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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.

In single-photon emission computed tomography (SPECT), a micro-sized

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

First introduced in 1976

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.

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.

Wound healing is regulated by a complex series of events and overlapping phases. A delicate balance of cytokines and mediators in tissue repair is required for optimal therapy in clinical applications. Molecular imaging technologies, with their versatility in monitoring cellular and molecular events in living organisms, offer tangible options to better guide tissue repair by regulating the balance of cytokines and mediators at injured sites. Methods: A murine cutaneous wound healing model was developed to investigate if incorporation of prostaglandin E2 (PGE2) into chitosan (CS) hydrogel (CS+PGE2 hydrogel) could enhance its therapeutic effects. Bioluminescence imaging (BLI) was used to noninvasively monitor the inflammation and angiogenesis processes at injured sites during wound healing. We also investigated the M1 and M2 paradigm of macrophage activation during wound healing. Results: CS hydrogel could prolong the release of PGE2, thereby improving its tissue repair and regeneration capabilities. Molecular imaging results showed that the prolonged release of PGE2 could ameliorate inflammation by promoting the M2 phenotypic transformation of macrophages. Also, CS+PGE2 hydrogel could augment angiogenesis at the injured sites during the early phase of tissue repair, as revealed by BLI. Furthermore, our results demonstrated that CS+PGE2 hydrogel could regulate the balance among the three overlapping phases—inflammation, regeneration (angiogenesis), and remodeling (fibrosis)—during cutaneous wound healing. Conclusion: Our findings highlight the potential of the CS+PGE2 hydrogel as a novel therapeutic strategy for promoting tissue regeneration via M2 macrophage polarization. Moreover, molecular imaging provides a platform for monitoring cellular and molecular events in real-time during tissue repair and facilitates the discovery of optimal therapeutics for injury repair by regulating the balance of cytokines and mediators at injured sites.

Transplantation of endothelial cells (ECs) holds great promise for treating various kinds of ischemic diseases. However, the major challenge in ECs-based therapy in clinical applications is to provide high quality and enough amounts of cells. In this study, we developed a simple and efficient system to direct endothelial differentiation of mouse embryonic stem cells (ESCs) using a controllable chitosan nitric oxide (NO)-releasing hydrogel (CS-NO). ESCs were plated onto the hydrogel culture system, and the expressions of differentiation markers were measured. We found that the expression of Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) increased obviously under the controlled NO releasing environment. Moreover, the Flk-1 upregulation was accompanied by the activation of the phospho-inositide-3 kinase (PI3K)/Akt signaling. We also found that in the presence of the PI3K inhibitor (LY294002), the endothelial commitment of ESCs was abolished, indicating the importance of Akt phosphorylation in the endothelial differentiation of ESCs. Interestingly, in the absence of NO, the activation of Akt phosphorylation alone by using AKT activator (SC-79) did not profoundly promote the endothelial differentiation of ESCs, suggesting an interdependent relationship between NO and the Akt phosphorylation in driving endothelial fate specification of ESCs. Taken together, we demonstrated that NO releasing in a continuous and controlled manner is a simple and efficient method for directing the endothelial differentiation of ESCs without adding growth factors. Statement of Significance Fascinating data continues to show that artificial stem cell niche not only serve as a physical supporting scaffold for stem cells proliferation, but also as a novel platform for directing stem cell differentiation. Because of the lack of proper microenvironment for generating therapeutic endothelial cells (ECs) in vitro, the source of ECs for transplantation is the major limitation in ECs-based therapy to clinical applications. The current study established a feeder cell-free, 2-dimensional culture system for promoting the differentiation processes of embryonic stem cells (ESCs) committed to the endothelial lineage via using a nitric oxide (NO) controlled releasing hydrogel (CS-NO). Notably, the NO releasing from the hydrogel could selectively up-regulate Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) in the absence of growth factors, which was of crucial importance in the endothelial differentiation of ESCs. In summary, the current study proposes a simple and efficient method for directing the endothelial differentiation of ESCs without extra growth factors.

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 the164 Consecutive patients were included who underwent coronary angiography results exhibited total occlusion of a single coronary artery and receivedCollateral 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.

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

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 0.05) measurements between GPET and CMR.In patients with MI, LV volumes and LVEF scores measured by both GSPECT and GPET imaging were comparable to those determined by CMR, but should not be interchangeable in individual patients.

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.

Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.

Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.