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Background: This study aimed to determine whether the repeatability of dyssynchrony assessment using gated myocardial perfusion SPECT (GSPECT) allows the detection of synchrony reserve during low-dose dobutamine infusion. Methods and Results: Sixty-one patients with ischemic cardiomyopathy and LV ejection fraction < 50% were prospectively included in 10 centers. Each patient underwent two consecutive rest GSPECT with 99mTc-labeled tracer (either tetrofosmin or sestamibi) to assess the repeatability of LV function and dyssynchrony parameters, followed by a GSECT acquisition during low-dose dobutamine infusion. LV dyssynchrony was assessed using QGS software through histogram bandwidth (BW), standard deviation of the phase (SD), and entropy. Repeatability was assessed with Lin's concordance correlation coefficient (CCC). Entropy showed a higher CCC (0.80) compared to BW (0.68) and SD (0.75). On average, dobutamine infusion yielded to improve both BW (P =.049) and entropy (P =.04) although significant improvements, setting outside the 95% confidence interval of the repeatability analysis, were documented in only 6 and 4 patients for BW and entropy, respectively. Conclusions: A synchrony reserve may be documented in patients with ischemic cardiomyopathy through the recording of BW and entropy with low-dose dobutamine GSPECT, with the additional advantage of a higher repeatability for entropy. [ABSTRACT FROM AUTHOR]

SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone β-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability. [ABSTRACT FROM AUTHOR]

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4−) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4− required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4−–mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects. [ABSTRACT FROM AUTHOR]

: Recombinant, replication-deficient serotype 5 adenovirus infects the liver upon in vivo, systemic injection in rodents. This infection requires the binding of factor X to the capsid of this adenovirus. Another organ, the adrenal gland is also infected upon systemic administration of Ad, however, whether this infection is dependent on the cocksackie adenovirus receptor (CAR) or depends on the binding of factor X to the viral capsid remained to be determined. In the present work, we have used a pharmacological agent (warfarin) as well as recombinant adenoviruses lacking the binding site of Factor X to elucidate this mechanism in mice. We demonstrate that, as observed in the liver, adenovirus infection of the adrenal glands in vivo requires Factor X. Considering that the level of transduction of the adrenal glands is well-below that of the liver and that capsid-modified adenoviruses are unlikely to selectively infect the adrenal glands, we have used single-photon emission computed tomography (SPECT) imaging of gene expression to determine whether local virus administration (direct injection in the kidney) could increase gene transfer to the adrenal glands. We demonstrate that direct injection of the virus in the kidney increases gene transfer in the adrenal gland but liver transduction remains important. These observations strongly suggest that serotype 5 adenovirus uses a similar mechanism to infect liver and adrenal gland and that selective transgene expression in the latter is more likely to be achieved through transcriptional targeting. [ABSTRACT FROM AUTHOR]

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replicationincompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used 99mTc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RTPCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to 'noisy', and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy. [ABSTRACT FROM AUTHOR]

Droogmans S, Roosens B, Cosyns B, Degaillier C, Hernot S, Weytjens C, Garbar C, Caveliers V, Pipeleers-Marichal M, Franken PR, Lahoutte T, Schoors D, Van Camp G. Cyproheptadine prevents pergolide-induced valvulopathy in rats: an echocardiographic and histopathological study. Am J Physiol Heart Circ Physiol 296: H1940-H 1948, 2009. First published April 3, 2009; doi: 10.1152/ajpheart.01177.2008.-Serotonergic drugs, such as pergolide, have been associated with the development of cardiac valvular myxoid thickening and regurgitation in humans and more recently in rats. These effects are potentially mediated by the 5-hydroxytryptamine (5-HT)[sub2B] receptor (5-HT[sub2B]R). Therefore, we sought to determine whether cyproheptadine, a 5-HT[sub2B]R antagonist, might prevent toxic valvulopathy in an animal model of pergolide-induced valvular heart disease. For this purpose, 50 male Wistar rats received daily intraperitoneal injections of pergolide (0.5 mg/kg, n = 14), pergolide (0.5 mg/kg) combined with cyproheptadine (10 mg/kg, n = 12), cyproheptadine (10 mg/kg, n = 12), or no injections (control, n = 12) for 20 Hk. Echocardiography was performed blindly at baseline and at 10 and 20 wk followed by pathology. At baseline, no differences between groups were found with chocardiography. At 20 wk, aortic regugitation was present in all pergolide-treated animals, whereas it was less frequently observed in the other groups (P < 0.0001). For the other valves, this difference was less pronounced. On histopathology, not only aortic but also mitral valves were thicker, myxoid, and exhibited more 5-HT[sub2B]R-positive cells in pergolidetreated animals compared with the other groups. Moreover, regurgitant aortic and mitral valves were thicker than nonregurgitant aortic and mitral valves. In conclusion, we found that cyproheptadine prevented pergolide-induced valvulopathy in rats, which was associated with a reduced number of 5-HT[sub2B]R-positive valvular cells. This may have important clinical implications for the prevention of serotonergic drug-induced valvular heart disease. [ABSTRACT FROM AUTHOR]

Aim: To find out if Doppler myocardial imaging (DMI) can detect early signs of left ventricular (LV) dysfunction in a rat model of diabetic cardiomyopathy. [ABSTRACT FROM PUBLISHER]

Background: The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with Streptozotocin-induced diabetic rats using contrast echocardiography. Methods: We prospectively studied 40 Wistar rats. Diabetes was induced by intravenous streptozotocin in 20 rats. All rats underwent baseline and stress (dipyridamole: 20 mg/kg) high power intermittent imaging in short axis view under anaesthesia baseline and after six months. Myocardial blood flow was determined and compared at rest and after dipyridamole in both populations. The myocardial blood flow reserve was calculated and compared in the 2 groups. Parameters of left ventricular function were determined from the M-mode tracings and histological examination was performed in all rats at the end of the study. Results: At six months, myocardial blood flow reserve was significantly lower in diabetic rats compared to controls (3.09 ± 0.98 vs. 1.28 ± 0.67 ml min-1 g-1; p < 0.05). There were also a significant decrease in left ventricular function and a decreased capillary surface area and diameter at histology in the diabetic group. Conclusion: In this animal study, diabetes induced a functional alteration of the coronary microcirculation, as demonstrated by contrast echocardiography, a decrease in capillary density and of the cardiac systolic function. These findings may offer new insights into the underlying mechanisms of diabetes cardiomyopathy. [ABSTRACT FROM AUTHOR]

123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. For the biodistribution study, six male volunteers received 60–95 MBq 123I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. 123I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, 123I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39–3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). 123I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that diabetes mellitus (DM) may cause left ventricular (LV) dysfunction directly resulting in increased susceptibility to heart failure. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The present study was aimed to assess this new imaging technique for quantifying LV function and remodeling from the Streptozotocin (STZ) rat model compared to controls. Methods: Twenty one rats were randomly assigned to control or diabetic group. Six months after the induction of diabetes by STZ, Pinhole 99 m Tc-sestamibi gated SPECT was performed for determining rat LV volumes and function. Post-mortem histopathologic analysis was performed to evaluate the determinant of LV remodeling in this model. Results: After six months, the normalized to body weight LV End-systolic volume was significantly different in diabetic rats compared to controls (0.46 ± 0.02 vs 0.33 ± 0.03 µL/g; p = 0.01). The normalized LV End-diastolic volume was also different in both groups (1.51 ± 0.03 vs 0.88 ± 0.05 µL/g; p = 0.001) and the normalized stroke volume was significantly higher in STZ-rats (1.05 ± 0.02 vs 0.54 ± 0.06 µL/g; p = 0.001). The muscular fibers were thinner at histology in the diabetic rats (0.44 ± 0.07 vs 0.32 ± 0.06 AU; p = 0.01). Conclusion: Pinhole 99 m Tc-sestamibi gated SPECT can successfully be applied for the evaluation of cardiac function and remodeling in STZ-induced diabetic rats. In this model, LV volumes were significantly changed compared to a control population, leading to a LV dysfunction. These findings were consistent with the histopathological abnormalities. Finally, these data further suggest the presence of diabetes cardiomyopathy. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Limited data are available about the use of Doppler myocardial imaging (DMI) in small animals. We intend to provide reference values for velocity, strain and strain rate in a large group of healthy rats and studied the reproducibility and repeatability of these parameters. Methods and results: A total of 33 male Wistar rats (503±41g) underwent baseline transthoracic echocardiography with DMI of the anterior and inferior wall in a short-axis view using a 13MHz linear probe. Adequate tissue Doppler measurements could be obtained in 30 rats. On average 10±4 consecutive cycles were studied in post-processing using dedicated software (SPEQLE). Mean radial peak systolic velocity, strain and strain rate were respectively −0.8±0.3cm/s, 38±8% and 9.1±2.0/s in the anterior wall and 3.1±0.6cm/s, 49±10% and 13.7±3.7/s in the inferior wall. The reproducibility and repeatability of the DMI measurements assessed in 10 rats was good. Conclusion: DMI is feasible and reproducible in healthy rats. Establishing reference values opens new perspectives towards the use of strain and strain rate imaging in small rodents in the assessment of myocardial diseases. [Copyright &y& Elsevier]

Purpose: Cell therapy using bone marrow mesenchymal stem cells (BMSCs) shows promise in the treatment of myocardial infarction (MI) but accurate cell delivery within MI areas remains critical. In the present study, we tested the feasibility of in vivo pinhole SPECT imaging for monitoring the sites of intramyocardial implanted BMSCs in relation to targeted MI areas in rats. Methods: BMSCs were labelled with 111Inoxine and injected within the fibrotic areas of 3-month-old MI in ten rats. Two days later, dual 111In/99mTc-sestamibi pinhole SPECT was recorded for localisation of 111In-BMSCs on a 15-segment left ventricular (LV) division. Additional 99mTc-sestamibi pinhole SPECT had been performed 1 month earlier and on the day before transplantation. In vitro counting on histological sections was used to validate the pinhole SPECT determination of 111In-BMSC activity within LV segments. Results: The underperfused MI area (segments with <70% uptake) was stable between the 99mTc-sestamibi SPECT study recorded at 1 month (4.6±1.9 segments) and at 1 day (4.7±2.3 segments) before transplantation. 111In-BMSCs were detected by dual-energy SPECT in 56 segments: 33 (59%) were underperfused MI segments but 23 (41%) were not (14 adjacent and nine remote segments). Finally, 111In-labelled BMSCs were not detected in 14 out of the 47 (30%) underperfused MI segments. Conclusion: When BMSCs are injected within MI areas in rats, sites of early cell retention do not always match the targeted MI areas. The dual-energy pinhole SPECT technique may be used for monitoring the sites of early retention of implanted BMSCs and the data obtained may have critical importance when analysing the effects of cardiac cell therapy. [ABSTRACT FROM AUTHOR]

Recent experimental and clinical studies have shown that autologous cell based therapy using skeletal myoblasts or bone marrow-derived stem cells might have beneficial effects in chronic ischemic heart disease. The underlying concept is based on the repopulation of necrotic tissue by either readily contractile myoblasts or by bone marrow-derived stem cells. However, there is a need to resolve a number of issues for determining the better way to perform these treatments and, moreover, for assessing the real beneficial functional effect of each of these cell therapies. In this mini-review, we will discuss (i) the issues of the selection of chronic infarct animal to truly determine the impact of cell therapy on cardiac function recovery, and (ii) the evaluation of the bio-availability and the bio-distribution of transplanted cells. Some new investigational methodologies based on clinical end-points are also proposed. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the intra-individual reproducibility of left ventricular volume and ejection fraction measurements in living rat using pinhole gated single-photon emission computed tomography (SPECT). Methods: Eight normal male Wistar rats underwent four pinhole gated SPECT acquisitions over a 1-month period. Two pinhole gated myocardial perfusion SPECT studies were acquired at a 1-week interval after injecting the animals with 439±52 MBq of 99mTc-sestamibi. Subsequently, 1 week after the perfusion studies, two pinhole gated blood pool SPECT studies were acquired at a 1-week interval after in vivo labelling of the red blood cells using 520±49 MBq of 99mTc-pertechnetate. Pinhole gated SPECT acquisitions were done on a single-head gamma camera equipped with a pinhole collimator with a 3-mm opening and 165-mm focal length. Parameters of acquisition were as follows: 44 mm radius of rotation, 360° rotation using a circular orbit, 64 projections, 64×64 matrix, gating using 16 time frames and 22-min acquisition time. The projection data were reconstructed with a modified version of OSEM taking into account the pinhole geometry and incorporating a prior assumption about the temporal properties of gated SPECT studies to reduce noise. Left ventricular volumes and ejection fraction were measured using automatic quantification algorithms. Inter-study, inter-observer and intra-observer reproducibility was investigated. Results: Pinhole gated myocardial perfusion and pinhole gated blood pool images were of high quality in all animals. No significant differences were observed between the repeated measurements. The pinhole gated myocardial perfusion SPECT studies indicated that differences between repeated measurements larger than 41 μl for end-diastolic volume, 17 μl for endsystolic volume and 3% for ejection fraction were significant. The pinhole gated blood pool SPECT studies indicated that differences between repeated measurements larger than 42 μl for end-diastolic volume, 38 μl for endsystolic volume and 5% for ejection fraction were significant. In addition to the reproducibility measures, the accuracy of volume measurements in pinhole gated blood pool SPECT was confirmed by a phantom study. Excellent correlations were observed between the measured volumes and the actual phantom volumes. Conclusion: Pinhole gated SPECT is an accurate and reproducible technique for cardiac studies of small animals. Because this technique is non-invasive, the same animal can be imaged repetitively, allowing follow-up studies. [ABSTRACT FROM AUTHOR]

Reducing the acquisition time of whole-body fluorine-18 fluorodeoxyglucose positron emission tomography (18F­FDG PET) (corrected for attenuation) is of major importance in clinical practice. With the introduction of lutetium oxyorthosilicate (LSO), the acquisition time can be dramatically reduced, provided that patients are injected with larger amounts of tracer and/or the system is operated in 3D mode. The aim of this study was to determine the optimal dose of 18F­FDG required in order to achieve good-to-excellent image quality when a ‘3-min emission, 2-min transmission/bed position’ protocol is used for an LSO PET camera. A total of 218 consecutive whole-body 18F­FDG PET studies were evaluated retrospectively. After excluding patients with liver metastases, hyperglycaemia and paravenous injections, the final study population consisted of 186 subjects (112 men, 74 women, age 59±15 years). Patients were injected with an activity of 18F­FDG ranging from 2.23 to 15.21 MBq/kg. Whole-body images corrected for attenuation (3 min emission, 2 min transmission/bed position) were acquired with an LSO PET camera (Ecat Accel,Siemens) 60 min after tracer administration. Patients were positioned with their arms along the body. Image reconstruction was done iteratively and a post-reconstruction filter was applied. Image quality was scored visually by two independent observers using a five-point scoring scale (poor, reasonable, good, very good, excellent). In addition, the coefficient of variability (COV) was measured in a region of interest over the liver in order to quantify noise. Of the images obtained in 118 patients injected with ≥8 MBq/kg 18F­FDG, 92% and 90% were classified as good, very good or excellent by observer 1 and observer 2, respectively. The COV averaged 10.63%±3.19% for doses 8 MBq/kg and 16.46%±5.14% for doses <8 MBq/kg. Administration of an 18F­FDG dose of ≥8 MBq/kg results in images of good to excellent quality in the vast majority of patients when using an LSO PET camera and applying a 3-min emission, 2-min transmission/bed position acquisition protocol. At lower doses, a rapid decline in image quality and increasing noise are observed. Alternative protocols should be adopted in order to compensate for the loss in image quality when doses <8 MBq/kg are used. [ABSTRACT FROM AUTHOR]

The purpose of this study was to address the issue of 180° versus 360° data collection for left ventricular ejection fraction (LVEF) and left ventricular volume measurements using gated myocardial perfusion tomography (gMPT) and gated blood pool tomography (gBPT). Thirty patients with known coronary artery disease were injected in a random sequence with 925 MBq of technetium-99m tetrofosmin and, within 2 days, with 740 MBq of [sup 99m]Tc-labelled human serum albumin. gMPT and gBPT were acquired using 360° data collection and reconstructed by filtered backprojection using all the acquired projection images and separately using only projection images acquired from 45° LPO to 45° RAO. In order to have the same global count densities, the counts in the 360° data set were redistributed using binomial deviates just before reconstruction. After reorientation along the left ventricular long axis, LVEF and left ventricular volumes were calculated using fully automatic algorithms. Twenty-eight patients also underwent planar radionuclide angiocardiography (PRNA) on the same day as the gBPT. For the gMPT studies, the correlation between 180° data collection and 360° data collection was excellent (r>0.98). Bland-Altman analysis revealed small systematic and random differences (<6%) between 180° and 360°. For the gBPT studies, the correlation between 180° data collection and 360° data collection was very good (r>0.93). However, Bland-Altman analysis revealed systematic differences of 26% and random differences of 17%. When PRNA was used as a reference, the best results were obtained with gMPT acquired using 180° data, while the worst results were obtained with gBPT acquired using 180° data. In conclusion, when evaluating LVEF and left ventricular volumes from gMPT, either 180° or 360° orbits can be used. However, 360° data acquisition is recommended when evaluating LVEF and left ventricular volumes from gBPT. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) volume, and not only ejection fraction (EF), is a crucial parameter for assessing the severity of cardiac disease and determining the patient's prognosis. The purpose of this study was to compare LV volumes and EF computed automatically from gated blood pool tomography (gBPT), using QUBE, and from gated myocardial perfusion tomography (gMPT), using QGS, in the same patients with a known history of myocardial infarction. The effects of the extent and severity of the myocardial perfusion defects were investigated. Thirty-seven patients were injected in a random sequence with 740 MBq of technetium-99m human serum albumin and 925 MBq of [sup 99m]Tctetrofosmin, within an interval of 2 days. gBPT and gMPT were acquired on the same triple-head gamma camera using the following acquisition parameters: 360° step-and shoot rotation, 32 stops (96 projections), 30 s per stop, 64x64 matrix (pixel size 5.8 mm), 8 time bins (75% forward/backward framing). Projection data were reconstructed by filtered back-projection using a Butterworth filter. LV volumes calculated from gBPT correlated well with LV volumes measured on gMPT (r=0.93 for end-diastolic volume and 0.95 for end-systolic volume). Volumes above 200 ml, however, were substantially higher with gMPT than with gBPT. These discrepancies were related to the severity, but not the extent, of the perfusion defects. There was also good agreement between gBPT and gMPT for the LVEF (r=0.91). On the Bland-Altman plot, no trend but a systematic error of 5.57% and a random error of 6.85% could be found. For the LVEF, the differences between the gated tomographic techniques were related neither to the extent nor to the severity of the perfusion defects. In conclusion, LV volumes and EF computed on gMPT correlated well with those measured on gBPT. Discrepancies were observed for large volumes presumably because of inaccuracies of gMPT in patients with severe perfusion defects. [ABSTRACT FROM AUTHOR]

Reconstruction of gated single-photon emission tomography (gSPET) is intrinsically a four-dimensional (4D) problem. In practice, the time frames are reconstructed independently as a sequence of frame-by-frame reconstructions. This approach is not optimal since the strong signal correlations among the individual time frames are not exploited. In this study we propose a simple but efficient algorithm to improve the image quality of myocardial perfusion gSPET by incorporating the cyclic temporal information within the reconstruction using Fourier filtering. The gSPET images were reconstructed using the Ordered Subsets Expectation Maximisation (OSEM) algorithm employing six iterations with eight subsets. Temporal filtering was applied either before (PreOSEM) or after image reconstruction (PostOSEM) or was incorporated within the OSEM algorithm (OSEM4D). The effect of temporal filtering was compared with conventional frame-by-frame OSEM using clinical data. Image quality was evaluated by estimating the systematic and statistical error. The results indicated that temporal filtering introduces a small (<1%) systematic error, while the statistical error was reduced from 15.0%±3.1% when conventional frame-by-frame OSEM was applied to 12.6%±2.7%, 12.0%±2.5% and 9.3%±2.4% when PreOSEM, PostOSEM and OSEM4D were used, respectively. It is concluded that temporal filtering incorporated within OSEM reconstruction dramatically reduces noise in gated SPET myocardial images. [ABSTRACT FROM AUTHOR]

Background: Two different algorithms, which are fast and automatic and which operate in 3-dimensional space, were compared in the same group of patients to compute left ventricular ejection fraction (LVEF) and volumes from gated blood pool tomography. One method, developed at Cedars-Sinai Medical Center (CS), was dependent on surface detection, whereas the other method, developed at the Free University of Brussels (UB), used image segmentation.Methods and Results: Gated blood pool tomograms were acquired in 92 consecutive patients after injection of 740 MBq of technetium 99m-labeled human serum albumin. After reconstruction and reorientation according to the left ventricular long axis, LVEF and left ventricular volumes were measured with the CS and UB algorithms. Measurements of LVEF were validated against planar radionuclide angiocardiography (PRNA) results. The success rates of the algorithms were 87% for CS and 97% for UB. Agreement between LVEF measured with CS and UB (LVEF(CS) = 0.91. LVEF(UB) - 0.85; r = 0.87) and between LVEF measured with CS and PRNA (LVEF(CS) = 1.04. LVEF(PRNA) - 4.75; r = 0.80) and UB and PRNA (LVEF(UB) = 0.98. LVEF(PRNA) + 4.42; r = 0.82) was good. For left ventricular volumes, linear regression analysis showed good correlation between both methods with regard to end-diastolic volumes (r = 0.81) and end-systolic volumes (r = 0.91). On average, end-diastolic volumes were similar and end-systolic volumes were slightly higher with CS than with UB. Consequently, significantly lower LVEFs were observed with CS than with UB.Conclusions: Good correlation was observed between CS and UB for both left ventricular volumes and ejection fraction. In addition, measurements of LVEF obtained with both algorithms correlated fairly well with those obtained from conventional PRNA over a wide range of values. [ABSTRACT FROM AUTHOR]

Abstract. Iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) can be used to image myocardial fatty acid regional distribution and utilisation with single-photon emission tomography (SPET). By visual analysis, a mismatching with regional uptake of BMIPP less than that of a perfusion tracer has been shown to predict myocardial viability and functional improvement after restoration of flow in patients with myocardial infarction. The current study aimed to evaluate a newly developed quantitative method of analysis of sestamibi and BMIPP uptake for the prediction of functional recovery after revascularization in patients with acute infarction. BMIPP and gated sestamibi SPET studies at rest were obtained before and >3 months after revascularization in 18 patients with recent infarction. A colour-coded polar map was generated from the comparison of sestamibi and BMIPP uptake. Depending on the relative distribution of the two tracers, different patterns of uptake were identified and their extent expressed as percentages of the surface of the whole left ventricle and of the three main coronary artery territories. At follow-up, recovery was defined as a >5% increase in ejection fraction compared with baseline. Receiver-operating characteristic curve analysis was performed to analyse the data. At baseline, significant correlations were found between ejection fraction and the % surface with decreased sestamibi or BMIPP uptake (r=-0.68, P= 0.001, and t=-0.72, P<0.0001, respectively). When combining both tracers, ejection fraction was significantly associated with the extent of myocardium showing decreased sestamibi uptake with lower BMIPP uptake (mismatching; r= -0.68, P=0.001). At follow-up, significant functional recovery was found in 13/18 patients. By ROC curve analysis, the optimal pattern of distribution predicting recovery was a mismatching with uptake of sestamibi <70% and uptake of BMIPP at least 10% lower. For this parameter, optimal cut-off of extent [ABSTRACT FROM AUTHOR]

Background. The [SUP 13]C urea breath test ([SUP 13]C-UBT) is the most convenient method for diagnosing Helicobacter pylori infection noninvasively. Nondispersive isotopeselective infrared spectrometry (NDIRS) is an inexpensive and easy alternative to mass spectrometry. The objective of this study was to evaluate: (1) the reproducibility of the [SUP 13]C-UBT as performed by using the NDIRS method; (2) the repeatability of bags analysis and the impact of delayed analysis; and (3) the need for fasting status for the [SUP 13]C-UBT. Methods. The [SUP 13]C-UBT was performed with 75 mg urea labeled with [SUP 13]C, with breath samples collected at times 0 and 30 minutes. Results are expressed as delta over baseline (0/00). Fifty-three patients underwent two successive [SUP 13]C-UBTs with an interval of 48 to 72 hours. The 106 collected bags were randomly reanalyzed immediately or 72 hours later. In 26 volunteer subjects, the [SUP 13]C-UBT was performed both in a fasting condition and after a nonstandardized meal. The reproducibility was assessed by the method of Bland and Altman. Results. The mean of difference between two successive tests was 0.14 0/00 (standard deviation, 0.90), and the coefficient of repeatability was 1.80 (confidence interval, 95%). The difference between two successive analyses was always less than 2.2% of the initial value. The coefficient of variation between two successive tests for the influence of a meal was 11.24. Conclusion. The [SUP 13]C-UBT as performed by using NDIRS is reproducible, analyses can be delayed up to 72 hours, and the test must be performed in fasting conditions. [ABSTRACT FROM AUTHOR]

Viability studies are often performed in patients receiving beta-blocking agents. However, the intake of beta-blocking agents could influence the identification of viable myocardium when low-dose dobutamine is used to demonstrate inotropic reserve. The aim of this study was to quantify the effect of beta-blockade on global and regional left ventricular function in healthy volunteers using low-dose dobutamine gated single-photon emission tomographic (SPET) myocardial perfusion scintigraphy. Ten subjects were studied once "on" and once "off" beta-blocker therapy (metoprolol succinate, 100 mg day[sup -1] ). On each occasion four consecutive gated SPET acquisitions (of 7 min duration) were recorded after injection of 925 MBq technetium-99m tetrofosmin on a triple-headed camera equipped with focussing (Cardiofocal) collimators. Acquisitions were made at rest (baseline 1 and 2) and 5 min after the beginning of the infusion of 5 and 10 µg kg[sup -1] min[sup -1] dobutamine. Wall thickening (WT) was quantified using a method based on circumferential profile analysis. Left ventricular ejection fraction (LVEF) was obtained using the Cedars-Sinai algorithm. Blood pressure (BP) and heart rate (HR) were recorded at the end of each acquisition. At baseline LVEF, WT and systolic BP values under beta-blockade were not significantly different from those obtained in the non-beta-blocked state. The mean HR and diastolic BP at baseline were lower under beta-blockade. Dobutamine administration (at 5 and 10 µg kg[sup -1] min[sup -1] ) induced a significant increase in WT, LVEF and systolic BP in all subjects both on and off beta-blockade. The increases in WT, LVEF and systolic BP in the beta-blocked state were less pronounced but not significantly different. HR increased significantly at 10 µg kg[sup -1] min[sup -1] dobutamine without beta-blocker administration, while no increase in HR was observed in the beta-blocked state. Beta-blocker therapy in healthy sub... [ABSTRACT FROM AUTHOR]

Perfusion scintigraphy provides important information regarding the presence of viable tissue after myocardial infarction. Defects of moderate severity, however, may represent viable myocardium, necrotic tissue or a mixture of both. In this study the presence or absence of inotropic response in the infarcted area was assessed by low-dose dobutamine tetrofosmin gated single-photon emission tomography (LDD gated SPET). Results were compared with those obtained with stress echocardiography (SE). Twenty-five patients with acute myocardial infarction were studied. Gated SPET myocardial perfusion imaging was performed 60 min after the injection of technetium-99m tetrofosmin (925 MBq) at rest using a triple-headed camera equipped with focussing collimators (Cardiofocal). Two consecutive acquisitions were performed according to a "fast" gated SPET protocol (3x20 stops, 9 s/stop, 64x64 pixel matrix, zoom 1.23) with the subjects remaining in the same position. The first acquisition was obtained at rest; the second acquisition was obtained under infusion of 10 µg kg[sup -1] min[sup -1] dobutamine. The severity of regional dysfunction, wall thickening severity (WT[sub sev] ), was assessed and quantified using a method based on circumferential profile analysis. SE was performed at rest and during infusion of 5 and 10 µg kg[sup -1] min[sup -1] dobutamine. Two patients could not be analysed because of disturbing gastro-intestinal activity on the perfusion study. Under dobutamine 11 patients presented a significant change in WT[sub sev] (three showed normalisation, five an improvement and three a deterioration), while in 12 patients the WT[sub sev] score remained unchanged. The overall concordance between LDD gated SPET and SE was 83%. In patients with perfusion defects of moderate severity the concordance was 90% (9/10). It may be concluded that functional changes in infarcted areas induced by dobutamine can be detected with gated SPET. Good agreement was obs... [ABSTRACT FROM AUTHOR]

Abstract. Pinhole single-photon emission tomography (SPET) has been proposed to improve the trade-off between sensitivity and resolution for small organs located in close proximity to the pinhole aperture. This technique is hampered by artefacts in the non-central slices. These artefacts are caused by truncation and by the fact that the pinhole SPET data collected in a circular orbit do not contain sufficient information for exact reconstruction. The ordered subsets expectation maximization (OS-EM) algorithm is a potential solution to these problems. In this study a three-dimensional OS-EM algorithm was implemented for data acquired on a single-head gamma camera equipped with a pinhole collimator (PH OS-EM). The aim of this study was to compare the PH OS-EM algorithm with the filtered back-projection algorithm of Feldkamp, Davis and Kress (FDK) and with the conventional parallel-hole geometry as a whole, using a line source phantom, Picker's thyroid phantom and a phantom mimicking the human cervical column. Correction for the angular dependency of the sensitivity in the pinhole geometry was based on a uniform flood acquisition. The projection data were shifted according to the measured centre of rotation. No correction was made for attenuation, scatter or distance-dependent camera resolution. The resolution measured with the line source phantom showed a significant improvement with PH OS-EM as compared with FDK, especially in the axial direction. Using Picker's thyroid phantom, one... [ABSTRACT FROM AUTHOR]

Background: Tetrofosmin gated single photon emission computed tomography (SPECT) allows simultaneous assessment of regional myocardial perfusion, global and regional left ventricular function, and function at rest and during pharmacologic intervention. SPECT with fatty acid analogues, such as beta-methyl-iodophenyl-pentadecanoic acid (BMIPP), can be used to monitor metabolic changes induced by myocardial ischemia. In this work, the results of both studies obtained in patients with recent myocardial infarction are integrated.Methods: Twenty patients underwent tetrofosmin and BMIPP scintigraphy with a 3-head camera. Two consecutive tetrofosmin gated SPECT acquisitions were performed 60 minutes after administration of technetium-99m tetrofosmin (925 MBq) at rest (3x20 stops of 9 s; matrix 64x64 over 360 degrees . One acquisition was made at rest, and the second was made during dobutamine infusion (10 microg/kg/min). Regional functional abnormalities were quantified and expressed as wall thickening severity (WTsev) in arbitrary units. Left ventricular ejection fraction and volumes were assessed with the Cedars Sinai algorithm. BMIPP imaging started 20 minutes after iodine 123-BMIPP (150 MBq) administration at rest (3x32 stops of 60 s; matrix 64x64 over 360 degrees; medium energy collimators). Tracer uptake was scored according to a 25-segment model.Results: Sixteen of 18 patients had regional functional abnormalities at baseline (average WTsev 13.7 units). The WTsev score at baseline correlated well with the degree of residual perfusion. During dobutamine infusion, WTsev did not change (from 23.4 to 23.6 units) in 5 patients; it decreased (from 16.1 to 5.9 units) in 11 patients; and it increased (from 13.0 to 22.3 units) in 3 patients. An increase or decrease in WTsev during dobutamine infusion was associated with the presence of a considerable amount of BMIPP mismatched myocardium, whereas no change in WTsev was preferentially associated with a BMIPP matched pattern and perfusion defects with a higher severity score.Conclusion: Immediately after infarction, the severity of regional dysfunction at rest correlated well with the perfusion defect severity. Improvement in regional function during dobutamine administration is associated with less severe perfusion defects and a considerable amount of BMIPP mismatched myocardium, both suggesting viability. [ABSTRACT FROM AUTHOR]

Abstract. We have evaluated the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) in the presence of increased lactate levels induced by short-term heavy exercise. Five healthy male subjects received 159 MBq (+/-13 MBq) [sup 123]I-BMIPP at rest and a week later after they performed a maximal exercise test using a bicycle ergometer. Planar and tomographic images were obtained with a dual-head gamma camera up to 4 h after administration of the tracer. Multiple blood samples were taken at different time points for blood clearance, substrate concentration measurements and for HPLC analysis of metabolites. The exercise test did not alter plasma glucose and non-esterified fatty acid concentrations, but blood lactate increased from 1.12 mmol/l at rest to 9.26 mmol/l with maximal exercise. After exercise, BMIPP showed a significantly faster plasma clearance than at rest and the production of PIPA, the end metabolite of BMIPP oxidation, was reduced. Activity in the heart was similar alter exercise and at rest on planar images 15 min after injection (4.83+/-0.50%ID vs 4.80+/-0.43%ID, P=NS), although the myocardium-to-cavity activity ratio, as determined on the SPET images 20 min after tracer injection, was slightly increased after the exercise test (4.20+/-0.63 vs 3.78+/-1.34 at rest, P=NS). Significantly increased activity was observed in a leg muscle region of interest after exercise (4.98+/-0.50%ID vs 3.93+/-0.44%ID at rest, P=0.02). Between early and late images, tracer washout from the... [ABSTRACT FROM AUTHOR]

Electrocardiography gated single-photon emission tomography (gated SPET) allows the assessment of regional perfusion and function simultaneously and in full spatial congruency. In this study changes in global and regional left ventricular function in response to dobutamine infusion were assessed in ten healthy volunteers using sequential gated SPET myocardial perfusion acquisitions. Four consecutive gated SPET images were recorded 60 min after injection of 925 MBq technetium-99m tetrofosmin on a three-head camera equipped with focussing collimators. Two acquisitions were made at rest (baseline 1 and 2), and the third and fourth acquisitions were started 5 min after the beginning of the infusion of 5 and 10 µg kg–1 min–1 dobutamine, respectively. Systolic wall thickening (WT) was quantified using a method based on circumferential profile analysis. Left ventricular ejection fraction (LVEF) and volumes were calculated automatically using the Cedars-Sinai program. Nine of the ten subjects presented a definite increase in WT during dobutamine infusion. WT increased on average from 46%±14% at baseline to 71%±23% (range: 37%–106%; P<0.05) during 5 µg kg–1 min–1 dobutamine infusion and to 85%±25% (range: 62%–123%; P<0.05 with respect to WT at 5 µg kg–1 min–1) during 10 µg kg–1 min–1 dobutamine infusion. Apical segments showed the largest WT at baseline. The average WT response to dobutamine was similar for all parts of the myocardium. It is concluded that changes in WT induced by infusion of low-dose dobutamine can be assessed by sequential gated SPET myocardial perfusion studies. The ”stress gated SPET” protocol proposed in this study might be helpful to distinguish viable from scar tissue in patients with coronary artery disease, by demonstrating a preserved inotropic response in hypoperfused myocardium. [ABSTRACT FROM AUTHOR]

Abstract. Using iodine-123 labelled radiotracers, the presence of 2.5% high-energy photons causes image deterioration due to increased scatter. To investigate the influence of these photons on image quality, we measured the spectrum of 123I with a medium-energy (ME), a low-energy all-purpose (LEAP) and a low-energy high-resolution (LEHR) collimator. Even in air, using low-energy collimators a high baseline activity was observed over the total energy detection range of the gamma camera. The 159-kev photopeak to scatter activity ratio fell from 5.9 for ME to 3.6 and 2.9 for LE collimators. Acquisition of images with LEHR collimators with energy windows set at 159 kev and 500 kev demonstrated that the 159-kev LEHR image is a combination of the ME image of the object and of the LEHR 500-kev image. Because of their important septal penetration and greater geometric detection efficiency compared with the 159-kev photons of [sup 123]I, the contribution of high-energy photons is dependent on the source-detector distance. For a small source placed in air, the scatter to photopeak activities varied from 17.4% at 80 cm to 37.8% at 5 cm distance from an LEHR collimator. Considering only the scatter problem, ME collimators are the best choice for [sup 123]I studies. When using LE collimators for high-resolution tomography with [sup 123]I-labelled compounds, scatter contribution from high-energy photons has to be corrected for quantitative analysis or when dual-isotope studies are performed, whether or not these studies are acquired simultaneously. [ABSTRACT FROM AUTHOR]

Objective: Two different algorithms operating in three-dimensional space, one dependent on surface detection developed at Cedars-Sinai Medical Center (CS) and another dependent on statistical parameters and developed at Stanford University Medical School (SU), were compared in the same patients to assess the left ventricular volumes and the left ventricular ejection fractions (LVEFs) from gated single-photon emission tomography (SPECT) myocardial perfusion images.Methods: Perfusion SPECT images gated in eight time bins were recorded in 40 patients with coronary artery disease 60 minutes after the injection of 925 MBq 99mTc-labeled tetrofosmin at rest. The LVEF values were validated against planar gated 99mTc-labeled blood pool studies (ERNA).Results: The software success rates were 95% (38/40 patients) for CS and 100% for SU. Agreement between LVEFs measured with CS and SU and agreement between both methods and ERNA were excellent (LVEF[CS] = 0.89LVEF[SU] + 6.21, r = 0.93; LVEF[SU] = 0.92LVEF[ERNA] + 0.99, r = 0.94; and LVEF[CS] = 0.88LVEF[ERNA] + 4.58, r = 0.93). Bland-Altman plots showed that differences between LVEFs from SU and CS and from ERNA were similar across a wide range (20% to 80%) of LVEF values. No relationship between these differences and the severity of perfusion defects was observed. For left ventricular volumes, linear regression analysis showed an excellent correlation between both methods (end-diastolic volume r = 0.97 end-systolic volume r = 0.98), but systematically higher values were obtained with SU (p = 0.013).Conclusion: Measurements of LVEF obtained with CS and SU correspond well with those from the standard, ERNA, even in patients with severe perfusion defects. A close relationship is observed between SU and CS when left ventricular volumes are considered. Measurements of LVEF (and left ventricular volumes) should be considered as an integral part of myocardial perfusion studies whenever possible. [ABSTRACT FROM AUTHOR]

Abstract. Short acquisition protocols for gated single-photon emission tomography (SPET) myocardial perfusion imaging are desirable for sequential imaging to evaluate the myocardial response during pharmacological intervention. In this study a less than 5 min gated SPET acquisition protocol is proposed. Perfusion characteristics (defect severity) and left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volumes (EDV, ESV), wall motion (WM) and wall thickening (WT) were calculated, checked for reproducibility and compared with data obtained using a standard gated SPET acquisition protocol. Gated SPET images were recorded in 20 patients starting 60 min after the administration of 925 MBq technetium-99m tetrofosmin at rest. The 5 min gated SPET studies were acquired with a three-head camera equipped with Cardiofocal collimators. This protocol was repeated twice. In addition gated SPET studies were acquired according to a standard protocol using parallelhole collimators. The severity of perfusion defects was quantified on polar maps using the non-gated image data and a normal database. LVEF, EDV, ESV, WM and WT were calculated from the gated images. The agreement between 5-min and standard gated SPET acquisitions was excellent for all investigated parameters. The reproducibility of repeated 5-min acquisitions for the quantification of perfusion defect severity was excellent (r=0.97). The agreement for segmental WT scores between repeated 5-min gated SPET acquisitions was good: kappa = 0.71; major differences in segmental classification were observed in 2.5%. For WM a good agreement was found for segments with a tracer uptake >30% of the maximum: kappa = 0.65, major differences =7.7%. Excellent reproducibility was found for... [ABSTRACT FROM AUTHOR]

Abstract. The uptake of iodine-123 alpha-methyl-L-tyrosine (IMT) in the primary tumours and metastatic lymph nodes of squamous cell carcinoma of the head and neck was examined with single-photon emission tomography (SPET). Eleven patients with biopsy-proven carcinomas were studied prior to any therapeutic action. The evaluation of cervical lymph node involvement was based on the findings of physical examination, computed tomography and magnetic resonance imaging, and in six patients on the histological data relating to tissue samples obtained by fine-needle lymph node aspiration or surgical intervention. SPET imaging was performed 10 min after the injection of 130-170 MBq IMT using a triplehead gamma camera equipped with medium-energy collimators. High-quality IMT SPET depicted the primary tumour in 10 of 11 patients (sensitivity: 91%). Tumours located in the larynx were visualized more clearly than those located in the mouth or oropharynx. The mean tumour-to-background ratio was 2.35 (range: 1.6-3.1) for laryngeal tumours and 1.67 (range: 1.2-2.2) for mouth and oropharyngeal tumours. Metastatic cervical lymph nodes were involved to various degrees in 8 of the 11 patients. Among these eight patients there were 16 sites, nine of which were detected by IMT SPET (sensitivity: 56%). If the IMT SPET findings were recorded per side of the neck, the sensitivity was 64%. Five of the seven missed metastatic lymph nodes were smaller... [ABSTRACT FROM AUTHOR]

Left ventricular ejection fraction (LVEF) can be derived from gated single-photon emission tomographic (SPET) myocardial perfusion studies using either manual or edge detection techniques. In the presence of severe perfusion defects, however, difficulties may be encountered. In this article a method based on the assumption that the average position of the myocardial wall can be localized by means of statistical analysis of the distribution count density, and not on edge detection, is used to measure LVEF. SPET myocardial perfusion images, gated in eight time bins, were recorded in 50 patients 60 min after the injection of 925 MBq technetium-99m tetrofosmin. Masking of non-myocardial structures and thresholding resulted in images in which only myocardial walls had significant non-zero values. The distance of the wall relative to the centre of the cavity was calculated in the three-dimentional space as the first moment of the count rate distribution along radii originating in the centre of the cavity. LVEF was calculated using, for each time bin, the sum of the cube of all distances as an estimate of the cavity volume. The method required minimal operator interventions and was successful in all patients, including those with severe perfusion defects. Intraobserver and interobserver variability was excellent, with regression coefficients of 0.97 and standard deviations of 4.5% and 4.7%, respectively. For 30 patients, the measurements were validated against planar equilibrium radionuclide angiography (ERNA) that was obtained within an interval of 1 week. LVEF ranged from 12% to 88%. Agreement between the two methods was excellent (LVEFE=1.05+0.92 LVEF, r=0.93, P=0.023, SEE=7.06). The Bland-Altman analysis did not show any apparent trend in the differences between ERNA and gated SPET over a wide range of ejection fractions. The standard deviation of the differences was 3.1%. In addition no relationship was found between the two methods and the severity of perfusion defects. In conclusion, accurate measurements of LVEF are obtained from gated SPET perfusion images using a method based on statistical analysis of the count rate density. This method did not deteriorate even in the presence of severe perfusion defects and could therefore be used in following patients after myocardial infarction. [ABSTRACT FROM AUTHOR]

Dual-isotope studies with technetium-99m and iodine-123 may be useful for various organs, including brain and myocardium. For the images obtained with each of the tracers to be comparable, it is important that activity ratios (activity in one part of the image/reference activity in the image) are preserved by the imaging method. We have used a Rollo phantom to study how collimator response affects such ratios. All investigations were performed withI(p,5n) and on a Siemens Orbiter 3700 camera fitted with either a low-energy high-resolution (LEHR) or a medium-energy (ME) collimator. Images were made of a Rollo phantom filled with an aqueous solution of eitherTc orI, and placed on the collimator surface with 8 cm of methyl-methacrylate interposed. Count densities were measured in ROIs drawn in each cell of the phantom, and normalised to the maximal ROI value in the image. The mean square error (MSE) was used to assess how well the ratios of count densities approximated the known activity ratios based on the dimensions of the cells of the phantom. ForTc, regardless of the collimator used, the count density ratios approximated the activity ratios fairly well (LEHR: MSE=0.008; ME: MSE=0.020). ForI, count density ratios obtained with the LEHR were consistently higher than activity ratios (MSE=0.235), whereas the differences between the measured and the theoretical values were less with the ME collimator (MSE=0.013). Contrast fidelity of theI images obtained with the LEHR collimator could be improved with Jaszczak scatter correction with k=1, but this led to unfavourable signal-to-noise ratios. For sequentialTc/I studies with extended sources, ME is to be preferred because of its higher contrast accuracy. Spatial resolution is less for the ME than for the LEHR collimator (FWHM with scatter: LEHR/Tc=6.9 mm, LEHR/I=7.4 mm, ME/Tc=10.1 mm, ME/I=11.1 mm), but remains similar for both tracers when the ME is used. [ABSTRACT FROM AUTHOR]

Dipyridamole is often used as an alternative to exercise in the detection of coronary artery disease by radionuclide techniques. For analyzing the dipyridamole-induced chest pain encountered during this test we studied a group of 47 patients who underwent MIBI SPECT imaging at rest and after the injection of up to 0.84 mg/kg dipyridamole. Coronary arteriography was available in a subgroup of 21 patients. A significant relation was found between chest pain during dipyridamole injection and ischemic electrocardiogram changes in the study group. In the subgroup of 21 patients with coronary angiography, an association was found between chest pain and the presence of collateral circulation. The MIBI perfusion defects were also more prevalent in the group with collaterals. These findings can be explained by the induction of coronary steal after dipyridamole in the group with a collateral circulation. This coronary steal causes real ischemia in the collateralized region. We conclude that in patients with known coronary artery disease, dipyridamole MIBI imaging allows for the selection of those patients with significant coronary stenosis with a collateral circulation. In this way, dipyridamole selects a group of patients who may be at lower risk in case of acute occlusion of the artery. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the ability to simultaneously assess left ventricular function and myocardial perfusion by using a single injection of technetium-99m Sestamibi at rest and during submaximal exercise to identify high-risk patients with left main, proximal left anterior descending (LAD), or three-vessel coronary artery disease (CAD) after an uncomplicated acute myocardial infarction (AMI). Multiple studies have evaluated the separate value of the exercise ECG, myocardial perfusion scintigraphy, and radionuclide angiocardiography (RNA) for identifying patients with severe CAD. The availability of technetium-99m (Tc99m)-labeled myocardial imaging agents offers the opportunity to evaluate simultaneously ventricular function and myocardial perfusion during a single exercise session. Only limited data are available about the value of this combined technique in the workout of patients early after an uncomplicated AMI. Combined first-pass RNA and myocardial perfusion tomoscintigraphy (SPFCT) at rest and during submaximal exercise were performed in 52 patients, less than six weeks after an uncomplicated AMI, with use of Tc99m Sestamibi. Patients were classified in two subgroups according to the presence of left main, proximal LAD, or three-vessel CAD. Stepwise logistic regression analysis was used to determine the independent predictors of severe CAD. All patients underwent the exercise testing without any medical complication. On univariate analysis, the global left ventricular ejection fraction (LVEF), wall motion score, and myocardial perfusion score, both at rest and at submaximal exercise, were significantly associated with the presence of severe CAD. The response of LVEF to exercise, and the presence of exercise-induced wall motion or myocardial perfusion abnormalities, were not associated with the severity of CAD. On multivariant analysis only the wall motion score during exercise was an independent predictor for the presence of severe CAD (P < 0.001, r=0.6). In analyzing patients with anterior AMI separately, LVEF at submaximal exercise was the most accurate predictive parameter. If a cutoff value of 40% was chosen, the LVEF at exercise had a sensitivity of 85% and a specificity of 78% for the detection of severe CAD. In patients with inferior AMI, neither LVEF nor wall motion or myocardial perfusion scores were useful for differentiating the two subgroups. In these patients the presence of an additional perfusion defect during exercise in one of the anterior wall segments yielded a sensitivity of 70% and a specificity of 75% for the presence of severe CAD. In conclusion: simultaneous evaluation of LV function and myocardial perfusion at submaximal exercise, using a single injection of Tc99m-Sestamibi, is a safe and accurate technique for selecting patients with severe CAD after an uncomplicated AMI. [ABSTRACT FROM AUTHOR]

In a subacute experiment the authors studied the effects of a fourteen-day treatment with nebivolol, 5 mg once a day, in 10 healthy male volunteers with a mean age of thirty-one, twenty-five to thirty-nine years, by comparing the results of the resting ratio of the preejection period (PEP,) to the left ventricular ejection time (LVETJ, as measured by systolic time intervals (STI), with the results obtained by equilibrium radionuclide angiocardiography (ERNA), using technetium 99m-labeled autologous red blood cells as a marker. A submaximal treadmill exercise test performed before and during treatment demonstrated that nebivolol significantly (p≤0.01) reduced peak exercise heart rate and systolic blood pressure from a mean value of 158 ± 5.4 bpm to 131 ± 4.3 bpm and from 171 ± 4.9 mmHg to 144 ± 4.5 mmHg respectively. The data from the STI and ERNA were calculated and analyzed independently by two observers. A highly significant (r = 0.8182, p = 0.0038) correlation was found between the changes of stroke volume (SV) and PEP,/LVET, during treatment with nebivolol. Furthermore end-diastolic volume significantly (p = 0.03) increased from a mean value of 177 ± 10.1 ml to 198 ± 6 ml and stroke volume significantly (p=0.01) increased from 120 ± 6.8 ml to 136 ± 6.3 ml. Systemic vascular resistance tended to decrease from a mean value of 11.4 ± 1.28 units to 10.6 ± 1.10 units. No changes could be observed either in ejection fraction or in cardiac output. The ratio of the PEPc/LVETc, as measured with STI, significantly (p = 0.03) improved from a mean value of 0.34 ± 0.011 to 0.30 ± 0.010, and these changes were due to both a decrease of PEPc and an increase of LVETc. The postexercise LVETc which is a marker of the positive inotropy of the exercise, significantly (p=0.002) shortened with 49 ± 4.6 msec in control conditions and also during treatment with nebivolol with 30 ± 4.6 msec (p=0.002). From all these data it appears that nebivolol, unlike classical beta-blockers, beneficially influences cardiac function at rest, owing to a combined effect on both preload and afterload. These ancillary hemodynamic activities of nebivolol may be useful in the treatment of elderly hypertensive patients with left ventricular damage. [ABSTRACT FROM AUTHOR]

Assessment of myocardial viability is an important clinical issue for patient management during the acute and chronic stages of myocardial infarction. BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) is a free fatty acid analogue which is trapped in the myocardium, thus permitting for metabolic imaging with single photon emission computerized tomography (SPECT). Less BMIPP than flow tracers that may be observed in the areas of infarction, may reflect the metabolic shift from fatty acid to glucose utilization in ischaemic myocardium. In this sense, the combined imaging of BMIPP and a flow tracer with SPECT may provide similar and important information as fluoro-18 deoxyglucose (FDG) and positron emission tomography (PET) regarding the assessment of myocardial viability. The purpose of this article is to review the clinical impact of BMIPP in patients with acute and with chronic left ventricular dysfunction for the identification of jeopardized but viable myocardium and the prediction of the functional outcome. [ABSTRACT FROM AUTHOR]