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Decreased 18fluorodeoxyglucose (FDG) uptake and blood flow at rest in the ventricular septum, as compared with the lateral wall, have been reported in mildly symptomatic patients with hypertrophic cardiomyopathy (HC). To assess whether regional metabolic heterogeneity in patients with HC is related to heterogeneous regional systolic function, 10 symptomatic patients (mean age 36 ± 17 years) with HC and no coronary artery disease underwent positron emission tomography with oxygen-15-water and FDG, and nuclear magnetic resonance imaging at rest to assess regional anatomy and systolic function. Regional absolute blood flow was similar between the ventricular septum and lateral wall. In contrast, FDG activity was significantly greater in the lateral wall than in the septum (1,023 ± 588 vs 767 ± 388 nCi/ml, respectively; p < 0.01). However, regional systolic wall thickening was also significantly greater in the lateral wall than in the septum (5.3 ± 4.3 vs 2.4 ± 4.0 mm, respectively; p < 0.001). Patients were then divided into group A (n = 5) with similar regional wall thickening in the septum and lateral wall, and group B (n = 5) with greater thickening in the lateral wall than in the septum. In both groups, regional blood flow was similar between the septum and lateral wall. However, the regional septal-to-lateral FDG activity ratio was 0.97 ± 0.31 in group A, and 0.74 ± 0.25 in group B (p < 0.01); the ratio in group A did not differ from that in 5 normal subjects (1.02 ± 0.58). Thus, myocardial Mood flow is normal at rest in patients with HC and no coronary artery disease; the heterogeneity in regional glucose uptake is parallel to that of regional systolic function and does not necessarily represent a metabolic abnormality at the cellular level.

To identify the presence of viable myocardium in areas of severe systolic dysfunction, we studied 22 patients (age 45 to 78 years) with chronic coronary artery disease and left ventricular dysfunction (mean ejection fraction 29 +/- 9%). All subjects underwent thallium-201 single photon emission computed tomography (SPECT), using the reinjection technique, positron emission tomography (PET) with H2(15)O and 18-fluorodeoxyglucose (FDG) to measure regional blood flow and exogenous glucose uptake, respectively, and nuclear magnetic resonance imaging (MRI). From matched transaxial PET, SPECT and MRI tomograms, a total of 290 left ventricular myocardial regions were analyzed. According to the regional wall thickening, measured from MRI, 3 groups of myocardial regions were identified: akinetic-dyskinetic (n = 60), showing either absence of systolic thickening or systolic thinning; hypokinetic (n = 97), showing an absolute wall thickening less than or equal to 2 mm; normal (n = 133), showing an absolute wall thickening greater than 2 mm. Of the 60 akinetic or dyskinetic regions, 3 were normal by SPECT and 37 corresponded to either a total or partially reversible thallium defect: 34 of these 40 regions also showed presence of FDG uptake by PET. The remaining 20 akinetic or dyskinetic regions showed a thallium defect that remained irreversible after reinjection: in 7 of these 20 regions, however, there was evidence of metabolic activity, as expressed by FDG uptake. Thus, 47 (78%) of the myocardial akinetic or dyskinetic regions showed presence of viable tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Im NIH, Bethesda, wurde ein “real-time” System für die Radionuklid-Ventrikulographie entwickelt mit folgenden Darstellungen:1) Sequenz der Bilder eines vollständigen Herzzyklus2) eine regionale Zeitaktivitätskurve mit exakter Darstellung der späten diastolischen Phase, und3) eine Verteilungsfunktion der Länge der Zyklen.Das System erwies sich als besonders geeignet für Belastungsuntersuchungen. Unter Belastung zeigten Herzgesunde einen Abfall, Patienten mit koronarer Herzerkrankung einen Anstieg der Auswurfsfraktion.

OBJECTIVES. The objective of this study was to assess the clinical significance of reduced regional fluorine-18 (18F) fluorodeoxyglucose uptake with normal flow in patients with chronic coronary artery disease. BACKGROUND. In patients with ischemic left ventricular dysfunction, 18F-fluorodeoxyglucose uptake may be reduced in some myocardial regions despite normal flow. The significance of this finding is unclear and has not been investigated systematically. METHODS. Twenty-three patients with coronary artery disease and impaired ventricular function (mean ejection fraction [+/- 1 SD] 28 +/- 10%) underwent positron emission tomography with 18F-fluorodeoxyglucose and oxygen-15-labeled water at rest, exercise thallium-201 tomographic imaging with rest reinjection and gated magnetic resonance imaging to measure end-diastolic wall thickness and systolic wall thickening. RESULTS. Of 168 regions with normal flow (> or = 0.7 ml/g per min), 125 (74%) had normal 18F-fluorodeoxyglucose uptake (98 +/- 10%), and the remaining 43 (26%) showed moderately reduced 18F-fluorodeoxyglucose uptake (69 +/- 8%). Systolic wall thickening was absent at rest in 14% of regions with normal 18F-fluorodeoxyglucose uptake compared with 32% of regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). Reversible thallium abnormalities were observed in 45 (36%) of 125 regions with normal 18F-fluorodeoxyglucose uptake compared with 27 (63%) of 43 regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). This difference was accounted for by a higher proportion of partially reversible defects in regions with reduced 18F-fluorodeoxyglucose uptake compared with regions with normal 18F-fluorodeoxyglucose uptake (42% vs. 18%, respectively, p < 0.01). CONCLUSIONS. Thus, regions with moderately reduced 18F-fluorodeoxyglucose uptake with normal flow occur commonly in patients with ischemic left ventricular dysfunction. The majority of these regions show impaired systolic function at rest and exercise-induced thallium abnormalities that are only partially reversible. These observations suggest that such regions represent an admixture of fibrotic and reversibly ischemic myocardium.

Although quantitation of exercise thallium tomograms has enhanced the noninvasive diagnosis and localization of coronary artery disease, the detection of stenosis of the left circumflex coronary artery remains suboptimal. Because posterolateral regional wall motion during exercise is well assessed by radionuclide angiography, this study determined whether regional dysfunction of the posterolateral wall during exercise radionuclide angiography is more sensitive in identifying left circumflex disease than thallium perfusion abnormalities assessed by single-photon emission computed tomography (SPECT). One hundred ten consecutive patients with CAD were studied, of whom 70 had a significant stenosis of the left circumflex coronary artery or a major obtuse marginal branch. Both regional function and segmental thallium activity of the posterolateral wall were assessed using visual and quantitative analysis. Left ventricular regional function was assessed objectively by dividing the left ventricular region of interest into 20 sectors; the 8 sectors corresponding to the posterolateral free wall were used to assess function in the left circumflex artery distribution. Similarly, using circumferential profile analysis of short-axis thallium tomograms, left ventricular myocardial activity was subdivided into 64 sectors; the 16 sectors corresponding to the posterolateral region were used to assess thallium perfusion abnormalities in the left circumflex artery territory. Qualitative posterolateral wall motion analysis detected 76% of patients with left circumflex coronary artery stenosis, with a specificity of 83%, compared with only 44% by qualitative thallium tomography (p A similar analysis applied to the interventricular septum revealed a higher predictive accuracy for detecting left anterior descending coronary artery stenosis by qualitative thallium SPECT, with a sensitivity of 80% and a specificity of 71%, compared with a sensitivity of 68% and a specificity of 57% by qualitative radionuclide angiography. Quantitation of thallium activity in both septal and anterior regions provided no additional insight for detection of left anterior descending artery stenosis. Thus, for noninvasive detection of left circumflex coronary artery disease, the data suggest that qualitative exercise radionuclide angiography is preferable to qualitative thallium SPECT and provides comparable information to quantitative thallium analysis.

In patients with chronic coronary artery disease and left ventricular dysfunction, the distinction between ventricular dysfunction arising from myocardial fibrosis and ischemic, but viable, myocardium has important clinical implications. By positron emission tomography (PET), enhanced fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and reduced blood flow is evidence of myocardial viability. Reinjection of thallium-201 at rest immediately after stress-redistribution imaging may also provide evidence of myocardial viability by demonstrating thallium uptake in regions with apparently "irreversible" defects. To compare these two methods, we studied 16 patients with chronic coronary artery disease and left ventricular dysfunction (ejection fraction, 27 +/- 9%), all of whom had irreversible defects on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT) imaging. Thallium was reinjected immediately after the redistribution study, and SPECT images were reacquired. The patients also underwent PET imaging with FDG and oxygen-15-labeled water. A total of 432 myocardial segments were analyzed from comparable transaxial tomograms, of which 166 (38%) had irreversible thallium defects on redistribution images before reinjection. FDG uptake was demonstrated in 121 (73%) of these irreversible defects. Irreversible defects were then subgrouped according to the degree of thallium activity, relative to peak activity in normal regions. Irreversible defects with only mild (60-85% of peak activity) or moderate (50-59% of peak) reduction in thallium activity were considered viable on the basis of FDG uptake in 91% and 84% of these segments, respectively. In contrast, in irreversible defects with severe reduction in thallium activity (less than 50% of peak), FDG uptake was present in 51% of segments. In such severe defects, an identical number of segments (51%) demonstrated enhanced uptake of thallium after reinjection. In these severe "irreversible" defects, data on myocardial viability were concordant by the two techniques in 88% of segments, with 45% identified as viable and 43% identified as scar on both PET and thallium reinjection studies. These observations suggest that thallium imaging can be used to identify viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Most irreversible defects with only mild or moderate reduction in thallium activity represent viable myocardium as confirmed by FDG uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

Left ventricular ejection fraction is normal at rest but may respond abnormally to exercise in many patients with essential hypertension. To assess the determinants of the abnormal ejection fraction response to exercise, we performed radionuclide angiography at rest and during exercise in 41 hypertensive patients without coronary artery disease. In 22 patients (group 1), the ejection fraction increased more than 5% during exercise; in the other 19 patients (group 2), the ejection fraction either increased by less than 5% or decreased with exercise. Left ventricular diastolic filling was impaired at rest in patients in group 2 compared with group 1, with reduced peak filling rate (2.5 +/- 0.4 vs. 3.1 +/- 0.7 end-diastolic volume/sec; p less than 0.01) and prolonged time to peak filling rate (175 +/- 28 vs. 153 +/- 22 msec; p less than 0.01). Impaired diastolic filling in group 2 was associated with less augmentation in end-diastolic volume during exercise compared with group 1 (p less than 0.01). These observations were not dependent on the threshold value that was arbitrarily chosen to define an abnormal ejection fraction response, as there were significant correlations for the entire group between the magnitude of change in ejection fraction with exercise and both the resting peak filling rate (r = 0.46) and the change in end-diastolic volume with exercise (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Thallium-201 reinjection imaging and positron emission tomography provide concordant information regarding myocardial viability in many patients with coronary artery disease and left ventricular (LV) dysfunction. It is unclear whether this concordance applies to patients with severe, as well as those with moderate, LV dysfunction. We studied 44 patients with chronic coronary artery disease and LV dysfunction, subgrouped on the basis of severity of dysfunction: 23 patients had moderate and 21 had severe dysfunction (ejection fractions 34 +/- 6% and 19 +/- 6%). Patients underwent exercise thallium single-photon emission computed tomography (SPECT) with 3- to 4-hour redistribution and reinjection imaging, as well as positron emission tomography (PET) imaging with 18fluorodeoxyglucose and 15O-water. Data were analyzed quantitatively in aligned transaxial PET and SPECT tomograms. A myocardial region was considered nonviable by PET if 18fluorodeoxyglucose activity was50% of that in a normal region, associated with proportional reduction in blood flow. Similarly, regions were considered nonviable by thallium if activity was50% of activity in normal regions on redistribution and reinjection studies. Thallium SPECT and PET data were concordant regarding viability in 98% and 93% of myocardial regions, respectively, in patients with moderate and with severe LV dysfunction. Lower concordance was observed only when regions with severe irreversible thallium perfusion defects on redistribution images were considered in both groups: 86% and 78%, respectively (p0.01). Thus, thallium SPECT with reinjection yields information regarding regional myocardial viability that is similar to that provided by PET in patients with severe as well as moderate LV dysfunction. However, there is discordance in20% of regions manifesting severe irreversible thallium defects in patients with severely reduced LV function.

BACKGROUND The clinical significance and pathophysiological mechanisms of reverse redistribution on stress-redistribution thallium-201 myocardial scintigraphy in patients with chronic coronary artery disease are unclear. Recent studies have shown that thallium-201 reinjection is a useful technique for the detection of myocardial viability in chronic coronary artery disease. In this investigation we determined whether thallium reinjection distinguishes viable from nonviable myocardium in regions with reverse redistribution. METHODS AND RESULTS We studied 39 patients with chronic stable coronary artery disease (age, 60 +/- 10 years), all of whom demonstrated reverse redistribution on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT). Reverse redistribution was defined as > or = 10% decrease in relative thallium-201 activity between stress and redistribution images and included either the worsening of a perfusion defect apparent on post-stress images or the appearance of a new defect on the redistribution images. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution study. Of 39 regions with reverse redistribution, 32 (82%) showed enhanced thallium-201 activity (> or = 10% increase) after reinjection. In the other 7 regions (18%), the scintigraphic defect persisted after reinjection. Abnormal Q waves were present in only 8 of 32 (25%) regions with enhanced thallium-201 uptake after reinjection compared with 5 of 7 (71%) regions not responding to reinjection (P < .05). Akinetic or dyskinetic wall motion was present in 3 of 32 (9%) regions showing enhanced uptake after reinjection, in contrast with 5 of 7 (71%) regions not responding to reinjection (P < .01). Critically stenosed or totally occluded coronary arteries supplied 24 of 29 (83%) regions with enhanced thallium-201 uptake after reinjection but only 2 of 7 (28%) regions not showing a positive response to reinjection (P < .05). Collateral circulation was detected in 23 of 29 (79%) regions with a positive thallium reinjection effect but in only 1 of the other 7 regions (P < .01). Sixteen of the 39 patients also underwent positron emission tomography using 18F-fluorodeoxyglucose (FDG) to assess glucose utilization and H2(15)O to assess regional blood flow. The 14 regions with reverse redistribution that responded to reinjection with enhanced thallium uptake all showed either normal patterns of FDG uptake and flow or an ischemic pattern with increased FDG uptake relative to flow. Reduced FDG uptake and reduced flow values were seen in the two regions not responding to thallium reinjection. CONCLUSIONS These observations indicate that reverse redistribution in chronic coronary artery disease usually reflects viable myocardium, critically dependent upon collateral circulation.

A method is described and tested which allows three-dimensional registration of two cardiac PET attenuation scans of the same subject acquired at different times. The alignment method is based on maximizing the correlation coefficient between the stacks of slices obtained during each of the two imaging sessions. The method appears accurate to better than 1 mm in x, y and z, and better than 1.5 degrees in the three angles of rotation. The method has been tested by using it to realign deliberately misaligned attenuation scans, and also by using realigned attenuation scans to correct fluorodeoxyglucose (FDG) emission scan data. The FDG emission data reconstructed with the realigned attenuation scans do not differ appreciably from the FDG data obtained using the original attenuation data. The method should be useful in realigning emission data (using the alignment coordinates predicted by realigning the attenuation scans), correcting for subject motion between scans (especially multiple intervention scans) and may allow a subject to leave the scanning table between scans during long imaging sessions.

BACKGROUND In previous studies comparing regional 201Tl (201Tl) and 18fluorodeoxyglucose (FDG) activity in patients with chronic coronary artery disease and left ventricular dysfunction, we hypothesized that regions with mild-to-moderate reduction in FDG activity and regions with mild-to-moderate irreversible 201Tl defects after 3- to 4-hour redistribution represent viable myocardium. In the present study, regional FDG and 201Tl activities were compared with regional systolic wall thickening by gated magnetic resonance imaging (MRI) to confirm the presence of viable myocardium in these territories. METHODS AND RESULTS Twenty-five patients with chronic stable coronary artery disease and left ventricular dysfunction (ejection fraction, 28 +/- 10) underwent exercise 201Tl tomographic imaging (SPECT), using a reinjection protocol, positron emission tomography (PET) with FDG and H2(15)O, and gated MRI. Matched SPECT, PET, and MRI tomograms were analyzed. From the PET data, 105 regions had matched reduction in FDG and blood flow, of which 69 regions had moderately reduced FDG uptake (50-79% uptake relative to a normal reference region) and 36 had severely reduced FDG uptake (less than 50% of normal activity). Regions with moderately reduced as compared with severely reduced FDG activity had greater end-diastolic wall thickness (9.4 +/- 2.6 versus 8.0 +/- 3.7 mm; p less than 0.05) and regional systolic wall thickening (1.7 +/- 2.7 versus -0.7 +/- 2.1 mm; p less than 0.01). From the SPECT data, 169 irreversible 201Tl defects after 3-4 hour redistribution were identified, of which 70 were mild (greater than 65 to less than 85% of maximal 201Tl activity), 52 were moderate (50-65% of maximal activity), and 47 were severe (less than 50% of maximal activity). Regional systolic wall thickening was greater in regions with normal 201Tl uptake (3.3 +/- 2.3 mm) as compared with all other regions. Regions showing only mild or moderate irreversible defects at redistribution, however, showed wall thickening (2.4 +/- 2.4 and 2.2 +/- 2.5 mm, respectively), which was similar to that observed in regions with reversible 201Tl defects (2.1 +/- 2.2 mm). Only regions with severe irreversible defects at redistribution showed absence of thickening (-0.1 +/- 2.9 mm, p less than 0.01 versus all other groups). After 201Tl reinjection, 12 of 47 (26%) regions with severe irreversible defects showed enhanced 201Tl uptake. The impairment in regional systolic wall thickening was not significantly different between 201Tl defects with and without enhanced 201Tl uptake after reinjection. FDG activity, however, was present in all 12 regions (100%) with enhanced 201Tl uptake after reinjection as compared with only five of 35 (14%) that were unchanged after reinjection (p less than 0.01). CONCLUSIONS Therefore, preserved wall thickness and systolic wall thickening in regions with moderate reduction in blood flow and FDG activity, and in irreversible 201Tl defects that are only mild-to-moderate, provide additional evidence that such regions represent viable myocardium. Moreover, the finding of metabolic activity and 201Tl uptake in regions with reduced blood flow and absent wall thickening provides clinical evidence of hibernating myocardium in humans.

Patients with coronary artery disease often have impaired left ventricular diastolic filling despite normal global systolic function. The influence of regional systolic asynchrony on diastolic function was assessed by radionuclide angiography in 60 patients with coronary artery disease and normal ejection fraction at rest: group 1 (n = 30) with normal wall motion at rest and group 2 (n = 30) with abnormal wall motion. Data were compared with those obtained from 19 normal volunteers.Age, heart rate, ejection fraction and echocardiographic enddiastolic dimension did not differ among the three groups. Peak filling rate in group 1 and group 2 was similar (2.5 ± 0.5 and 2.3 ± 0.6 end-diastolic counts/s, respectively) and significantly lower than that in the normal subjects (2.8 ± 0.7 end-diastolic counts/s; p < 0.01 vs. group 2, p < 0.05 vs. group 1). Time to peak filling rate was prolonged in group 2 (184 ± 27 ms) compared with that in normal subjects (162 ± 19 ms; p < 0.01) and group 1 (172 ± 15 ms; p < 0.05). Left ventricular end-diastolic pressure was significantly higher in group 2 than in group 1 (14 ± 7 vs. 10 ± 5 mm Hg, respectively; p < 0.05).Asynchrony was assessed by sector analysis of the radionuclide left ventricular region of interest. Diastolic asynchrony was similar in the two patient groups (30 ± 23 ms in group 2, 26 ± 16 ms in group 1) and was higher in both groups than in the normal subjects (16 ± 8 ms; p < 0.61). However, systolic asynchrony was higher in group 2 (32 ± 15 ms) than in both group 1 (14 ± 6 ms; p < 0.01) and the normal group (9 ± 6 ms; p < 0.01). In the total group of patients with coronary artery disease, systolic asynchrony correlated with global time to peak filling rate (r = 0.53; p < 0.001). This correlation became stronger when only group 2 was considered (r = 9.62; p < 0.001). Moreover, in group 2 systolic asynchrony correlated with the duration of the isovolumetric relaxation period (r = 0.58; p < 0.001) and the isovolumetric relaxation period, in turn, correlated with global time to peak filling rate (r = 0.72; p < 0.001).Thus, left ventricular systolic asynchrony affects both the relaxation and filling phases of diastole, thereby contributing to the impairment of diastolic function commonly observed in patients with coronary artery disease.

Reduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 +/- 10%) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) greater than 50% of that in normal regions. Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxyglucose uptake was observed in 97% of the hypokinetic and normokinetic regions and in 74% of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 +/- 4 vs. 7 +/- 3 mm, p less than 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74% and 79%, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end-diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32). Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium.

Patient movement between PET scanning sequences can produce misalignment between attenuation and emission scans. Such misalignment introduces errors in the emission image. This study evaluates the severity of these errors and their effect upon quantitation of regional myocardial activity. Myocardial FDG scans from 14 patients were reconstructed with simulated translational, rotational and out-of-plane patient movement. Eight myocardial regions from each patient were examined to determine the effect such misalignment might have on regional myocardial activity. A 2-cm shift between attenuation and emission scans produced up to a 30% change in regional activity. Some regions of the myocardium increased while others decreased for a given magnitude and direction of shift, producing anomalous regional myocardial inhomogeneities in the image. Such changes could easily cause qualitative and quantitative misinterpretations. We present data permitting the reader to assess the magnitude of this effect in his/her own clinical setting.