A simple method for the study of cytosolic content of oligonucleotides in cells

BACKGROUND: Nonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement. METHODS AND RESULTS: The attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201Tl study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients. CONCLUSIONS: The results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.     

Non-uniform attenuation correction for myocardial SPET using two Gd-153 line sources

AIM: This study deals with the effect of the non-uniform attenuation correction method on myocardial tomograms of normal subjects. METHOD: A total of 35 patients (20 female, 15 male) without evidence of cardiac disease underwent SPET with and without attenuation correction using a dual head camera and transmission data obtained by two scanning Gd-153 line sources after administration of 400 MBq Tc-99m-tetrofosmin RESULTS: In non-corrected (NC) stress studies the lowest count rates were found in the inferior segments with mean differences in count rates between maxima and minima of 35.8 +/- 10.8%. In attenuation corrected (AC) images the respective segmental differences averaged only 20.9 +/- 3.3% and the images did not show significant count deficiency in the inferior segments. The effects of correction revealed to be sex dependent, but independent of body mass on average. CONCLUSION: AC using the above technique significantly reduces the variability of count rate distribution in normal subjects and improves the preconditions for accurate diagnostic evaluation of coronary artery disease using SPET.     

Transmission-based scatter correction of 180 degrees myocardial single-photon emission tomographic studies

Meaningful comparison of single-photon emission tomographic (SPET) reconstructions for data acquired over 180 degrees or 360 degrees can only be performed if both attenuation and scatter correction are applied. Convolution subtraction has appeal as a practical method for scatter correction; however, it is limited to data acquired over 360 degrees. A new algorithm is proposed which can be applied equally well to data acquired over 180 degrees or 360 degrees. The method involves estimating scatter based on knowledge of reconstructed transmission data in combination with a reconstructed estimate of the activity distribution, obtained using attenuation correction with broad beam attenuation coefficients. Processing is implemented for planes of activity parallel to the projection images for which a simplified model for the scatter distribution may be applied, based on the measured attenuation. The appropriate broad beam (effective) attenuation coefficients were determined by considering the scatter buildup equation. It was demonstrated that narrow beam attenuation coefficients should be scaled by 0.75 and 0.65 to provide broad beam attenuation coefficients for technetium-99m and thallium-201 respectively. Using a thorax phantom, quantitative accuracy of the new algorithm was compared with conventional transmission-based convolution subtraction (TDCS) for 360 degrees data. Similar heart to lung contrasts were achieved and correction of 180 degrees data yielded a 10.4% error for cardiac activity compared to 5.2% for TDCS. Contrast for myocardium to ventricular cavity was similarly good for scatter-corrected 180 degrees and 360 degrees data, in contrast to attenuation-corrected data, where contrast was significantly reduced. The new algorithm provides a practical method for correction of scatter applicable to 180 degrees myocardial SPET.     

Significance of nonuniform attenuation correction in quantitative brain SPECT imaging

The purposes of this study were to develop a method for nonuniform attenuation correction of 123I emission brain images based on transmission imaging with a longer-lived isotope (i.e., 57Co) and to evaluate the relative improvement in quantitative SPECT images achieved with nonuniform attenuation correction. METHODS: Emission and transmission SPECT scans were acquired on three different sets of studies: a heterogeneous brain phantom filled with 1231 to simulate the distribution of dopamine transporters labeled with 2beta-carbomethoxy-3beta-(4-123I-iodophenyl)tropane (123I-beta-CIT); nine healthy human control subjects who underwent transmission scanning using two separate line sources (57Co and 123I); and a set of eight patients with Parkinson's disease and five healthy control subjects who received both emission and transmission scans after injection of 123I-beta-CIT. Attenuation maps were reconstructed using a Bayesian transmission reconstruction algorithm, and attenuation correction was performed using Chang's postprocessing method. The spatial distribution of errors within the brain was obtained from attenuation correction factors computed from uniform and nonuniform attenuation maps and was visualized on a pixel-by-pixel basis as an error image. RESULTS: For the heterogeneous brain phantom, the uniform attenuation correction had errors of 2%-6.5% for regions corresponding to striatum and background, whereas nonuniform attenuation correction was within 1%. Analysis of 123I transmission images of the nine healthy human control subjects showed differences between uniform and nonuniform attenuation correction to be in the range of 6.4%-16.0% for brain regions of interest (ROIs). The human control subjects who received transmission scans only were used to generate a curvilinear function to convert 57Co attenuation values into those for 123I, based on a pixel-by-pixel comparison of two coregistered transmission images for each subject. These values were applied to the group of patients and healthy control subjects who received transmission 57Co scans and emission 123I scans after injection of 123I-beta-CIT. In comparison to nonuniform attenuation correction as the gold standard, uniform attenuation with the ellipse drawn around the transmission image caused an approximately 5% error, whereas placement of the ellipse around the emission image caused a 15% error. CONCLUSION: Nonuniform attenuation correction allowed a moderate improvement in the measurement of absolute activity in individual brain ROIs. When images were analyzed as target-to-background activity ratios, as is commonly performed with 123I-beta-CIT, these outcome measures showed only small differences when Parkinson's disease patients and healthy control subjects were compared using nonuniform, uniform or even no attenuation correction.     

Importance of bone attenuation in brain SPECT quantification

The purpose of this study was to determine the effects of nonuniform attenuation on relative quantification in brain SPECT and to compare the ability of the Chang and Sorenson uniform attenuation corrections (UACs) to achieve volumetric relative quantification. METHODS: Three head phantoms (dry human skull, Rando and Radiology Support Devices (RSD) phantoms) were compared with a human head using a gamma camera transmission CT (gammaTCT) SPECT system and x-ray CT. Subsequently, the RSD phantom's brain reservoir was filled with a uniform water solution of 99mTc, and SPECT and gammaTCT data were acquired using fanbeam collimation. The attenuating effects of bone, scalp and head-holder in individual projections were determined by an analytical projection technique using the SPECT and gammaTCT reconstructions. The Chang UAC used brain and head contours that were segmented from the gammaTCT reconstruction to demarcate its attenuation map, whereas the Sorenson UAC fit slice-specific ellipses to the SPECT projection data. For each UAC, volumetric relative quantification was measured with varying attenuation coefficients (mus) of the attenuation map. RESULTS: Gamma camera transmission CT and x-ray CT scans showed that the dry skull and Rando phantoms suffered from a dried trabecular bone compartment. The RSD phantom most closely reproduced the attenuation coefficients of the human gammaTCT and x-ray CT scans. The analytical projections showed that the attenuating effects of bone, scalp and head-holder were nonuniform across the projections and accounted for 18%-37% of the total count loss. Volumetric relative quantification was best achieved with the Chang (zero iterations) attenuation correction using the head contour and mu = 0.075 cm(-1); however, cortical activity was found to be 10% higher than cerebellar activity. For all UACs, the optimal choices of mu were experimentally found to be lower than the recommended 0.12 cm(-1) for brain tissue. This result is theoretically supported here. CONCLUSION: The magnitude of errors resulting from uniform attenuation corrections can be greater than the magnitudes of regional cerebral blood flow deficits in patients with dementia, as compared with normal controls. This suggests that nonuniform attenuation correction in brain SPECT imaging must be applied to accurately estimate regional cerebral blood flow.     

Noninvasive quantification of regional myocardial metabolic rate for oxygen by use of 15O2 inhalation and positron emission tomography. Theory, error analysis, and application in humans

BACKGROUND: A method has been developed to measure the regional myocardial metabolic rate of oxygen consumption (rMMRO2) and oxygen extraction fraction (rOEF) quantitatively and noninvasively in humans by use of 15O2 inhalation and positron emission tomography. This article describes the theory, an error analysis of the technique, and procedures of the method used in a human feasibility study. METHODS AND RESULTS: Inhaled 15O2 is transported to peripheral tissues, where it is converted to 15O-labeled water of metabolism, which exchanges with the relatively large extravascular tissue space. Quantification of this buildup of radioactivity allows the calculation of rMMRO2 and rOEF. However, a correction for the spillover of the pulmonary gas radioactivity signal into myocardial regions is required and has been made by use of a gas volume distribution estimated from the transmission scan. This was validated by comparative measurements using the inert gas [11C]CH4 in four greyhounds. Spillover of the cardiac chamber radioactivity has been corrected for with an inhaled [13O]CO (blood volume) scan. The underestimation of myocardial radioactivity due to wall motion and thickness has been corrected for by use of values of tissue fraction obtained from the flow measurement [15OKCO2 scan). Values of rOEF were similar (within 4%) whether obtained from gas volume measurements determined from the transmission or [11C]CH4 scan data. 15O2 scan information from six healthy volunteers showed a clear distribution of myocardial radioactivity after the vascular and pulmonary gas 15O background was subtracted. Subsequent compartmental analysis resulted in values for rOEF and rMMRO2 of 0.60 +/- 0.11 and 0.10 +/- 0.03 mL.min-1.g-1 in the human myocardium at rest. CONCLUSIONS: The results of this study are in good agreement with established values. This is the first known approach to allow the direct quantitative determination of rOEF and oxygen metabolism to be made noninvasively on a regional basis.     

Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis

BACKGROUND: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. METHODS AND RESULTS: We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest 201Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001). CONCLUSIONS: Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.     

Technetium-99m sestamibi tomographic evaluation of residual ischemia after anterior myocardial infarction

OBJECTIVES: This study investigated the value of sestamibi scintigraphy in assessing residual ischemia after anterior myocardial infarction. BACKGROUND: Serial imaging with sestamibi, the uptake and retention of which correlate with regional myocardial blood flow and viability, has been used to estimate salvaged myocardium and risk area after acute infarction. We recently documented that recovery of perfusion and contraction in the infarcted area may continue well after the subacute phase, suggesting myocardial hibernation. Some underestimation of viability in the setting of hibernating myocardium by sestamibi imaging has been reported. METHODS: We studied 58 patients in stable condition after Q wave anterior infarction. Regional perfusion and function were quantitatively assessed by sestamibi tomography and two-dimensional echocardiography at 4 to 6 weeks and at 7 months after infarction. In sestamibi polar maps, abnormal areas with tracer uptake > 2.5 SD below our reference values were computed at rest and after symptom-limited exercise. On two-dimensional echocardiography the ejection fraction and extent of rest wall motion abnormalities were assessed by a computerized system. All patients had coronary angiography between the two studies. RESULTS: At 7 months the extent of rest sestamibi defect was significantly reduced in 40 patients (69%, group 1) and unchanged in 18 (31%, group 2). Rest wall motion abnormalities and ventricular ejection fraction significantly improved in group 1 but not in group 2. Underlying coronary disease, patency of the infarct-related vessel and rest sestamibi defect extent at 5 weeks were comparable between the two groups. At 7 months, an increase in the reversible (stress-rest defect) tracer defect was observed in group 1 (p < 0.05) despite a smaller stress-induced hypoperfusion (p < 0.05). Reversible sestamibi defects and stress hypoperfusion were unchanged in group 2. In 38 (95%) of 40 group 1 patients, the area showing reversible sestamibi defects at 7 months matched the area showing fixed hypoperfusion at 5 weeks. CONCLUSIONS: The reduction in the rest tracer uptake defect that can occur late after infarction may affect the assessment of ischemic burden by sestamibi imaging early after anterior myocardial infarction.     

Application of models of working at the interface between primary care and mental health services in Israel

A practical method for scatter and attenuation compensation was employed in thallium-201 myocardial single-photon emission tomography (SPET or ECT) with the triple-energy-window (TEW) technique and an iterative attenuation correction method by using a measured attenuation map. The map was reconstructed from technetium-99m transmission CT (TCT) data. A dual-headed SPET gamma camera system equipped with parallel-hole collimators was used for ECT/TCT data acquisition and a new type of external source named "sheet line source" was designed for TCT data acquisition. This sheet line source was composed of a narrow long fluoroplastic tube embedded in a rectangular acrylic board. After injection of 99mTc solution into the tube by an automatic injector, the board was attached in front of the collimator surface of one of the two detectors. After acquiring emission and transmission data separately or simultaneously, we eliminated scattered photons in the transmission and emission data with the TEW method, and reconstructed both images. Then, the effect of attenuation in the scatter-corrected ECT images was compensated with Chang's iterative method by using measured attenuation maps. Our method was validated by several phantom studies and clinical cardiac studies. The method offered improved homogeneity in distribution of myocardial activity and accurate measurements of myocardial tracer uptake. We conclude that the above correction method is feasible because a new type of 99mTc external source may not produce truncation in TCT images and is cost-effective and easy to prepare in clinical situations.     

Correction of partial volume effects in myocardial SPECT

BACKGROUND: Marked partial volume effects occur in myocardial single photon emission computed tomographic (SPECT) studies because of limited resolution in imaging the myocardial wall and contractile motion of the heart. Little work has been undertaken to develop correction techniques for SPECT except for efforts to improve the reconstructed resolution. Our purpose was to examine the extent of the problem and propose a correction method. METHODS AND RESULTS: A potential correction method, developed initially for positron emission tomography, involved estimation of extravascular density by means of subtracting vascular density derived in a blood pool study from total density derived from a transmission study. Provided partial volume errors are the same for transmission and emission data, activity per gram of extravascular tissue can be obtained by means of dividing the perfusion regional data by extravascular density for the same region. Simulations were designed to assess the importance of partial volume errors and the use of extravascular density to correct the errors. Recovery coefficients for the myocardium were estimated by means of simulation of the beating heart on the basis of published values for ventricular dimensions. Resolution for transmission with a scanning line source system was compared with emission resolution. The effect of spillover on measured partial volume losses was assessed, and a method for matching spillover for emission and extravascular density was demonstrated. Correction for partial volume effects was demonstrated for a phantom with variable wall thickness. Significant variation in recovery coefficient was demonstrated between posterior and septal walls for individual patients independent of heart size. Filtering was necessary to account for the difference in transmission resolution measured in the axial direction. Spillover effects had a significant influence on the measured recovery for small objects; however, for a specific reconstruction algorithm and defined region size, correction was implemented to match the spillover effects for emission and extravascular density. Use of extravascular density for correction of partial volume loss, for ordered subsets expectation maximization reconstruction with compensation for resolution, was demonstrated to be accurate to within 10%. CONCLUSIONS: The feasibility of correcting partial volume effects with extravascular density was demonstrated. Correction is effective provided care is taken to match both resolution and spillover for emission and extravascular density.     

Regional cardiac sympathetic nerve dysfunction and the diagnostic efficacy of metaiodobenzylguanidine tomography in stable coronary artery disease

The present study endeavors to correlate regional myocardial sympathetic nerve dysfunction with reversible and persistent perfusion abnormalities and depressed regional wall motion, and to determine the diagnostic efficacy of radio-iodinated metaiodobenzylguanidine (MIBG) tomography for detecting coronary artery disease. In 28 consecutive patients with stable coronary artery disease and 7 patients with atypical chest pain but no coronary stenosis, regional MIBG uptake was semiquantitatively evaluated in 13 left ventricular segments early (30 minutes) and late (4 hours) after injection. Regional MIBG uptake was reduced in 68 of 90 segments (76%) showing reversible perfusion abnormality and 72 of 81 segments (89%) showing persistent abnormality 4 hours after injection. Although the sensitivity and negative predictive values of late MIBG scanning for detecting myocardial perfusion abnormalities were relatively high (82% and 85%, respectively), the specificity, positive predictive value, and kappa value were low (63%, 57%, and 0.41, respectively). Right coronary lesions were detected by late MIBG scanning with a high sensitivity (85%) but a low specificity (41%). Conversely, the sensitivities for detecting lesions in the other 2 major left coronary arteries were low (55%). The overall diagnostic accuracy of late MIBG scanning was 66% and the positive and negative predictive values and kappa value were low; 60%, 70%, and 0.31, respectively. Similarly, regional sympathetic dysfunction was observed in 42 of 49 asynergic segments (86%) on late MIBG scans, of which 32 segments were viable and 10 nonviable; but the low specificity (73%) and positive predictive value (44%) reduced the kappa value (0.43). Thus, regional cardiac sympathetic innervation is impaired in ischemic, asynergic but noninfarcted myocardium as well as in myocardium which is infarcted or has a persistent perfusion abnormality. The diagnostic efficacy of MIBG tomography to detect coronary artery disease, however, is limited probably because of nonspecific reductions of MIBG uptake in the inferior and posterolateral regions.     

Simultaneous acquisition of iodine-123 emission and technetium-99m transmission data for quantitative brain single-photon emission tomographic imaging

The aim of this study was to obtain quantitative iodine-123 brain single-photon emission tomographic (SPET) images with scatter and attenuation correction. We used a triple-headed SPET gamma camera system equipped with fan-beam collimators with a technetium-99m line transmission source placed at one of the focal lines of the fan-beam collimators. Four energy windows were employed for data acquisition: (a) 126-132 keV, (b) 132-143 keV, (c) 143-175 keV and (d) 175-186 keV. A simultaneous transmission-emission computed tomography scan (TCT-ECT) was carried out for a brain phantom containing 123I solution. The triple energy window scatter correction was applied to the 123I ECT data measured by means of the windows (b), (c) and (d) acquired by two detectors. Attenuation maps were reconstructed from 99mTc TCT data measured by means of the windows (a), (b) and (c) acquired by one detector. Chang's iterative attenuation correction method using the attenuation maps was applied to the 123I ECT images. In the phantom study cross-calibrated SPET values obtained with the simultaneous mode were almost equal to those obtained with the sequential mode, and they were close to the true value, within an error range of 5.5%. In the human study corrected images showed a higher grey-to-white matter count ratio and relatively higher uptake in the cerebellum, basal ganglia and thalamus than uncorrected images. We conclude that this correction method provides improved quantification and quality of SPET images and that the method is clinically practical because it requires only a single scan with a 99mTc external source.     

Whither paediatric dentistry?

The noninvasive assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function has proven clinically useful for identifying those patients with ischemic cardiomyopathy who benefit most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has been the radionuclide imaging technique most often utilized for distinguishing viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to 201Tl for imaging of regional myocardial perfusion. Whether these new agents, which have better physical properties for imaging with a gamma camera than 201Tl, are valid for use in assessing myocardial viability is still uncertain. Recent clinical studies have demonstrated that these agents, when imaged using quantitative SPECT, can identify patients with myocardial hibernation who exhibit improved regional systolic function following revascularization. Experimental laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc-tetrofosmin in ischemic myocardium is only slightly lower than the uptake of 201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of viable myocytes under conditions of myocardial stunning and short-term hibernation, producing severe myocardial asynergy. With respect to determination of viability, the inferior wall region is at times problematic since attenuation of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration of preserved systolic thickening on ECG-gated SPECT images is indicative of viability in the instance of decreased regional 99mTc counts due to attenuation and not scar. Administration of nitrates prior to tracer injection improves the sensitivity for identifying viable myocardial segments using rest imaging with 99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc perfusion imaging agents can be successfully employed for the determination of myocardial viability in the setting of severe regional dysfunction and chronic coronary artery disease. The greater the myocardial uptake of these agents in the resting state, the greater the probability of improved systolic function after coronary revascularization.     

Mechanism of impaired left ventricular wall motion in the diabetic heart without coronary artery disease

OBJECTIVE: To elucidate whether impairment of the myocardial free fatty acid (FFA) metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease. RESEARCH DESIGN AND METHODS: We performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum. RESULTS: Nine patients with reduced wall motion documented by left ventriculography (LVG), (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 +/- 0.2, mean +/- SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 +/- 0.2, P < 0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P < 0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS: Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes.     

Relation of myocardial perfusion at rest and during pharmacologic stress to the PET patterns of tissue viability in patients with severe left ventricular dysfunction

BACKGROUND: Stress perfusion imaging can assess effectively the amount of jeopardized myocardium, but its use for identifying underperfused but viable myocardium has yielded variable results. We evaluated the relation between measurements of myocardial perfusion at rest and during pharmacologic stress and the patterns of tissue viability as determined by positron emission tomographic (PET) imaging. METHODS AND RESULTS: We studied 33 patients with coronary artery disease and left ventricular (LV) dysfunction (LV ejection fraction, 30%+/-8%). PET imaging was used to evaluate regional myocardial perfusion at rest and during pharmacologic stress with [13N]-ammonia as a flow tracer, and to delineate patterns of tissue viability (i.e., perfusion-metabolism mismatch or match) using [18F]-deoxyglucose (FDG). We analyzed 429 myocardial regions, of which 229 were dysfunctional at rest. Of these, 30 had normal perfusion and 199 were hypoperfused. A severe resting defect (deficit >40% below normal) predicted lack of significant tissue viability; 31 of 35 regions (89%) had a PET match pattern denoting transmural fibrosis. Although regions with mild or moderate resting defects (deficit <40% below normal) showed evidence of metabolic activity, perfusion measurements alone failed to identify regions with PET mismatch (reflecting hibernating myocardium). Reversible stress defects were observed with slightly higher frequency in regions with a PET mismatch (10 of 37) than in those with a PET match (36 of 162) pattern of viability. A reversible stress defect was a specific (78%) marker, but was a relatively insensitive marker (27%) of viable myocardium as defined by the PET mismatch pattern. CONCLUSIONS: In patients with LV dysfunction, the severity of regional contractile abnormalities correlates with the severity of flow deficit at rest. Severe reductions in resting blood flow in these dysfunctional regions identify predominantly nonviable myocardium that is unlikely to have improved function after revascularization. Although dysfunctional myocardium with mild to moderate flow reductions contains variable amounts of viable tissue (as assessed by FDG uptake), flow measurements alone do not distinguish between regions with PET mismatch (potentially reversible dysfunction) and PET match (irreversible dysfunction). The presence of an irreversible defect on stress imaging is a relatively specific (78%) marker of PET match, whereas a reversible stress defect is a rather insensitive (27%) marker of viability, as defined by the PET mismatch pattern.     

Flow versus uptake comparisons of thallium-201 with technetium-99m perfusion tracers in a canine model of myocardial ischemia

We investigated the myocardial flow kinetics of six putative radioperfusion agents (99mTc-Q3, 99mTc-Q4, 99mTc-Q12, 99mTc-sestamibi, 99mTc-tetrofosmin and 99mTcN-NOET) and 201Tl in a canine model of myocardial ischemia with pharmacologic coronary artery vasodilation. METHODS: In 31 open-chest dogs with acute coronary occlusion, dipyridamole (approximately 0.56 mg/kg) was infused intravenously, followed by a perfusion tracer injection and radioactive microspheres for myocardial blood flow (MBF) measurement. The paired data were normalized using three techniques; average, normal or maximum myocardial tracer activity and MBF. RESULTS: The upper limit of MBF obtained for the group of tracers ranged from 4.2 ml/min/g to 8.2 ml/min/g. There was a statistically significant (p < 0.0001) linear correlation (r = 0.87-0.98) between the normalized myocardial activity and the normalized MBF values of each of the tracers. The slope of the curve normalized by average for 201Tl (0.83) was greater than those for the 99mTc tracers, and the intercept (0.07) was lower than those for the 99mTc tracers. Slopes and intercepts for the 99mTc agents were as follows: 99mTc-Q3, 0.81 and 0.18; 99mTc-Q4, 0.61 and 0.41; 99mTc-Q12, 0.63 and 0.39; 99mTc-sestamibi, 0.62 and 0.34; 99mTc-tetrofosmin, 0.68 and 0.32; and 99mTcN-NOET, 0.71 and 0.29, respectively. CONCLUSION: In an anesthetized open-chest canine model of regional myocardial ischemia with dipyridamole induced hyperemia, 201Tl shows a more ideal relationship between tracer uptake and MBF than do the 99mTc-based agents. Of the various 99mTc-based imaging agents studied, the myocardial flow kinetics of 99mTc-Q3 appear to be closest to ideal. This relationship is maintained regardless of the normalization technique used. This may, in theory, imply a higher sensitivity in discerning ischemic from normal myocardium and a role in diagnostic nuclear imaging for 99mTc-Q3.     

Myocardial tactile stiffness: a variable of regional myocardial function

OBJECTIVES: We developed a new sensor system for in situ measurement of myocardial tactile stiffness-stiffness in a direction perpendicular to the wall-and validated its use for providing a reasonable estimation of regional myocardial function. BACKGROUND: Numerous attempts have been made to directly assess regional myocardial function. The complexity and highly invasive nature of the measuring devices have hampered their in situ application. METHODS: In open chest mongrel dogs, myocardial tactile stiffness, ventricular pressure and ventricular volume were monitored. Under the preload reduction, these variables were measured to determine the relation between the end-systolic pressure-volume relation (ESPVR) and the end-systolic tactile stiffness-volume relation (ESSVR). The changes in myocardial tactile stiffness were monitored in the regional ischemic myocardial model and infarcted model to evaluate their usefulness as indexes of regional myocardial function. RESULTS: Myocardial tactile stiffness changed cyclically and followed a time course similar to left ventricular pressure. When preload was altered, the ESSVR was as linear as the ESPVR. The slope of the ESSVR and that of the ESPVR showed a strong correlation over a wide range of contractility. These results suggest that myocardial tactile stiffness can be a good index of regional wall stress or fiber stress. End-systolic myocardial tactile stiffness of ischemic and infarcted regions decreased significantly, with a concomitant increase in end-diastolic stiffness compared with that of intact myocardium. CONCLUSIONS: Using our tactile sensor system, regional myocardial tactile stiffness of a beating heart was measured with reasonable temporal resolution. We consider myocardial tactile stiffness to be a useful index of regional myocardial function.     

Localization of cardiac myosin-specific antibody in myocardial infarction

Specific localization of purified antibody against cardiac myosin has been demonstrated in areas of altered myocardial membrane permeability after experimental myocardial infarction. Intravenously administered radioiodine-labeled antimyosin was selectively localized in infarcted myocardium of seven dogs 24 h after coronary occlusion. The mean ratio (+/-SE) of antimyosin antibody in infarcted to normal myocardium in the center of the infarct was 4.2+/-0.4 for endocardial and 2.9+/-0.3 for epicardial layers. By utilizing (Fab')2 fragments of antimyosin obtained by pepsin digestion of purified antibody, the ratio of uptake was increased in eight dogs to 6.1+/-0.6 in the endocardial and 3.3+/-0.4 in the epicardial layers at the infarct center 24 h after occlusion. These ratios were further increased in the infarct center to 13.8+/-1.2 in the endocardial and 7.3+/-0.8 in the epicardial layers when eight dogs were sacrificed 72 h after coronary occlusion. The specificity of antimyosin (Fab')2 localization in infarcted myocardium was demonstrated in four dogs by simultaneous intravenous administration of 125I-labeled antimyosin (Fab')2 and 131I-labeled normal rabbit gamma globulin (Fab')2. Nonspecific trapping of normal rabbit IgG (Fab')2 was observed to be about 38% of total antimyosin (Fab')2 uptake in the central zone of infarction. Regional blood flow was related to antimyosin (Fab')2 uptake in infarcted myocardium by utilizing simultaneous administration of 85Sr-labeled microspheres. An inverse exponential relationship between antimyosin (Fab')2 uptake and regional blood flow was observed (r=0.85). The specific localization of antimyosin antibody or its (Fab')2 components in infarcted myocardium suggests a conceptually new approach to myocardial infarct localization and sizing.     

Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection

BACKGROUND: The purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. METHODS AND RESULTS: Based on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P < .001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y = 0.24x + 0.73, SEE = 0.36, r = .88, P < .001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. CONCLUSIONS: Myocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.     

Multiple line source array for SPECT transmission scans: simulation, phantom and patient studies

Accurate attenuation and scatter corrections in quantitative SPECT studies require attenuation maps of the density distribution in the scanned object. These can be obtained from simultaneous emission/transmission scans. METHODS: A new method has been developed using a multiple line source array (MLA) for transmission scans, and its performance has been investigated using computer simulations and experimental data. The activity in the central lines of the MLA was higher than at the edges of the system, so that more transmission photons would be directed toward the thicker parts of the human body. A series of transmission-only and simultaneous emission/transmission studies were performed for different phantom configurations and human subjects. Attenuation maps were generated and used in reconstruction of attenuation-corrected emission images. RESULTS: The mu coefficients for attenuation maps obtained using the MLA system and simulated and experimental data display no artifacts and are qualitatively and quantitatively correct. For phantoms, the agreement between the measured and the true value of mu for water was found to be better than 4%. The attenuation-corrected emission images for the phantom studies demonstrate that the activity in the heart can be accurately reconstructed. A significant qualitative improvement was also obtained when the attenuation correction was used on patient data. CONCLUSION: Our results indicate that the MLA transmission source can be used in simultaneous transmission/emission imaging to generate accurate attenuation maps. These maps allow for performing an object-specific, attenuation correction of the emission images.