Distribution and dynamics of Tc-99m-pertechnetate uptake in the thyroid and other organs assessed by single-photon emission computed tomography in living mice

Background: Tc-99m pertechnetate is a well-known anion, used for clinical imaging of thyroid function. This gamma emitter is transported by the sodium iodide symporter but is not incorporated into thyroglobulin. Scintigraphy using Tc-99m pertechnetate or 123 iodide represents a powerful tool for the study of sodium iodide symporter activity in different organs of living animal models. However, in many studies that have been performed in mice, the thyroid could not be distinguished from the salivary glands. In this work, we have evaluated the use of a clinically dedicated single-photon emission computed tomography (SPECT) camera for thyroid imaging and assessed what improvements are necessary for the development of this technique. Methods: SPECT of the mouse neck region, with pinhole collimation and geometric calibration, was used for the individual measurement of Tc-99m pertechnetate uptake in the thyroid and the salivary glands. Uptake in the stomach was studied by planar whole-body imaging. Uptake kinetics and biodistribution studies were performed by sequential imaging. Results: This work has shown that thyroid imaging in living mice can be performed with a SPECT camera originally built for clinical use. Our experiments indicate that Tc-99m pertechnetate uptake is faster in the thyroid than in the salivary glands and the stomach. The decrease in Tc-99m pertechnetate uptake after injection of iodide or perchlorate as competitive inhibitors was also studied. The resulting rate decreases were faster in the thyroid than in the salivary glands or the stomach. Conclusions: We have shown that a clinically dedicated SPECT camera can be used for thyroid imaging. In our experiments, SPECT imaging allowed the analysis of Tc-99m pertechnetate accumulation in individual organs and revealed differences in uptake kinetics

Effect of streptozotocin-induced diabetes on left ventricular function in adult rats: an in vivo Pinhole Gated SPECT study

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p

Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

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

Normalisation to Blood Activity Is Required for the Accurate Quantification of Na/I Symporter Ectopic Expression by SPECT/CT in Individual Subjects

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, replication-incompetent 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 RT-PCR 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

Left ventricular ejection fraction and volumes from gated blood pool tomography: comparison between two automatic algorithms that work in three-dimensional space

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 (LVEFCS = 0.91 . LVEFUB - 0.85; r = 0.87) and between LVEF measured with CS and PRNA (LVEFCS = 1.04 . LVEFPRNA - 4.75; r = 0.80) and UB and PRNA (LVEFUB = 0.98 . LVEFPRNA + 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

Effect of beta-blockade on low-dose dobutamine-induced changes in left ventricular function in healthy volunteers: assessment by gated SPET myocardial perfusion scintigraphy

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(-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 mu g kg(-1) min(-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 mu g kg(-1) min(-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 mu g kg(-1) min(-1) dobutamine without beta-blocker administration, while no increase in HR was observed in the beta-blocked state. Beta-blocker therapy in healthy subjects attenuates the inotropic and chronotropic myocardial response to low-dose dobutamine. At doses of 5 and 10 mu g kg(-1) min(-1) dobutamine, however, significant increases in global and regional left ventricular function can still be measured using consecutive gated SPET myocardial perfusion scintigraphy acquisitions even under beta-blocker therapy

Gated SPET myocardial perfusion acquisition within 5 minutes using focussing collimators and a three-head gamma camera

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 Introduction (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 parallel-hole 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 greater than or equal to 30% of the maximum: kappa=0.65, major differences =7.7%. Excellent reproducibility was found for LVEF EDV and ESV measurements: r=0.97, 0.99 and 0.99, respectively. It is concluded that fast gated SPET perfusion studies acquired in less than 5 min yield accurate and reproducible measurements of myocardial perfusion and function (global and regional), In addition the results obtained with the 5-min gated SPET protocol correlate well with those obtained using a standard acquisition protocol

Assessment of perfusion, function, and myocardial metabolism after infarction with a combination of low-dose dobutamine tetrofosmin gated SPECT perfusion scintigraphy and BMIPP SPECT imaging

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 (3 x 20 stops of 9 s; matrix 64 x 64 over 360 degrees. One acquisition was made at rest, and the second was made during dobutamine infusion (10 mu g/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 (3 x 32 stops of 60 s; matrix 64 x 64 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

Low-dose dobutamine gated single-photon emission tomography: comparison with stress echocardiography

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 mu g kg(-1) min(-1) dobutamine. The severity of regional dysfunction, wall thickening severity (WTsev), was assessed and quantified using a method based on circumferential profile analysis. SE was performed at rest and during infusion of 5 and 10 mu g kg(-1) min(-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 WTsev (three showed normalisation, five an improvement and three a deterioration), while in 12 patients the WTsev score remained unchanged. The overall concordance between LDD gated SPET and SE was 83%. In patients with per fusion 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 observed between LDD gated SPET and SE for the identification of inotropic reserve in infarcted areas