Chen-Chang Lee

Adipose-Derived Mesenchymal Stem Cell Exosomes Suppress Hepatocellular Carcinoma Growth in a Rat Model: Apparent Diffusion Coefficient, Natural Killer T-Cell Responses, and Histopathological Features

We sought to evaluate the effects of adipose-derived mesenchymal stem cells (ADMSCs) exosomes on hepatocellular carcinoma (HCC) in rats using apparent diffusion coefficient (ADC), natural killer T-cell (NKT-cell) responses, and histopathological features. ADMSC-derived exosomes appeared as nanoparticles (30–90 nm) on electron microscopy and were positive for CD63, tumor susceptibility gene-101, and β-catenin on western blotting. The control (n = 8) and exosome-treated (n = 8) rats with N1S1-induced HCC underwent baseline and posttreatment day 10 and day 20 magnetic resonance imaging and measurement of ADC. Magnetic resonance imaging showed rapidly enlarged HCCs with low ADCs in the controls. The exosome-treated rats showed partial but nonsignificant tumor reduction, and significant ADC and ADC ratio increases on day 10. On day 20, the exosome-treated rats harbored significantly smaller tumors and volume ratios, higher ADC and ADC ratios, more circulating and intratumoral NKT-cells, and low-grade HCC (P < 0.05 for all comparisons) compared to the controls. The ADC and volume ratios exhibited significant inverse correlations (P < 0.001, R 2 = 0.679). ADMSC-derived exosomes promoted NKT-cell antitumor responses in rats, thereby facilitating HCC suppression, early ADC increase, and low-grade tumor differentiation. ADC may be an early biomarker of treatment response.

31P MR Spectroscopic Assessment of Muscle in Patients with Myasthenia Gravis before and after Thymectomy: Initial Experience

PURPOSE To prospectively assess muscle metabolism in myasthenia gravis (MG) patients before and after thymectomy by using phosphorus 31 (31P) magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS With institutional review board approval and informed consent, resting and dynamic (31)P MR spectroscopy were performed in 14 healthy volunteers (five men, nine women; mean age, 33 years; range, 23-48 years) and 16 MG patients (six men, 10 women; mean age, 37 years; range 18-50 years) before and after thymectomy. Patients were stratified into groups according to the modified Osserman classification: mild-MG group (classes I-IIA) and moderate-to-severe-MG group (classes IIB-IV). Variables compared among the three groups (Kruskal-Wallis test) included the inorganic phosphate (P(i))-adenosine triphosphate (ATP) (P(i)/ATP) ratio, phosphocreatine (PCr)-ATP (PCr/ATP) ratio, P(i)/PCr ratio, muscle pH at resting and at end-exercise ( 31)P MR spectroscopy, rate constant for PCr recovery (k(PCr)), and maximum oxidative capacity (V(max)). These variables were also compared in MG patients before and after thymectomy (Wilcoxon signed rank test). RESULTS There were no significant differences in resting P(i)/ATP, PCr/ATP, and P(i)/PCr ratios and resting muscle pH among the three groups (control group, 14; mild-MG group, nine; moderate-to-severe-MG group, seven). Comparison of the control group with the mild-MG group and comparison of the mild-MG group before thymectomy with the mild-MG group after thymectomy showed no significant differences in end-exercise P(i)/ATP, PCr/ATP, and P(i)/PCr ratios; end-exercise muscle pH; k(PCr); and V(max). Compared with the control and mild-MG groups, the moderate-to-severe-MG group had significantly higher end-exercise P(i)/ATP and P(i)/PCr ratios and significantly lower end-exercise muscle pH, k(PCr), and V(max) before thymectomy (P < or = .001), but these values showed significant restoration to normal after thymectomy (P = .018). CONCLUSION Mild-MG group patients have muscle oxidative metabolism similar to that of healthy control subjects, whereas moderate-to-severe-MG group patients have impaired V(max) during exercise and a noticeable shift to glycolytic metabolism, but these abnormalities are reversible after thymectomy.

Immediate intramyocardial bone marrow-derived mononuclear cells implantation in minipig myocardium after permanent coronary artery ligation: magnetic resonance imaging with histopathologic and immunochemical correlation.

Objectives:To investigate the effects of immediate intramyocardial implantation of autologous bone marrow-derived mononuclear cells (BMDMNCs) in minipig myocardium after coronary artery ligation with magnetic resonance imaging (MRI), histopathologic, and immunochemical studies. Materials and Methods:Of the 12 minipigs subjected to permanent left anterior descending coronary artery ligation, 6 were immediately treated with intramyocardial BMDMNCs (3 × 107 cells) implantation in the infarct area, whereas the other 6 were treated with intramyocardial injection of an equal amount of saline served as controls. Cardiovascular MRIs, including cine, first-pass, and late gadolinium enhancement (LGE) sequences, were performed on postoperative days 3 and 90. Postmortem infarct size and the degree of fibrosis on histopathologic examination were compared between 2 groups. The degree of BMDMNC differentiation was assessed with flow cytometry, whereas engraftment of BMDMNCs and vascular density was evaluated with confocal immunofluorescence microscopy and immunohistochemical staining, respectively. Results:There were no significant differences in cardiac function, first-pass dynamics, and LGE between the BMDMNC-treated group and the control group on day 3. On day 90, the BMDMNC-treated group had significantly higher left ventricular (LV) mass/body-weight ratio, lower end-diastolic or end-systolic LV volume/body-weight ratios, higher ejection fraction, better contractility, greater upslope and peak enhancement of the infarct areas, smaller hypoperfused area on first-pass study, and smaller enhanced area and infarct transmurality on LGE MRI than the control group. Flow cytometry revealed high cellular positivity of mesenchymal stem cell surface markers (CD90 and CD271) of the in vitro expanded cells on day 21 after cell culture. In the infarct and peri-infarct areas of the BMDMNC-treated group, there was limited myogenic-like cell differentiation, some engrafted undifferentiated cells, but prominent CD31-positive endothelial cells. On the other hand, a significantly higher number of &agr;-smooth muscle actin-positive small vessel (≤25 &mgr;m) was noted in the BMDMNC-treated group compared with that in the controls. Conclusions:After myocardial infarction in a swine model, immediate intramyocardial BMDMNCs implantation may promote neovascularization with resultant improvement in LV function, perfusion, and myocardial viability as demonstrated on cardiovascular MRI.

Effect of Age-Related Cartilage Turnover on Serum C-Telopeptide of Collagen Type II and Osteocalcin Levels in Growing Rabbits with and without Surgically Induced Osteoarthritis

This study aims to determine the effect of age-related cartilage turnover on the serum C-telopeptide of type II collagen (CTX-II) and osteocalcin (OC) levels in growing rabbits with and without surgically induced osteoarthritis. Twenty-four New Zealand male 3-month-old rabbits were randomized into three operated groups (n = 6 per group, with surgically induced osteroarthritis in the right knee; after blood sampling, the knees were harvested following euthanization at 2, 3, and 6 months after surgery) and a control group (n = 6, blood samples were obtained monthly between 3 and 15 months). Histomorphologically, the medial femoral condyles, particularly the central parts, harbored the most severe osteoarthritic changes among the operated rabbits. The serum levels of CTX-II and OC decreased in the controls from 3 to 11 months and then remained stable. No significant differences in the serum CTX-II and OC levels between the osteoarthritic rabbits and controls were observed. The osteoarthritic-to-normal ratios (ONRs, the ratios of serum CTX-II or OC levels in osteoarthritic rabbits to those of the controls at same ages) enabled an overall assessment of osteoarthritis and age-related cartilage turnover. Elevated CTX-II ONRs were observed in rabbits with mild to advanced osteoarthritis. However, the OC ONRs were unhelpful in assessing osteoarthritic growing rabbits.

Severe bilateral ischemic-reperfusion renal injury: hyperacute and acute changes in apparent diffusion coefficient, T1, and T2 mapping with immunohistochemical correlations

The aim of this study was to investigate the hyperacute and acute changes in apparent diffusion coefficient (ADC), T1, and T2 mapping in rat kidneys after severe bilateral renal ischemic-reperfusion injury (IRI). After baseline MRI, 24 Spraque-Dawley rats with renal IRI were divided equally as group 1 (post-IRI MRI at 6 hours, days 1, 3, and 7) and groups 2, 3, and 4 (post-IRI MRI at 6 hours; 6 hours and day 1; 6 hours, days 1 and 3, respectively), while six other rats without IRI (group 5) were used as sham control. ADC, T1, and T2 values of the cortex and outer and inner stripes of outer medulla (OSOM and ISOM), and immunohistochemical studies assessing monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and collagen deposition in three zones at different time points were evaluated. Significantly reduced ADCs in OSOM and ISOM are noninvasive biomarkers denoting hyperacute damages after IRI. Linear regression analysis revealed a significant inverse correlation between 6-hour/baseline ADC ratios and MCP-1 staining (P < 0.001, r2 = 0.738). ADC, T1, and T2 values are useful for assessing variable IRI changes in different layers depending on underlying microstructural and histopathological changes at different time points.

TRICKS Magnetic Resonance Angiography at 3-Tesla for Assessing Whole Lower Extremity Vascular Tree in Patients with High-Grade Critical Limb Ischemia: DSA and TASC II Guidelines Correlations

The entire vascular tree of 58 lower extremities with high-grade critical limb ischemia (CLI) was assessed with three-station time resolved imaging of contrast kinetics (TRICKS) magnetic resonance angiography (T-MRA) and correlated with digital subtraction angiography (DSA) examinations and Trans-Atlantic Inter-Society Consensus II (TASC II) guidelines. Kappa (κ) statistics were utilized to evaluate the agreement of stenosis scores (5-point scale; 0 normal to 4 occlusion) based on T-MRA and DSA. With DSA as the standard, significant stenosis instances (stenosis score ≥2) among vascular segments were compared. The κ-statistics of image quality (4-point scale; 1 nondiagnostic to 4 excellent) of T-MRA and TASC II classification assessed by a radiologist and a vascular surgeon were also evaluated. Among 870 vascular segments, excellent agreement was observed between T-MRA and DSA (mean κ = 0.883) in revealing stenosis (mean stenosis score, 2.1  ±  1.3 versus 2.0  ±  1.3). T-MRA harbored overall high sensitivity (99.5%), specificity (93.6%), positive predictive value (95.4%), negative predictive value (99.6%), and accuracy (97.7%) in depicting significant stenosis. Excellent interobserver agreement (mean κ = 0.818) of superb image quality (mean score = 3.5–3.6) of T-MRA and outstanding agreement of TASC II classification of aortoiliac and femoral-popliteal lesions (κ = 0.912–0.917) between two raters further verified the clinical feasibility of T-MRA for treatment planning.

Acute Epididymo-orchitis-Related Global Testicular Infarction: Clinical and Ultrasound Findings With an Emphasis on the Juxta-epididymal String-of-Bead Sign.

Abstract Acute epididymo-orchitis (AEO)–related global testicular infarction (GTI) is rare. We report herein the clinical and ultrasound findings of 6 patients with AEO-related GTI. Seventeen patients with torsion-related GTI were also reviewed and compared. The echotexture of AEO-related GTI ranged from mildly inhomogeneous to diffuse heteroechoic, depending on the severity of testicular necrotic changes. All of the patients showed a juxta-epididymal string-of-bead pattern on color Doppler ultrasound, which was ascribed to patent arteries (5/6, 87%) and collateral vessels (1/6, 13%) in the tunica albuginea. There were no significant differences in age, laterality, leukocyte count, testicular volume ratio (infarcted/normal), frequencies of heteroechoic testicular parenchyma, scrotal skin thickening, and hydrocele between the 2 groups. However, the left testis was predominantly affected in both groups. Compared with torsion-related GTI, patients with AEO-related GTI had significantly longer duration from scrotal pain onset to surgery (13.5 ± 5.2 vs 2.6 ± 2.0 days, P < 0.001), a higher level of serum C-reactive protein (110.0 ± 82.0 vs 41.2 ± 35.9 mg/dL, P = 0.013), a higher frequency of the juxta-epididymal string-of-bead sign (100% vs 12%, P < 0.001), and a lower frequency of the whirlpool/knot sign (0% vs 88%, P = 0.002). Although the testis in AEO-related GTI may appear variable from mildly to extensively heteroechoic on gray-scale ultrasound, this unusual disease can be characterized by an avascular testis with a juxta-epididymal string-of-bead sign on color Doppler ultrasound.

Effectiveness of a Tailored Anterior Saturation Band in the Improvement of the Image Quality of Pelvic Magnetic Resonance for Assessing Rectal Cancer

Purpose: We sought to test the effectiveness of the application of a tailored anterior saturation band (ASB) to improve the image quality of pelvic magnetic resonance imaging (MRI) for assessing rectal cancer. Methods: A total of 165 patients with MRI assessment of rectal cancer between 2013 and 2015 were included. The image quality scores (4‐point scale: 1, nondiagnostic through 4, excellent) of MRI without and with tailored ASBs were compared. Sensitivity, specificity, positive and negative predictive values, and accuracy of pelvic MRIs with and without a tailored ASB for T‐staging in 65 patients with direct surgery and 67 patients with chemoradiotherapy before surgery were evaluated. Results: Two independent raters exhibited moderate‐to‐excellent interobserver agreements (&kgr; = 0.529‐0.879) in the grading of MRI image quality. Overall, the quality scores of sagittal and axial T2‐weighted images with tailored ASBs were significantly improved compared with MRIs without ASBs (3.5 ± 0.3 vs. 2.7 ± 0.8 [mean ± SD]; P < .001, and 3.6 ± 0.3 vs. 2.8 ± 0.8; P < .001, respectively). The application of tailored ASBs in MRIs improved the averaged accuracies for staging of ≤ T2, T3, and T4 tumors from 87.7%, 78.5%, and 90.8% to 93.1%, 86.9%, and 97.7%, respectively. In post‐chemoradiotherapy MRI follow‐ups, the use of tailored ASBs also improved the average accuracies for staging of yT0, yT1‐2, yT3, and yT4 tumors from 80.6%, 73.1%, 73.9%, and 91.0%, to 85.8%, 82.9%, 85.1%, and 94.0%, respectively. Conclusions: Application of a tailored ASB in pelvic MRI is effective in substantially reducing motion artifacts, significantly upgrading image quality, and improving accuracies of rectal tumor staging. &NA; Pelvic magnetic resonance imaging is useful for the pretreatment assessment of rectal cancer, but motion artifacts can compromise clear tumor delineation. We tested the effectiveness of the application of a tailored anterior saturation band to improve the image quality of magnetic resonance imaging. This technique is effective in reducing motion artifacts with significant improvement of image quality and accuracies of rectal tumor staging.

Therapeutic Potential of Tacrolimus on Acute Myocardial Infarction in Minipigs: Analysis with Serial Cardiac Magnetic Resonance and Changes at Histological and Protein Levels

This study investigates the therapeutic potential of intracoronary tacrolimus against acute myocardial infarction (AMI) in minipigs with serial cardiac magnetic resonance (CMR) and changes at histological and protein levels. Twelve minipigs subjected to permanent left anterior descending artery ligation were randomized as tac-treated group (n = 6, with intracoronary tacrolimus treatment) and controls (n = 6). CMR with cine and late gadolinium enhancement (LGE) studies were performed on postoperative days 2, 5, and 21. There were no significant differences in left ventricular function (LVF), contractility, and LGE between the two groups on day 2. On day 5, the tac-treated group showed a significantly higher ejection fraction, smaller infarct, and lower day-5/day-2 infarct ratio than controls. On day 21, the controls demonstrated further deterioration of LVF and infarct. Contrastingly, the tac-treated animals demonstrated preservation of LVF, contractility, significantly smaller infarct, and lower day-21/day-2 infarct ratios compared with those on day 5 and controls. The in vivo CMR results were correlated with in vitro findings on histology, immunostaining, and Western blotting which revealed significantly less fibrosis, higher vascularities, less CD68+ and CD40+ inflammatory cells, lower expressions of inflammatory (MMP-9, NF-κB, and TNF-α), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers, respectively, in tac-treated AMI minipigs than controls.