Hye Jeong Lee

Tumor perfusion‐related parameter of diffusion‐weighted magnetic resonance imaging: Correlation with histological microvessel density

We obtained intravoxel incoherent motion (IVIM) parameters through biexponential analysis on diffusion‐weighted MR imaging (DWI) using multiple b values. Correlation was evaluated between these parameters and histological microvessel density (MVD) for the possibility of noninvasive evaluation of MVD with DWI.

Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation.

The structural and functional characteristics of left atrial appendage (LAA) in patients with atrial fibrillation (AF) with previous stroke remain incompletely elucidated. This study investigated whether a larger LAA orifice is related to decreased LAA flow velocity and stroke in nonvalvular AF. The dimension, morphology, and flow velocity of LAA were compared in patients with nonvalvular AF with (stroke group, n = 67, mean age 66 ± 9 years) and without ischemic stroke (no-stroke group, n = 151, mean age 56 ± 10 years). Compared with no-stroke group, the stroke group had larger LA dimension (4.7 ± 0.8 vs 4.2 ± 0.6 cm, p <0.001), larger LAA orifice area (4.5 ± 1.5 vs 3.0 ± 1.1 cm(2), p <0.001), and slower LAA flow velocity (36 ± 19 vs 55 ± 20 cm/s, p <0.001). LAA flow velocity was negatively correlated with LAA orifice size (R = -0.48, p <0.001). After adjustment for multiple potential confounding factors including CHA2DS2-VASc score, persistent AF, and LA dimension, large LAA orifice area (odds ratio 6.16, 95% confidence interval 2.67 to 14.18, p <0.001) and slow LAA velocity (odds ratio 3.59, 95% confidence interval 1.42 to 9.08, p = 0.007) were found to be significant risk factors of stroke. In patients with LAA flow velocity <37.0 cm/s, patients with large LAA orifice (>3.5 cm(2)) had greater incidence of stroke than those with LAA orifice of ≤3.5 cm(2) (75% vs 23%, p <0.001). In conclusion, LAA orifice enlargement was related to stroke risk in patients with nonvalvular AF even after adjustment for other risk factors, and it could be the cause of decreased flow velocity in LAA.

Evaluation of coronary artery in-stent restenosis by 64-section computed tomography: factors affecting assessment and accurate diagnosis.

Purpose To determine factors affecting the ability of 64-multislice computed tomography (MSCT) to detect, assess, and accurately diagnose significant coronary arterial in-stent restenosis (ISR). Materials and Methods The institutional review board approved this study and waived informed consent. Sixty patients underwent CT coronary angiography using 64-MSCT, after implantation of coronary artery stents (n=91). We assessed diagnostic accuracy for ISR with CT in comparison with conventional coronary angiography as the gold standard, visually and with measurement of in-stent coronary lumen density. Possible factors that influenced the diagnostic performance of CT were evaluated, which included image quality (IQ), stent characteristics, and location. Results Sixty-nine stents (75.8%) were assessable. Low IQ, location in the left circumflex coronary artery, and narrow stent diameter were associated with poor assessment (P<0.05). In stents that could be assessed, sensitivity, specificity, positive predictive value, and negative predictive value of 64-MSCT were 90.0%, 73.5%, 58.1%, and 94.7%, respectively, for significant ISR. The diagnostic accuracy in assessable stents showed a significant increase with better IQ, thinner strut thickness, and nondrug eluting stent. False-positive diagnoses of ISR by CT were explained by coronary lumen density measurements. Conclusions Evaluation of stents by 64-MSCT is not recommended in stents with diameters of ≤2.75u2009mm or stents located at the left circumflex coronary artery. The diagnostic accuracy of 64-MSCT is affected by IQ and strut thickness in assessable stents. Significant ISR can be excluded with high reliability in selected patients.

Autophagy Is Involved in the Reduction of Myelinating Schwann Cell Cytoplasm during Myelin Maturation of the Peripheral Nerve

Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination.

Use of Contrast Enhancement and High-Resolution 3D Black-Blood MRI to Identify Inflammation in Atherosclerosis

OBJECTIVESnWe investigated the contributing factors for plaque enhancement and examined the relationships between regional contrast enhancement and the inflammatory activity of atherosclerotic plaques in an experimental rabbit model using contrast-enhanced high-resolution 3-dimensional (3D) black-blood magnetic resonance imaging (MRI) in comparison with histopathologic analysis.nnnBACKGROUNDnInflammation plays a critical role in plaque initiation, progression, and disruption. As such, inflammation represents an emerging target for the treatment of atherosclerosis. MRI findings suggest that contrast agent-induced signal enhancement is associated with the degree of macrophage infiltration and neovessels that can be detected in plaque.nnnMETHODSnTen atherosclerotic rabbits and 3 normal control rabbits underwent high-resolution 3D contrast-enhanced black-blood MRI. Magnetic resonance images and the corresponding histopathologic sections were divided into 4 quadrants. Plaque composition was analyzed for each quadrant according to histopathologic criteria (percent of lipid-rich, fibrous, macrophage area and microvessel density) and imaging criteria (enhancement ratio [ER], ER = signal intensity(post)/signal intensity(pre)). Multiple linear regression analysis was performed to determine independent factors for plaque enhancement.nnnRESULTSnA total of 62 noncalcified plaques (n = 248; 156 lipid-rich quadrants and 92 fibrous quadrants) were identified based on histopathologic analysis. Mean ER values were significantly higher in atherosclerotic vessel walls than in normal vessel walls (2.03 ± 0.25 vs. 1.58 ± 0.15; p = 0.017). The mean ER values were significantly higher in lipid-rich quadrants compared with the fibrous quadrants (2.14 ± 0.31 vs. 1.84 ± 0.21; p = 0.001). Mean ER values were significantly higher in macrophage-rich plaques compared with the macrophage-poor plaques (2.21 ± 0.28 vs. 1.81 ± 0.22; p = 0.001). Using multiple regression analysis, macrophage area and microvessel density were associated independently with ER values that reflected plaque enhancement (p < 0.001).nnnCONCLUSIONSnContrast-enhanced high-resolution 3D black-blood MRI may be an efficient method to detect plaque inflammation.

Measurement of Opening and Closing Angles of Aortic Valve Prostheses In Vivo Using Dual-Source Computed Tomography: Comparison with Those of Manufacturers' in 10 Different Types

Objective The aims of this study were to compare opening and closing angles of normally functioning mechanical aortic valves measured on dual-source computed tomography (CT) with the manufacturers values and to compare CT-measured opening angles according to valve function. Materials and Methods A total of 140 patients with 10 different types of mechanical aortic valves, who underwent dual-source cardiac CT, were included. Opening and closing angles were measured on CT images. Agreement between angles in normally functioning valves and the manufacturer values was assessed using the interclass coefficient and the Bland-Altman method. CT-measured opening angles were compared between normal functioning valves and suspected dysfunctioning valves. Results The CT-measured opening angles of normally functioning valves and manufacturers values showed excellent agreement for seven valve types (intraclass coefficient [ICC], 0.977; 95% confidence interval [CI], 0.962-0.987). The mean differences in opening angles between the CT measurements and the manufacturers values were 1.2° in seven types of valves, 11.0° in On-X valves, and 15.5° in ATS valves. The manufacturers closing angles and those measured by CT showed excellent agreement for all valve types (ICC, 0.953; 95% CI, 0.920-0.972). Among valves with suspected dysfunction, those with limitation of motion (LOM) and an increased pressure gradient (PG) had smaller opening angles than those with LOM only (p < 0.05). Conclusion Dual-source cardiac CT accurately measures opening and closing angles in most types of mechanical aortic valves, compared with the manufacturers values. Opening angles on CT differ according to the type of valve dysfunction and a decreased opening angle may suggest an elevated PG.

Analysis of Tumor Markers in the Cytological Fluid Obtained from Computed Tomography-Guided Needle Aspiration Biopsy for the Diagnosis of Non-small Cell Lung Cancer

Purpose: The aim of this study was to prospectively assess whether analysis of the tumor markers cytokeratin 19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), and squamous cell carcinoma (SCC) antigen in cytological fluid can improve the performance of computed tomography (CT)-guided needle aspiration biopsy (NAB) in the diagnosis of non-small cell lung cancer (NSCLC). Methods: A total of 100 patients (men:women = 41:59, mean age: 63 years) with suspected malignant pulmonary lesions were prospectively enrolled for CT-guided NAB procedures. Levels of CYFRA 21-1, CEA, and SCC in the cytological fluid were measured by immunoradiometric assays. The cutoff value for tumor markers was selected on the basis of best accuracy through receiver operating characteristic curves. The sensitivity and areas under the curve (AUC) of NAB alone were compared with those of NAB combined with cytological tumor markers (CYFRA 21-1, CEA, and SCC). Results: Among 100 patients, 71 (71%) had NSCLC and 29 (29%) had benign lesions. The sensitivity, specificity, and accuracy for diagnosing NSCLC were 85.7%, 100%, and 89%, respectively, for NAB alone. The sensitivity increased significantly for NAB combined with a tumor marker compared with NAB alone (100% for CYFRA 21-1, 92.9% for CEA, and 94.2% for SCC; p = 0.001, p = 0.025, and p = 0.014, respectively). The AUC of NAB with CYFRA 21-1 was significantly larger than the AUC of NAB alone (p = 0.001). Conclusion: Evaluation of tumor markers CYFRA 21-1, CEA, and SCC in the cytological fluid can improve the diagnostic performance of CT-guided NAB for NSCLC. Of these markers, CYFRA 21-1 is the most useful cytological tumor marker.

Added value of cardiac computed tomography for evaluation of mechanical aortic valve: Emphasis on evaluation of pannus with surgical findings as standard reference

BACKGROUNDnThe added value of cardiac computed tomography (CT) with transesophageal echocardiography (TEE) for evaluating mechanical aortic valve (AV) dysfunction has not yet been investigated. The purposes of this study were to investigate the added value of cardiac CT for evaluation of mechanical AVs and diagnoses of pannus compared to TEE, with surgical findings of redo-aortic valve replacement (AVR) used as a standard reference.nnnMETHODSn25 patients who underwent redo-AVR due to mechanical AV dysfunction and cardiac CT before redo-AVR were included. The presence of pannus, encroachment ratio by pannus, and limitation of motion (LOM) were evaluated on CT. The diagnostic performance of pannus detection was compared using TEE, CT, and CT+TEE, with surgical findings as a standard reference. The added value of CT for diagnosing the cause of mechanical AV dysfunction was assessed compared to TTE+TEE.nnnRESULTSnIn two patients, CT analysis was not feasible due to severe metallic artifacts. On CT, pannus and LOM were found in 100% (23/23) and 60.9% (14/23). TEE identified pannus in 48.0% of patients (12/25). CT, TEE, and CT+TEE correctly identified pannus with sensitivity of 92.0%, 48.0%, and 92.0%, respectively (P=0.002 for CT vs. TEE). In 11 of 13 cases (84.6%) with inconclusive or negative TEE results for pannus, CT detected the pannus. Among 13 inconclusive cases of TTE+TEE for the cause of mechanical AV dysfunction, CT suggested 6 prosthetic valve obstruction (PVO) by pannus, 4 low-flow low-gradient PVO, and one LOM without significant PVO.nnnCONCLUSIONSnCardiac CT showed added diagnostic value with TEE in the detection of pannus as the cause of mechanical AV dysfunction.

Assessment of Mitral Paravalvular Leakage After Mitral Valve Replacement Using Cardiac Computed Tomography: Comparison With Surgical Findings.

Background—The diagnostic performance of cardiac computed tomography (CT) for detection of paravalvular leakage (PVL) after mitral valve replacement has not been investigated in a large population. We aimed to investigate the diagnostic accuracy of CT for diagnosis of mitral PVL using surgical findings as the standard reference and to compare the diagnostic performance of CT with those of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE). Methods and Results—A total of 204 patients with previous mitral valve replacement who underwent cardiac CT were retrospectively included. The presence of mitral PVL was analyzed on CT, TTE, and TEE. In 78 patients who underwent redo-surgery, diagnostic performance for the detection of PVL for CT, TTE, and TEE were compared with surgical findings as the standard reference. The location of mitral PVL on CT and TEE was compared with surgical findings. Mitral PVL was present in 18.1% (37/204) on CT, in 16.2% (32/198) on TTE, and in 42.6% (29/68) on TEE. On the surgical field, PVL was identified in 41.0% (32/78). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of PVL were 96.9%, 97.8%, 96.9%, 97.8%, and 97.4% for CT; 81.3%, 95.6%, 92.9%, 87.8%, and 89.6% for TTE; and 96.2%, 95.8%, 96.2%, 95.8%, and 96.0% for TEE. CT and TEE identified the correct location of PVL in 75.9% (22/29) and 85.6% (19/23). Conclusions—Cardiac CT may have better diagnostic accuracy compared with TTE for the detection of mitral PVL and may be comparable to TEE for the detection and localization of PVL.

Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer

BackgroundEGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers.The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation status in non-small cell lung cancer (NSCLC).MethodsWe prospectively collected tumor aspirates of 61 patients who underwent EGFR mutation analysis. Serum and cytologic CYFRA 21-1, CEA, and SCCA levels were measured and correlated with EGFR gene mutations. FDG PET/CT was performed on 58 patients for NSCLC staging, and SUV was correlated with EGFR mutation status.ResultsThirty (50xa0%) patients had EGFR mutation and 57 patients had adenocarcinoma subtype. Univariate analysis showed that female gender, never smoker, high levels of cytologic CYFRA 21-1 (c-CYFRA) and lower maximum standard uptake value (SUVmax) were correlated with EGFR mutations. ROC generated cut-off values of 20.8xa0ng/ml for c-CYFRA and SUVmax of 9.6 showed highest sensitivity for EGFR mutation detection. Multivariate analysis revealed that female gender [hazard ratio (HR): 18.15, pu2009=u20090.025], higher levels of c-CYFRA (HR: 7.58, and lower SUVmax (HR: 0.08, pu2009=u20090.005) were predictive of harboring EGFR mutation.ConclusionsThe cytologic tumor marker c-CYFRA was positively associated with EGFR mutations in NSCLC. EGFR mutation-positive NSCLCs have relatively lower glycolysis compared with NSCLCs without EGFR mutation.