessed appear to sensitively delineate the duration, time course of recovery, and reversibility of ischemic injury in response to reperfusion. The results suggest that early recovery of time-averaged IB corresponds in part to the restoration of tissue ultrastructural integrity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Early identification with ultrasonic integrated backscatter of viable but stunned myocardium in dogs

It has been shown that canine and human hearts exhibit a cardiac cycle-dependent variation of integrated backscatter (cyclic variation) that reflects intrinsic regional contractile performance. To determine whether ultrasound tissue characterization can identify viable though stunned myocardium before recovery of regional wall thickening, transient ischemic injury was produced in eight open chest dogs for 15 min followed by reperfusion for 2 h. Cyclic variation and wall thickening were measured before ischemia, at 15 min after the onset of ischemia and at selected intervals after the onset of reperfusion from multiple sites within the ischemic zone with a novel combined two-dimensional and M-mode acquisition system. Cyclic variation and wall thickening were computed from digitized M-mode integrated backscatter images with an algorithm developed and validated for this purpose. Magnitude and "delay" of cyclic variation and wall thickening were compared. Delay represents the degree of synchrony of regional cyclic variation or wall thickening with global ventricular mechanical systole. Baseline cyclic variation and wall thickening magnitudes were 3.8 +/- 0.2 dB and 37 +/- 1.4%, respectively. With ischemia, cyclic variation and wall thickening decreased to 1.7 +/- 0.2 dB and 17 +/- 2%, respectively (p less than 0.05, compared with baseline). Cyclic variation recovered to baseline levels within 20 min after reperfusion (3.3 +/- 0.4 dB, p = NS). Wall thickening remained depressed for 2 h after the onset of reperfusion (23 +/- 2%, p less than 0.05 compared with baseline). Delay of cyclic variation in a unitless ratio expressed as delay (in milliseconds) divided by the QT interval (in milliseconds) increased from 0.87 +/- 0.03 at baseline to 1.10 +/- 0.12 with ischemia, a change consistent with mild asynchrony, and returned to baseline (0.95 +/- 0.07, p = NS compared with baseline) within 20 min after reperfusion. Delay of wall thickening was 0.88 +/- 0.02 at baseline, increased to 1.23 +/- 0.09 with ischemia and remained significantly increased 2 h after reperfusion (1.07 +/- 0.05, p less than 0.05 compared with baseline). Recovery time constants for cyclic variation and wall thickening with reperfusion reflected earlier restoration of cyclic variation (8.1 min) than of wall thickening (420.5 min). Thus, cyclic variation recovers before wall thickening with reperfusion. Its analysis appears to provide a useful index of the presence of viable and potentially salvageable tissue in regions of stunned myocardium that is independent of wall thickening.     

Ultrasonic integrated backscatter discloses intramyocardial hemorrhage in patients with acute myocardial infarction

BACKGROUND: It has been reported that intramyocardial hemorrhage (IH) can be detected by magnetic resonance imaging (MRI) and IH correlates with the poor prognosis of acute myocardial infarction (AMI). We examined whether integrated backscatter (IBS) can disclose IH in patients with AMI. We recorded IBS images in 34 patients with AMI who underwent coronary angioplasty within 12 hours of symptom onset. METHODS: We measured calibrated IBS (C-IB) and cyclic variation (CV) in the center of the risk area on the third day after reperfusion. C-IB was calculated as: average IBS value of risk area--average IBS value of intraventricular blood. MRI was performed within 3 days after reperfusion. Regional wall motion score index (RWMSI) was calculated as follows: sum of scores (0 - 4) in risk area/number of segments of risk area. We evaluated left ventricular function using RWMSI shortly and one month after reperfusion. RESULTS: RWMSI in the IH group (12 cases) was significantly higher than in the non-IH group (2.3+/-0.5 vs. 1.8+/-0.6: P<0.01) one month later, while RWMSI in both groups was almost the same shortly after reperfusion. The IH group showed a significantly higher value of C-IB than the non-IH group (18.6+/-2.0 vs. 16.0+/-1.4: P<0.01), while there were no significant differences in CV values between two groups. Using 17 as a cutoff value of C-IB, C-IB can detect IH with 92% sensitivity and 91% specificity. Using both CV and C-IB, however, IH can be detected more specifically. CONCLUSION: Ultrasonic IBS, especially C-IB, discloses intramyocardial hemorrhage in patients with reperfused AMI.     

Prognostic implications derived from ultrasonic tissue characterization with myocardial integrated backscatter in patients with dilated cardiomyopathy

BACKGROUND: Various clinical parameters have been reported to predict survival in patients with dilated cardiomyopathy (DCM). Myocardial ultrasonic integrated backscatter (IB) imaging has a potential to perform in vivo tissue characterization. The present study was performed to examine whether myocardial IB analysis can predict the prognosis of DCM patients. METHODS AND RESULTS: We prospectively carried out echocardiographic examinations with IB analysis in 43 patients with DCM (31 males, 12 females) under the standard treatment. IB analysis was performed in the left ventricular wall and the calibrated (subtracting pericardial data) myocardial IB intensity (IBI) was obtained from the interventricular septum and the left ventricular posterior wall. After the follow-up (8-39 months), 31 followed a good clinical course, but eight had cardiac death, one had partial left ventriculectomy for uncontrolled heart failure and three were hospitalized for worsening heart failure. Beta-blocker responded in 27 (87%) of the 31 with good clinical course, but it did not respond in 11 among the 12 with poor course. In these 12 DCM, left ventricular fractional shortening (LVFS) was lower (good: 18+/-5%, poor: 14+/-4, P<0.03) and calibrated IBI was higher in both the septum (good: -16.4+/-5.6 dB, poor: -11.1+/-4.2 dB, P<0.006) and the posterior wall (good: -19.5+/-3.6 dB, poor: -13.8+/-5.6 dB, P<0.004). On the Cox proportional hazard model analysis, only calibrated IBI in the septum >-17 dB, the cut-off score of calibrated IBI discriminating non-responders to beta-blocker therapy in our previous report, was related to the poor outcome (chi(2)=4.43, P=0.035). The stepwise multivariate analysis revealed that both calibrated IBI in the septum>-17 dB (chi(2)=4.43, P=0.035) and LVFS<15% (chi(2)=3.89, P=0.049) were useful to predict the poor clinical outcome. The event free rate assessed by the Kaplan-Meier method was also significantly reduced in patients with calibrated IBI in the septum >-17 dB (chi(2)=6.594, P=0.01) and calibrated IBI in the posterior wall>-17 dB (chi(2)=4.215, P=0.04). However, LVFS<15% (chi(2)=3.576, not significant) did not contribute to discriminating the event free rate in the clinical course. CONCLUSIONS: The present study demonstrated that myocardial IB intensity was higher in DCM patients who followed a poor clinical course rather than in those with a good outcome. Therefore, it is clarified that myocardial ultrasonic tissue characterization in DCM patients is useful for assessing their clinical outcome after receiving not only the standard treatment but also beta-blocker therapy.     

Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter.

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.     

超声背向散射对急诊冠状动脉介入治疗后心肌存活性的检测

目的:探讨超声背向散射技术(IBS)对急性心肌梗死(AMI)行急诊经皮冠状动脉介入治疗术(PCI)后的患者识别存活心肌的临床应用价值。方法:应用IBS对13例首次AMI并行急诊PCI的患者在入院后第1、3、10天进行参数采集,并脱机进行分析,以3个月后室壁节段运动恢复者作为判断心肌存活的最终标准。结果:IBS在第3天时就可以较敏感地检测到存活心肌,较室壁运动的恢复提前。第3天和第10天检测存活心肌的敏感性、特异性、阳性预测值、阴性预测值分别为63.0%、73.7%、72.3%、58.3%;78.9%、78.9%、82.7%、65.2%。结论:IBS可以较早地检测AMI行急诊PCI的患者的存活心肌,并对功能恢复有较高的预测价值。     

超声组织定征在心血管疾病诊断中的应用

超声组织定征(Ultrasonic Tissue Characterization,UTC)技术是通过检测组织的声学参数来定量描述正常和病理组织的物理(声学)特性。研究表明,背向散射积分作为组织定征的参数,可以识别缺血心肌、顿抑心肌、梗死心肌、左心室心肌肥厚及心脏移植排斥反应,评价和分析系统性疾病如糖尿病等引起的弥漫性心肌受累的状态、心腔内血栓和动脉斑块的成份等。因而UTC技术具有很大的临床价值和发展潜力,将成为常规超声心动图诊断的辅助手段。本文就超声组织定征技术在心血管疾病诊断中的应用及进展作一综述。     

Sensitive detection of myocardial contraction abnormality in chronic hemodialysis patients by ultrasonic tissue characterization with integrated backscatter

Since acoustic properties of the myocardium are sensitive to the myocardial structure and the contractile conditions of myocyte, the authors evaluated cardiac dysfunction based on the integrated ultrasonic backscatter in 18 hemodialysis (HD) patients (duration: 102 +/- 84 months, mean age: 57.6 +/- 9.7 years) and 11 age-matched normals. The cyclic variation of integrated backscatter (CV-IB) at interventricular septum (IVS) and left ventricular posterior wall (PW) was measured and compared with percent fractional shortening (%FS) and percent wall thickening (%Th). The CV-IB of HD patients was smaller than that of control subjects (IVS: 6.2 +/- 1.1 dB vs 8.2 +/- 1.1 dB, p = 0.0003 and PW: 8.4 +/- 2.2 vs 10.3 +/- 1.3, p= 0.025). No significant difference was observed in %FS and %Th between HD patients and control subjects. In HD, the ratio of velocities of early diastolic inflow (E) to late atrial inflow was decreased (0.7 +/- 0.2 vs 1.1 +/- 0.7, p = 0.049) and deceleration time of E was prolonged significantly (200 +/- 28 msec vs 159 +/- 30 msec, p = 0.0082). In the absence of overt cardiac systolic dysfunction, myocardial damage indicated as a decrease in CV-IB and diastolic dysfunction identified on transmitral velocity waveform were detected, which may reflect from the myocardial fibrosis. As a mechanism, pressure overload, hyperparathyroidism, and anemia were neglected, and the other humoral factors may contribute to the myocardial damage in chronic renal failure.     

Ultrasound integrated backscatter tissue characterization of remote myocardial infarction in human subjects

To determine whether quantitative ultrasound tissue characterization differentiates normal myocardial regions from segments of remote infarction, 32 consecutive patients with a diagnosis of previous myocardial infarction were evaluated. Images were obtained in real time with a modified two-dimensional ultrasound system capable of providing continuous signals in proportion to the logarithm of integrated backscatter along each A line. In 15 patients, adequate parasternal long-axis images that delineated both normal and infarct segments were obtained with standard time-gain compensation. Image data were analyzed to yield both magnitude and delay (electrocardiographic R wave to nadir normalized for the QT interval) of the cyclic variation of backscatter. Cyclic variation was present in 55 of 56 normal myocardial sites, averaging (mean +/- SEM) 3.2 +/- 0.2 dB in magnitude and exhibiting a mean normalized delay of 0.87 +/- 0.03. The magnitude of cyclic variation in infarct segments was significantly reduced to 1.1 +/- 0.2 dB (42 sites), and the delay was markedly increased to 1.47 +/- 0.12 (21 sites) (p less than 0.0001 for both). In 20 of 42 infarct sites, no cyclic variation was detectable. Thus, ultrasound tissue characterization quantitatively differentiated infarct segments from normal myocardium in patients with remote myocardial infarction.     

Ultrasonic tissue characterization of human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter

Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent variation of IB was noninvasively measured using a quantitative IB imaging system in 12 patients with uncomplicated pressure-overload hypertrophy and 13 patients with hypertrophic cardiomyopathy. Sixteen normal subjects served as a control. The magnitude of cardiac cycle-dependent variation of IB for the posterior wall was 6.0 +/- 0.9 dB in normal subjects, 5.7 +/- 0.8 dB in the patients with uncomplicated pressure-overload hypertrophy, and 6.7 +/- 2.1 dB in the patients with hypertrophic cardiomyopathy. There were no significant differences among any of these groups. In contrast, the magnitude of cardiac cycle-dependent variation of IB for the septum was significantly smaller in the patients with uncomplicated pressure-overload hypertrophy (2.8 +/- 1.3 dB) and in the patients with hypertrophic cardiomyopathy (3.1 +/- 2.3 dB) than in normal subjects (4.9 +/- 1.0 dB). The magnitude of cardiac cycle-dependent variation of IB was smaller as the wall-thickness index increased (r = -0.53, p less than 0.01, n = 82 for all data). This IB measure also correlated with percent-systolic thickening of the myocardium (r = 0.67, p less than 0.01, n = 82). Thus, alteration in the magnitude of cardiac cycle-dependent variation of IB was observed in hypertrophic hearts and showed apparent regional myocardial differences.     

Ultrasound tissue characterization by integrated backscatter for analyzing Fluorouracil induced myocardial damage

BACKGROUND: 5-Fluorouracil (5-FU) cardiotoxicity is a well-known clinical phenomenon whose pathophysiology remains controversial. Cyclic variation of integrated backscatter (CVIBS) assesses acoustic properties of myocardium that may reflect both contractility and structural changes. The aim of this study was to evaluate CVIBS alterations in cancer patients under high-dose leucovorin and infusional 5-FU (HDLV5FU) chemotherapy. METHOD: We prospectively evaluated 37 cancer patients under HDLV5FU treatment. Transthoracic echocardiography and CVIBS were performed at the 0th, 48th hours, and on day 15 of the first cycle. The parasternal long-axis view was preferred to obtain the image of integrated backscatter and mainly two regions of interest--interventricular septum (IVS) and posterior wall (PW)--were used. RESULTS: Clinical cardiotoxicity was observed in two patients. No significant differences were detected in pre- and posttreatment conventional echocardiography evaluations. However, both the IVS (9.3 +/- 1.0 to 8.1 +/- 1.2 dB, P < 0.001) and PW (9.1 +/- 0.7 to 7.8 +/- 0.9 dB, P < 0.001) CVIBS values significantly decreased in all patients. All values were returned to pretreatment levels (9.2 +/- 0.9 dB in the CVIBS-IVS and 8.9 +/- 0.6 dB in CVIBS-PW, respectively) on day 15 after the treatments. CONCLUSION: This study suggests that HDLV5FU may cause acute transient alterations in CVIBS values in the absence of clinical symptoms and signs of cardiotoxicity. The clinical value of CVIBS should be further studied in patients receiving 5-FU-based therapy.     

Ultrasonic tissue characterization with a real time integrated backscatter imaging system in normal and aging human hearts

Experimental studies have shown that variation in the magnitude of integrated ultrasonic backscatter during the cardiac cycle represents acoustic properties of myocardium that are affected by pathologic processes; however, there are few clinical studies using integrated backscatter. Forty subjects without cardiovascular disease (aged 22 to 71 years, mean 41) were studied with use of a new M-mode format integrated backscatter imaging system to characterize the range of cyclic variation of integrated backscatter in normal subjects. Cyclic variation in integrated backscatter was noted in both the septum and the posterior wall in all subjects. The magnitude of the cyclic variation of integrated backscatter and the interval from the onset of the QRS wave of the electrocardiogram to the minimal integrated backscatter value were measured using an area of interest of variable size for integrated backscatter sampling and a software resident in the ultrasound scanner. The magnitude of cyclic variation was larger for the posterior wall than for the septum (6.3 +/- 0.8 versus 4.9 +/- 1.3 dB, p less than 0.01). The interval to the minimal integrated backscatter value was 328 +/- 58 ms for the septum and 348 +/- 42 ms for the posterior wall (p = NS). There was a weak correlation between the magnitude of cyclic variation of integrated backscatter and subject age for the posterior wall (r = -0.47, p less than 0.01), but this was not significant for the septum (r = -0.21) (partially because of inability to exclude specular septal echoes) and septal endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrasonic tissue characterization of the atherosclerotic carotid artery: histological correlates or carotid integrated backscatter.

Histological abnormalities of the atherosclerotic lesion are closely related to the stability of the plaque. Specifically, the plaque is likely to be unstable if the fibrous cap is thin. However, ultrasonic characterization of the atherosclerotic lesion has not been done from this viewpoint. Thus, in the present study ultrasonic tissue characterization of the carotid atherosclerotic lesion was attempted to assess the stability of the plaque. Integrated ultrasonic backscatter (IBS) in the atherosclerotic lesion was compared with histological findings of the respective tissue in 35 patients with carotid artery stenosis who underwent carotid endarterectomy. Carotid IBS was determined by locating the region-of-interest (ROI) in the center of the atherosclerotic lesion and calibrating by subtracting the IBS in the tunica externa of the vessel from the IBS of the ROI. IBS was also determined at the interface of the plaque, and at this site it was analyzed in relation to the thickness of the fibrous cap. Lipid content, fibrous tissue, thrombus, hemorrhage and calcification were histologically assessed in the respective tissue. Carotid IBS in the lipid lesion (-22.5+/-4.1 dB) was significantly different from that of fibrous, hemorrhagic or calcified lesions (-11.1+/-7.1, -27.5+/-4.1, +2.1+/-6.5 dB, respectively), but there was no significant difference in IBS between the lipid lesion and thrombus (-15.2+/-8.8 dB). IBS was lower in the thin fibrous cap than in the thick lesion (-10.9+/-6.4 vs -2.4+/-6.2 dB, p<0.001). IBS can be used to characterize atherosclerotic lesions in the carotid artery; a low value at the interface suggests a thin fibrous cap, which is frequently associated with unstable plaque.     

Ultrasonic tissue characterization: detection of acute myocardial ischemia in dogs

Ultrasonic tissue characterization is a new area of investigation in the field of cardiac ultrasound. The amplitude and frequency of the ultrasound signal are normally altered as the signal penetrates through tissue. It is assumed that the amplitude distribution and frequency shift of diseased or edematous tissue are different than those of normal tissue. A statistical approach to the analysis of the unprocessed radiofrequency signal in the amplitude domain was used to study the effect of acute myocardial ischemia on the parameter mean amplitude/standard deviation of the amplitude (MSR). Ten dogs were anesthetized and underwent left lateral thoracotomy. Baseline mean MSR from the interventricular septum was 1.99 +/- 0.05, but increased by 30 min after coronary artery occlusion and started to plateau at 1 hr (mean 2.24 +/- 0.06). Reproducibility in noninfarcted myocardium (left ventricular inferoposterior wall) was good, with a mean MSR of 2.00 +/- 0.05 at baseline and 1.98 +/- 0.04 3 to 4 hr later. There was no difference in mean MSR when data were obtained through chest wall and when they were obtained directly from the surface of the heart. We conclude that statistical analysis in the amplitude domain of the unprocessed radiofrequency signal can detect acute myocardial ischemia within 30 min after coronary artery occlusion, provides reproducible measurements, and is unaffected by chest wall filtering.     

Ultrasonic backscatter and collagen in normal ventricular myocardium

Integrated ultrasonic backscatter has been related to collagen deposition in fibrotic myocardium. The purpose of our study was to measure the integrated ultrasonic backscatter in the right and left ventricles of 10 normal freshly excised canine hearts and five normal formalin-fixed human hearts. A 2.25 MHz, 50% fractional bandwidth transducer was positioned at the transducer focal distance from the epicardium. The radio frequency backscatter signal, excluding specular reflections, was digitized, squared, and integrated to yield the integrated ultrasonic backscatter (in decibels down from a 100% reflector). The segment of myocardium corresponding to the integrated ultrasonic backscatter sample volume was excised and assayed for hydroxyproline, a marker for collagen. A second purpose of our study was to evaluate the influence of fixation with formalin on the backscatter. Regional integrated ultrasonic backscatter was therefore measured in 10 freshly excised canine left ventricles, which were fixed in 10% formalin for 2 weeks. Integrated ultrasonic backscatter measurements were then repeated. In freshly excised canine hearts, the integrated ultrasonic backscatter from right ventricle was higher than that from left ventricle (-60.4 +/- 1.6 [SEM] vs -66.9 +/- 1.0 dB; p less than .001). The collagen content of right ventricle was also higher than that of left ventricle (4.40 +/- 0.26 [SEM] vs 3.58 +/- 0.13 micrograms/mg dry weight; p less than .005). Similar results were obtained in human hearts. There were no correlations between integrated ultrasonic backscatter and collagen content (r = .28 and .32 for dogs and humans, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrasonic tissue characterization of normal and ischemic myocardium

Cardiac ultrasonic tissue characterization is designed to use the alterations in acoustic signals from the myocardium to differentiate normal from ischemic or infarcted tissue due to their characteristic backscatter attenuation. Various approaches such as use of a gray scale, color display, or quantitative image analysis have been used for tissue characterization, but all depend on subjective assessments and are not necessarily reproducible. The most promising method has been the use of "raw" radiofrequency signals and measure changes in the ultrasonic attenuation with an index of backscatter to distinguish normal from abnormal myocardium called "integrated backscatter" (IB). Various studies have demonstrated the changes in the ultrasonic backscatter with ischemia or infarction. In this review we summarize our experience with a research prototype instrument in tissue characterization and differentiation of normal, ischemic, infarcted, and post ischemic reperfused myocardium in anesthetized open chest dogs. Currently we are investigating the role of ultrasonic tissue characterization to estimate infarct size and plan to apply these observations to patients in order to detect viable myocardium and quantitate infarct size.     

Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia

It is unknown whether human chronically ischemic dysfunctional myocardium degenerates over time or adapts to chronic ischemia. We studied whether perfusion, metabolism, and contractile function and reserve can be preserved in nonrevascularized human chronically stunned and hibernating myocardium. We studied 16 event-free, medically treated patients with ejection fractions of 31 +/- 2% and chronically stunned or hibernating myocardium in 56 +/- 5% of the left ventricle on technetium-99m sestamibi single-photon emission computed tomography/fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography. Patients underwent repeat single-photon emission computed tomography, positron emission tomography, and tissue Doppler echocardiography at rest and during stress at follow-up after 25 +/- 4 months, and we investigated whether measurements of myocardial viability remained stable over time. Patients were stable with respect to New York Heart Association class and global left ventricular function (30 +/- 2%, p = 0.81). Wall motion score was unaltered in hibernating myocardium and chronically stunned regions, and a contractile reserve by tissue Doppler stress echocardiography was preserved. Overall, 74% of hibernating myocardium and chronically stunned regions retained their initial perfusion/metabolism pattern at follow-up. In hibernating myocardium, initial and follow-up sestamibi uptakes (53 +/- 1% and 53 +/- 2%, p = 0.85) and FDG uptakes (76 +/- 1% and 74 +/- 1%, p = 0.21) did not differ. In chronically stunned regions, sestamibi uptake displayed a minor decrease at follow-up (70 +/- 1% vs 67 +/- 1%, p <0.01) and FDG uptake remained constant (68 +/- 2% and 67 +/- 1%, p = 0.21). In conclusion, myocardial perfusion, FDG uptake, and contractile function in nonrevascularized chronically stunned and hibernating myocardium adapt to chronic ischemia in patients who are free of events. In chronically stunned regions, adaptation may be less complete than in hibernating myocardium.     

Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging in normal human subjects and in patients with dilated cardiomyopathy

We have shown previously that the physical properties of myocardium in dogs can be characterized with quantitative ultrasonic integrated backscatter and that interrogation of the tissue with ultrasound can delineate cardiac cycle-dependent changes in ultrasonic backscatter in normal tissue that disappear with ischemia and reappear with reperfusion if functional integrity is restorable. To determine whether this approach can be applied to man, we implemented an automatic gain compensation and continuous data acquisition system to characterize myocardium with quantitative ultrasonic backscatter and to detect cardiac cycle-dependent changes in real time. We developed a two-dimensional echocardiographic system with quantitative integrated backscatter imaging capabilities for use in human subjects that can automatically differentiate ultrasonic signals from blood as opposed to those obtained from tissue and adjust the slope of the gain compensation appropriately. Real-time images were formed from a continuous signal proportional to the logarithm of the integrated backscatter along each A-line. In our initial investigation, 15 normal volunteers (ages 17 to 40 years, heart rates 44 to 88 beats/min) and five patients with dilated cardiomyopathy (ages 22 to 52, heart rates 82 to 120 beats/min) were studied with conventional parasternal long-axis echocardiographic views. Diastolic-to-systolic variation of integrated backscatter in the interventricular septum and left ventricular posterior wall was seen in each of the normal subjects averaging 4.6 +/- 1.4 dB (SD) and 5.3 +/- 1.5 dB (n = 127 sites), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)