Assessment of myocardial viability in dysfunctional myocardium by resting myocardial blood flow determined with oxygen 15 water PET

BACKGROUND: There is controversy about the role of decreased resting blood flow as the pathophysiologic correlate of hibernating myocardium. The aim of this study was an absolute quantification of volumetric myocardial blood flow (MBFvol) in dysfunctional myocardium with different viability conditions as defined by fluorine 18 deoxyglucose (FDG) positron emission tomography (PET) while taking into consideration the functional recovery after revascularization. The impact of MBFvol in the diagnosis of functional recovery was also investigated. METHODS AND RESULTS: Forty-two patients with severe coronary artery disease and dysfunctional myocardium underwent resting oxygen 15 water PET, as well as FDG PET and technetium 99m tetrofosmin single photon emission computed tomography, all attenuation-corrected. Relative FDG and Tc-99m tetrofosmin uptake (normalized to the segment with 100% Tc-99m tetrofosmin uptake), as well as MBFvol (myocardial blood flow multiplied by the water-perfusable tissue fraction to account for the flow to the entire segment volume), were determined in 18 myocardial segments per patient. Viability in dysfunctional segments (estimated by ventriculography) with reduced Tc-99m tetrofosmin uptake of 70% or lower was classified as viable (FDG >70%, mismatch) or nonviable (FDG < or =70%, match). Fifteen patients underwent revascularization and were followed up. Mismatch segments with improved function were classified as hibernating myocardium. Mean MBFvol in viable myocardium was slightly reduced (0.60 +/- 0.02 mL x min(-1) x mL(-1)) compared with that in normokinetic myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)) (P = .036) and was significantly higher than in nonviable myocardium (0.36 +/- 0.01 mL x min(-1) x mL(-1)) (P < .001). Receiver operating characteristic analysis confirmed an FDG uptake greater than 70% as the optimal threshold to predict functional recovery (diagnostic accuracy [ACC], 76%). MBFvol in hibernating myocardium (0.62 +/- 0.04 mL x min(-1) x mL(-1)) was not significantly reduced compared with that in normokinetic myocardium (0.66 +/- 0.02 mL x min(-1) x mL(-1)) and was significantly higher than in persistently dysfunctional myocardium (0.51 +/- 0.04 mL x min(-1) x mL(-1)) (P < .05). The ACC of MBFvol greater than 0.40 mL x min(-1) x mL(-1) as the threshold to predict functional recovery was 61% but did not improve the accuracy of FDG PET by itself. CONCLUSIONS: In patients with severe coronary artery disease and dysfunctional myocardium, MBFvol as determined with O-15 water differs significantly between viable and nonviable myocardium as determined by FDG PET and is not significantly reduced in hibernating compared with normokinetic myocardium. Therefore chronically reduced resting blood flow appears unlikely to be the pathophysiologic correlate of the functional state of hibernation. However, MBFvol does not improve the ACC of FDG PET by itself.     

A report system for PET assessment of myocardial viability.

Coronary bypass surgery can improve the prognosis of patients with heart failure due to coronary artery disease. However, these patients have a high operative risk and should be operated on only if they have a sizeable amount of viable tissue (i.e. asynergic myocardium) that can recover contractile function following coronary revascularization. In the clinical setting, regional wall motion is usually evaluated by two-dimensional echocardiography, whereas retained metabolic activity assessed by positron emission tomography (PET) and 18F-fluorodeoxyglucose is a well-established means for the evaluation of myocardial viability. Unfortunately, the two-dimensional echocardiography and PET reports are often different, and this renders the matching of information difficult and the estimation of the risk-benefit ratio of the operation unreliable. In this paper, we present a report system for the evaluation of myocardial viability with PET. We divided the left ventricle into 16 segments following the proposal of the American Society of Echocardiography for wall motion analysis by two-dimensional echocardiography. Following this partition, three portions of the left ventricle are identified along the long axis: basal, mid and apical. Each plane of the basal and mid portions is automatically divided into six segments with the super-imposition of a radial divider over the short-axis images. Similarly, each plane of the apical portion is automatically divided, but into four segments. This partition of the left ventricle permits a precise match between the information on wall motion obtained with two-dimensional echocardiography and that on viability obtained with PET.     

Semiquantitative assessment of myocardial blood flow and viability using polar map displays of cardiac PET images.

Preserved glucose metabolism in ischemically injured, dysfunctional myocardial tissue as demonstrated on PET imaging predicts functional improvement after revascularization. To characterize more precisely the relationship between regional myocardial blood flow, viability and extent and severity of flow and metabolism abnormalities, we developed a PC-based semiquantitative analysis technique using 13N-ammonia and 18F-deoxyglucose polar map displays. A data base for mean values (m) and standard deviations (s.d.) for relative 13N activities reflecting regional myocardial blood flow, relative 18F activities normalized to normal flow regions reflecting regional glucose utilization and the difference of normalized 18F and 13N activities as an index of a flow-metabolism mismatch was established in 11 normals. Parametric polar maps were derived by comparing patient data to a normal range defined as greater than m - 2 s.d. for relative myocardial blood flow and less than m + 2 s.d. for both relative glucose utilization and the difference between normalized 18F and 13N activities. Semiquantitative indices of extent and severity of blood flow defects, of relative increases in glucose utilization and of flow-metabolism mismatch areas are generated for the entire myocardium and the three coronary territories. The approach promises to be clinically useful to confirm presence and absence of flow and metabolic abnormalities and to assess their extent as a potential predictor of functional outcome after therapy.     

Myocardial blood flow, metabolism, and inotropic reserve in dogs with dysfunctional noninfarcted collateral-dependent myocardium.

There is intense controversy as to the mechanisms underlying chronic but reversible left ventricular (LV) ischemic dysfunction. The aim of this study was to investigate the physiology underlying this condition in a canine model of noninfarcted collateral-dependent myocardium. METHODS: Six mongrel dogs were instrumented with ameroid constrictors on the left circumflex and right coronary arteries and a partial occluder on the left anterior descending coronary artery. The animals were followed up for 6 mo. Every 6 wk, measurements of regional wall thickening (M-mode echo), myocardial blood flow ((13)N-ammonia PET), oxygen consumption ((11)C-acetate PET), and glucose uptake ((18)F-FDG PET) were obtained. After 6 mo, myocardial blood flow reserve (during adenosine infusion) and regional contractile reserve (during infusion of a low dose of dobutamine) were also investigated. RESULTS: Following ameroid implantation, regional thickening decreased in the posterior wall (to 34% +/- 13% of baseline; P < 0.001) but not in the septum. Resting myocardial blood flow (56 +/- 10 vs. 58 +/- 15 mL.[min.100 g](-1)), myocardial oxygen consumption (21 +/- 3 vs. 22 +/- 3 J.[beat.100 g](-1)), and insulin-stimulated glucose uptake (39 +/- 8 vs. 42 +/- 11 micromol.[min.100 g](-1)) were similar among dysfunctional and normal segments. Myocardial blood flow reserve was blunted in dysfunctional versus normal segments (3.7 +/- 0.5 vs. 5.2 +/- 1.5; P = 0.06). With dobutamine, wall thickening (to 69% +/- 8% and 77% +/- 11%, respectively) and oxygen consumption (to 36 +/- 5 and 39 +/- 5 J.[beat.100 g](-1), respectively) improved to the same extent in both segments. As a consequence, mechanical efficiency decreased in septal but remained unchanged in posterior segments during infusion of dobutamine. Biopsy specimens from both walls were free from any morphological alterations. CONCLUSION: Our data indicate that ameroid occlusion in dogs induces sustained reduction in regional contraction, which occurs despite normal levels of transmural blood flow and recruitable inotropic reserve. Since myocardial perfusion reserve was blunted, such perfusion-contraction mismatch could reflect repetitive stunning.     

Clinical significance of denervated but viable myocardium in patients with recanalized acute myocardial infarction.

In patients with acute myocardial infarction (MI), myocardial sympathetic innervation evaluated by 123I-metaiodobenzylguanidine myocardial scintigraphy is more sensitive to ischaemia than the associated perfusion abnormality of 201Tl myocardial scintigraphy. The purpose of this study was to evaluate the scintigraphic indices related to the recovery of left ventricular function after acute MI. 123I-metaiodobenzylguanidine and 201Tl-chloride imaging were performed in 15 patients (mean age 60 years, 13 men and 2 women) 2 weeks after the onset of acute MI. Using a 20-segment visual interpretation of the 201Tl image, myocardial segments were classified into persistent defect, redistribution or reverse redistribution, and normal 201Tl uptake. The extent of denervated segments showed a fair correlation with the ejection fraction on admission (r = -0.53, P = 0.04), whereas the extent of persistent defect had a close correlation with the ejection fraction at 4 months (r = -0.79, P = 0.01). There was a good correlation between the extent of denervated but viable myocardium and the change in ejection fraction from admission to 4 months (r = 0.68, P = 0.01). Thus, denervated but viable myocardium is a scintigraphic index related to the functional recovery of left ventricular pump function after acute MI.     

Serial assessment of denervated but viable myocardium following acute myocardial infarction by using 123I-MIBG and 201TlCl myocardial SPECT

123I-MIBG is taken up by sympathetic nerve ending and provides a scintigraphic image of myocardial sympathetic innervation. We investigated the scintigraphic detection of denervated but viable myocardium following acute myocardial infarction by serial 123I-MIBG and 201TlCl myocardial SPECT. Fourteen patients were studied at acute (10 +/- 2 days) and chronic stage (86 +/- 10 days). Simultaneous dual SPECT was carried out after IV administration of 111 MBq (3 mCi) of 201TlCl and 123I-MIBG. The defect size of 123I-MIBG and 201TlCl were compared visually by using Bull's eye display generated from each myocardial SPECT. In all patients, 123I-MIBG defect showed larger compared to 201T1Cl defect at acute stage, which suggest the existence of denervated but viable myocardium. Of these patients, seven showed significant improvement of both defects, though 123I-MIBG defect showed slightly larger compared to 201TlCl defect, even at chronic stage. These patients had exercise induced thallium transient defect at infarcted area. The remaining 7 patients had no improvement of both defects at chronic stage, which suggest the complete scar at infarcted area. In addition to above study, 4 patients of old myocardial infarction demonstrated larger 123I-MIBG defect compared to 201TlCl defect even at old stage, which thought to be pathogenesis of ventricular tachycardia. In conclusion, 123I-MIBG could evaluate sympathetic denervation and reinnervation noninvasively in the patients with acute myocardial infarction.     

Low-dose dobutamine electrocardiograph-gated myocardial SPECT for identifying viable myocardium: comparison with dobutamine stress echocardiography and PET.

The identification of severely dysfunctional but viable myocardium is of particular importance for the selection of patients with depressed left ventricular function who will benefit from coronary revascularization. Assessment of inotropic reserve with dobutamine has recently been used for this purpose. This study compared the accuracy of low-dose dobutamine stress gated myocardial SPECT (DS SPECT) with the accuracy of dobutamine stress echocardiography (DSE) and resting perfusion SPECT for the identification of viable myocardium in patients with previous myocardial infarction. METHODS: Resting and low-dose dobutamine (7.5 microg/kg/min) gated (99m)Tc-tetrofosmin SPECT and echocardiography and resting (18)F-FDG PET were prospectively studied in 23 patients with previous myocardial infarction and severely depressed regional function. Twenty-one of them were successfully studied with each technique. The left ventricular wall was divided into 14 segments to assess wall motion using a 5-point scale. PET viability was defined as FDG uptake >/= 50% of the maximum uptake in a region with normal wall motion. For DS SPECT and DSE studies, viable myocardium was defined as hypokinetic areas with > or = 1 point improvement in wall motion. For resting perfusion SPECT, viable myocardium was defined as hypokinetic areas with a relative uptake > or = 50% of the maximum uptake. RESULTS: Of a total of 294 segments, 55 had severe resting dyskinesis. Thirty-four segments were identified as viable on FDG PET, and 21 segments were identified as nonviable. Eleven segments were inadequately visualized with DSE, including 5 segments in the apex. Sensitivities (78% vs. 76%) and specificities (94% vs. 100%) were similar for DSE and DS SPECT, with a concordance of 86% (kappa = 0.72). DS SPECT and perfusion SPECT did not significantly differ with respect to sensitivities (76% vs. 85%, respectively). However, specificity was significantly higher for DS SPECT than for perfusion SPECT (100% vs. 52%, respectively, P < 0.05). CONCLUSION: This study indicated that DS SPECT correlates well with DSE in the assessment of viability. In addition, gated SPECT can evaluate regional wall motion, even in areas inadequately assessed by echocardiography. DS SPECT may also provide additional information for identifying viable myocardium, which is often overestimated by routine perfusion scans.     

Oestrogen increases myocardial blood flow in men: assessment by 13N-ammonia positron emission tomography

OBJECTIVES: Oestrogen has been shown to increase nitric oxide-mediated vasodilatation and modulate sympathetic tone in postmenopausal women. We investigated the acute effects of oestrogen on the coronary microcirculation in men. METHODS: Myocardial blood flow was quantified using N-ammonia positron emission tomography before and 20 min after an intravenous administration of conjugated oestrogen (10 mg) in nine healthy men. RESULTS: There were no significant changes in either systemic blood pressure or heart rate before and after oestrogen infusion. However, myocardial blood flow was increased by oestrogen from 0.88 +/-0.06 to 1.05+/-0.09 ml x g x min (P<0.05). Although serum levels of nitrite/nitrate (end products of nitric oxide) were not increased, circulating norepinephrine (noradrenaline) levels were decreased after the administration of oestrogen from 401+/-114 to 346+/-112 pg x ml (P<0.01). A significant negative correlation was found between myocardial blood flow and plasma norepinephrine levels (r=-0.67, P<0.05). CONCLUSIONS: A single administration of oestrogen enhanced myocardial circulation in healthy men. The oestrogen-induced increase in myocardial blood flow may be due to direct effects on the coronary circulation or through the modulation of norepinephrine levels, rather than the production of nitric oxide.     

Noninvasive assessment of myocardial viability in a small animal model: comparison of MRI, SPECT, and PET.

Acute myocardial infarction (AMI) research relies increasingly on small animal models and noninvasive imaging methods such as MRI, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). However, a direct comparison among these techniques for characterization of perfusion, viability, and infarct size is lacking. Rats were studied within 18-24 hr post AMI by MRI (4.7 T) and subsequently (40-48 hr post AMI) by SPECT ((99)Tc-MIBI) and micro-PET ((18)FDG). A necrosis-specific MRI contrast agent was used to detect AMI, and a fast low angle shot (FLASH) sequence was used to acquire late enhancement and functional images contemporaneously. Infarcted regions showed late enhancement, whereas corresponding radionuclide images had reduced tracer uptake. MRI most accurately depicted AMI, showing the closest correlation and agreement with triphenyl tetrazolium chloride (TTC), followed by SPECT and PET. In some animals a mismatch of reduced uptake in normal myocardium and relatively increased (18)FDG uptake in the infarct border zone precluded conventional quantitative analysis. We performed the first quantitative comparison of MRI, PET, and SPECT for reperfused AMI imaging in a small animal model. MRI was superior to the other modalities, due to its greater spatial resolution and ability to detect necrotic myocardium directly. The observed (18)FDG mismatch likely represents variable metabolic conditions between stunned myocardium in the infarct border zone and normal myocardium and supports the use of a standardized glucose load or glucose clamp technique for PET imaging of reperfused AMI in small animals.     

Serial assessment of denervated but viable myocardium following acute myocardial infarction in dogs using iodine-123 metaiodobenzylguanidine and thallium-201 chloride myocardial single photon emission tomography.

Iodine-123 metaiodobenzylguanidine (mIBG) is taken up by sympathetic nerve endings, allowing scintigraphic imaging of myocardial sympathetic innervation. We investigated the denervated but viable canine myocardium after acute myocardial infarction by serial mIBG and thallium-201 chloride (201TlCl) single photon emission tomography (SPET). In 12 dogs, acute myocardial infarction was produced by ligation of the left circumflex coronary artery. Images of mIBG and thallium SPET were obtained 6 h, 1, 4 and 6 weeks later. The defect size was calculated in percentage points from short axial views, and the 123I-mIBG/201TlCl ratio was determined. The uptake ratio was high at 1 week but gradually decreased. Three dogs were killed at each time point, and tissue samples were obtained from infarcted (both 201TlCl and 123I-mIBG defects), peri-infarcted (123I-mIBG defect and 201TlCl normal) and normal myocardium (both mIBG and 201TlCl normal). The changes in tissue content of noradrenaline in these lesions were measured. Noradrenaline tissue content gradually recovered in the peri-infarcted area. However, no recovery was noted in the infarcted area at 6 weeks. We conclude that sympathetic denervation and re-innervation occur following acute myocardial infarction, and the denervated but viable myocardium could be detected non-invasively by combined mIBG and thallium SPET.     

Effects of patient movement on measurements of myocardial blood flow and viability in resting 15O-water PET studies

Background

Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous ¹⁵O-water PET.

Methods

Nineteen ¹⁵O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated.

Results

In nine scans, motions during ¹⁵O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 ± 0.366 to 0.780 ± 0.360 mL/minute/g (P < .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 ± 0.118 to 0.504 ± 0.087 g/mL (P< .05), but no significant change was found in MBF values.

Conclusions

This study demonstrates that IF motion during ¹⁵O-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and ¹⁵O-water emission scans.     

Analysis of first-pass and delayed contrast-enhancement patterns of dysfunctional myocardium on MR imaging: use in the prediction of myocardial viability

OBJECTIVE: The purpose of the study was to analyze first-pass and delayed contrast-enhancement patterns of dysfunctional myocardial regions on MR imaging after injection of gadopentetate dimeglumine to predict myocardial viability in patients with coronary artery disease. SUBJECTS AND METHODS: Twelve patients with wall motion abnormalities and related coronary artery disease revealed by conventional coronary angiography underwent MR imaging at 1.5-T before and 3 months after revascularization therapy. Short-axis images were acquired using a cine gradient-echo sequence. Each slice was divided into eight segments. Overall, 73 segments with impaired contractility were imaged during the first-pass and 14 +/- 2 min after injection of 0.05-mmol/kg gadopentetate dimeglumine at a flow of 3 ml/sec using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as the criterion of viability. RESULTS: At study entry, 26 dysfunctional segments showed delayed hyperenhancement compared with the adjacent functional segments within the same slice, and 47 did not reveal hyperenhancement. After revascularization, 25 (96%) of the 26 hyperenhanced segments did not recover function, whereas 39 (83%) of the 47 segments without hyperenhancement showed mechanical improvement. Segment-related sensitivity and specificity for the correlation of lack of delayed hyperenhancement with myocardial viability were 39 (98%) of 40 and 25 (76%) of 33, respectively. Hypoenhancement during first-pass did not serve as a reliable criterion of viability. CONCLUSION: Evidence of delayed hyperenhancement of dysfunctional myocardium may be used to predict lack of mechanical improvement or nonviability, whereas the lack of hyperenhancement can be correlated with improvement of regional contractility or viability after revascularization.     

Nitrate administration to enhance the detection of myocardial viability by technetium-99m tetrofosmin single-photon emission tomography

A comparison was performed between technetium-99m tetrofosmin myocardial perfusion tomography at baseline and after nitrate administration, using a 2-day protocol, and rest-reinjection thallium-201 single-photon emission tomography (SPET) studies in order to assess whether nitrates enhance the detection of viable myocardium with^99mTc-tetrofosmin. Fifteen patients with coronary artery disease, previous myocardial infarction and a left ventricular ejection fraction <40% underwent²⁰¹T1 rest-injection and^99mTc-tetrofosmin. baseline-postnitroglycerin (0.4 mg sublingually) SPET studies, within 48 h. Tomograms based on the three spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake >50% of peak activity on baseline studies or after reversibility. The percentage of peak activity of^99mTc-tetrofosmin at baseline correlated with that of 201T1 (r=0.82,P <0.001). On baseline^99mTc-tetrofosmin studies, 73 of the 225 segments that were analysed had <50% of peal. activity. Fifteen percent of these segments showed reversibility after nitrate administration, with an increase in^99mTc-tetrofosmin uptake from 40%±9% to 57%±9% of peak activity (P=0.003). All reversible segments after nitrate administration had viability criteria on²⁰¹Tl studies, but 20 segments that were non-viable on^99mTc-tetrofosmin. studies were viable on²⁰¹Tl studies. Using a threshold value of >40% of peak activity, only seven segments remained non-viable on^99mTc-tetrofosmin studies. Overall agreement between^99mTc-tetrofosmin with nitrates and²⁰¹Tl-reinjection regarding the presence of myocardial viability was 90%. Detection of myocardial viability with^99mTc-tetrofosmin. was enhanced after nitrate administration, correlating with viability criteria observed on thallium studies.     

Fluorine-18 deoxyglucose PET for assessment of viable myocardium in perfusion defects in 99mTc-MIBI SPET: a comparative study in patients with coronary artery disease.

Extent and frequency of viable tissue in myocardial segments yielding a perfusion defect on technetium-99m methoxyisobutylisonitrile (99mTc-MIBI), single photon emission tomography (SPET) at rest was prospectively investigated with 2-18F-2-deoxyglucose (18FDG) positron emission tomography (PET) in 46 patients with chronic coronary artery disease (CAD). Of these, 43 had a history of old myocardial infarction. For comparative visual and quantitative evaluation of identical anatomical slices, PET image files were converted into the SPET file structure and into the same matrix size. SPET and PET images were documented and visually (9 segments/patient) or semiquantitatively evaluated by a target-like polar map. Relative perfusion was expressed in percentage of peak 99mTc-MIBI uptake. Sample 18FDG uptake was related to the 18FDG uptake in the area of such maximal perfusion (18FDG uptake was 100% at the 100% 99mTc-MIBI uptake area). Of 414 segments, 167 (40%) revealed a resting perfusion defect. 18FDG uptake was present in 38 (23%) of the defects, while another 40 (24%) segments yielded 18FDG uptake in the periphery of the defect. When grouped according to the degree of 99mTc-MIBI uptake-reduction (in percentage of peak activity), 80% of severe defects (less than or equal to 30% of peak uptake), 48% of moderate (31%-50% of peak uptake) and 31% of mild (greater than 50% of peak uptake) defects were considered as non-viable on the basis of 18FDG uptake. Complete viability was found in none of the severe defects in contrast to 29% of moderate and 35% of mild perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial assessment of denervated but viable myocardium following acute myocardial infarction in dogs using iodine-123 metaiodobenzylguanidine and thallium-201 chloride myocardial single photon emission tomography

Iodine-123 metaiodobenzylguanidine (mIBG) is taken up by sympathetic nerve endings, allowing scintigraphic imaging of myocardial sympathetic innervation. We investigated the denervated but viable canine myocardium after acute myocardial infarction by serial mIBG and thallium-201 chloride (²⁰¹TIC1) single photon emission tomography (SPET). In 12 dogs, acute myocardial infarction was produced by ligation of the left circumflex coronary artery. Images of mIBG and thallium SPET were obtained 6 h, 1, 4 and 6 weeks later. The defect size was calculated in percentage points from short axial views, and the ¹²³I-mIBG/²⁰¹TlCl ratio was determined. The uptake ratio was high at 1 week but gradually decreased. Three dogs were killed at each time point, and tissue samples were obtained from infarcted (both ²⁰¹TICl and ¹²³I-mIBG defects), peri-infarcted (¹²³I-mIBG defect and ²⁰¹TICl normal) and normal myocardium (both mIBG and ²⁰¹TIC1 normal). The changes in tissue content of noradrenaline in these lesions were measured. Noradrenaline tissue content gradually recovered in the peri-infarcted area. However, no recovery was noted in the infarcted area at 6 weeks. We conclude that sympathetic denervation and re-innervation occur following acute myocardial infarction, and the denervated but viable myocardium could be detected non-invasively by combined mIBG and thallium SPET. Offprint requests to: T. Nishimura     

Reversible impairment of coronary flow reserve in takotsubo cardiomyopathy: A myocardial PET study

Background. The precise etiology of takotsubo cardiomyopathy remains unclear. The study of myocardial blood flow (MBF) and coronary flow reserve (CFR) by use of positron emission tomography might help in understanding this syndrome. Methods and Results. Three postmenopausal women underwent adenosine/rest perfusion with nitrogen 13 ammonia and metabolism with fluorine 18 fluorodeoxyglucose positron emission tomography, coronary angiography, cardiac magnetic resonance, and echocardiography in the acute phase of takotsubo cardiomyopathy and at 3 months’ follow-up, after normalization of left ventricular function. PET study was performed in 2 parts: the perfusion analysis with nitrogen ammonia and the metabolism of the heart using FDG. MBF and CFR were analyzed quantitatively in the acute phase and at follow-up. The images highlighted the impairment of tissue metabolism in the dysfunctioning left ventricular segments in the acute phase, mainly in the apical segments and progressively less in the medium segments. At the same time, a clear inverse metabolic/perfusion mismatch emerged, which normalized 3 months later. The quantitative analysis of MBF showed a reduction in the acute phase in apical segments in comparison to basal segments without differences between midventricular and basal segments. In the acute phase CFR proved to be reduced in apical versus basal segments. CFR impairment of apical segments recovered completely after 3 months. Conclusion. The acute phase of takotsubo cardiomyopathy is characterized by an inverse perfusion/metabolism mismatch with a reduction in CFR in the apical segments. However, the impairment of CFR and the reduction of metabolism in the apical segments recovered completely after 3 months.     

硝酸甘油介入99Tcm-tetrofosmin SPECT与18F-FDG PET显像评估心肌活力比较

目的 比较硝酸甘油介入^99Tc^m-tetrofosmin SPECT心肌血流灌注显像与^18F-FDG PET心肌代谢显像评估心肌活力的价值。方法 既往有心肌梗死史伴左心功能不全经冠状动脉造影确诊为冠心病的患者36例，行二日法静息和硝酸甘油介入^99Tc^m-tetrofosmin SPECT显像，并在1周内再行^18F-FDG PET心肌代谢显像及静息超声心动图检查。将左心室分成13个节段，分析超声心动图室壁运动，并分析相同节段^99Tc^m-tetrofosmin与^18F-FDG的相对摄取比值，以^18Tc^m-tetrofosmin摄取比值55％，^18F—FDG摄取比值50％为判断心肌活力有无的阈值。以k统计比较3种方法的一致性。结果 超声心动图示131个节段呈无运动或反向运动。^99Tc^m-tetrofosmin静息显像示其中78个节段（60％）心肌有活力，53个节段（40％）无活力。该53个节段中14个（26％）在硝酸甘油介入后可见再填充，余39个节段无改变。在^18F—FDGPET显像中，硝酸甘油介入显像再填充节段的心肌放射性摄取明显增高。再填充节段与无填充节段比较，心肌FDG摄取分别为（76±15）％和（58±17）％，差异有统计学意义（P〈0．01）。硝酸甘油介入显像中，92个心肌节段（70％）有活力，39个无活力。tetrofosmin静息显像评估心肌活力与FDG PET显像比较，k值为0．35，而硝酸甘油介入^99Tc^m-tetrofosmin SPECT与^18F—FDGPET显像结果比较，k值为0．53。结论 硝酸甘油介入^99Tc^m-tetrofosmin SPECT显像可提高对心肌活力的检测能力，与^18F—FDG PET心肌代谢显像有很好的一致性。     

PET measurement of adenosine stimulated absolute myocardial blood flow for physiological assessment of the coronary circulation

Considerable awareness has been raised of late of the need to reduce radiation exposure and control costs of x-ray and radionuclide imaging procedures. PET/CT cameras are now widely available and in conjunction with appropriate radionuclides and commercially available software make quantitative measurement of absolute MBF feasible for routine clinical practice. Quantitative measurement of absolute MBF under condition of coronary vasodilation permits independent assessment of the functional status of each of the three major coronary perfusion zones and so obviates the need for rest MBF determination in the great majority of cases. Coronary microvascular function also may be assessed in this same way. Thus, the stress-only protocol with quantitative PET measurement of MBF provides essential information required for clinical decision making related to need for catheterization and intervention for patients with known or suspected ischemic heart disease. Moreover, the single PET determination of maximal MBF in contrast to the usual rest/stress procedure addresses both safety and cost concerns. The present review focuses on: (1) quantitative PET measurements of myocardial blood flow for physiological assessment of the coronary circulation and (2) the value and potential limitations of performing stress only imaging in the clinical context.