Consideration of perfusion reserve in viability assessment by myocardial Tl-201 rest-redistribution SPECT: A quantitative study with dual-isotope SPECT

BACKGROUND: To optimize the use of thallium 201 rest-redistribution study in Tl-201/technetium 99m sestamibi dual-isotope single photon emission computed tomography (SPECT), the predictability of Tl-201 rest-redistribution for viable myocardium was examined according to the degree of perfusion reserve. METHODS AND RESULTS: Twenty patients with both unstable angina and left ventricular dysfunction were enrolled. Tl-201 rest-dipyridamole stress Tc-99m sestamibi gated SPECT/Tl-201 24-hour redistribution SPECT was performed before and 3 months after coronary artery bypass grafting. Through use of a 20-segment model, segmental stress perfusion, rest perfusion, and systolic thickening were quantified on gated SPECT by means of automatic quantitation software. Perfusion was expressed as the average percentage of maximal radioactivity uptake. To represent perfusion reserve, the perfusion difference score (PDS) was defined as rest perfusion minus stress perfusion. A low PDS indicated little or no inducible ischemia, and a high PDS indicated inducible ischemia. In dysfunctional myocardium, viability was defined by the improvement of thickening after coronary artery bypass grafting. The overall predictability of Tl-201 redistribution for viability was 0.709 of the area under the curve (AUC) in receiver operating characteristic analysis. With a cutoff of 7, predictability was significantly better in the low PDS group (AUC = 0.785) than in the high PDS group (AUC = 0.582). CONCLUSIONS: The predictability of Tl-201 rest-redistribution for viability differs according to perfusion reserve. It was more reliable for dysfunctional myocardium with persistent perfusion decrease. On the basis of the continuum hypothesis of chronic stunning and hibernation, we suggest that dysfunctional myocardium with persistent perfusion decrease should be assessed by Tl-201 redistribution SPECT.     

Avoiding full corrections in dynamic SPECT images impacts the performance of SPECT myocardial blood flow quantitation

Journal of Nuclear Cardiology - This study investigated the performance of SPECT myocardial blood flow (MBF) quantitation lacking full physical corrections (All Corr) in dynamic SPECT (DySPECT)...     

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: Comparison with rest-redistribution thallium 201 imaging

Background

This study examined the ability of dynamic ¹²³I-labeled iodophenylpentade-canoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease.

Methods and Results

Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi ¹²³I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34%±11%). The segmental uptake was compared with that of rest-redistribution ²⁰¹Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11±5 vs 10±5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (κ=0.78±0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (κ=0.54±0.04). However, there were more reversible IPPA defects than reversible thallium defects (7±4 vs 3±4 segments/patient; p=0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33%±11% to 39%±12% (p=0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10±4 vs 5±4 segments/patient; p=0.075).

Conclusions

¹²³I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.     

Reverse redistribution in the stress thallium scan--correlation of coronary blood flow and myocardial damage

In order to make clear 'reverse redistribution (RR)' phenomenon in stress thallium scan we investigated 477 consecutive patients who were consisted of 74 cases with PTCA (PTCA group), 86 cases with coronary artery bypass graft (CABG group) and 317 cases without any revascularization (N group). RR was detected in 12 cases out of PTCA group (16%), in 11 cases out of CABG group (13%) and in 10 cases out of N group (3.2%), and the incidence of RR in PTCA or CABG group was higher than that of N group (p less than 0.01). In 33 patients with RR the cases without significant coronary artery stenosis were more than those with stenosis (p less than 0.01) and the cases with myocardial damage were more than those without damage (p less than 0.01). In quantitative analysis washout rate at the RR areas showed relatively high value, but it was not significant compared with normal value (53 +/- 9.0% vs. 49 +/- 1.9%). In conclusion, RR had a tendency to appear in the condition of normal myocardium mingled with scar and of sufficient coronary blood flow. The mechanism of the phenomenon was thought to be that initial uptake of thallium in the partially scarred area was as high as in the normal myocardium, but washout of thallium from its remaining normal myocardium is normal or faster so that the defect appears at the myocardium mingled with scar. Therefore existence of reverse redistribution suspects the myocardium mingled with scar and sufficient coronary blood flow to the remaining normal myocardium.     

The effect of hypoxia on thallium kinetics in cultured chick myocardial cells

To assess the effect of hypoxia on cellular thallium-201 (201Tl) uptake and washout independent of coronary flow, we studied thallium kinetics during normoxia and hypoxia in cultured chick ventricular cells. Monolayers of contracting ventricular cells grown on coverslips were placed in a chamber and perfused to asymptote with media containing 201Tl. Perfusates were equilibrated with 5% CO2-95% air or 5% CO2-95% nitrogen for normoxia and hypoxia, respectively. Washout thallium kinetics were then observed during perfusion with unlabeled media. Twenty paired experiments were performed, randomly alternating the sequence of normoxia and hypoxia. Pharmacokinetics for thallium were determined by computer using standard formulae. Thallium uptake and washout were best described by assuming that intracellular thallium was contained within a single compartment. Cellular thallium uptake, as well as transfer rate constants for thallium uptake and for thallium washout during normoxia and hypoxia, were compared using paired t-tests. During normoxia and hypoxia, respectively, thallium uptake was 22 +/- 7% and 19 +/- 7% of asymptote (p less than 0.01); the compartmental rate constant for uptake by the cell was 0.16 +/- 0.07 min-1 and 0.15 +/- 0.06 min-1 (N.S.); and the transfer rate constant for washout from the cell was 0.26 +/- 0.06 min-1 and 0.23 +/- 0.05 min-1 (p less than 0.01). We conclude that there was a small (14%) decrease in thallium uptake during hypoxia. The rate of thallium uptake and washout was slightly less during hypoxia, although only the rate of washout was significantly less. These data show that cellular accumulation of thallium and the rate of washout of thallium were minimally decreased by hypoxia independent of blood flow.     

Comparison between rest technetium-99m-tetrofosmin and rest-redistribution thallium-201 SPECT in stable patients with healed myocardial infarction.

Resting (99m)Tc-tetrofosmin (TF) uptake was compared with thallium ((201)Tl) rest-redistribution (R-RD) uptake in patients with previous myocardial infarction (MI) and significant coronary artery disease (CAD) to assess the ability of TF to detect viable myocardium. We studied 30 patients (21 males and nine females, mean age 53.9+/-12.5 years) with prior MI and left ventricular dysfunction who had been referred for coronary revascularization procedures. Myocardial single photon emission computed tomography (SPECT) images were obtained 1 h after injection of 750 MBq of TF. Within 1 week of the TF study, R-RD (201)Tl SPECT imaging was performed after injection of 111 MBq of (201)Tl . Quantitative analysis was performed in 21 segments. Viability was defined as the presence of tracer uptake greater than 50% of the peak activity on baseline studies or after reversibility. There was significant correlation between the quantitative regional R-RD (201)Tl activity and the resting TF activity (r=0.88, P<0.001). Quantitative analysis showed that the uptake of the two tracers was comparable in normal segments as well as in segments with fixed (201)Tl defects. In contrast, in segments with reversible (201)Tl defects, TF uptake was significantly greater than resting (201)Tl uptake, but lower than R-RD (201)Tl uptake. There were 52 segments (47% of the severely reduced segments on TF images) that showed no viability with TF, but were viable on the redistribution (201)Tl studies. We conclude that quantitative resting TF SPECT underestimates the presence of viable myocardium compared with R-RD (201)Tl imaging on the basis of using 50% of the peak activity as the viability threshold.     

Quantitative assessment of regional myocardial blood flow with thallium-201 and SPECT

Thallium-201 has been used extensively as a myocardial perfusion agent and to assess myocardial viability. Unlike other ^99mTc-labeled agents such as ^99mTc-sestamibi and ^99mTc-tetrofosmine, the regional concentration of ²⁰¹Tl varies with time, and its kinetics make it a potential candidate for estimating absolute physiologic parameters with kinetic model analysis. This article outlines a strategy for quantitative assessment of regional myocardial blood flow in man using ²⁰¹Tl and dynamic single photon emission computed tomography (SPECT). Quantitatively accurate SPECT images that are proportional to the true radioactivity distribution are prerequisites for model-based kinetic analysis. Our technique for quantitative SPECT includes ordered-subset maximum likelihood-expectation maximization (ML-EM) reconstruction with transmission data-based attenuation correction and transmission-dependent convolution subtraction scatter correction. A three-compartment model was found to reproduce the observed regional time-activity curves well, and dog experiments demonstrated that influx rate constant (K₁) values estimated from the dynamic SPECT data correlated well with absolute myocardial blood flow determined by in vitro microspheres for a physiologically wide range of flows. Several possible strategies for simplifying the study procedures, without compromising accuracy, are also presented, which should make absolute quantitation of regional myocardial blood flow feasible using ²⁰¹Tl and a conventional SPECT camera in a clinical setting. Supported by a research grant for cardiovascular diseases (8C-5, 1996-1998) from the Ministry of Health and Welfare.     

A new method for quantification of pulmonary thallium uptake in myocardial SPECT studies

Quantified pulmonary thallium 201 (Tl) uptake was assessed in 32 normal subjects and 66 patients with suspected coronary artery disease (CAD) by a new method utilizing SPECT acquisition data. In 26 subjects pulmonary uptake was assessed with both SPECT and planar techniques. Pulmonary/myocardial (PM) ratios for the whole right lung (PM1) and for the upper left lung (PM2) were computed and compared with stress test, coronary angiography, radionuclide angiography (ERNA), and quantified Tl single photon emission computed tomography (SPECT) results. Excellent correlation between pulmonary uptake assessed by planar and SPECT technique was disclosed (r = 0.92). The PM ratios (PM1/PM2) sensitivity and specificity in patients with CAD were 88%/92% and 60%/70%, for predicting perfusion abnormalities 90%/87% and 88%/88%, and an inverse correlation to left ventricular ejection fraction (LVEF) was found (r = -0.40/r = -0.37, P less than 0.01). Significant correlations to coronary angiography findings (r = 0.54/r = 0.49, P less than 0.001) and to number of vessel territories with abnormal perfusion (r = 0.70/r = 0.69, P less than 0.001) were seen. Thus, pulmonary Tl uptake can be assessed in SPECT studies. The new method's discriminative ability seems higher than that of the standard planar techniques currently employed. Positive correlations to coronary angiography findings and even stronger ones to perfusion abnormalities were observed.     

A new method for quantification of pulmonary thallium uptake in myocardial SPECT studies

Quantified pulmonary thallium 201 (TI) uptake was assessed in 32 normal subjects and 66 patients with suspected coronary artery disease (CAD) by a new method utilizing SPECT acquisition data. In 26 subjects pulmonary uptake was assessed with both SPECT and planar techniques. Pulmonary/myocardial (PM) ratios for the whole right lung (PM1) and for the upper left lung (PM2) were computed and compared with stress test, coronary angiography, radionuclide angiography (ERNA), and quantified TI single photon emission computed tomography (SPECT) results. Excellent correlation between pulmonary uptake assessed by planar and SPECT technique was disclosed (r=0.92). The PM ratios (PM1/PM2) sensitivity and specificity in patients with CAD were 88%/92% and 60%/70%, for predicting perfusion abnormalities 90%/87% and 88%/88%, and an inverse correlation to left ventricular ejection fraction (LVEF) was found (r=–0.40/r=–0.37,P<0.01). Significant correlations to coronary angiography findings (r=0.54/r=0.49,P<0.001) and to number of vessel territories with abnormal perfusion (r=0.70/r=0.69,P< 0.001) were seen. Thus, pulmonary TI uptake can be assessed in SPECT studies. The new method's discriminative ability seems higher than that of the standard planar techniques currently employed. Positive correlations to coronary angiography findings and even stronger ones to perfusion abnormalities were observed.     

Measurement of myocardial blood flow.

This paper represents a review of the recent literature on techniques to measure myocardial blood flow in man. A short discussion on flow meters in followed by a more detailed discussion of the radionuclide techniques used to measure myocardial blood flow. The radionuclide techniques are discussed in two groups: (1) qualitative measurement of blood flow using static images; and (2) quantitative measurements of blood flow using diffusible substances that actively enter the cell, radioactive labeled particles, and radioactive diffusible gases.     

The effect of coronary revascularization on regional myocardial blood flow as assessed by stress positron emission tomography

Journal of Nuclear Cardiology - We examined whether regional improvement in stress myocardial blood flow (sMBF) following angiography-guided coronary revascularization depends on the existence of a...     

A comparison of rest sestamibi and rest-redistribution thallium single photon emission tomography: Possible implications for myocardial viability detection in infarcted patients

Thirty patients (26 men, 4 women, mean age 61 ± 8 years) who had suffered myocardial infarction 15 ± 6 months previously, were submitted to (1) standard stress-redistribution thallium-201 single photon emission tomography (SPET), (2) rest-redistribution²⁰¹Tl SPET and (3) stress-rest technetium-99m sestamibi SPET. Uptake modifications in relation to exercise-induced defects were evaluated in a total of 390 myocardial segments. Tracer uptake was scored as normal (=0), mildly reduced (=1), apparently reduced (=2), severely reduced (=3) or absent (=4). Comparison of stress studies failed to show any statistical difference (58% segmental abnormalities with sestamibi vs 61% with thallium). Uptake abnormalities (score 1–4) were detected in 55% of the segments wiliest sestamibi, 55% with standard thallium redistribution, 55% with early imaging after thallium injection at rest and 54% with 3-h delayed rest imaging (P = NS). Absence of tracer uptake (score = 4) under resting conditions was recorded in 75 (19%) segments with standard²⁰¹Tl redistribution, 75 (19%) with rest sestamibi, 70 (18%) with rest²⁰¹Tl imaging and 62 (16%) with rst-rdistruion²⁰¹Tl (P<0.05 vs other imaging modalities). Thus, 3-h delayed rest thallium imaging detected reversibility of uptake defects in a significantly higher number of myocardial segments. This finding might have important implications for both tracer and technique selection when myocardial viability is the main clinical issue.     

Comparison of two three-dimensional gated SPECT methods with thallium in patients with large myocardial infarction

BACKGROUND: Two different commercially available gated single photon emission computed tomography (GSPECT) methods were compared in a population of patients with a major myocardial infarction. METHODS: Rest thallium GSPECT was performed with a 90-degree dual-detector camera, 4 hours after injection of thallium-201 (Tl-201; 185 MBq) in 43 patients (mean age, 62+/-12 years) with a large myocardial infarction (mean defect size, 33%+/-16%). End-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were calculated by using QGS (Cedars Sinai) and MultiDim (Sopha Medical Vision International, Buc, France). Images were reconstructed by using a 2.5 zoom and a Butterworth filter (order, 5; cut-off frequency, 0.20). LVEF was calculated in all patients by using equilibrium radionuclide angiocardiography (ERNA). EDV, ESV, and LVEF were also measured by using left ventriculography (LVG). RESULTS: Compared with LVG, QGS underestimated LVEF by means of an underestimation of mean EDV. MultiDim overestimated EDV and ESV. GSPECT EDV and ESV overestimation was demonstrated by means of Bland-Altman analysis to increase with left ventricular volume size (P<.05). The difference between LVG and GSPECT volumes was demonstrated by means of regression analysis to be correlated with infarction size. This effect was particularly important with MultiDim (P<.0001). CONCLUSION: In Tl-201 GSPECT, LVEF and volume measurements will vary according to the type of software used.     

The effect of liniment on blood flow

The effect of liniment applied by massage or stick on skin and calf blood flow was studied in 12 subjects. The blood flow was recorded with laser Doppler flowmetry with skin probe and strain gauge plethysmography. A massage liniment used to lower the friction that is not supposed to have any therapeutic effect (Frisco) was massaged into the right lower leg for 10 min and the registration was performed for 60 min. Then the liniment studied, Tiger Balm was massaged into the left lower leg and another registration was carried out. This procedure was performed a second time and the liniments were applied with a stick and wiped off after 10 min. Liniments with massage resulted in an increase in both skin and calf blood flow. The effect was greater and longer lasting when using Tiger Balm. When the liniments were applied with a stick, a decrease in skin and calf blood flow was noted when using Frisco. Tiger Balm caused a slight increase in the skin blood flow but had no influence on the calf blood flow.