Prognostic evaluation of patients after myocardial infarction: Incremental value of sestamibi single-photon emission computed tomography and echocardiography

Background

This study compares the prognostic value of ^99mTc-labeled methoxyisobutyl isonitrile (MIBI) single-photon emission computed tomographic (SPECT) imaging, echocardiography, and other clinical and laboratory prognostic factors in the long-term risk stratification of patients with stable uncomplicated infarcts.

Methods and Results

Ninety-one consecutive patients affected by a first myocardial infarction without serious complications were enrolled. After at least 3 months from the infarction, they were submitted to stress-rest MIBI SPECT and rest echocardiography. Eighty-six patients completed a follow-up of at least 4 years (range 48 to 72 months; mean 55 months). By univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), the main clinical, electrocardiographic, scintigraphic, and echocardiographic findings were evaluated and correlated statistically with the incidence of ensuing cardiac events. Twenty-five patients had cardiac events during the follow-up (four cardiac deaths, four myocardial infarctions, and 17 cases of unstable angina). At the multivariate analysis, the presence of reversible defects on MIBI SPECT (p=0.008 and relative risk [RR]=7.09), the wall motion score index, and the ejection fraction at echocardiography (respectively, p=0.010, RR=3.67, p=0.036, and RR=3.12), and stress angina (p=0.007 and RR=3.40) were significant and independent prognostic factors.

Conclusions

In our long-term follow-up, MIBI SPECT and echocardiography appeared to be significant and independent prognostic tools in the risk stratification of patients with stable, uncomplicated infarcts, furnishing complementary information. The reversibility of MIBI defects appeared the best indicator for a bad prognosis.     

SPECT myocardial blood flow quantitation toward clinical use: a comparative study with <Superscript>13</Superscript>N-Ammonia PET myocardial blood flow quantitation

Objectives

The aim of this study was to evaluate the accuracy of myocardial blood flow (MBF) quantitation of ^99mTc-Sestamibi (MIBI) single photon emission computed tomography (SPECT) compared with ¹³N-Ammonia (NH3) position emission tomography (PET) on the same cohorts.

Background

Recent advances of SPECT technologies have been applied to develop MBF quantitation as a promising tool to diagnose coronary artery disease (CAD) for areas where PET MBF quantitation is not available. However, whether the SPECT approach can achieve the same level of accuracy as the PET approach for clinical use still needs further investigations.

Methods

Twelve healthy volunteers (HVT) and 16 clinical patients with CAD received both MIBI SPECT and NH3 PET flow scans. Dynamic SPECT images acquired with high temporary resolution were fully corrected for physical factors and processed to quantify K1 using the standard compartmental modeling. Human MIBI tracer extraction fraction (EF) was determined by comparing MIBI K1 and NH3 flow on the HVT group and then used to convert flow values from K1 for all subjects. MIBI and NH3 flow values were systematically compared to validate the SPECT approach.

Results

The human MIBI EF was determined as [1.0-0.816*exp(?0.267/MBF)]. Global and regional MBF and myocardial flow reserve (MFR) of MIBI SPECT and NH3 PET were highly correlated for all subjects (global R²: MBF?=?0.92, MFR?=?0.78; regional R²: MBF?≥?0.88, MFR?≥?0.71). No significant differences for rest flow, stress flow, and MFR between these two approaches were observed (All p?≥?0.088). Bland-Altman plots overall revealed small bias between MIBI SPECT and NH3 PET (global: ΔMBF?=??0.03Lml/min/g, ΔMFR?=?0.07; regional: ΔMBF?=??0.07???0.06 , ΔMFR?= ?0.02 ??0.22).

Conclusions

Quantitation with SPECT technologies can be accurate to measure myocardial blood flow as PET quantitation while comprehensive imaging factors of SPECT to derive the variability between these two approaches were fully addressed and corrected.

     

Evaluation of left ventricular ejection fraction from radial long-axis tomography: A new reconstruction algorithm for ECG-gated technetium-99m sestamibi SPECT

Methods

ECG-gated Tc-99m MIBI SPECT was performed with a temporal resolution of 10 frames per R-R interval. LVEF was calculated on the basis of left ventricular volume estimates at end diastole (ED) and end systole (ES) with using an ellipsoid body model. To validate this method, LVEF’s derived from ECG-gated Tc-99m MIBI SPECT were compared with those from LVG in 11 patients with coronary artery disease.

Results

There was a close linear correlation between LVEF values calculated from Tc-99m MIBI SPECT and those from LVG (r = 0.89, p < 0.001), although the gated SPECT underestimated LVEF compared to LVG. The technique showed excellent reproducibility (intra-observer variability, r = 0.96, p < 0.001; inter-observer variability, r = 0.71, p < 0.005).

Conclusion

The radial long-axis tomography technique gives a good estimate of LVEF, in agreement with estimates based on LVG. ECG-gated Tc-99m MIBI SPECT can, therefore, be applicable to assess myocardial perfusion and ventricular function at the same time.     

Quantitative analysis of technetium 99m 2-methoxyisobutyl isonitrile single-photon emission computed tomography and isosorbide dinitrate infusion in assessment of myocardial viability before and after revascularization

Background

Assessment of viable myocardium in territories of hypoperfused myocardium is important for predicting functional recovery after revascularization. This study was designed to evaluate quantitative analysis of ^99mTc-labeled 2-methoxyisobutyl isonitrile (MIBI) myocardial perfusion imaging combined with isosorbide dinitrate (ISDN) infusion to detect myocardial viability in patients with chronic coronary artery disease before and after revascularization.

Methods and Results

Twenty-seven consecutive patients with previous myocardial infarction and left ventricular dysfunction (left ventricular ejection fraction 35.2%±13.5%) referred for coronary artery bypass (CABG) were studied with ^99mTc-labeled MIBI single-photon emission computed tomograpy at rest and during ISDN infusion before CABG followed by resting imaging after CABG. Quantitative analysis was performed with circumferential profiles. Left ventricular function (global and regional) was assessed by radionuclide ventriculography before and after CABG. Out of 212 abnormal perfusion segments with resting ^99mTc-labeled MIBI SPECT, 99 segments (47%) showed improved uptake of ^99mTc-labeled MIBI during ISDN infusion. The mean ratio of myocardial uptake was 0.58±0.25 (resting 0.53±0.23; p<0.05). After CABG, of 212 segments with hypoperfusion, 108 segments (51%; p>0.05 vs ISDN) showed improved uptake of ^99mTc-labeled MIBI. The mean ratio of myocardial uptake was 0.60±0.26 (resting 0.53±0.23; p<0.05). The concordance between the improvement of post-CABG wall motion and that of pre-CABG ISDN perfusion imaging was 83%, between the improvement of wall motion and perfusion imaging after CABG 94%, and between the improvement of pre-CABG ISDN and post-CABG perfusion imaging 83%, respectively.

Conclusion

ISDN infusion can improve the uptake of ^99mTc-labeled MIBI in hypoperfused myocardium and increase the efficiency of ^99mTc-labeled MIBI in the detection of viable myocardium in patients with previous myocardial infarction and left ventricular dysfunction.     

A qualitative and quantitative assessment of the impact of three processing algorithms with halving of study count statistics in myocardial perfusion imaging: filtered backprojection, maximal likelihood expectation maximisation and ordered subset expectation maximisation with resolution recovery

Introduction

Ordered subset expectation maximisation with depth-dependent resolution recovery (OSEM-RR) is a processing algorithm reported to improve images with halved tracer activity in myocardial perfusion scintigraphy (MPS) compared to filtered backprojection (FBP) using conventional activities. OSEM-RR has not yet been compared with maximal likelihood expectation maximisation (MLEM).

Methods

39 patients undergoing MPS and two anthropomorphic phantoms (one with, one without an inferior wall insert) had full-time (FT) and half-time (HT) SPECT datasets acquired simultaneously and processed by FBP, MLEM and OSEM-RR. Two experienced reporters scored images of all clinical studies (n=234) for conspicuity of a perfusion defect, with results being compared using Wilcoxon paired and Kappa tests. A quantitative assessment based on mean segmental pixel counts taken from numbers automatically displayed over the 20 segments of Cedars Sinai Autoquant QPS image were compared using Pearson??s correlation and Bland Altman analysis.

Results

A small but consistent superior concurrence between FT and HT datasets for OSEM-RR compared to FBP and MLEM was observed for both qualitative and quantitative analyses. OSEM-RR resulted in better definition of the inferior wall defect on the phantom study.

Conclusion

OSEM-RR appears superior to both FBP and MLEM in terms of handling reduced count statistics.     

Evaluation of regional myocardial perfusion in patients with severe left ventricular dysfunction: Comparison of 13N-ammonia PET and 99mTc sestamibi SPECT

Objective

Positron emission tomography (PET) scanning with ¹³N-ammonia and ¹⁸FDG is well established for the detection of myocardial viability. Due to the limited availability of PET facilities, recent studies have combined technetium 99m sestamibi single photon emission computed tomography (SPECT) with ¹⁸FDG PET or ¹⁸FDG SPECT. This approach enables simultaneous assessment of regional myocardial blood flow and metabolism and substantially increases the capacity for viability detection. To validate whether ^99mTc-Sestamibi SPECT can replace ¹³N-ammonia PET, we compared these two modalities in patients with severe left ventricular dysfunction due to coronary artery disease.

Materials and Methods

Thirty-one patients (mean age 57±8 years; mean ejection fraction 27%±8%) with angiographically verified coronary artery disease were included. In random order, ammonia-PET and sestamibi-SPECT scans were performed. In a 20-segment model of the left ventricle, two blinded observers scored a total of 610 segments on a five-point scale. In a subset of 20 patients, 400 segments were scored twice to evaluate the observer variations of the two techniques. Segmental score differences were used to compare the imaging modalities. The impact on viability detection was assessed by combining the two flow tracers with FDG PET.

Results

Segmental comparison of the PET and SPECT studies yielded similar (difference ≤1) results in 74% of segments, reflecting regional concordance values in the lateral, apical, anterior, septal, and inferior myocardial walls of 86%, 82%, 71%, 66%, and 63%, respectively. The differences in the septal and inferior walls were primarily due to overestimation of perfusion defects by sestamibi SPECT, which yielded a higher proportion of mismatch patterns in those regions. The overall observer variations of the PET and SPECT studies were 7.5% and 5.8%.

Conclusion

Myocardial perfusion imaging with ¹³N-ammonia PET and ^99mTc-sestamibi SPECT yielded similar results in patients with severe left ventricular dysfunction, except for the septal and inferior regions. In these regions, SPECT tended to overestimate perfusion defects. Hence, attenuation correction should be considered when combining FDG PET and sestamibi SPECT for diagnosing myocardial viability to avoid overestimation of mismatch patterns in those regions.     

Fractional flow reserve and myocardial viability as assessed by SPECT perfusion scintigraphy in patients with prior myocardial infarction

Background

In patients with previous myocardial infarction (MI), assessment of myocardial viability and physiological significance of coronary artery stenoses are essential for appropriate guidance of revascularization. The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and myocardial viability as assessed by gated SPECT MIBI perfusion scintigraphy in patients with previous MI undergoing elective PCI.

Methods

The study population consisted of 26 patients (mean age 55 ± 7 years; 21 male) with a previous MI and a significant coronary stenosis in a single infarct-related coronary vessel for which PCI was being performed. In all patients, FFR was evaluated before and immediately after PCI. SPECT imaging was done before and 3 ± 1 months after PCI. A region representing the MI was considered viable if MIBI uptake was ≥55% of the normal region. Improvement in perfusion after revascularization was considered achieved if perfusion abnormalities decreased by 5% or more and there was a decrease in segmental score of ≥1 in three segments in PCI-related vascular territory.

Results

Extent of perfusion abnormalities decreased from 32 ± 16% to 27 ± 19% after PCI (P < .001). In patients with myocardial viability in comparison to patients with no viability, there was significant difference in FFR before PCI (.57 ± .14 vs .76 ± .12, P = .002), despite almost the same values of diameter stenosis of infarct-related artery (63 ± 8% vs 64 ± 3%, respectively, P = .572). In addition, FFR prior to PCI was related to improvement in perfusion abnormalities after revascularization (P = .047), as well as with peak activity of creatine-kinase measured during previous MI (r = .56, P = .005).

Conclusion

Lower values of FFR before angioplasty are associated with myocardial viability and functional improvement as assessed by SPECT perfusion scintigraphy.     

A randomized study of the effect of carbonated water prior to myocardial SPECT

Objective

In myocardial perfusion single-photon emission computed tomography (SPECT), abdominal activity often interferes with the evaluation of perfusion in the inferior wall, especially after pharmacological stress. In this randomized study, we examined the effect of carbonated water intake versus still water intake on the quality of images obtained during myocardial perfusion images (MPI) studies.

Methods

A total of 467 MIBI studies were randomized into a carbonated water group and a water group. The presence of intestinal activity adjacent to the inferior wall was evaluated by two observers. Furthermore, a semi-quantitative analysis was performed in the adenosine subgroup, using a count ratio of the inferior myocardial wall and adjacent abdominal activity.

Results

The need for repeated SPECT in the adenosine studies was 5.3 % in the carbonated water group versus 19.4 % in the still water group (p = 0.019). The inferior wall-to-abdomen count ratio was significantly higher in the carbonated water group compared to the still water group (2.11 ± 1.00 vs. 1.72 ± 0.73, p < 0.001). The effect of carbonated water during rest and after exercise was not significant.

Conclusions

This randomized study showed that carbonated water significantly reduced the interference of extra-cardiac activity in adenosine SPECT MPI.     

Quantitative comparison of single-isotope and dual-isotope stress-rest single-photon emission computed tomographic imaging for reversibility of defects

Background

Dual-isotope rest/stress single-photon emission computed tomographic (SPECT) imaging is a time-saving imaging protocol. However, the stress radiotracer, technetium 99m-labeled sestamibi, and the rest radiotracer, thallium 201, have different physical properties and myocardial kinetics. In patients with abnormal resting myocardial perfusion, these differences may affect quantification of rest defect size and defect reversibility. The purpose of the study was to compare myocardial perfusion defect reversibility quantitatively by single-isotope (rest/stress sestamibi) and dual-isotope (rest thallium/stress sestamibi) SPECT.

Methods and Results

Thirty patients with prior myocardial infarction underwent rest/stress sestamibi SPECT imaging and rest thallium SPECT imaging. Defects were quantified according to circumferential count profiles with a normal sestamibi database. The images of a subgroup of 21 patients were processed with radiotracer-specific normal databases. Defect size and defect reversibility were compared quantitatively for single-isotope and dual-isotope SPECT. Rest sestamibi defect size was significantly larger than rest thallium defect size (19±15 vs 14±16; p=0.007). Defect reversibility was larger with thallium than with sestamibi (10±9 vs 6±6; p=0.002). With radiotracer-specific normal databases, mean rest sestamibi and thallium defect sizes in 21 patients were not different (23±19 vs 21±17; difference not significant). With radiotracer-specific normal databases, mean defect reversibility was not different with either sestamibi or thallium (6±6 vs 8±9; difference not significant), although correlation among individual patients was only fair (r ²=0.48).

Conclusion

In patients with prior myocardial infarction, stress-induced defect reversibility is quantitatively larger with dual-isotope imaging than with single-isotope imaging. Quantitative processing of dual-isotope images requires radiotracer-specific normal databases. Because of different characteristics of sestamibi and thallium, assessment of defect reversibility on dual-isotope images should be made with caution. Only relatively large defect reversibility can be assumed to represent true stress-induced myocardial ischemia.     

Experimental verification of technetium 99m-labeled teboroxime kinetic parameters the the myocardium with dynamic single-photon emission computed tomography: Reproducibility,correlation to flow,and susceptibility to extravascular contamination

Background

This research was undertaken to investigate the ability of dynamic singlephoton emission computed tomographic (SPECT) imaging to quantify myocardial perfusion in vivo with ^99mTc-labeled teboroxime. The objectives of this experiment were (1) to determine the reproducibility of the model parameters f_v, K₁, and k₂ (volume fraction of blood in the tissue and wash-in and wash-out of ^99mTc-labeled teboroxime correlate, with an independent measure of myocardial blood perfusion, and (3) to determine the amount of extravascular activity in the arterial blood time-activity curve generated from the dynamic SPECT images

Methods and Results

Twenty-nine studies were performed on 10 dogs. The dogs were divided into three groups: reproducibility, occlusion, and vasodilation. In the reproducibility protocol, the physiology was kept as constant as possible. In the occlusion and vasodilation protocols, myocardial perfusion was either decreased by occluding the left anterior descending coronary artery or increased by continuous adenosine infusion, respectively. In all studies an independent measure of myocardial perfusion was obtained with either radiolabeled microspheres or a flow probe, and the activity of ^99mTc-labeled teboroxime in the arterial blood was monitored continuously. The root-mean-square errors calculated with data from the reproducibility group were 19.9%±8.5%, 14.0%±5.7%, and 14.5%±5.0% for f_v, K₁, and k₂, respectively. The occlusion group data showed that K₁ demonstrated a higher correlation (r=0.887) with microsphere myocardial perfusion than did k₂ (r=0.689). The results from the vasodilation group showed that K₁ demonstrated a stronger relationship to myocardial blood flow (MBF) measured with a flow probe (K₁=0.237+0.629 MBF [r=0.935] and k₂=0.177+0.263 MBF [r=0.904]). Finally, the amount of extravascular activity in the blood time-activity curve generated from the dynamic SPECT images was determined to be 45.5%±16.4%.

Conclusions

The wash-in parameter K₁ correlates with myocardial perfusion in dogs; therefore dynamic SPECT imaging of ^99mTc-labeled teboroxime has the potential for measuring regional myocardial perfusion in patients.     

99m Tc－M IBI心肌灌注断层显像对实验性心肌梗塞的评价

目的：评价９９ｍ锝一甲氧基异丁基异腈（９９ｍＴｃ－ＭＩＢＩ）ＳＰＥＣＴ显像对心肌梗塞范围的估测及硝酸甘油介入后对存活心肌检测的价值。材料和方法：７条杂种犬通过结扎冠状动脉造成心肌梗塞模型，分别在实验第一天及实验第七天行９９ｍＴｃ－ＭＩＢＩＳＰＥＣＴ静息显像及硝酸甘油介入９９ｍＴｃ－ＭＩＢＩ心肌显像。用圆周剖面法定量分析短轴６个断面心肌缺损面积大小。结果：末次显像缺损面积与病理梗塞面积有良好相关性（ｒ＝０．８６和ｒ＝０．８７分别为硝酸甘油介入前后心肌缺损面积与病理梗塞面积的相关系数），末次显像与首次显像相比缺损面积明显缩小（Ｐ＜０．０５），硝酸甘油介入后心肌显像的平均缺损面积在首次和末次显像均明显减小（Ｐ＜０．０１），且缺损区的平均计数在硝酸甘油介入后均明显增高（Ｐ＜０．０５）。结论：９９ｍＴｃ－ＭＩＢＩ心肌断层显像是了解急性心肌梗塞范围的较好手段及硝酸甘油介入９９ｍＴｃ－ＭＩＢＩＳＰＥＣＴ显像可以提高检测低灌注区残存的存活心肌。     

Estimation of myocardial blood flow for longitudinal studies with 13N-labeled ammonia and positron emission tomography

Background

Although several modeling strategies have been developed and validated for quantification of myocardial blood flow (MBF) from ¹³N-labeled ammonia positron emission tomographic data, a comparison of noise characteristics of the various techniques in serial studies is lacking.

Methods and Results

Dynamic ¹³N-labeled ammonia positron emission tomographic imaging was performed at baseline and after pharmacologic stress in (1) single studies of four dogs with concomitant measurement of microsphere blood flow and (2) initial and follow-up studies of eight normal volunteers. Data were obtained from short-axis images for the blood pool and myocardial regions corresponding to the three arterial vascular territories. Indexes of MBF were obtained by four distinct techniques: (1) University of California, Los Angeles, twocompartment model, (2) Michigan two-compartment model, and (3) a one-compartment model with variable blood volume term. Coronary flow reserve (CFR) was measured as the ratio of stress/rest MBF. The estimated standard deviation of the measurement error for the relative change between studies of rest and stress MBF and CFR was determined for each technique. Estimates of MBF from all techniques showed good correlation with microsphere blood flow (r=0.95 to 0.96) in canine myocardium. In human studies, similar mean estimates of MBF were found with all techniques. Techniques 1 and 3 showed the smallest interstudy variability in MBF and CFR. The estimated standard deviations for these techniques were approximately 20%, 30%, and 27% for rest MBF, stress MBF, and CFR, respectively.

Conclusion

Noninvasive quantification of MBF and CFR from dynamic ¹³N-labeled ammonia positron emission tomography is most reproducible with technique 1 or 3. The ability to account for differences in myocardial partial volume gives preference to technique 3. However, substantial interstudy variability in regional MBF remains, suggesting the importance of procedural factors or real temporal fluctuations in MBF.     

Mechanism for abnormal thallium-201 myocardial scintigraphy in patients with left bundle branch block in the absence of angiographic coronary artery disease

Patients with left bundle branch block (LBBB) often show abnormal images on exercise thallium (T1)-201 scintigraphy without evidence of significant coronary stenosis. We investigated the mechanism for this phenomenon. Six patients with LBBB and without significant coronary stenosis underwent T1-201 SPECT, ECG-gated SPECT imaging with Tc-99m-methoxyisobutyl-isonitrile (MIBI), and atrial pacing stress test. The % count amplitude in Tc-99m-MIBI images was calculated as [(maximal counts) - (minimal counts)]/(minimal counts) x 100. Though all patients had a low count in the septal and inferior wall in T1-201 SPECT images, there was no ischemic production of lactate during an atrial pacing stress test. Nevertheless, gated SPECT images showed attenuated septal activity during systole. In patients with LBBB, the ratios of % count amplitude at the septum to that at the lateral wall at rest (0.47 +/- 0.05, mean +/- SE) were significantly less than the controls (n = 5, 0.83 +/- 0.12, p = 0.014). In conclusion, these results suggest that abnormal T1-201 SPECT images of the septum in patients with LBBB are partially caused by impaired septal wall thickening during systole. Such an abnormal wall motion may reduce blood flow demands to the septum, resulting in reduction of coronary blood flow with little ischemia.     

Evaluation of simultaneous 201Tl/99mTc dual-isotope cardiac SPECT imaging with model-based crosstalk compensation using canine studies

Background

Simultaneous ²⁰¹Tl/^99mTc-sestamibi dual-isotope myocardial perfusion SPECT imaging can reduce imaging time and produce perfectly registered rest/stress images. However, crosstalk from ^99mTc into ²⁰¹Tl images can significantly reduce ²⁰¹Tl image quality. We have developed a model-based compensation (MBC) method to compensate for this crosstalk. The method has previously been validated with phantom and simulation studies. In this study, we evaluated the MBC method using a canine model.

Methods

Left anterior descending or left circumflex coronary artery stenoses were created in 50 adult mongrel dogs weighing 20-30 kg. The dogs were injected with 111 MBq (3 mCi) of ²⁰¹Tl at rest, and a SPECT study acquired. Stress was induced by administering adenosine to the dog, followed by injection of 740 MBq (20 mCi) of ^99mTc-sestamibi at peak stress. A second SPECT study was performed with data acquired in both ²⁰¹Tl and ^99mTc energy windows to provide simultaneous dual-isotope projection data. The images were reconstructed using the ordered-subsets expectation-maximization reconstruction algorithm with compensation for attenuation, scatter, and detector response. For simultaneously acquired ²⁰¹Tl data, we also applied the MBC method to compensate for crosstalk contamination from ^99mTc.

Results

Without compensation, ^99mTc crosstalk increased the estimated ²⁰¹Tl activity concentration in the rest images and reduced defect contrast. After MBC, the ²⁰¹Tl images were in good agreement with the registered single-isotope images and ex vivo count data. The ischemic (IS) to non-ischemic (NIS) region ²⁰¹Tl activity concentration ratios were computed for single-isotope and dual-isotope studies. The correlation with ex vivo IS-NIS ratios was 0.815 after MBC, compared to the 0.495 from data without compensation. In addition, the regression line for the IS-NIS ratios with MBC was almost parallel to the line of identity with a slope of 0.93, compared to a slope of 0.45 without compensation.

Conclusions

These results demonstrate that model-based crosstalk compensation can provide substantial reduction of crosstalk effects in simultaneously acquired myocardial perfusion SPECT images in living biological systems.     

Noninvasive quantification of coronary endothelial function by SPECT imaging in children with a history of Kawasaki disease

Purpose

The feasibility of coronary function estimation by single photon emission computed tomography (SPECT) has been recently demonstrated. The aim of this study was to apply SPECT imaging in patients with previous Kawasaki disease (KD) to assess the coronary functional status at long-term follow-up of the acute phase of the disease.

Methods

Sixteen children with a history of KD underwent ^99mTc-sestamibi imaging at rest and during the cold pressor test (CPT). Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Coronary endothelial function was expressed as the ratio of the CPT to rest MBF.

Results

Six KD patients without coronary artery lesions served as controls and ten with coronary artery aneurysms during the acute phase of the disease were separated into two groups: group 1 (n?=?4) with regressed and group 2 (n?=?6) with persistent aneurysm at follow-up. The estimated coronary endothelial function was higher in controls compared to patients with coronary artery aneurysms (2.5?±?0.3 vs 1.7?±?0.7, p?<?0.05). A significant difference in coronary endothelial function among groups was found (F?=?5.21, p?<?0.02). Coronary endothelial function was higher in patients of group 1 than in those of group 2 (1.9?±?0.6 vs 1.4?±?0.7, p?<?0.02).

Conclusion

SPECT may be applied as a noninvasive method for assessing coronary vascular function in children with a history of KD, demonstrating an impaired response to the CPT, an endothelial-dependent vasodilator stimulus. These findings reinforce the concept that coronary endothelial dysfunction may represent a long-term sequela of KD.     

Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver: technical aspects studied in a large animal model

Objective

To assess the accuracy of a scout dose of holmium-166 poly(L-lactic acid) microspheres (¹⁶⁶Ho-PLLA-MS) in predicting the distribution of a treatment dose of ¹⁶⁶Ho-PLLA-MS, using single photon emission tomography (SPECT).

Methods

A scout dose (60 mg) was injected into the hepatic artery of five pigs and SPECT acquired. Subsequently, a ‘treatment dose’ was administered (540 mg) and SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) of the total dose performed. The two SPECT images of each animal were compared. To validate quantitative SPECT an ex vivo liver was instilled with ¹⁶⁶Ho-PLLA-MS and SPECT acquired. The liver was cut into slices and planar images were acquired, which were registered to the SPECT image.

Results

Qualitatively, the scout dose and total dose images were similar, except in one animal because of catheter displacement. Quantitative analysis, feasible in two animals, tended to confirm this similarity (r ²?=?0.34); in the other animal the relation was significantly better (r ²?=?0.66). The relation between the SPECT and planar images acquired from the ex vivo liver was strong (r ²?=?0.90).

Conclusion

In the porcine model a scout dose of ¹⁶⁶Ho-PLLA-MS can accurately predict the biodistribution of a treatment dose. Quantitative ¹⁶⁶Ho SPECT was validated for clinical application.     

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

Objectives

Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of <1?mm, but few studies have focused on the evaluation of intratumoral heterogeneity. We investigated the optimal conditions related to high resolution imaging of heterogeneous tumor interiors using a small animal SPECT scanner.

Methods

The conditions related to SPECT/CT visualization of heterogeneous tumor interiors were investigated using phantoms with ¹¹¹In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice.

Results

Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30?min, better image quality was obtained with pinhole apertures diameter of 1.4?mm than of 1.0?mm. The obtained best spatial resolution was 1.3?mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0?mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2?C0.5?MBq/mL. Liposomes containing ¹¹¹In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous ¹¹¹In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2?MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes.

Conclusion

Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.     

Acetazolamide induced myocardial ischemia in patients with severe coronary artery disease

Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause myocardial ischemia in patients with coronary artery disease. To evaluate the risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc-99m HMPAO brain SPECT in patients with severe coronary artery disease.Methods: Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1) For qualitative analysis, SPECT images were divided into 13 segments to calculate the total defect scores. (2) Six ROIs were placed on the slices in the myocardial SPECT short-axis images and the regional uptake ratio was obtained as the ratio of the mean counts in the myocardium to the maximal count in the slice. The total defect score and regional uptake ratio of ACZ-myo SPECT were compared with those of early and delayed dipyridamole T1-201 myocardial SPECT (DP-T1 SPECT) images.Results: (1) In the 21 coronary artery territories with coronary stenosis ≧ 75%, the total defect score in ACZ-myo SPECT, early and delayed DP-T1 SPECT images were 3.52 ± 4.14*, 4.19 ± 4.65* and 2.25 ± 3.34, respectively (*: p < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary stenosis ≧75%, the regional uptake ratio of ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 0.670 ± 0.166**, 0.677 ± 0.194**, 0.721 ± 0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T changes or chest pain.Conclusion: As ACZ has the potential to cause myocardial ischemia, ACZ-augmented brain SPECT should be performed with caution in patients with severe coronary artery disease associated with cerebrovascular disease.     

Comparing slow- versus high-speed CT for attenuation correction of cardiac SPECT perfusion studies

Background

For SPECT, CT-based attenuation correction is preferred. Many different models of CT are available with SPECT/CT systems. Our study compares clinical cardiac SPECT images that were attenuation corrected using slow-rotation CT and high-speed CT transmission scans.

Methods

We evaluated 59 rest/stress perfusion studies from patients who had undergone both a SPECT/CT with a slow-rotation CT and a perfusion study on a PET/CT camera equipped with a high-speed CT scanner. Each SPECT study was reconstructed with transmission maps from both CT scans and the relative perfusion was assessed using semi-automated software. The summed stress/rest/and difference scores (SSS/SRS/SDS) were compared as well as the test classification.

Results

The intraclass correlation coefficients for the SSS, SRS, and SDS were 0.97, 0.96, and 0.80 respectively. There were no significant differences in the mean SSS, SRS, or SDS with the use of either CT for attenuation corrections. Classifying SSS?>?3 as abnormal, there was 97% concordance (???=?0.88). Classifying SDS?>?1 as abnormal, there was 95% concordance (???=?0.54). A McNemar??s test showed no significant differences.

Conclusions

There were no significant differences between using a high-speed CT and using a slow-rotation CT for attenuation correction of SPECT myocardial perfusion images.     

Detection of misery perfusion in the cerebral hemisphere with chronic unilateral major cerebral artery steno-occlusive disease using crossed cerebellar hypoperfusion: comparison of brain SPECT and PET imaging

Purpose

In patients with unilateral internal carotid or middle cerebral artery (ICA or MCA) occlusive disease, the degree of crossed cerebellar hypoperfusion that is evident within a few months after the onset of stroke may reflect cerebral metabolic rate of oxygen in the affected cerebral hemisphere relative to that in the contralateral cerebral hemisphere. The aim of the present study was to determine whether the ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on positron emission tomography (PET) and single photon emission computed tomography (SPECT) correlates with oxygen extraction fraction (OEF) asymmetry in the cerebral hemisphere on PET in patients with chronic unilateral ICA or MCA occlusive disease and whether this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere in such patients.

Methods

Brain blood flow and OEF were assessed using ¹⁵O-PET and N-isopropyl-p-[¹²³I]iodoamphetamine (¹²³I-IMP) SPECT, respectively. All images were anatomically standardized using SPM2. A region of interest (ROI) was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a three-dimensional stereotaxic ROI template, and affected-to-contralateral asymmetry in the MCA territory or contralateral-to-affected asymmetry in the cerebellar hemisphere was calculated. Sixty-three patients with reduced blood flow in the affected cerebral hemisphere on ¹²³I-IMP SPECT were enrolled in this study.

Results

A significant correlation was observed between MCA ROI asymmetry of PET OEF and the ratio of cerebellar hemisphere asymmetry of blood flow to MCA ROI asymmetry of blood flow on PET (r?=?0.381, p?=?0.0019) or SPECT (r?=?0.459, p?=?0.0001). The correlation coefficient was higher when reanalyzed in a subgroup of 43 patients undergoing a PET study within 3 months after the last ischemic event (r?=?0.541, p?=?0.0001 for PET; r?=?0.609, p?<?0.0001 for SPECT). The blood flow ratio on brain perfusion SPECT in all patients provided 100 % sensitivity and 58 % specificity, with 43 % positive and 100 % negative predictive values for detecting abnormally elevated MCA ROI asymmetry of PET OEF.

Conclusion

The ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on PET and SPECT correlates with PET OEF asymmetry in the cerebral hemisphere, and this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere.