Optimization of DARTEL Settings for the Detection of Alzheimer Disease.

BACKGROUND AND PURPOSE: Although Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) has been introduced as an alternative to conventional voxel-based morphometry, there are scant data available regarding the optimal image-processing settings. The aim of this study was to optimize image-processing and ROI settings for the diagnosis of Alzheimer disease using DARTEL. MATERIALS AND METHODS: Between May 2002 and August 2014, we selected 158 patients with Alzheimer disease and 198 age-matched healthy subjects; 158 healthy subjects served as the control group against the patients with Alzheimer disease, and the remaining 40 served as the healthy data base. Structural MR images were obtained in all the participants and were processed using DARTEL-based voxel-based morphometry with a variety of settings. These included modulated or nonmodulated, nonsmoothed or smoothed settings with a 4-, 8-, 12-, 16-, or 20-mm kernel size. A z score was calculated for each ROI, and univariate and multivariate logistic regression analyses were performed to determine the optimal ROI settings for each dataset. The optimal settings were defined as those demonstrating the highest χ2 test statistics in the multivariate logistic regression analyses. Finally, using the optimal settings, we obtained receiver operating characteristic curves. The models were verified using 10-fold cross-validation. RESULTS: The optimal settings were obtained using the hippocampus and precuneus as ROIs without modulation and smoothing. The average area under the curve was 0.845 (95% confidence interval, 0.788-0.902). CONCLUSIONS: We recommend using the precuneus and hippocampus as ROIs without modulation and smoothing for DARTEL-based voxel-based morphometry as a tool for diagnosing Alzheimer disease.

P-glycoprotein expression is associated with FDG uptake and cell differentiation in patients with untreated lung cancer.

In vitro studies demonstrated that the accumulation of 2-deoxy-D-glucose was reduced in multidrug resistant cell lines. In animal study, it has been suggested that 2-[18F]fluoro-2-deoxy-D-glucose (FDG) may be a marker for multidrug resistance (MDR). The aim of this clinical study was to compare MDR characteristics by immunohistochemical assay with FDG uptake and investigate whether FDG is a marker for MDR in patients with untreated lung cancer. Forty-seven patients with 49 untreated lung cancers, who had undergone both preoperative FDG PET imaging and thoracotomy, were enrolled in this study. Before surgery, FDG PET was performed 40 min after injection, and standardized uptake values (SUVs) were obtained. Patients were classified into low-SUV (< or = 5) and high-SUV (> 5) groups. After surgery, the expression of P-glycoprotein (Pgp) was investigated by immunohistochemistry, and the lung cancer FDG uptake was analysed for possible association with Pgp expression. The strong intensity of Pgp immunoreactivity was seen only in the low-SUV group. The percentage of the Pgp positive area was significantly lower in the high-SUV group (21.7 +/- 13.4%) than in the low-SUV group (44.1 +/- 29.7%) (P = 0.015). In the high-SUV group, the percentage of Pgp positive area did not exceed 50%. In lung adenocarcinoma, the intensity of Pgp immunoreactivity and the percentage of Pgp positive area increased with degree of cell differentiation, while FDG uptake decreased with degree of cell differentiation. Bronchioloalveolar carcinoma, in particular, showed overexpression of Pgp and modest uptake of FDG. In conclusion, Pgp expression was found to be inversely related to FDG uptake in untreated lung cancer. Pgp expression correlated with the degree of cell differentiation in adenocarcinomas, whilst FDG uptake was inversely related to cell differentiation. FDG may be an in vivo marker for MDR in patients with untreated lung cancer.

(99m)Tc-sestamibi retention characteristics during pharmacologic hyperemia in human myocardium: comparison with coronary flow reserve measured by Doppler flowire.

UNLABELLED: The aim of the study was to investigate the increase in myocardial (99m)Tc-methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic vasodilation. METHODS: For calculation of the increase in (99m)Tc-sestamibi retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced hyperemic stress sestamibi studies were performed using a same-day rest-stress protocol. On the injection of sestamibi, left ventricular dynamic data were obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia was calculated by the formula [abstract: see text] where Cm(h)(t) and Cm(b)(t) are myocardial counts on the tomographic image, and Cb(b)(tau) and Cb(h)(tau) are the left ventricular blood-pool counts during the first transit of sestamibi at baseline and during hyperemia, respectively. Coronary flow increase during intravenous ATP stress was measured using intracoronary Doppler flow guide wire and compared with the scintigraphic results of 28 measurements in 22 patients. RESULTS: Sestamibi retention increased as coronary flow velocity increased but plateaued at >2.5-3 times baseline flow velocity. The relationship between the increase in sestamibi retention (Y) and the increase in flow (X) is expressed as follows: Y = 0.44 + 0.60X - 0.068X(2) (r = 0.82). CONCLUSION: In humans, the increase in (99m)Tc-sestamibi myocardial retention underestimates coronary flow reserve, particularly at high flow rates. Knowledge of these tracer retention characteristics will contribute to a more comprehensive understanding of the manner and interpretation of stress sestamibi imaging.

Phantom studies for estimation of defect size on cardiac (18)F SPECT and PET: implications for myocardial viability assessment.

UNLABELLED: SPECT with (18)F-FDG has emerged as an alternative to dedicated PET for the assessment of myocardial viability. However, whether FDG SPECT can reliably quantify the extent of viable and scarred myocardium is uncertain. The aim of this study was to investigate whether SPECT with an (18)F-labeled agent would provide information on defect size similar to that provided by dedicated PET. METHODS: Imaging was performed using an elliptic cylinder chest phantom with simulated bone, lung, mediastinum, liver, and heart. (18)F was administered into the myocardium, mediastinum, right and left ventricular cavities, and liver. Plastic inserts (n = 11) ranging in size from 2% to 60% of the myocardium were used to simulate transmural myocardial infarctions. The chest phantom was imaged with a dedicated PET camera and with a double-head SPECT camera equipped with ultra-high-energy collimators. Both SPECT and PET data were analyzed using a semiquantitative polar map approach. Defects were quantified using various cutoff thresholds ranging from 30% to 80% of peak activity and were expressed as a percentage of the left ventricular myocardium. Defect size as measured by SPECT or PET was compared with true defect size. RESULTS: The measured SPECT defect size was highly variable depending on the cutoff used, whereas PET defect size was relatively constant over the range of cutoffs tested. The mean absolute difference between measured and true defect sizes was minimal at a cutoff of 50% of peak activity for both SPECT (3.3% +/- 3.3%) and PET (2.7% +/- 2.5%). For this threshold, both SPECT and PET measurements showed an excellent correlation with true defect size (r = 0.98 for SPECT and 0.99 for PET). The correlation between SPECT and PET measurements was also excellent (r = 0.99; P < 0.01). CONCLUSION: If an appropriate threshold is used to define a defect, SPECT with an (18)F-labeled agent can accurately measure defect size similarly to the manner of PET.

Comparison of sestamibi, tetrofosmin, and Q12 retention in porcine myocardium.

UNLABELLED: Although there are several 99mTc perfusion tracers introduced for clinical use, there are no data available directly comparing these tracers with microsphere-determined flow. The aim of this study was to compare the myocardial retention of sestamibi, tetrofosmin, and Q12 in a porcine model. METHODS: We used a pig model with (n = 6) or without (n = 3) coronary occlusion. Each pig received a simultaneous injection of sestamibi and either tetrofosmin (group 1, n = 5) or Q12 (group 2, n = 4) labeled with either 99mTc or 95mTc (physical half-life, 61 d; photon energy, 204 keV) during pharmacologic vasodilation. Absolute myocardial retention of each tracer was calculated from the myocardial tracer activity and arterial input function. RESULTS: The plot of all three tracers versus flow achieved a plateau at a higher flow range. However, sestamibi showed a higher mean retention than either tetrofosmin (group 1, 0.27 +/- 0.11 vs. 0.16 +/- 0.06 mL/g/min, respectively; P < 0.01) or Q12 (group 2, 0.32 +/- 0.13 vs. 0.09 +/- 0.03 mL/g/min, respectively; P < 0.01). Furthermore, when a linear regression analysis was performed to assess the relationship between retention and microsphere-determined flow, sestamibi showed a greater increment in retention than did tetrofosmin or Q12. CONCLUSION: Although all of the tracers showed a nonlinear increase in retention as flow increased, sestamibi may display more favorable characteristics as a flow tracer in the porcine heart.

Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific. taki@med.kanazawa-u.ac.jp.

UNLABELLED: The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63+/-9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61+/-0.29) was significantly lower than that in the control group (2.24+/-0.14, P<0.01), P-nism (2.15+/-0.31, P<0.01), MSA (2.08+/-0.31, P<0.05) and PSP (2.30+/-0.24, P<0.01). The delayed H/M ratio in PD (1.47+/-0.34) was also significantly lower than that in the control group (2.37+/-0.14, P<0.01), P-nism (2.13+/-0.38, P<0.01), PSP (2.36+/-0.36, P<0.01) and MSA (2.17+/-0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%+/-8.0% vs. 11%+/-4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA were significantly lower than those in the control group (P<0.05). IN CONCLUSION: In patients with PD without autonomic failure, only cardiac MIBG uptake was severely reduced in the earliest phase of the disease (stage I). Parkinsonian syndromes other than PD did not demonstrate significant reduction in MIBG uptake in any organs except for the lower legs in MSA. In patients with PD without autonomic failure, reduction in MIBG uptake occurs selectively in the heart; this is considered to be a specific finding for PD and useful for the differential diagnosis of the parkinsonian syndromes.

Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes.

BACKGROUND: Prior studies have demonstrated that acute ischemic injury causes sympathetic neuronal damage exceeding the area of necrosis. The aim of this study was to test the hypothesis that sympathetic neuronal damage measured by (123)I-metaiodobenzylguanidine (MIBG) imaging would be determined by the area of ischemia as reflected by area at risk in patients undergoing reperfusion therapy for acute coronary syndromes. METHODS AND RESULTS: In 12 patients, the myocardium at risk was assessed by (99m)Tc-sestamibi SPECT before reperfusion, and infarct size was measured by follow-up (99m)Tc-sestamibi SPECT 1 week later. All patients also underwent (123)I-MIBG SPECT within a mean of 11 days after onset. The SPECT image analysis was based on a semiquantitative polar map approach. Defect size on the (123)I-MIBG or (99m)Tc-sestamibi SPECT was measured for the left ventricle (LV) with the use of a threshold of -2.5 SD from the mean value of a normal database and was expressed as %LV. The (123)I-MIBG defect size (47+/-18%LV) was larger than the infarct size (27+/-23%LV, P<0. 001) but was similar to the risk area (49+/-18%LV, P=NS). Furthermore, the (123)I-MIBG defect size was closely correlated with the risk area (r=0.905, P<0.001). CONCLUSIONS: Sympathetic neuronal damage measured by (123)I-MIBG SPECT is larger than infarct size and is closely related to risk area, suggesting high sensitivity of neuronal structures to ischemia compared with myocardial cells.

99mTc-tetrofosmin SPECT for prediction of functional recovery defined by MRI in patients with severe left ventricular dysfunction: additional value of gated SPECT.

UNLABELLED: This study was designed to evaluate gated 99mTc-tetrofosmin SPECT for prediction of functional recovery proven by sequential MRI. 99mTc-labeled tetrofosmin is a recently introduced tracer for myocardial perfusion. However, its role for viability assessment is still under investigation. METHODS: 99mTc-tetrofosmin uptake in 19 patients with coronary artery disease and severe left ventricular dysfunction was correlated to regional wall thickening before and 4.5 +/- 0.8 mo after successful coronary artery bypass grafting, as derived from corresponding gated short-axis MRI. Preoperative wall thickening determined by gated SPECT was used as an additional parameter for prediction of functional outcome. Optimal threshold cutoffs to separate reversible from irreversible dysfunction were determined by receiver operator characteristic (ROC) analysis. RESULTS: The sensitivity and specificity of regional 99mTc-tetrofosmin for prediction of functional recovery was 87% and 42%, respectively (cutoff: 50% of maximum tracer retention). The area under ROC curves for prediction of functional recovery measured 0.66 +/- 0.01. Segments with > or =50% uptake and impaired but detectable wall thickening determined by gated SPECT had a significantly higher likelihood for functional improvement compared with segments with absent wall thickening (P < 0.05). There was no difference in segments with <50% tracer retention. There was good agreement for ejection fraction measurements by MRI and gated SPECT (mean ejection fraction 32 +/- 12 versus 34 +/- 11; r = 0.71, P < 0.001). CONCLUSION: Regional 99mTc-tetrofosmin uptake provided high sensitivity but limited specificity for prediction of functional recovery after revascularization, leading to fair overall accuracy. Wall thickening assessment derived from gated SPECT may improve the specificity of 99mTc-tetrofosmin uptake for prediction of functional recovery but not the sensitivity in low-flow areas. In addition to the assessment of global function, gated data acquisition can be helpful to improve the overall accuracy of 99mTc-tetrofosmin SPECT for prediction of functional recovery after bypass surgery.

Forward cardiac output measurement with first-pass technique using 99mTc-labeled myocardial perfusion imaging agents.

UNLABELLED: The aim of this study was to develop and validate a new first-pass method for the measurement of forward cardiac output (CO) using 99mTc-labeled myocardial perfusion imaging agents. METHODS: In protocol 1, to test the new method for measuring CO, the conventional method and the new method for CO measurement were performed in 1 d in 57 patients (32 men, 25 women; age 68 +/- 11 y). In the conventional method, radionuclide angiography (1 frame/s) with in vivo 99mTc labeling (110 MBq) of red blood cells was performed for 2 min in the left anterior oblique projection. Five minutes later, a 1-min equilibrium image was obtained, and a blood sample was taken for calculation of the distribution volume. To obtain data for the new method, further radionuclide angiography (1 frame/sec) with 99mTc labeling (600-740 MBq) of red blood cells was then performed in the anterior projection. CO was calculated using the following equation: CO = Cmax x V(LV)/integral of f(t)dt, where Cmax is the background-corrected peak count of the whole thorax during angiography, integral of f(t)dt is the area under the gamma variate-fitted left ventricular (LV) time-activity curve after background correction and V(LV) is the LV volume obtained by the area length method applied to the radionuclide angiography and myocardial tomography. In protocol 2, to evaluate the new method, 24 patients (16 men, 8 women; age 71 +/- 9.2 y) underwent radionuclide angiography with 99mTc-tetrofosmin (600-740 MBq), and the measured CO was compared with the CO obtained by the conventional method with 99mTc-labeled red blood cells. RESULTS: In protocol 1, good correlation was observed between the CO by the new method (Y) and the CO by the conventional method (X): Y = 1.0X + 57 mL/min and r = 0.95. There was good agreement between the two methods (mean difference -56 +/- 381 mL/min). Inter- and intraobserver correlation coefficients were 0.96 and 0.98, respectively. In protocol 2, the CO by the new method using 99mTc-tetrofosmin (Y) showed a good correlation with the CO by the conventional method (X): Y = 0.90X + 453 mL/min and r = 0.93. Good agreement between the two methods was observed (mean difference 73 +/- 390 mL/min). Inter- and intraobserver correlation coefficients were 0.95 and 0.98, respectively. CONCLUSION: This new method permits accurate forward CO measurement using the first-pass data with 99mTc-terofosmin, which is applicable to other 99mTc-labeled myocardial perfusion imaging agents.

Early recovery of coronary flow reserve after stent implantation as assessed by positron emission tomography.

OBJECTIVES: The aim of this study was to quantitatively evaluate myocardial flow reserve in patients early after coronary stent implantation using positron emission tomography. BACKGROUND: Delayed restoration of coronary flow reserve after percutaneous transluminal coronary angioplasty (PTCA) has been observed using a variety of techniques. Altered distal vasoregulation as well as residual stenosis have been considered possible explanations for this phenomenon. Although the implantation of stents may influence some of these mechanisms, little data are available characterizing coronary flow reserve early after stent placement. METHODS: In 14 patients 1.6 +/- 0.6 days after stenting, N-13-ammonia positron emission tomographic studies were performed at rest and during adenosine-induced vasodilation. Myocardial blood flow was quantified using a three-compartment model. Rest and stress flow data, as well as coronary flow reserve of stented vascular territories, were compared with that of remote areas. RESULTS: The stenosis decreased from 72.1 +/- 7.3% to 3.7 +/- 6.7% after stent implantation. Coronary flow in the stented areas did not differ significantly from that in remote areas either at rest (76.1 +/- 18.5 and 75.7 +/- 17.7 ml/min/100 g, respectively), or during maximal vasodilation (205.5 +/- 59.9 and 179.4 +/- 47.4 ml/min/100 g, respectively). In addition, there was no significant difference in the calculated values of coronary reserve of these two regions (2.74 +/- 0.64 and 2.43 +/- 0.55, respectively). CONCLUSIONS: The mechanical support of dilated arteries by a stent not only restores the macroscopic integrity of epicardial arteries, but also results, in contrast to conventional PTCA procedures, in early recovery of flow reserve.

Kinetics of 123I-MIBG after acute myocardial infarction and reperfusion therapy.

UNLABELLED: Metaiodobenzylguanidine (MIBG) washout from the myocardium has been thought to reflect sympathetic nerve tone. After acute myocardial infarction, however, little is known about this parameter. The aim of this study was to determine the significance of cardiac washout after myocardial infarction and early reperfusion by investigating MIBG kinetics and correlating those kinetics to clinical parameters. METHODS: Sixty patients with acute myocardial infarction underwent planar MIBG and thallium imaging within 14 d of early reperfusion therapy. Global uptake and washout in myocardium, lungs and liver were calculated from early and delayed images. A regional analysis of myocardial kinetics in normal and infarcted myocardium and in an infarct border zone was also performed. Scintigraphic data were correlated with heart-rate variability as an electrophysiologic marker for autonomic tone and prevalence of arrhythmia in 52 patients. Heart-rate variability was described by time-domain indices from long-term electrocardiogram recordings. An age-matched normal control group for MIBG consisted of 10 individuals without heart disease. RESULTS: The infarct patients had preserved left-ventricular ejection fraction (LVEF) (56% +/- 17%). Although late myocardial uptake was expectedly lower in infarct patients compared with healthy volunteers (2.36 +/- 0.66 versus 2.80 +/- 0.55; P = 0.04), global myocardial MIBG washout was faster (11.6% +/- 7.9% versus 0.2% +/- 10.2%, respectively; P = 0.002). Lung and liver kinetics did not differ in patients and healthy volunteers. Global MIBG washout showed a weak but significant positive correlation with the baseline heart rate (r = 0.28, P = 0.03) and an inverse correlation with LVEF (r = -0.28, P = 0.04). Washout was faster in a subgroup of 8 patients with reduced heart-rate variability (16.5% +/- 9.9% versus 10.3% +/- 8.3%; P = 0.04). Regional analysis revealed similar degrees of enhanced MIBG washout for infarcted (low perfusion, low MIBG uptake) and remote myocardium (normal perfusion, high MIBG uptake), whereas the border zone (normal perfusion, low MIBG uptake) showed a nonsignificant trend toward higher washout. CONCLUSION: After myocardial infarction, changes in MIBG kinetics occur specifically in the myocardium, whereas kinetics in lung and liver remain unchanged. Even in patients with left-ventricular function preserved by reperfusion therapy, MIBG washout is abnormal and globally increased. Enhanced washout may reflect increased sympathetic nerve tone and represent increased catecholamine turnover or impaired reuptake in the subacute phase of myocardial infarction.

BMIPP compared with thallium redistribution.

I-123 labeled methyl-branched fatty acid, BMIPP, has been used mainly in Europe and Japan for the evaluation of various cardiac diseases. BMIPP uptake abnormality is usually more prominent tan perfusion, representing discordant BMIPP uptake less than thallium. This finding is observed in various cardiac disease conditions such as acute myocardial infarction, stable and unstable angina, hypertrophic and dilated cardiomyopathies. Many BMIPP studies combined stress thallium imaging in patients with coronary artery disease and hypertrophic cardiomyopathy demonstrated that such discordant BMIPP uptake less than thallium is related to stress-induced ischemia as evidenced by reversible thallium defect after exercise. BMIPP imaging is able to detect metabolic alteration in the heart which is not available by perfusion imaging alone.

Residual cardiomyocytes and scintigraphic findings in advanced coronary artery disease: correlation with technetium-99m-tetrofosmin and thallium-201 single photon emission computed tomography.

A 68-year-old man suffering from chronic heart failure due to coronary artery disease (CAD) underwent rest technetium-99m (99mTc)-tetrofosmin and thallium-201 (201Tl) with reinjection studies, but died thereafter. The heart was removed and sectioned into short-axis slices and examined by gross and microscopic pathologic methods. A close correlation between the amount of residual cardiomyocytes and the level of regional tracer activity in the left ventricular wall was obtained for redistribution 201Tl, reinjection 201Tl and rest 99mTc tetrofosmin images. The correlation coefficients were r=0.901 for the 201Tl redistribution images, r=0.913 for the 201Tl reinjection images and r=0.917 for the rest 99mTc-tetrofosmin images. This case report provides further evidence of the validity of SPECT tetrofosmin imaging for the determination of myocardial viability in CAD.

Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects.

OBJECTIVES: The purpose of the study was to compare myocardial blood flow (MBF) in hyperlipidemic postmenopausal women and age-matched hyperlipidemic men, and to analyze the relationship between cholesterol subfractions and myocardial blood flow in men and women. BACKGROUND: Women are protected from coronary artery disease (CAD) events until well after menopause, in part due to gender-specific differences in lipid profiles. METHODS: To examine the effect of these influences on coronary microcirculation, MBF was quantitated with N-13 ammonia/PET (positron emission tomography) at rest and during adenosine hyperemia in 15 women and 15 men, all nondiabetic, who were matched for age and total cholesterol levels (53+/-4 vs. 50+/-8 years, p = NS, 6.44+/-1.1 vs. 6.31+/-0.85 mmol/liter, or 249+/-41 vs. 244+/-33 mg/dl, p = NS). RESULTS: Women had significantly higher high density lipoprotein (HDL) and lower triglyceride (Tg) levels than did men, and they showed significantly higher resting MBF and stress MBF levels. Significant correlations were found between resting and hyperemic MBF and HDL and Tg levels (r = 0.44, p < 0.02 for stress MBF vs. HDL; r = 0.48, p < 0.007 for stress MBF vs. Tg). Gender was the strongest predictor of hyperemic MBF in multivariate analysis. Women responded to adenosine hyperemia with a significantly higher heart rate than did men, and hemodynamic factors correlated significantly with blood flow both at rest and during stress. CONCLUSIONS: These data suggest that the favorable lipid profile seen in women may be associated with preserved maximal blood flow in the myocardium.

Absent myocardial iodine-123-BMIPP uptake and platelet/monocyte CD36 deficiency.

UNLABELLED: Global absence of myocardial 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) uptake is occasionally noted, and it reflects myocardial long-chain fatty acid uptake abnormality. CD36, a membrane glycoprotein expressed on platelet, monocyte and endothelial cells, may contribute to myocardial fatty acid transport, and its deficiency has been reported in a small subset of the population. We hypothesized that CD36 deficiency may be related to absent myocardial BMIPP uptake. Thus, we investigated CD36 expression of platelet/monocyte in patients with absent myocardial BMIPP uptake. METHODS: Peripheral blood of 7 patients with global absence of myocardial BMIPP uptake (3 of 7 patients in one family) and 3 control subjects were examined in flow cytometric analysis. Platelet/monocyte surface CD36 was detected by using OKM5, an anti-CD36 mouse monoclonal antibody. RESULTS: There were no apparent relationships between specific clinical symptoms and absent myocardial BMIPP uptake. None of the blood samples of the 7 patients were stained with OKM5 on the platelet/monocyte cell surface, indicating that all of these patients were Type I CD36-deficient subjects. In contrast, all the control subjects showed normal staining. CONCLUSION: The fact that rare Type I CD36 deficiency was observed in all patients with absent myocardial BMIPP uptake suggests that CD36 plays a role in the myocardial long-chain fatty acid uptake process in humans.

Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed tomography in the detection of viable myocardium: comparison with positron emission tomography using 18F-fluorodeoxyglucose.

OBJECTIVES: The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: The role of 99mTc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images. METHODS: Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT and FDG PET imaging. Both AC and non-attenuation-corrected (NC) SPECT images were generated. RESULTS: Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG on the patient basis increased from 79.8%+/-14.0% (mean+/-SD) on the NC images to 90.8%+/-10.6% on the AC images (p=0.002). The percentage of 99mTc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8%+/-15.2% on the NC images to 9.7%+/-12.6% on the AC images (p=0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region. CONCLUSIONS: The results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/overestimation of viability may still occur even with attenuation correction.

[Estimation of cardiac output by first-pass data with technetium-99m-labeled myocardial perfusion imaging agent].

Technetium-99m-tetrofosmin, a myocardial perfusion imaging agent was used for estimation of cardiac output by means of first-pass radionuclide angiography performed in the anterior projection. Region of interests (ROIs) were assigned over right ventricle, left ventricle and whole chest, and time activity curves (TACs) were obtained. Cardiac output indices (COIs) were calculated by the following equation; COI = p3/2. Qc/[symbol: see text] A(s)ds, where p = number of pixels of the ventricular ROI, Qc = the peak count rate of the TAC obtained from the whole chest's ROI and [symbol: see text] A(s)ds = the area under ventricular TAC. The COI (y) determined by ROI over the left ventricle yield the best correlation with the cardiac output by conventional radionuclide method (x) (y = 0.0381x + 6.22, r = 0.828, n = 48, p < 0.001). In conclusion, cardiac output can be easily measured with first pass data using myocardial perfusion imaging agent.

Myocardial perfusion scintigraphy to evaluate patients after coronary stent implantation.

UNLABELLED: Coronary stent implantation is an increasingly accepted revascularization method. The 20%-30% restenosis rate during the first 6 mo requires a close follow-up of the patients. Since there is very little data available defining the role of perfusion scintigraphy in the management of this population, the aim of this study was to assess the diagnostic performance of stress myocardial perfusion imaging for detecting restenosis in patients after coronary stent implantation. METHODS: In 82 patients, 93 rest or stress SPECT studies were performed using 201Tl and 99mTc-hexakis-2-methoxyisobutyl isonitrile to evaluate 99 vascular territories with implanted coronary stents. The average interval between the stent implantation and the scintigraphic study was 210.5 +/- 129.6 days. The scintiscans were visually evaluated. A stress-induced perfusion defect with reversibility at rest was used as the criterion for stent restenosis. RESULTS: Coronary angiography revealed a stenosis of > 50% diameter in the region of the stent in 19 arteries, while in 80 arteries there was no evidence of restenosis angiographically. With perfusion scintigraphy, 15/19 vascular territories with restenosed stents showed stress-induced perfusion abnormalities (sensitivity = 79%), while 62/80 territories without restenosis did not (specificity = 78%). In territories without a myocardial infarction (n = 48), sensitivity and specificity values were 8/8 (100%) and 36/44 (82%), and in territories with a myocardial infarction (n = 47) 7/11 (64%) and 26/36 (72%), respectively. Side branch stenosis was fairly frequent in patients without stent restenosis but with a reversible perfusion pattern on their scintiscan (8/18); however, these stenoses were induced infrequently by the stents (3 cases). CONCLUSION: Using the criterion of defect reversibility, stress perfusion SPECT can accurately detect restenoses of coronary artery stents. This method is most accurate for evaluating patients without a previous myocardial infarction in the stented vascular territory.

Regional myocardial wall thickening and global ejection fraction in patients with low angiographic left ventricular ejection fraction assessed by visual and quantitative resting ECG-gated 99mTc-tetrofosmin single-photon emission tomography and magnetic resonance imaging.

We investigated the use of visual and quantitative technetium 99m tetrofosmin ECG-gated single-photon emission tomography (SPET) for the assessment of regional myocardial wall thickening (WT) and left ventricular (LV) ejection fraction (EF) in comparison with gated magnetic resonance imaging (MRI) in patients with a low angiographic LVEF. Gated SPET using 99mTc-labelled flow tracers offers potential for simultaneous assessment of myocardial perfusion and LV function. Few data are available on the use of visual and quantitative gated SPET in patients with low LVEF. In this study 21 patients with low angiographic LVEF (mean 37%+/-5%) were studied. Resting gated 99mTc-tetrofosmin SPET and gated MRI were performed within 48 h. WT was assessed by visual interpretation (five point score) and quantitative analysis based on count increase. There was good agreement for EF measurements by MRI and gated SPET (mean EF: 33%+/-12% vs 35%+/-11%, r = 0.86, P<0.001). Areas under receiver operator characteristic curves (AUC) for differentiation between MRI WT score points ranged from 0.60 to 0.66 for visual SPET WT analysis, from 0.59 to 0.71 for delta count increase values and from 0.46 to 0.60 for % WT, indicating substantial overlap between WT categories. Absolute agreement for visual WT between MRI and gated SPET ranged from 25% to 57% (kappa 0.03-0.25) depending on tracer uptake, and was limited in areas with moderate to severe perfusion defects (kappa 0.03-0.13). It is concluded that gated SPET provided reliable estimates of regional WT and global function in patients with low angiographic LVEF.

Value of iodine-123 metaiodobenzylguanidine scintigraphy in patients with vasospastic angina.

To assess the presence and location of presynaptic myocardial sympathetic abnormality in patients with vasospastic angina, iodine-123 labelled metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET) was performed. Fifty patients suspected of having vasospastic angina pectoris were enrolled in the study. All patients underwent a provocative test with intracoronary ergonovine infusion during coronary angiography, in which 99%-100% obstructive spasm was defined as a positive result. Twenty-five patients were diagnosed as having vasospastic angina based on a positive provocative test. MIBG SPET was performed at 20 min and 3 h after administration of 111 MBq or MIBG. On early images, only 5 of 25 patients with vasospastic angina showed a mild reduction in MIBG uptake, whereas 3-h delayed images demonstrated MIBG abnormality in 20 patients (80%). The location of the MIBG abnormality was completely or partially consistent with the spastic coronary territory in 18 patients. On the other hand, only 4 of 25 patients (16%) with negative provocative test demonstrated reduced MIBG uptake. Accordingly, positive and negative predictive values of MIBG SPET for the provocative test were 83% (20/24) and 81% (21/26) respectively. In conclusion, MIBG scintigraphy with SPET can permit the non-invasive detection and evaluation of suspected vasospastic angina.