Yoshikazu Tamura

Absolute quantitation of myocardial blood flow with 201 Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

Purpose201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT.MethodsDynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K1) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments.ResultsRegional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBFSPECT) correlated well with the MBF values obtained by the radio-labelled microspheres (MBFMS) (MBFSPECT = −0.067 + 1.042 × MBFMS, p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression.ConclusionAbsolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT.

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure.

This study investigated whether abnormal cardiac sympathetic nerve activity (SNA) is associated with the severity of central sleep apnoea (CSA) and whether adaptive servo‐ventilation (ASV) therapy can improve cardiac SNA in heart failure (HF) patients with predominant CSA.

Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Japan.

Abstract.Recently, a method has been proposed for the quantitative measurement of regional myocardial blood flow (MBF) using oxygen-15-labelled water and positron emission tomography (PET). A multicentre project was organized with the intention of evaluating the accuracy of this method, particularly as a multicentre clinical investigative tool. Each of seven institutions performed PET studies on more than five normal volunteers following a specified protocol. The PET study included a transmission scan, a 15O-carbon monoxide static scan and a 15O-water dynamic scan, thereby yielding MBF values which should have been independent of the spatial resolution of the PET scanner employed. Fifty-three subjects (aged 20–63 years, mean±SD 36±12 years) were studied at rest, and 31 of these subjects were also studied after dipyridamole in five institutions. Inter-institution consistency and intra-subject variation in MBF values were then evaluated. MBF averaged for all subjects was 0.93±0.34 ml min–1 g–1 at rest and 3.40±1.73 ml min–1 g–1 after the administration of dipyridamole, and the flow reserve (defined as the ratio of the two MBF values) was 3.82±2.12; these values are consistent with previous reports. Resting MBF values were significantly correlated with the heart rate–blood pressure product (RPP) (y=0.31+6.56E-5x, P<0.010), and RPP was in resting MBF observed in all institutions was well explained by the age-dependent RPP. No significant difference was observed in resting MBF among the institutions. Except in one institution, no significant difference was seen in dipyridamole MBF or myocardial flow reserve. No significant difference was found among the myocardial segments. Regional variation was reasonably small in five institutions, but was not acceptable in two institutions, which was attributed to the scanner performance. These observations suggest that the 15O-water PET technique is useful for a multicentre clinical study if the PET scanner can provide time-activity data with good count statistics.

Optimized acquisition time and image sampling for dynamic SPECT of Tl-201

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: (1) Continuous data collection for total study duration ranging from 30-240 min. (2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K/sub 1/-k/sub 4/) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). The authors found that OSS can reliably estimate the blood flow related K/sub 1/ and V/sub d/ comparable to DynSS. A 30-min continuous collection was sufficient if only K/sub 1/ was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K/sub 1/ and V/sub d/ avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers.

Design and experimental validation of a quantitative myocardial /sup 201/Tl SPECT system

We have developed a quantitative SPECT system, and evaluated its potential for quantitative assessment of bio-physiological functions in the myocardium particularly with /sup 201/Tl. Our approach included development of a transmission system that provides accurate attenuation /spl mu/ maps, and implementation of ordered-subset EM reconstruction with transmission data based attenuation correction in addition to scatter correction using the transmission-dependent convolution subtraction (TDCS) technique. The transmission system was designed using Monte Carlo simulation to minimize the scatter in the transmission projection data while keeping loss of sensitivity minimal, and was attached to an opposing 2-head gamma camera fitted with parallel beam collimators. Observed /spl mu/ values agreed quantitatively well with the theoretical expected values in both phantoms and human thorax. Phantom experiments with /sup 201/Tl also demonstrated that, with both corrections for attenuation and scatter, observed images were directly proportional to the actual radioactivity distribution for various phantom geometries. Attenuation correction without scatter correction improved images in deep structure, but resulted in significant artifacts in the chest phantom in addition to dependency of observed radioactivity concentrations on the diameter of cylindrical phantoms. Absolute quantitation of bio-physiological functions, which is well established in PET, is shown to be feasible using SPECT, if both quantitative attenuation and scatter corrections are employed.

Beneficial effects of adaptive servo-ventilation therapy on albuminuria in patients with heart failure.

BACKGROUND Short-duration adaptive servo-ventilation (ASV) therapy can be effective for heart failure (HF) patients. Albuminuria is recognized as a prognostic marker for HF. We investigated whether short-duration and short-term ASV therapy reduced albuminuria in HF patients. METHODS AND RESULTS Twenty-one consecutive HF patients were divided into two groups: those who tolerated ASV therapy (ASV group, n=14) and those who did not (non-ASV group, n=7). ASV therapy was administered to enrolled patients for 1 week for 2h per day (1h in the morning and 1h in the afternoon). The urinary albumin to creatinine ratio (UACR), urinary 24h norepinephrine (NE) excretion, high-sensitivity C-reactive protein (hs-CRP), and plasma brain natriuretic peptide (BNP) levels were measured before and 1 week after ASV therapy. In the ASV group, but not the non-ASV group, the UACR significantly decreased, together with a decrease in urinary NE and hs-CRP levels. There were significant correlations between the changes in UACR and hs-CRP and between the changes in urinary NE and hs-CRP. Multiple linear regression analyses indicated that ASV use was the strongest predictor of decreased UACR. CONCLUSION Albuminuria, urinary NE, and hs-CRP levels reduced in HF patients who could receive short-duration and short-term ASV therapy. Anti-inflammatory effects of ASV therapy may partly mediate the reduction of albuminuria.

Regional Changes in Human Cerebral Blood Flow during Dipyridamole Stress: Neural Activation in the Thalamus and Prefrontal Cortex

Intravenous dipyridamole increases the concentration of circulating adenosine and produces coronary vasodilation. However, it decreases global cerebral blood flow (CBF) due to hyperventilation side effect of adenosine. In the present study, changes in regional CBF during dipyridamole stress were identified in detail. In 11 healthy men (51-71 years of age), CBF was measured by positron emission tomography with oxygen-15-labeled water at rest (baseline) and during dipyridamole stress. All images were normalized to global CBF and transformed to standard brain anatomy. A t map between baseline and dipyridamole stress conditions was then created on a pixel-by-pixel basis. CBF was globally decreased during dipyridamole stress. However, a significant relative increase in CBF was observed bilaterally in the thalamus and prefrontal cortex, indicating neural activation in these regions. Adenosine plays an important role in the production of anginal pain by stimulation of A(1) adenosine receptors. Neural activation in the thalamus and prefrontal cortex during angina pectoris has been reported. Although no subject felt chest pain during dipyridamole stress, neural activation in the thalamus and prefrontal cortex indicates that stimulation of A(1) adenosine receptors during dipyridamole stress may produce input from the heart to the thalamus through the vagal fiber.

Reduction of ST elevation in repeated coronary occlusion model depends on both altered metabolic response and conduction property

The aim of this study was to elucidate the mechanisms of altered electrical response to ischemia in repeated coronary occlusion model. To test its dependence on metabolic response, extracellular K+ concentration (eKC), myocardial pH and PCO2 were simultaneously measured with epicardial ECG during three consecutive 4 min of left anterior descending coronary artery (LAD) occlusion separated by 15 min of reperfusion in canine hearts. ECG changes induced by infusion of high K+-buffer (10 mM) into the coronary arterial bed via carotid artery-LAD bypass (referred to as high K+-challenges: HKC) were also tested prior to (the first HKC), and during each reperfusion period (the second to the fourth HKC). ST elevation was significantly reduced in subsequent occlusions (3.14 +/- 0.48 and 2.98 +/- 0.47 mV in the second and third occlusion, both P<0.05, compared to 4.91 +/- 0.78 mV in the first). This was accompanied by significant attenuation of the changes in eKC, tissue pH and PCO2. ST elevation induced by HKC also significantly reduced after repeated occlusion (4.09 +/- 0.79 mV in the fourth HKC vs. 5.64 +/- 0.68 mV in the first, P<0.05) in spite of the identical changes in eKC during HKC. This progressive decrease in ST changes by HKC was rather consistent with augmented conduction delay (86.4 +/- 7.1% increase in activation time in the fourth vs. 54.3 +/- 3.4% in the first, P<0.01). These findings indicate that repeated ischemia induces altered electrical response to subsequent ischemia based on both attenuated metabolic response and altered conduction property.

Assessment of Myocardial Viability Using 15O-Water

It has become apparent that successful coronary reperfusion by thrombolysis, angioplasty, or bypass graft surgery is often associated with improvement of function in patients with coronary artery disease. This suggests the presence of dysfunctional but viable myocardium within the area of abnormal wall motion. Myocardial tissue necrosis is a complex pathophysiological process that is dependent upon several factors, such as myocardial metabolism [1,2] and the duration and severity of the blood flow reduction [3–5]. Therefore, in the clinical setting this process can result in asynergic segments containing an admixture of both necrotic and reversibly injured myocardium. Clinically, the identification of such functionally recoverable myocardium in regions of ventricular dysfunction has become an increasingly relevant issue, especially in the management of patients with severely impaired ventricular function.