• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.314-317
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• 2002

The purpose of this study was to evaluate the clinical application of Patlak tool on GE PET workstation for quantitative analysis of dynamic PET images in cardiac patients. Three patients including coronary artery disease (CAD), myocardial infarction (MI), and angina were studied. All subjects underwent dynamic cardiac PET scan using a GE Advance scanner. After 10 min transmission scan for attenuation correction using two rotating $\^$68/Ge rod sources, three patients with cardiac disease were performed dynamic cardiac PET scan after the administration of approximately 370 MBq of FDG. The dynamic scan consisted of 36 frames with variable frame length (12${\times}$10s, 6${\times}$20s, 6${\times}$60s, 12${\times}$300s) for a total time of 70 min. Blood samples were obtained to determine the plasma substrate concentration. Region of interest of circular and rectangular shape to acquire input functions and tissue data were placed on left ventricle and myocardium. A value of 0.67 was used for lumped constant. Mean plasma substrate concentrations for three patients were 100 mg/dl (CAD), 100 mg/dl (MI), 132 mg/dl (angina), respectively. Regional MMRGlc values (mean${\pm}$SD) at lateral myocardium area for CAD, MI, and angina were 8.43${\pm}$0.24, 4.08${\pm}$0.16, and 6.15${\pm}$0.23 mg/min/100ml, respectively. Patlak tool on GE PET workstation appeared to be useful for quantitative analysis of dynamic PET images in cardiac patients, although further studies may be required for absolute quantitation.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.274-279
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• 1992

Clinical role of $^{99m}Tc-MIBI$ myocardial scintigraphy in the diagnosis of coronary artery disease (CAD) is now well accepted, however, the role of it in the identification of viable myocardium in patients with chronic CAD has not yet been clarified. To determine the usefulness of rest-injected $^{99m}Tc-MIBI$ scan as a marker of myocardial viability, the regional uptake of this agent at rest was compared with that of $^{201}Tl$ on reinjection and 24 hours after reinjection images. Subject patients were 13 chronic CAD patients who showed irreversible perfusion defect(s) on standard pharmacologic (dipyridamole) stress-redistribution images. Immediately after the redistribution images were obtained, 37 MBq thallium was injected at rest, and images were reacquired at 10 minutes and 24 hours after reinjection. After then 740 MBq $^{99m}Tc-MIBI$ was injected, and 1 hour later rest MIBI myocardial imaging was performed. Five sets of imagestress, redistribution, reinjection, delayed images of thallium, and rest image of MIBI) were then analyzed qualitatively and quantitatively. Left ventricle was arbitrarily divided into 9 segments (apex, basal and apical portions of anterior, septal, inferior, and lateral walls). Seven patients and 30 regions showed a fixed perfusion defect on the stress-redistribution images. Among 30 regions, 15 showed positive uptakes and 6 showed negative uptakes on both $^{201}Tl$ reinjection/delayed images and $^{99m}Tc-MIBI$ rest images. Five regions showed only thallium uptake and were regarded as viable clinically. Of four regions which showed only $^{99m}Tc-MIBI$ uptake, two were regarded as viable, while the other two were regarded as a nonviable scar tissue clinically. In conclusion, $^{201}Tl$ reinjection technique was more reliable in the identification of viable myocardium. However, the role of $^{99m}Tc-MIBI$ in identification of viable myocardium was still remained to be clarified because 2 of 9 regions showed only $^{99m}Tc-MIBI$ uptake and were regarded as viable tissues.

• Applied Microscopy
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• v.22 no.1
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• pp.42-54
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• 1992

To understand the structural changes of the myocardial myocytes and endothelial cells in ischemic and reperfused heart, and to elucidate their roles in those conditions, the authors observed cat and rat myocardium ultrastructurally and evaluated them with morphometric techniques. In cat, mild ischemia and moderate degree reperfusion injury was induced by ligation of the anterior interventricular branch of left coronary artery and reperfusion. In rat, severe ischemia and irreversible reperfusion iniury was made using in vitro Langendorff techniques. In normal cat myocytes, the volume densities of cytoplasm, myofibrils, mitochondria, sarcoplasmic reticulum and T tubules were $0.11{\pm}0.013,\;0.51{\pm}0.096,\;0.25{\pm}0.082,\;0.09{\pm}0.008,\;0.02{\pm}0.010$ (Mean${\pm}$S.D.) respectively, and the myofibril/mitochondria ratio was $2.33{\pm}1.379$. The numerical density and average volume of mitochondria were $0.76{\pm}0.210/{\mu}m^3$ and $0.33{\pm}0.057{\mu}m^3$ respectively. In normal cat endothelial cells, the volume densities of cytoplasm, cytoplasmic vesicles, tubular systems (including endoplasmic reticulum and Golgi apparatus) and mitochondria were $0.43{\pm}0.023,\;0.28{\pm}0.007,\;0.22{\pm}0.021,\;0.03{\pm}0.014$ respectively. The mean thickness of endothelial cells was $230{\pm}45.2{\mu}m$. The numerical density and average volume of cytoplasmic vesicles were $508{\pm}55.0/{\mu}m^3,\;578{\pm}104.8nm^3$ respectively. In cat myocytes which received mild ischemic injury, the volume densities of organelles were not changed significantly in ischemic and reperfusion states. In reperfusion group myocytes, the numerical density of mitochondria was decreased significantly and the average volume was increased significantly. In endothelial cells, the volume density of tubular system in ischemic group and the average volume of cytoplasmic vesicles in reperfusion group were increased significantly. In rat myocytes which received severe ischemic injury, the volume density and average volume of mitochondria were increased significantly, and the volume density of sarcoplasmic reticulum and numerical density of mitochondria were decreased significantly in both ischemic and reperfusion groups. In ischemic and reperfused endothelial cells, the volume density and numerical density of cytoplasmic vesicles, the volume density of cytoplasm were decreased significantly. The volume densities of tubular system were increased significantly in both ischemic and reperfused groups. The volume density of mitochondria in ischemic group and the average volume of cytoplasmic vesicles in reperfusion group showed significant increase. The authors, based on the above observations, conclude that the mitochondria of myocytes and the cytoplasmic vesicles of endothelia are the first group of targets in ischemic and reperfusion injury and in this respect, the degree of ischemic insult is not significant. The role of myocyte mitochondria in reperfusion injury may be insignificant, but endothelial cells may contribute actively to reperfusion injury.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.743-754
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• 2023

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10^-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.1964-1973
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• 2021

Objective: To investigate the diagnostic performance of CT fractional flow reserve (CT-FFR) for myocardial bridging-related ischemia using dynamic CT myocardial perfusion imaging (CT-MPI) as a reference standard. Materials and Methods: Dynamic CT-MPI and coronary CT angiography (CCTA) data obtained from 498 symptomatic patients were retrospectively reviewed. Seventy-five patients (mean age ± standard deviation, 62.7 ± 13.2 years; 48 males) who showed myocardial bridging in the left anterior descending artery without concomitant obstructive stenosis on the imaging were included. The change in CT-FFR across myocardial bridging (ΔCT-FFR, defined as the difference in CT-FFR values between the proximal and distal ends of the myocardial bridging) in different cardiac phases, as well as other anatomical parameters, were measured to evaluate their performance for diagnosing myocardial bridging-related myocardial ischemia using dynamic CT-MPI as the reference standard (myocardial blood flow < 100 mL/100 mL/min or myocardial blood flow ratio ≤ 0.8). Results: ΔCT-FFR_systolic (ΔCT-FFR calculated in the best systolic phase) was higher in patients with vs. without myocardial bridging-related myocardial ischemia (median [interquartile range], 0.12 [0.08-0.17] vs. 0.04 [0.01-0.07], p < 0.001), while CT-FFR_systolic (CT-FFR distal to the myocardial bridging calculated in the best systolic phase) was lower (0.85 [0.81-0.89] vs. 0.91 [0.88-0.96], p = 0.043). In contrast, ΔCT-FFR_diastolic (ΔCT-FFR calculated in the best diastolic phase) and CT-FFR_diastolic (CT-FFR distal to the myocardial bridging calculated in the best diastolic phase) did not differ significantly. Receiver operating characteristic curve analysis showed that ΔCT-FFR_systolic had largest area under the curve (0.822; 95% confidence interval, 0.717-0.901) for identifying myocardial bridging-related ischemia. ΔCT-FFR_systolic had the highest sensitivity (91.7%) and negative predictive value (NPV) (97.8%). ΔCT-FFR_diastolic had the highest specificity (85.7%) for diagnosing myocardial bridging-related ischemia. The positive predictive values of all CT-related parameters were low. Conclusion: ΔCT-FFR_systolic reliably excluded myocardial bridging-related ischemia with high sensitivity and NPV. Myocardial bridging showing positive CT-FFR results requires further evaluation.

• Journal of Cardiovascular Imaging
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• v.31 no.3
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• pp.125-132
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• 2023

BACKGROUND: There is limited data on the residual echocardiographic findings including strain analysis among post-coronavirus disease (COVID) patients. The aim of our study is to prospectively phenotype post-COVID patients. METHODS: All patients discharged following acute COVID infection were systematically followed in the post-COVID-19 Recovery Clinic at Vancouver General Hospital and St. Paul's Hospital. At 4-18 weeks post diagnosis, patients underwent comprehensive echocardiographic assessment. Left ventricular ejection fraction (LVEF) was assessed by 3D, 2D Biplane Simpson's, or visual estimate. LV global longitudinal strain (GLS) was measured using a vendor-independent 2D speckle-tracking software (TomTec). RESULTS: A total of 127 patients (53% female, mean age 58 years) were included in our analyses. At baseline, cardiac conditions were present in 58% of the patients (15% coronary artery disease, 4% heart failure, 44% hypertension, 10% atrial fibrillation) while the remainder were free of cardiac conditions. COVID-19 serious complications were present in 79% of the patients (76% pneumonia, 37% intensive care unit admission, 21% intubation, 1% myocarditis). Normal LVEF was seen in 96% of the cohort and 97% had normal right ventricular systolic function. A high proportion (53%) had abnormal LV GLS defined as < 18%. Average LV GLS of septal and inferior segments were lower compared to that of other segments. Among patients without pre-existing cardiac conditions, LVEF was abnormal in only 1.9%, but LV GLS was abnormal in 46% of the patients. CONCLUSIONS: Most post-COVID patients had normal LVEF at 4-18 weeks post diagnosis, but over half had abnormal LV GLS.

• Journal of Chest Surgery
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• v.38 no.5 s.250
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• pp.323-334
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• 2005

Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.317-325
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• 1994

The accuracy of dipyridamole stress/rest $^{99m}Tc$-MIBI myocardial imaging for detection of ischemia depends on reproducible image interpretation. To evaluate the reproducibility of visual assessment, agreement in interpretation among two independent observers, blind-ed to clinical data, was evaluated in SPECT images of 131 patients (94 males, 38 females; mean age $58{\pm}7yr$) with suspected coronary artery disease who underwent both dipyridamole stress/rest $^{99m}Tc$-MIBI myocardial SPECT and coronary angiography. The left ventricle was divided into twenty-nine segments in stress and rest SPECT images and each segment was visually graded according to a five-point scale (segmental score : 0=normal, 1=equivocal, 2=mild decrease, 3=severe decrease and 4=absent uptake). Overall concordance of segmental scoring between the two observers was 80%. The Pear-son's correlation coefficient (r) of the segmental scores for stress and rest images were 0.67 and 0.65, respectively, while the difference in score between the two images showed a correlation of 0.45 (all p<0.001). Agreement between two observers in final SPECT diagnosis as absence or presence of disease was 93%. The degree of agreement in segmental scoring showed no difference between patients with or without agreement as to the presence of disease. Therefore it appeared that cases with inconcordant diagnosis between the 2 observers were mainly due to a difference in individual threshold for interpretating the significance of a particular decreased uptake area rather than to a difference in perceiving the degree of the hypoactivity Thus, establishment of individual optimum thresholds in visual interpretation of myocardial SPECT may be helpful to improve reproducibility and accuracy of scan diagnosis.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.430-437
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• 2005

Purpose: The objectives of this study were - First, to determine the normal range of left ventricular end diastolic volume (EDV), end systolic volume (ESV) and election fraction (EF) from gated myocardial perfusion SPECT for Quantitative Gated SPECT (QGS) and 4D-MSPECT (4DM), respectively. Second, to evaluate the relationships between values produced by both software packages. Materials & Methods: Tc-99m MIBI gated myocardial perfusion SPECT were performed for 77 patients (mean age: $49.6{\pm}13.7y$, n=37(M), 40(F)) with a low likelihood (<10%) of coronary artery disease (CAD) using dual head gamma camera (E.CAM, Siemens, USA). Left ventricular EDV, ESV and EF were automatically measured by means of QGS and 4DM, respectively. Results: in QGS, the mean EDV, ESV and EF for all patients were $78.2{\pm}25.2ml,\;27.4{\pm}12.9ml\;and\;66.6{\pm}8.0%$ at stress test respectively, not different from rest test (p>0.05). In 4DM, the mean EDV, ESV and EF for all patients were $89.1{\pm}26.4ml,\;29.1{\pm}12.8ml\;and\;68.5{\pm}6.7%$ at stress test. Most cases in 4DM, there was no significant difference statistically between stress and rest test (p>0.05). But statistically significant difference was found in EF ($68.5{\pm}6.7%$ at stress vs $70.9{\pm}8.0%$ at rest, p<0.05). Correlation coefficients between the methods for EDV, ESV and EF were comparatively high (0.95, 0.93, 0.71 at stress test and 0.95, 0.90, 0.69 at rest test, respectively). However, Bland-Altman plots showed a large range of the limit value of agreement for EDV, ESV and EF between both methods ($-30ml{\sim}10ml,\;-12ml{\sim}8ml,\;-14%{\sim}11%$ at stress test and $-32ml{\sim}5ml,\;-13ml{\sim}13ml,\;-18%{\sim}12%$ at rest test). Conclusion: We found the normal ranges of EDV, ESV and EF for patients with a low likelihood of CAD in both methods. We expect these values will be a good reference to interpret gated myocardial perfusion SPECT. Although good correlation was observed between both methods, they should not be used interchangeably. Therefore, when both programs are used at the same site, it will be important to apply normal limits specific to each method.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.316-326
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• 1999

Purpose: We evaluated the feasibility of extracting pure left ventricular blood pool and myocardial time-activity curves (TACs) and of generating factor images from human dynamic N-13 ammonia PET using factor analysis. The myocardial blood flow (MBF) estimates obtained with factor analysis were compared with those obtained with the user drawn region-of-interest (ROI) method. Materials and Methods: Stress and rest N-13 ammonia cardiac PET imaging was acquired for 23 min in 5 patients with coronary artery disease using GE Advance tomograph. Factor analysis generated physiological TACs and factor images using the normalized TACs from each dixel. Four steps were involved in this algorithm: (a) data preprocessing; (b) principal component analysis; (c) oblique rotation with positivity constraints; (d) factor image computation. Area under curves and MBF estimated using the two compartment N-13 ammonia model were used to validate the accuracy of the factor analysis generated physiological TACs. The MBF estimated by factor analysis was compared to the values estimated by using the ROI method. Results: MBF values obtained by factor analysis were linearly correlated with MBF obtained by the ROI method (slope = 0.84, r = 0.91), Left ventricular blood pool TACs obtained by the two methods agreed well (Area under curve ratio: 1.02 ($0{\sim}1min$), 0.98 ($0{\sim}2min$), 0.86 ($1{\sim}2min$)). Conclusion: The results of this study demonstrates that MBF can be measured accurately and noninvasively with dynamic N-13 ammonia PET imaging and factor analysis. This method is simple and accurate, and can measure MBF without blood sampling, ROI definition or spillover correction.