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First introduced in 1976, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has become an indispensable tool for diagnosis and prognostic evaluation of tumors, heart disease, as well as other conditions, including inflammation and infection. Because 18F-FDG can accurately reflect the glucose metabolism level of organs and tissues, it is known as a "century molecule" and is currently the main agent for PET imaging. The degree of 18F-FDG uptake by cells is related to both the rate of glucose metabolism and glucose transporter expression. These, in turn, are strongly influenced by hypoxia, in which cells meet their energy needs through glycolysis, and 18F-FDG uptake increased due to hypoxia. 18F-FDG uptake is a complex process, and hypoxia may be one of the fundamental driving forces. The correct interpretation of 18F-FDG uptake in PET imaging can help clinics make treatment decisions more accurately and effectively. In this article, we review the application of 18F-FDG PET in tumors, myocardium, and inflammation. We discuss the relationship between 18F-FDG uptake and hypoxia, the possible mechanism of 18F-FDG uptake caused by hypoxia, and the associated clinical implications.

Conventional single photon emission computed tomography (SPECT) relies on mechanical collimation whose resolution and sensitivity are interdependent, the best performance a SPECT system can attain is only a compromise of these two equally desired properties. To simultaneously achieve high resolution and sensitivity, we propose to use sensitive detectors constructed in a m ulti-l a yer in t e r spaced mosa ic d e tector s (MATRICES) architecture to accomplish part of the collimation needed. We name this new approach self-collimation. We evaluate three self-collimating SPECT systems and report their imaging performance: 1) A simulated human brain SPECT achieves 3.88% sensitivity, it clearly resolves 0.5-mm and 1.0-mm hot-rod patterns at noise-free and realistic count-levels, respectively; 2) a simulated mouse SPECT achieves 1.25% sensitivity, it clearly resolves 50- $\mu \text{m}$ and 100- $\mu \text{m}$ hot-rod patterns at noise-free and realistic count-levels, respectively; 3) a SPECT prototype achieves 0.14% sensitivity and clearly separates 0.3-mm-diameter point sources of which the center-to-center neighbor distance is also 0.3 mm. Simulated contrast phantom studies show excellent resolution and signal-to-noise performance. The unprecedented system performance demonstrated by these 3 SPECT scanners is a clear manifestation of the superiority of the self-collimating approach over conventional mechanical collimation. It represents a potential paradigm shift in SPECT technology development.

To assess the benefits of coronary collateral circulation on myocardial perfusion, viability and function in patients with total occlusion of a single coronary artery using the 99mTc-sestamibi SPECT and 18F-fluorodeoxyglucose PET. 164 Consecutive patients were included who underwent coronary angiography results exhibited total occlusion of a single coronary artery and received 99mTc-MIBI SPECT and 18F-FDG PET within 90 days of angiography. Myocardial perfusion and viability in patients with collateral circulation and those without it were compared. Long-term follow-up was performed through a review of patient clinical records. Collateral circulation was present in 56 patients (34%) and absent in 108 patients (66%). The total perfusion defect size in patients with collateral circulation decreased when compared to those without (30% ± 13% to 35% ± 14%, P < .05). The myocardial viability was 22% ± 12% in patients with collateral circulation, and 12% ± 9% in those without (P < .001). The left ventricular ejection fraction was higher, and the end-diastolic and end-systolic left ventricular volumes were lower in patients with collateral circulation (39% ± 11%, 138 ± 66, 89 ± 57) compared to patients without collateral circulation (31% ± 9%, 177 ± 55, 125 ± 48, all P < .001, respectively). Multi-factor logistic regression identified that concerning the variables of sex, age, viable myocardium, collateral circulation, treatment type and others, only treatment type was significantly associated with therapeutic effects (OR 3.872, 95% CI 1.915-7.830, P < .001). Collateral circulation can preserve resting myocardial blood perfusion and myocardial viability, and help maintain the function of the left ventricular myocardium. The appropriate treatment strategy will have a substantial impact on the therapeutic outcome.

BACKGROUND: Establishing appropriate reference value limits of left ventricular (LV) functional parameters is fundamental for the assessment of cardiac function. At present, there are no reports aimed at establishing reference limits using gated myocardial perfusion imaging (MPI) in mainland China. METHODS: A total of 175 consecutive patients who were defined as low-risk coronary artery disease patients underwent stress Technetium-99m sestamibi ((99m)Tc-MIBI)-gated myocardial perfusion single-photon emission computed tomography (SPECT) imaging. The LV ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) were obtained by 3 quantitative algorithms: quantitative-gated SPECT, emory cardiac toolbox, and 4-dimensional model SPECT, respectively. The threshold values were obtained using Gaussian distribution or percentiles. The influence of gender, age, and weight on cardiac functional parameters was analyzed by multiple regressions for linear models. RESULTS: For males, the lower reference limits of EF were 52%, 63%, and 58%, respectively; and the upper limits of EDV/ESV were 106/45, 152/55, and 135/55 mL, respectively. For females, the lower reference limits of EF were 58%, 66%, and 65%, respectively; and the upper limits of EDV/ESV were 73/27, 105/31, and 88/29 mL, respectively. Compared to females, males had greater cardiac volume values and lower mean EF values. Bland-Altman plots revealed that the cardiac function parameters calculated by the three quantitative algorithms were in high agreement. CONCLUSIONS: In this study, the reference limits of cardiac parameters calculated by the 3 methods based on single-center data in China were preliminarily established. The threshold values determined by three quantitative algorithms were not interchangeable but were highly correlated.

This study aimed to compare the accuracy of gated-SPECT (GSPECT) and gated-PET (GPET) in the assessment of left ventricular (LV) end-diastolic volumes (EDVs), end-systolic volumes (ESVs) and LV ejection fractions (LVEFs) among patients with prior myocardial infarction (MI). One hundred and sixty-eight consecutive patients with MI who underwent GSPECT and GPET were included. Of them, 76 patients underwent CMR in addition to the two imaging modalities. The measurements of LV volumes and LVEF were performed using Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB), and 4D-MSPECT (4DM). The correlation between GPET, GSPECT, and CMR were excellent for LV EDV (r = 0.855 to 0.914), ESV (r = 0.852 to 0.949), and LVEF (r = 0.618 to 0.820), as calculated from QGS, ECTB, and 4DM. In addition, subgroup analysis revealed that EDV, ESV, and LVEF measured by GPET were accurate in patients with different extents of total perfusion defect (TPD), viable myocardium, and perfusion/metabolic mismatch. Furthermore, multivariate regression analysis identified that mismatch score was associated with the difference in EDV (P

PURPOSE 18F-FDG PET myocardial metabolic imaging is used to estimate myocardial viability. However, poor image quality can affect the accurate quantification of viable myocardium. We assessed the feasibility of a rescue protocol that reinjected low-dose 18F-FDG with simultaneous 1 to 2 U of insulin injection and oral administration of 10 g of glucose to improve the image quality of 18F-FDG PET myocardial metabolic imaging. PATIENTS AND METHODS Fifty-one consecutive patients with poor quality to uninterpretable 18F-FDG PET/CT myocardial metabolic images received the rescue protocol immediately after the initial image acquisition. The postrescue image acquisition was performed 1 hour later. The rescue image quality was compared with the initial image. The qualitative visual estimation of the images was graded as follows: grade 0, homogeneous, minimal uptake; grade 1, predominantly minimal or mild uptake; grade 2, moderate uptake; and grade 3, good uptake. The myocardium-to-blood pool activity ratio (M/B) was measured to assess the image quality quantitatively. RESULTS The grades of 0 to 3 were observed in 24 (47%), 27 (53%), 0 (0%), and 0 (0%) patients, respectively, for the initial imaging, and in 0 (0%), 3 (5.9%), 4 (7.8%), and 44 (86.3%) patients for the rescue imaging (P < 0.001). The rescue M/B was significantly higher than the initial M/B (3.4 ± 1.4 vs 1.6 ± 0.6, respectively; P < 0.001). CONCLUSIONS The rescue protocol successfully and rapidly improved the quality of myocardial 18F-FDG metabolic imaging.

Background: It has been confirmed that the α7-nicotinic acetylcholine receptor (α7nAChR) is an important target for identifying vulnerable atherosclerotic plaques. Previously, we successfully designed and synthesized a series of 18F-labeled PET molecular probes targeting α7nAChR, which are mainly used in the diagnosis of Alzheimer's disease. Based on the characteristics of α7nAChR in blood vessels, we have firstly screened for a suitable novel 18F-labeled PET molecular probe ([18F]YLF-DW), with high selectivity for α7nAChR over α4β2nAChR and a good effect for the imaging of atherosclerotic animal models, to effectively identify vulnerable atherosclerotic plaques at an early stage. Meanwhile, we compared it with the “gold standard” pathological examination of atherosclerosis, to verify the reliability of [18F]YLF-DW in early diagnosis of atherosclerosis.Methods: The vulnerable atherosclerotic plaques model of ApoE-/-mice were successfully established. Then based on the methods of 3D-QSAR and molecular docking, we designed oxazolo[4,5-b] pyridines and fluorenone compounds, which are targeted at α7nAChR. Through further screening, a novel alpha7 nicotinic acetylcholine receptor radioligand ([18F]YLF-DW) was synthesized and automatically 18F-labeled using a Stynthra RNplus module. Subsequently, we employed [18F]YLF-DW for the targeting of α7nAChR in atherosclerotic plaques and control group, using a micro-PET/CT respectively. After imaging, the mice were sacrificed by air embolism and the carotid arteries taken out for making circular sections. The paraffin embedded specimens were sectioned with 5 μm thickness and stained with oil red. After staining, immunohistochemistry experiment was carried out to verify the effect of micro-PET/CT imaging.Results: The micro-PET/CT imaging successfully identified the vulnerable atherosclerotic plaques in the carotid arteries of ApoE-/-mice; whereas, no signal was observed in normal control mice. In addition, compared with the traditional imaging agent [18F]FDG, [18F]YLF-DW had a significant effect on the early plaques imaging of carotid atherosclerosis. The results of oil red staining and immunohistochemistry also showed early formations of carotid plaques in ApoE-/-mice and provided pathological bases for the evaluation of imaging effect.Conclusion: We innovated to apply the novel molecular probe ([18F]YLF-DW) to the identification of vulnerable atherosclerotic plaques in carotid arteries, to detect atherosclerosis early inflammatory response and provide powerful input for the early diagnosis of atherosclerotic lesions, which may play an early warning role in cardiovascular acute events.

Aims Patients with unexplainable giant T-wave inversion in the precordial leads and apical wall thickness

Comparing with small animals, large animal models are more suitable for a variety of translational research. For large animal, existing SPECT systems are less optimal, due to limited FOV, spatial resolution and/or sensitivity. With the development of pharmacokinetics research, dynamic imaging capability becomes more and more important. Dynamic imaging requires high sensitivity and stationary structure, which conventional SPECT systems often do not possess. In this work, we aim at developing a large-animal dynamic SPECT/CT system with multi-pinhole collimators. The large animal SPECT consists of six stationary clinical SPECT detectors arranged in hexagon (radius: 470mm). The large FOV collimator consists of six 2×4 pinhole groups whose position and opening angle are designed to cover whole FOV (Φ200mm×300mm). The theoretical calculation and simulation are performed to evaluate performance of the collimator. For large FOV collimator, spatial resolution and sensitivity over pinhole diameter curves are calculated and pinhole diameter is determined to 2.7mm. In the center of FOV, spatial resolution is 5.9 mm and sensitivity is 0.0393%. In the hotrod phantom (3.0~5.5mm) simulation, 3.0mm hotrod can be clearly distinguished. The proposed system has capability to realize large animal dynamic imaging. The multi-pinhole collimator was designed and performance were evaluated by calculation and simulation. The prototype system with two detectors will be accomplished to perform preliminary experiment.

The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99mTc-sestamibi and 18F–FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

A 57-year-old man with a history of hypertrophic cardiomyopathy diagnosed by echocardiography experienced atypical chest pain and dyspnea for 6 months. A rest Tc-MIBI myocardial SPECT imaging and a F-FDG myocardial PET/CT imaging were performed, which showed multiple matched myocardial perfusion/metabolism defects in the left ventricle, indicating scar tissue. Surprisingly, subsequent contrast coronary angiography revealed no significant coronary artery stenosis.

Myocardial perfusion imaging (MPI), using radiotracers, has been in routine clinical use for over 40 years. This modality is used for the detection of coronary artery disease (CAD), risk stratification, optimizing therapy, and follow-up of patients with CAD. Molecular cardiovascular imaging using targeted radiotracers provides a unique opportunity for imaging biochemical and metabolic processes, and cell membrane transporter and receptor functions at a cellular and molecular level in experimental animal models as well as in humans. Cardiac imaging using radiolabeled free fatty acid analogues and glucose analogues enable us to image myocardial ischemia directly as an alternative to stress-rest MPI. Direct ischemia imaging techniques can avoid and overcome some of the limitations of standard stress-rest MPI. This article describes recent studies using (18) F-fluorodeoxyglucose ((18) FDG) for myocardial ischemia imaging.

Myocardial perfusion imaging is the mainstay of nuclear cardiovascular imaging. It has been in extensive clinical use for well over 35 years for diagnosing, risk-stratification, and long-term follow-up of patients with suspected or known coronary artery disease. A unique strength of nuclear imaging is its ability to provide a repertoire of tools for imaging metabolic and biochemical processes, receptor and transporter function, inflammation, and gene expression at molecular and cellular levels in intact organisms, under a wide variety of physiological conditions. With this approach, only selective myocardium with targeted abnormality can be visualized (hot spot imaging). This provides an opportunity for imaging complex biochemical, metabolic, and inflammatory processes of the cardiovascular system. (18)F-labeled (18)FDG, a radiolabeled glucose analogue, tracks cellular uptake and metabolism of glucose in the tissue and organs. Profound changes in regional glucose metabolism accompany several cardiovascular disease processes, which can be imaged using (18)FDG. However, caution is required while performing and interpreting these images. Because myocardial glucose uptake can vary widely under different metabolic and physiological states and this variation can overlap with the changes in myocardial glucose uptake under pathologic conditions, a strict and careful regulation of metabolic milieu is required while performing (18)FDG imaging. Cardiac (18)FDG imaging can be used for imaging myocardial ischemia, viability, and sarcoidosis. These techniques can overcome many of the limitations of current imaging techniques. In this article, we describe recent studies using (18)FDG for imaging myocardial ischemia and cardiac sarcoidosis.

OBJECTIVE This study was designed to evaluate the left ventricular myocardial perfusion and function in hypertrophic obstruction cardiomyopathy patients following percutaneous transluminal septal myocardial ablation (PTSMA) using rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging. PATIENTS AND METHODS Thirty-five patients (24 men and 11 women, 48±11 years old) with hypertrophic obstruction cardiomyopathy underwent rest-gated Tc-MIBI SPECT imaging 4±10 days before (baseline) and 4.7±1.0 days (short-term) and 15.5±8.2 months (mid-term) after PTSMA. Semiquantitative and QGS quantitative evaluations of perfusion and function were carried out in 17 left ventricular segments. RESULTS Myocardial perfusion of the septum following PTSMA was significantly reduced compared with baseline in all patients (P

The prevalence of myocardial perfusion and glucose metabolic abnormalities and their significance in patients with isolated left ventricular non-compaction (ILVNC) have not been well investigated.Seventeen ILVNC patients who underwent cardiac magnetic resonance (CMR) and (99m)Tc-sestamibi SPECT/fluorine-18 deoxyglucose ((18)F-FDG) PET imaging were included. Left ventricular non-compaction, regional wall motion abnormalities, left ventricular ejection fraction (LVEF), and delayed enhancement (DE) were estimated using CMR. Myocardial perfusion and metabolism were evaluated with SPECT/PET.Ninety-five (32.9%) segments were considered non-compacted. DE was present in 52 (18.0%) segments and 10 (58.8%) patients. The rate of occurrence of DE was significantly higher in compacted segments than in non-compacted segments (22.7% vs 8.4%, P = .003). Myocardial perfusion abnormalities were present in 92 (31.8%) segments, of which 66 were perfusion/metabolism match and 26 were perfusion/metabolism mismatch. The rate of occurrence of perfusion abnormality was similar between compacted and non-compacted segments (32.0% vs 31.6%, P = .948), but it was significantly higher in segments with DE than in those without DE (51.9% vs 27.4%, P = .001). None of the imaging features alone (non-compaction, DE, perfusion abnormalities, match or mismatch) showed significant correlations with LVEF (all P.05).In the current study, myocardial perfusion/metabolism mismatch and match were observed in both non-compacted and compacted myocardium in ILVNC patients. Further research is warranted to determine their pathologic and clinical significance.

INTRODUCTION The relationship between luminal stenosis measured by coronary CT angiography and stress-induced ischemia by SPECT myocardial perfusion imaging is not clearly defined. The aims of this study were to evaluate the relationship between stenosis severity by coronary CT angiography and abnormal SPECT finding and to explore the impact of clinical factors on this relationship. PATIENTS AND METHODS Seven hundred six consecutive patients with suspected coronary artery disease between January 2008 and October 2010 were prospectively enrolled. RESULTS SPECT revealed 348 reversible and 58 fixed defects in 91 patients. Coronary CT angiography revealed that 339 patients had a maximal luminal stenosis 50% or greater. Total coronary artery calcium score was calculated in 428 patients, including 193 without calcification as well as 128 with mild, 59 with moderate, and 48 with severe-to-extensive calcification. Sensitivity, specificity, positive predictive value and negative predictive value (NPV) of coronary CT angiography for detecting abnormal SPECT finding were, respectively, 48.4%, 90.4%, 42.7%, and 92.2% on a patients' level and 40.2%, 95.6%, 33.6%, and 96.6% on vascular level when cutoff value of stenosis was set at 75%. Receiver operating characteristic analysis showed that the best cutoff value of stenosis for detecting abnormal SPECT finding was 55% on patients' level and 43% on vascular level. Patients with severe-to-extensive calcification had lowest specificity (56.3%) and NPV (69.2%). The sensitivity and positive predictive value of coronary CT angiography were not affected by any clinical factors (P = nonsignificant), whereas the specificity was higher in female patients, population younger than 60 years, and population without hypertension or family history of coronary artery disease (P < 0.05), and the NPV was higher among female patients and population without hypertension (P < 0.05). CONCLUSIONS Coronary CT angiography has good agreement with stress/rest myocardial perfusion SPECT imaging. Coronary calcification and several clinical factors could affect the specificity and NPV of coronary CT angiography for detecting abnormal SPECT finding.

Background Our preliminary study suggested that patients with chronic myocardial infarction (MI) and heart failure could potentially benefit from CABG combined with aBM-MNC by improving global left ventricular (LV) function. The purpose of this sub-study was to quantitatively evaluate the effectiveness of aBM-MNC transplantation during CABG in patients with chronic MI by intensively analyzing the global and segmental LV function, the scar, and the relationships between the function recovery and the scar transmural extent. Methods A randomized, double-blinded, placebo-controlled study was performed in 50 patients with chronic MI. The patients were randomly allocated into CABG with stem cell transplantation (group A) and CABG only (group B) groups. CMR assessments of global and segmental left ventricular function and scar tissue were performed before surgery and repeated at 12months after CABG and aBM-MNC transplantation. Results The left ventricular ejection fraction (LVEF) improved by 13.5% and 8.0% in group A and B respectively (P=0.04). Segmental analysis of regional LV function recovery indicated that more improvement in contractility was found in group A within the same degree of the infarct transmurality (P=0.017) and showed a predominant interaction in the most severely affected segments (76–100%, P=0.016). Decrease in infarct size between the two groups did not reach statistical difference (9.4% vs. 6.0%, P=0.100). Conclusions CMR assessments revealed reversed ventricular remodeling and improved systolic function and scar reduction in patients who underwent aBM-MNC transplantation during CABG. And the conjunctional use of CABG and stem cell therapy could improve the left ventricular function in patients with chronic MI.

Purpose The study aimed to investigate the value of clinical variables and rest gated single-photon emission computed tomography (SPECT) in predicting cardiac deaths in medically treated dilated cardiomyopathy (DCM) patients. Methods This is a retrospective study. Fifty-six consecutive hospitalized DCM patients who underwent rest gated SPECT myocardial perfusion imaging were initially recruited. Patients were further excluded for receiving heart transplantation, cardiac resynchronization treatment, and noncardiac death during follow-up. The remaining 48 medically treated DCM patients were selected into the final analysis. Phase analysis of gated SPECT was conducted to identify left ventricular (LV) dyssynchrony. Cardiac death during follow-up was considered as the only endpoint. Univariate and multivariate Cox proportional hazards regression analysis were performed to identify the independent predictors of cardiac death. Kaplan-Meier cumulative survival analysis with stratification was performed, and survival curves were compared by log-rank test. Results The mean age was 47.5 ± 15.8 years (range, 15-76 yrs) and 85.4% were men. The mean LV ejection fraction was 22.2 ± 7.7%. During the follow-up period (22.7 ± 5.1 mos), 12 (25.0%) cardiac deaths occurred. Compared to survivors, patients with cardiac death had lower body mass index (BMI, P = 0.010), higher percent of prolonged QRS duration (QRSD, P = 0.043), and severe LV dyssynchrony (P = 0.002). Multivariate Cox analysis demonstrated that severe LV dyssynchrony [hazard ratio = 9.607, 95% confidential interval (95% CI) 2.064-44.713, P = 0.004] and BMI (hazard ratio = 0.851, 95% CI 0.732-0.989, P = 0.036) were predictive of cardiac death. Conclusion Left ventricular dyssynchrony assessed by phase analysis of gated SPECT and BMI are predictive of cardiac death in medically treated DCM patients.

To confirm that shortened acquisition time or reduced-activity dose in single-photon emission computed tomography (SPECT) myocardial perfusion imaging reconstructed with Astonish software (AS) does not compromise image quality or diagnostic accuracy. One hundred patients referred for SPECT myocardial perfusion imaging were prospectively studied. The patients were randomly selected to receive the full-dose protocol (group A, n = 54) or the half-dose protocol (group B, n = 46). The patients of group A underwent a 2-day stress/rest protocol. After half-time acquisition, they underwent a full-time acquisition for stress and rest SPECT. Group B underwent a 1-day stress/rest protocol. During peak stress, all patients received an intravenous injection of (99m)Tc-methoxyisobutylisonitrile (MIBI; 5.2 ± 0.6 mCi). After the full-time stress acquisition, the patients underwent a double-time stress acquisition. If the stress image showed a defect, a patient received (99m)Tc-MIBI (19.5 ± 1.7 mCi) at rest on the same day. The rest SPECT acquisition protocol was the same in both groups. The low count (LC) and high count (HC) were acquired for each patient. AS and filtered back projection (FBP) reconstructed each set of raw data. Image quality of perfusion was assessed on a four-point scale. Perfusion parameters and function parameters were calculated by quantitative perfusion SPECT and quantitative gated SPECT. Mean image quality for LC-AS and HC-AS (3.5 ± 0.5 and 3.7 ± 0.5, respectively) was superior to HC-FBP (3.1 ± 0.4) in group A (for all, p < 0.001). LC-AS and HC-AS (3.5 ± 0.5 and 3.6 ± 0.5, respectively) in group B were superior to HC-FBP (3.1 ± 0.3) (for all, p < 0.001). LC-AS, HC-AS and LC-FBP showed high diagnostic concordance with HC-FBP (kappa value was 0.92, 0.92, and 0.94, respectively; all p < 0.001). Cardiac SPECT studies can be acquired with half of the scan time or reduced radioactivity dose and reconstructed by using the AS algorithm without compromising image quality.

Objectives: Gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging is useful in assessing left ventricular (LV) myocardial perfusion and function. This study evaluated the LV functional changes after adenosine vasodilator stress, using gated SPECT. Methods: The study population consisted of 70 patients who underwent adenosine-mediated stress and rest SPECT. All patients underwent coronary angiography. Semi-quantitative assessment of perfusion was analyzed and produced the summed rest score (SRS), the summed stress score (SSS) and the summed difference score (SDS). The global LV function parameters [ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV)] and regional LV function [the summed motion score (SMS) and the summed thickening score (STS)] were quantified by gated SPECT. Results: Patients were divided into 2 groups: group 1 comprised 16 patients with worsening of LVEF (LVEFrest-LVEFado ≥5%), and group 2 comprised the other 54 patients. Compared with group 2, patients in group 1 had a significantly higher SSS and SDS (9.1 ± 6.8 vs. 5.6 ± 4.5 and 6.6 ± 3.8 vs. 3.6 ± 4.0, respectively; p < 0.05) and the severity of coronary artery stenosis was more serious (p < 0.05). Conclusion: Worsening of LVEF after adenosine-induced vasodilator stress, as shown by 99mTc-MIBI gated SPECT, is a valuable nonperfusion marker of significant CAD.

Background— Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required. Methods and Results— One-hundred and two consecutive subjects with hypertrophic obstructive cardiomyopathy who underwent cardiovascular magnetic resonance imaging, transthoracic echocardiography, and ASA were enrolled in this study. Successful ASA was defined as reduction of LVOT gradient ≥50% of baseline by echocardiographic follow-up 6 months post ASA. The relationships between segmental thickness assessed by cardiovascular magnetic resonance imaging and echocardiography and outcomes of ASA were compared between the 2 groups. The survival rate after ablation was 100% at 6-month follow-up. The LVOT gradient decreased ≥50% of baseline in 72% (73/102) patients. There were good correlations between the reduction of postoperative LVOT gradient and the thickness of basal anterior segment ( r =0.371; P r =0.527; P r =0.672; P P Conclusions— Both echocardiography and cardiovascular magnetic resonance imaging can be used effectively as noninvasive tools for patient selection for ASA procedure. A significantly thickened septum among hypertrophic obstructive cardiomyopathy patients may be associated with a poor outcome after ASA.

Purpose To evaluate the feasibility of free-breathing three-dimensional (3D) phase sensitive inversion recovery (PSIR) Turbo FLASH late gadolinium enhancement (LGE) magnetic resonance images (MRI) on left ventricular scar in patients with coronary artery disease (CAD) compared with clinically established breathhold two-dimensional (2D) PSIR Turbo FLASH images. Materials and Methods In 58 consecutive patients with confirmed CAD, LGE MRI using the two sequences have been acquired. Image quality was graded on a four-point scale according to the image appearance. Qualitative evaluation including the distribution area and the transmural extent of the scar based on the American Heart Association's (AHA's) 17-segment model was performed in both of 2D and 3D images. The scar volumes were compared quantitatively between 2D and 3D images. Results A total of 51 individuals were used for final statistical analysis. No differences were noted in image quality (P = 0.80), scar distribution area (P = 0.17), and scar transmural extent (P = 0.20) between 3D and 2D images. There was strong correlation in scar volume between the 3D and 2D results (r = 0.940; P < 0.001; Y = 0.298 + 1.251X, R2 = 0.876). But the scar volume derived from 3D images was significantly larger than that derived from 2D images (2D versus 3D, 20.08 ± 9.41 cm3 versus 25.41 ± 12.57 cm3, t = −7.60; P < 0.001). The trend toward a larger scar volume identified by 3D method was indicated through Bland-Altman analysis. Conclusion Free-breathing 3D PSIR Turbo FLASH imaging is another feasible method to identify left ventricular myocardial scar in patients with CAD and detects more scar volume compared with breathhold 2D PSIR Turbo FLASH imaging. J. Magn. Reson. Imaging 2013;38:72–79. © 2012 Wiley Periodicals, Inc.

Introduction Rapid and timely diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) is important to improve patient outcome. The goal of this study was using 99mTc-chSZ21-F(ab)2, F(ab)2 fragment of anti-glycoprotein IIIa chimeric monoclonal antibody, to image experimental thromboembolism (DVT and PE) in dogs. Materials and Methods Flow cytometry assay and adenosine diphosphate (ADP) stimulated platelet aggregation was performed to determine the specificity and affinity of chSZ21-F(ab)2 to the GPIIb/IIIa receptor on human or canine platelets. Both PE and DVT were induced in 12 beagle canines by catheter under X-ray direction. After 99mTc-chSZ21-F(ab)2 injection,animals were imaged for up to 3 hours then heparinized and sacrificed. Results Specific binding of chSZ21-F (ab)2 to GPIIb/IIIa on human or canine platelets was verified by flow cytometry assay. chSZ21-F (ab)2 inhibited ADP induced platelet aggregation with a dose-dependent manner, the concentration required to inhibit 50% (IC50) of platelet aggregation was 11.6 ± 7.9 nM and 24.9 ± 18.8 nM for human and canine, respectively. In vivo, focal uptake was observed in planar images as early as 30 min (DVT) and 60 min (PE), and became clearer within 3 hours after injection. Lesion-to-background ratio averaged 12.8 (PE-to-lung), 7.2 (DVT-to-blood), and 117.0(DVT-to-muscle), respectively. Conclusions These results suggested that 99mTc-chSZ21-F(ab)2 with high DVT and PE uptake is a promising agent for imaging vascular thrombosis.

Myocardial ischemia is associated with profound changes in substrate utilization by the myocardium for energy production. This change occurs with the onset of ischemia, but persists much longer, perhaps for several hours or even days after an episode of myocardial ischemia, which is termed ischemic memory. Recently, radiolabeled glucose analogue (Fluorine-18 labeled deoxyglucose, 18FDG) and free acid analogue (β-methyl-p-123I-iodophenyl-pentadecanoic acid, 123I-BMIPP) have been investigated to detect myocardial ischemia in stable coronary artery disease (CAD) or suspected acute coronary syndrome (ACS). These studies demonstrate that BMIPP imaging holds promise for evaluation of patients with suspected ACS in the emergency department. Exercise 18FDG imaging offers several potential advantages over conventional stress-rest perfusion imaging for the detection of CAD. Furthermore, ischemia-induced 18FDG uptake may persist for several to 24 hours in patients with stress-induced myocardial ischemia. Therefore, 18FDG may also be a useful memory marker in detection of antecedent myocardial ischemia in suspected ACS. However, some important issues about 18FDG ischemic imaging need to be further investigated. In this article the advances of myocardial ischemic imaging with 18FDG are reviewed. Several unresolved issues and the perspective of this modality are also discussed.

This study measured glucose uptake in the right ventricle (RV) of patients with pulmonary hypertension and investigated the relationship to hemodynamics and survival. Myocardial 18F-fluorodeoxy-glucose (FDG) uptake was measured using single-photon positron emission tomography (SPECT) in 24 patients with idiopathic pulmonary arterial hypertension (IPAH) and 43 patients with congenital heart disease (CHD). In both IPAH and CHD-PAH, RV FDG uptake (RV/LV ratio) was associated with pulmonary vascular resistance (PVR). A second SPECT scan was performed in nine patients after 6 months treatment with sildenafil. PVR decreased from 1683±426 to 1207±383 dyn s-1 cm-5 (P < 0.05) and cardiac index improved from 2.2±0.2 to 2.8±0.5 L/min/m2 (P < 0.01). RV/LV FDG uptake decreased from 1.28±0.32 before treatment to 0.99±0.23 (P < 0.05). Survival in the IPAH group with a baseline RV/LV FDG uptake greater than the median value of 1.20 was significantly lower than that of the group with RV/LV FDG uptake below 1.20 (log-rank test, P < 0.05). In contrast, baseline RV/LV FDG was of little informative value in CHD. FDG uptake by the RV reflects the severity of PVR in PAH. Increased RV FDG uptake is a marker of poor prognosis in IPAH and is reduced in patients receiving effective therapy. It could prove useful in the early clinical assessment of novel therapies for PAH.

The correct and prompt diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) plays a pivotal role in determining appropriate therapy. This study aimed to compare the diagnostic efficacy of pulmonary ventilation/perfusion (V/Q) scanning and computed tomography pulmonary angiography (CTPA) using pulmonary angiography as the golden standard.A total of 114 consecutive patients (49 men and 65 women, age 43.3 ± 15.3 years) suspected of having CTEPH were prospectively enrolled. All patients underwent V/Q scanning, CTPA, and pulmonary angiography within an interval of 7 days from one another. Interpretation of V/Q images was based on the refined Pulmonary Embolism Diagnosis criteria. For threshold 1, high-probability and intermediate-probability V/Q scan findings were considered to be positive, and low-probability/normal V/Q scan findings were negative. For threshold 2, only a high-probability V/Q scan finding was considered to be positive, and intermediate-probability and low-probability/normal V/Q scan findings were considered to be negative.Fifty-one patients (44.7%) had a final diagnosis of CTEPH. V/Q scan showed high probability, intermediate probability, and low probability/normal scan in 52, three, and 59 patients, respectively. CTPA revealed 50 patients with CTEPH and 64 patients without CTEPH. The sensitivity, specificity, and accuracy of the V/Q scan were 100, 93.7, and 96.5%, respectively, with threshold 1, and 96.1, 95.2, and 95.6%, respectively, with threshold 2; similarly, the sensitivity, specificity, and accuracy of CTPA were 92.2, 95.2, and 93.9%, respectively.In conclusion, both V/Q scanning and CTPA are accurate methods for the detection of CTEPH with excellent diagnostic efficacy.

This prospective study evaluated the accuracy of electrocardiogram-gated blood-pool SPECT (GBPS) for the assessment of left ventricular (LV) and right ventricular (RV) ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) in patients with dilated cardiomyopathy (DCM), using cardiac magnetic resonance (CMR) imaging as the reference standard.Thirty-two patients (24 men and 8 women; mean age, 51 y) with a diagnosis of idiopathic DCM underwent GBPS and CMR. LV and RV parameters including EDV, ESV, and EF from GBPS were calculated using fully automated gradient software and compared with those obtained by CMR.Biventricular volumes were underestimated by GBPS, compared with CMR (P0.001). We found no statistical difference between these 2 methods in the assessment of LV EF (P = 0.23), whereas RV EF was overestimated by GBPS (P0.001 vs. CMR). Regression analysis yielded significant correlations between GBPS and CMR in the assessments of biventricular parameters (r = 0.83 for LV EDV, 0.88 for LV ESV, 0.89 for LV EF, 0.86 for RV EDV, 0.86 for RV ESV, and 0.62 for RV EF; all P0.001). Comparison of the deviations of RV indices between GBPS and CMR with the ratio of RV EDV to LV EDV showed that there was a statistically significant trend for RV volumes to be underestimated and for RV EF to be overestimated as the biventricular volumetric ratio decreased (r = 0.61 for RV EDV, 0.68 for RV ESV, and -0.55 for RV EF; all P0.001).For patients with DCM, GBPS correlated well with CMR for the assessment of biventricular parameters, but RV indices should be cautiously interpreted.

Objectives This study aimed at examining the efficacy of bone marrow mononuclear cell (BMMNC) delivery through graft vessel for patients with a previous myocardial infarction (MI) and chronic heart failure during coronary artery bypass graft (CABG). Background Little evidence exists supporting the practice of BMMNC delivery through graft vessel for patients with a previous MI and chronic heart failure during CABG. Methods From November 2006 to June 2009, a randomized, placebo-controlled trial was conducted to test the efficacy and safety of CABG for multivessel coronary artery disease combined with autologous BMMNCs in patients with congestive heart failure due to severe ischemic cardiomyopathy. Sixty-five patients were recruited, and 60 patients remained in the final trial and were randomized to a CABG + BMMNC group (n = 31) and a placebo-control group (i.e., CABG-only group, n = 29). All patients discharged received a 6-month follow-up. Changes in left ventricular ejection fraction from baseline to 6-month follow-up, as examined by magnetic resonance imaging, were of primary interest. Results The overall baseline age was 59.5 ± 9.2 years, and 6.7% were women. After a 6-month follow-up, compared with the placebo-control group, the CABG + BMMNC group had significant changes in left ventricular ejection fraction (p = 0.029), left ventricular end-systolic volume index (p = 0.017), and wall motion index score (p = 0.011). Also, the changes in the distance on the 6-min walking test as well as B-type natriuretic peptide were significantly greater in the CABG + BMMNC group than in the control group. Conclusions In summary, patients with a previous MI and chronic heart failure could potentially benefit from isolated CABG (i.e., those who received CABG only) combined with BMMNCs delivered through a graft vessel. (Stem Cell Therapy to Improve Myocardial Function in Patients Undergoing Coronary Artery Bypass Grafting [CABG]; NCT00395811)

To analyze cardiac magnetic resonance imaging (CMR) characteristics in patients with isolated left ventricular noncompaction (IVNC) and assess its value in the diagnosis of IVNC in a Chinese adult Han population. We collected a consecutive series of 30 patients with IVNC from January 1, 2007, to December 31, 2008. During the same period, we prospectively included patients drawn from groups given a potential differential diagnosis for IVNC. All magnetic resonance images were analyzed using 17-segment model. Left ventricular ejection fraction was significantly lower for patients with DCM (16.2 ± 5.2%, P 0.001) and higher in AR (47.6 ± 16.2%, P = 0.009), AS (54.6 ± 21.1%, P = 0.001) and HHD (62.4 ± 6.8%, P 0.001) compared with IVNC (33.0 ± 14.1%). The two-layered structure was most frequently seen at the apical segments, followed by the mid-cavity and basal segments in patients with INVC. The anterior and lateral walls were more commonly involved in patients with IVNC. The number of noncompacted segments and end-diastolic ratio of non-compacted to compacted myocardium (NC/C ratio) was greater in patients with IVNC than in other five groups. The end-diastolic NC/C ratio of2.5 had 96.4% sensitivity and 97.4% specificity for identifying patients with IVNC. CMR provides an accurate and reliable evaluation of the localization and extent of noncompacted myocardium at end-diastole. The end-diastolic NC/C ratio of2.5 had high diagnostic accuracy for IVNC in a Chinese adult Han population.

Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and systolic dysfunction with normal ventricular wall thickness. More recent studies have shown that the coronary microcirculation may be directly affected in cardiomyopathies. Left ventricular regional myocardial perfusion, wall motion, and metabolism abnormalities are often present in patients with DCM. These data support the possibility that myocardial ischemia may play an important role in the development of DCM and have important prognostic value in patients with DCM. We need to pay attention to the assessment of myocardial blood flow and myocardial ischemia in patients with DCM. Furthermore, anti-ischemic therapy may improve left ventricular function and clinical outcomes in patients with heart failure resulted from DCM.

Myocardial perfusion imaging has been in extensive clinical use for well over 30 years. This technique is used for diagnosing, risk stratification, and long-term follow-up of patients with suspected or known coronary artery disease (CAD). A unique strength of nuclear imaging is its ability to provide a repertoire of tools for imaging metabolic and biochemical processes and receptor and transporter functions at molecular and cellular levels in intact organisms, under a wide variety of physiological conditions. Despite their high resolution and technical sophistication, other imaging modalities do not have this capability. Metabolic imaging techniques using radiolabeled free fatty acid and glucose analogues provide a unique ability to image myocardial ischemia directly in patients with known or suspected CAD. These techniques can overcome many of the limitations of currently used stress-rest perfusion imaging. In this article, we describe recent studies using 18FDG for imaging myocardial ischemia.

In 2005, 80% of cardiovascular disease (CVD) deaths occurred in low- to middle-income countries (i.e., developing nations). Cardiovascular imaging, such as myocardial perfusion SPECT, is one method that may be applied to detect and foster improved detection of at-risk patients. This document will review the availability and utilization for nuclear cardiology procedures worldwide and propose strategies to devise regional centers of excellence to achieve quality imaging around the world. As a means to establish the current state of nuclear cardiology, International Atomic Energy Agency member and non-member states were queried as to annual utilization of nuclear cardiology procedures. Other sources for imaging statistics included data from medical societies (American Society of Nuclear Cardiology, European Society of Cardiology, and the European Association of Nuclear Medicine) and nuclear cardiology working groups within several nations. Utilization was calculated by dividing annual procedural volume by 2007 population statistics (/100,000) and categorized as high (>1,000/100,000), moderate-high (250-999/100,000), moderate (100-249/100,000), low-moderate (50-99/100,000) and low (

PURPOSE To compare the diagnostic efficacy of lung perfusion scans combined with ventilation (V/Q) scans and/or chest radiography (CR) with contrast-enhanced multislice spiral CT pulmonary angiography (CTPA) in diagnosing pulmonary embolism (PE). MATERIALS AND METHODS Eighty-two consecutive patients with suspected PE underwent CTPA, lung perfusion scan, and CR. Of them, 28 patients underwent V/Q scans. The final diagnosis was made using a composite reference test. RESULTS The overall sensitivity and specificity were 89.2% and 92.1% for V/Q scan or perfusion scan combined with CR, and 97.3% and 97.4% for CTPA. For the 28 patients with V/Q scan, the sensitivity and specificity were 91.7% and 92.9% for V/Q scan, and 91.7% and 100.0% for CTPA. The segmental agreement rate between perfusion scan and CTPA was 69.5% (kappa = 0.30, P < 0.05). The perfusion scan revealed significantly more subsegmental abnormalities than CTPA (59 vs. 10, chi2 test, P < 0.05). CONCLUSIONS V/Q scan, perfusion scan combined with CR and CTPA all show high efficacy in diagnosing PE. V/Q scan or perfusion scan combined with CR is as accurate as CTPA.

We have recently demonstrated the potential of (18)F-FDG as an imaging marker of myocardial ischemia if injected at peak exercise. However, how long increased (18)F-FDG uptake can be observed after an episode of exercise-induced myocardial ischemia is not known. We performed the current study to determine whether increased regional myocardial (18)F-FDG uptake at exercise in patients with coronary artery disease (CAD) persists on rest imaging (24 h later), after an episode of exercise-induced myocardial ischemia.Twenty-four patients with suspected CAD underwent exercise (99m)Tc-sestamibi and (18)F-FDG imaging. Repeated (18)F-FDG imaging was performed 24 h after exercise imaging, after an injection of a second dose of (18)F-FDG at rest in 20 patients. Perfusion imaging with (99m)Tc-sestamibi was simultaneously performed with (18)F-FDG imaging. All patients underwent coronary angiography.Eighteen patients had greater than or equal to 70% luminal narrowing of 1 or more coronary vessels. Fifteen patients (83%) showed increased regional (18)F-FDG uptake on exercise imaging, but only 11 patients (61%) had perfusion abnormalities. Of these 15 patients with increased regional (18)F-FDG uptake on exercise imaging, 8 (53%) had no discernible (18)F-FDG uptake, 5 (33%) had decreased (18)F-FDG uptake, and only 2 (13%) had persistent (18)F-FDG uptake on rest (18)F-FDG images. The summed (18)F-FDG uptake score significantly decreased, from 14.4 +/- 10.3 at exercise to 6.7 +/- 9.2 at rest (P = 0.01). Patients with persistent (18)F-FDG uptake at rest had more (18)F-FDG uptake and lower peak rate-pressure product at exercise, compared with patients with no residual (18)F-FDG uptake at rest.Exercise-induced regional myocardial (18)F-FDG uptake is highly specific and sensitive for exercise-induced myocardial ischemia. Regional myocardial (18)F-FDG uptake may persist 24 h after an episode of exercise-induced myocardial ischemia in some patients.

OBJECTIVES This study was designed to evaluate the biodistribution and blood clearance characteristics of 99mTcN-15C5 and its potential as a myocardial perfusion radiotracer. METHODS Five normal mongrel dogs were injected with 99mTcN-15C5 intravenously. Blood samples were collected at 0.5, 1, 2, 3, 4, 5, 10, 15, and 30 min postinjection (p.i.). Anterior planar images were acquired at 5, 15, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around heart, liver, and lungs. The raw activity in each ROI was expressed as counts/pixel/min. Heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in liver and lung ROI, respectively. For comparison, 99mTc-sestamibi was also evaluated in the same five dogs. In dogs with coronary stenoses, single photon emission computed tomography images were acquired at 30, 60, and 120 min after administration of 99mTcN-15C5 with/without adenosine. RESULTS 99mTcN-15C5 and 99mTc-sestamibi had very similar blood clearance characteristics during the first 30 min p.i. The heart/liver ratio of 99mTcN-15C5 increased from 0.48+/-0.05 at 5 min p.i. to 1.85+/-0.11 at 120 min p.i., whereas the heart/liver ratio of 99mTc-sestamibi was improved only slightly from 0.45+/-0.04 at 5 min p.i. to 0.74+/-0.15 at 120 min p.i. SPECT imaging studies in canines with coronary stenoses indicated that good visualization of the perfusion defect could be achieved at 30 min after administration of 99mTcN-15C5 with the adenosine stress. CONCLUSION The combination of high heart uptake and rapid liver clearance makes 99mTcN-15C5 a promising new radiotracer for myocardial perfusion imaging.

Objectives: This study was aimed to compare the properties of [99mTc(PNP5)(DBODC)]+ with 99mTc-MIBI in normal swine and in canine models of myocardial ischemia. Methods: Seven anesthetized swine were injected intravenously with [99mTc(PNP5)(DBODC)]+. Serial planar images were acquired meanwhile. Twelve adult dogs were studied. A critical stenosis of left anterior descending artery was produced. [99mTc(PNP5)(DBODC)]+ or 99mTc-MIBI (randomly) was injected intravenously at the end of 3 min of adenosine infusion. The occluder was released after adenosine infusion. Myocardial SPECT imaging was obtained at 30, 60, 90 and 180 min, respectively, after tracer injection. Rest myocardial SPECT imaging was acquired on the next day. Results: Blood disappearance of [99mTc(PNP5)(DBODC)]+ was biexponential with an initial half-time of 2.97 ± 0.48 min and a late half-time of 52.49 ± 19.49 min. Myocardial [99mTc(PNP5)(DBODC)]+ uptake was similar to 99mTc-MIBI. Heart-to-liver ratio of [99mTc(PNP5)(DBODC)]+ was significantly higher than that of 99mTc-MIBI (0.99 ± 0.03 vs. 0.46 ± 0.10, p < 0.05) 30 min after injection. In canine models of myocardial ischemia, image quality of [99mTc(PNP5)(DBODC)]+ was better than 99mTc-MIBI. Segments with perfusion defects by [99mTc(PNP5)(DBODC)]+ was 3.60 ± 1.52 and 4.25 ± 0.96 by 99mTc-MIBI (p = n.s.). Conclusions: [99mTc(PNP5)(DBODC)]+ seems to be a promising new myocardial perfusion imaging agent.

Aims To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium. Methods and results Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium. Conclusion Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.

BACKGROUND Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

In this review, we focus mainly on the clinical applications of myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) and metabolic imaging in clinical practice. Important advances have been made in the clinical applications of MPI, including its role in stratifying risk and guiding management decisions. The impact of incomplete and complete myocardial ischemia correction on long-term outcomes was analyzed and compared with complete and incomplete diseased vessel intervention. Importantly, a new pharmacologic stress testing agent—higenamine—was developed and has completed phase III clinical trials. Ventricular synchrony was assessed by phase analysis of gated MPI in healthy Chinese subjects and in patients with or without left ventricular (LV) dysfunction. Finally, the clinical value of technetium (99mTc) sestamibi SPECT and fludeoxyglucose (18F-FDG) positron emission tomography (PET) in patients with LV aneurysms was deeply investigated. Viability of LV aneurysm in patients with ischemic cardiomyopathy was a negative independent predictor of survival. The diagnostic accuracy of LV parameters analyzed by both gated SPECT and gated PET was investigated in patients with LV aneurysm, who revealed severe perfusion defects and LV remodeling. Additionally, end-systolic volume measured by gated PET was the only independent predictor of cardiac death among all the LV functional parameters evaluated by gated SPECT, gated PET, cardiac magnetic resonance imaging, and echocardiography.

The purpose of this study was to evaluate the long-term prognostic value of exercise technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission tomography (SPET) imaging in patients after percutaneous coronary intervention (PCI). Three hundred and eighteen consecutive post-PCI patients who underwent exercise and rest (99m)Tc-MIBI SPET myocardial perfusion imaging (MPI) were followed up for 38+/-27 months. Patients with early revascularisation (3 months after MPI) were excluded. A semiquantitative visual analysis employing a 20-segment and four-point scoring system was used to define the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS). Death and non-fatal myocardial infarction (MI) were considered as hard events, and late revascularisation procedures (/=3 months after MPI) as soft events. Fifty-one patients (16.0%) suffered from cardiac events during follow-up, including 1 (0.3%) death, 13 (4.1%) non-fatal MIs, 9 (2.8%) coronary artery bypass grafting procedures and 28 (8.8%) PCIs. According to the SPET results, patients were classified into three groups: patients with normal MPI (SSS=0, n=153), patients with irreversible defects (SDS3 and SRS1, n=100) and patients with reversible defects (SDS/=3, n=65). The annual hard cardiac event rate in patients with reversible defects was 3.9%, which was significantly higher than that in patients with normal MPI (0.2%, chi(2)=7.71; P0.01). The annual soft cardiac event rate in patients with reversible defects was 10.7%, which was significantly higher than that in patients with irreversible defects (2.5% chi(2)=17.69; P0.001), and also significantly higher than that in patients with normal MPI (1.5%, chi(2)=33.89; P0.001). In patients with normal and reversible defects, there was no significant difference in soft and hard cardiac event rates according to whether patients were symptomatic or asymptomatic ( P0.05). However, the annual soft event rate in patients with irreversible defects and symptoms was 5.0%, which was higher than that of 0.6% in asymptomatic patients (chi(2)=6.11, P0.05). Multivariate Cox analysis showed that SSS was the best independent predictor for hard cardiac events (chi(2)=12.70; P0.001) and SDS was the strongest independent predictor for soft cardiac events (chi(2)=11.72; P0.001). Post-PCI patients who have normal exercise (99m)Tc-MIBI SPET MPI have a good long-term prognosis, while those with reversible defects are at a higher risk for future cardiac events, without correlation to the chest pain symptoms. However, symptomatic patients with irreversible defects have a higher risk for repeat revascularisation, but not for hard events, compared with asymptomatic patients. Exercise (99m)Tc-MIBI SPET MPI has important clinical value for risk stratification and management decision-making in post-PCI patients.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Molecular imaging techniques provide valuable information at cellular and molecular level, as opposed to anatomical and structural layers acquired from traditional imaging modalities. More specifically, molecular imaging employs imaging probes which interact with specific molecular targets and therefore makes it possible to visualize biological processes in vivo. Molecular imaging technology is now progressing towards preclinical and clinical application that gives an integral and comprehensive guidance for the investigation of cardiovascular disease. In addition, cardiac stem cell therapy holds great promise for clinical translation. Undoubtedly, combining stem cell therapy with molecular imaging technology will bring a broad prospect for the study and treatment of cardiac disease. This review will focus on the progresses of molecular imaging strategies in cardiovascular disease and cardiac stem cell therapy. Furthermore, the perspective on the future role of molecular imaging in clinical translation and potential strategies in defining safety and efficacy of cardiac stem cell therapies will be discussed.

Transcoronary ethanol septal ablation (TESA) is a novel treatment for obstructive hypertrophic cardiomyopathy (HOCM). Our objective was to evaluate the use of gated single photon emission computed tomography (SPECT) in patients with HOCM and the effects of TESA on myocardial perfusion.We performed gated SPECT and Doppler echocardiography before and 6 weeks after TESA in 30 patients with severe HOCM. The lung-to-heart and septal-to-lateral wall count-activity ratios were calculated. Before ablation, SPECT showed perfusion abnormalities in only 6 patients. Asymmetric septal hypertrophy was noted in 21 patients (70%). In patients with a lung-to-heart ratio greater than 0.50 before ablation, the ratio decreased from 0.56 +/- 0.04 to 0.45 +/- 0.08 after ablation (P.01). The septal-to-lateral wall ratio also decreased significantly after ablation. Mean Doppler pressure gradient across the left ventricular outflow tract decreased from 52 +/- 39 mm Hg to 13 +/- 13 mm Hg (P.01) immediately after ablation and to 10 +/- 21 mm Hg 6 weeks later (P.01). There were no significant changes in left ventricular ejection fraction by gated SPECT after the procedure. SPECT studies done after ablation showed fixed septal defects in 29 of 30 patients (96.7%). The defects involved the basal and mid septum in 100% and 38% of patients, respectively, and ranged in size from 2% to 30% of the left ventricle (mean, 8.8% +/- 7.0%).TESA is an effective technique for relieving left ventricular outflow obstruction in patients with HOCM. Myocardial gated SPECT can identify the presence and location of infarction after TESA.

1162 Objectives In 1925 Blumgart demonstrated that he could measure serial blood levels of isotope activity to determine cardiac contractility through the measurement of “circulation time.” Todays modern SPECT cameras replace the cloud chambers of Blumgarts era, allowing us the opportunity to measure serial changes in isotope concentration needed to measure ischemia. This study determines the clinical utility of Blumgarts method using todays SPECT camera. Methods One hundred twenty individuals underwent diagnostic study measuring changes in sestamibi activity in eight regions of interest (ROIs) using a SPECT camera. Subjects were stressed and using Blumgarts method of measuring isotope scintillations, serial measurements were compared in each of the eight regions with results found on coronary angiography. Results Parabolic regression of stenosis from coronary angiography (figure 1) on changes in isotope activity were compared for each of the vascular territories. The result yielded an effect size of R(95%)=0.72 to 0.95, p=3.8x10-8. Conclusions Prior investigations suggested that changes in isotope distribution over time could be employed to more accurately measure ischemia. A thorough literature search and investigation and application of Blumgarts method of serial measurements of isotope scintillation, when applied using todays SPECT camera reveals that changes in sestamibi distribution can be accurately measured, allowing clinicians to employee SPECT cameras to obtain angiographic results, while improving diagnostic accuracy and reducing patient radiation exposure. Research Support CVISM sponsored

The objectives of this study were 2-fold: (1) to determine the tolerance of adenosine perfusion tomography with the use of an abbreviated (3-minute) infusion in comparison to the standard (6-minute) infusion, and (2) to assess the relative diagnostic accuracy of a 3-minute adenosine infusion in patients referred for arteriography. An abbreviated adenosine infusion may decrease the frequency and duration of side effects and be a more cost-effective alternative.We prospectively randomized 599 patients undergoing adenosine myocardial perfusion tomography to either a 3-minute or 6-minute adenosine infusion at 140 microg/kg per minute. Among the 599 enrolled patients, 142 subsequently underwent coronary angiography. Patients randomized to the 3-minute adenosine infusion tolerated the procedure better than those randomized to the standard infusion (P.01). Flushing, headache, neck pain, and atrioventricular block were all significantly less frequent (P.01) with the abbreviated infusion. Moreover, patients receiving the abbreviated infusion had less hypotension and tachycardia (P.05). The sensitivity of the test for detection of coronary artery disease was 88% for both the 3- and 6-minute infusions. In patients with abnormal scan results, perfusion defect size was slightly larger in those receiving a 6-minute infusion versus those receiving a 3-minute infusion (P =.05).An abbreviated 3-minute adenosine infusion, in combination with perfusion tomography, has similar sensitivity for detection of coronary artery disease and is better tolerated than the standard 6-minute infusion.

Previous studies that investigated the effects of coronary collateral circulation on myocardial perfusion were compromised by inclusion of patients with multivessel coronary artery disease, incomplete occlusion, prior myocardial infarction, or a combination of these. In this study we ascertained the relationship between angiographic collateral circulation and myocardial perfusion only in patients with total occlusion of a single coronary artery, in the absence of myocardial infarction or significant stenosis in the other coronary arteries.Seventy-one consecutive patients underwent stress myocardial single photon emission computed tomography within 90 days of angiography. Collateral circulation was present in 49 patients and absent in 22 patients. All but 2 patients had abnormal perfusion by single photon emission computed tomography imaging, with a mean defect size of 19% +/- 12%, and most (83%) had reversible perfusion defects. Defect count activities improved from stress to rest (or redistribution) (45% +/- 13% to 59% +/- 14%, P.001). Abnormal myocardial perfusion occurred with similar frequency in patients with collateral circulation and in those without it. Total defect size was 19% +/- 12% in patients with and 18% +/- 11% in those without collateral circulation (P = not significant). The extent of reversibility and defect count activity during stress and rest were similar in patients with collateral circulation and in those without it.In patients with a single-vessel total coronary occlusion and without myocardial infarction, stress-induced myocardial ischemia is almost always present, irrespective of presence or absence of angiographic collaterals. These data lend support to the premise that collateral circulation is rather insufficient to prevent stress-induced ischemia, although it can preserve myocardial viability.

There is scanty information on the angiographic and myocardial perfusion correlates of dobutamine-induced ST-segment elevation.We studied 39 patients who exhibited ST-segment elevation during dobutamine perfusion tomography and had recent coronary angiography performed (ie, within 3 months of the dobutamine study). Baseline characteristics, extent of coronary artery disease, relationship of Q waves to ST-segment elevation, ischemic burden, and angiographic findings were assessed. Twenty-nine patients (74%) had prior myocardial infarction, and 77% had abnormal Q waves at baseline. Ninety-three percent of patients had abnormal perfusion imaging. Eighty percent of patients had multivessel coronary artery disease. The left ventricular ejection fraction by contrast ventriculography was 35% +/- 7% (mean +/- SD), the perfusion defect size was 32% +/- 15%, and 73% of patients had some degree of myocardial ischemia. A predominance of ischemia (50% reversibility) occurred in 38% of patients with Q waves and in 70% of those without Q waves. There was also good agreement between the site of ST-segment elevation and the site of ischemia by perfusion imaging (79%) and between the site of ST-segment elevation and the location of the vessel with significant coronary stenosis (95%).Patients with dobutamine-induced ST-segment elevation have a depressed left ventricular ejection fraction, a high frequency of multivessel disease, and markedly abnormal myocardial perfusion tomography. In patients with ST-segment elevation and abnormal Q waves, substantial scarring and superimposed ischemia coexist, whereas in patients without Q waves, ST-segment elevation usually denotes severe ischemia.

Background —We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A 2A agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy. Methods and Results —A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to 201 Tl (0.5 mCi) and 99m Tc-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion ( P P P P P =NS), and transmural 201 Tl and 99m Tc-sestamibi count-activity ratios (0.48±0.11 and 0.51±0.09, respectively) were also comparable ( P =NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. Conclusions —CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of 201 Tl and 99m Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.

OBJECTIVES The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (Tl-201) scintigraphy. BACKGROUND Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution Tl-201 tomography before revascularization and a repeat resting echocardiogram ≥2 months later. RESULTS Global wall motion score index decreased from 2.38 ± 0.73 to 1.94 ± 0.82 after revascularization (p 0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a Tl-201 maximal uptake of ≥60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum Tl-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to Tl-201 scintigraphy. Importantly, a simple measurement of EDWT ≤0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.