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Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B‐type) mice were fed a normal‐protein (NP: 20% protein), or low‐protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, JO2${J_{{{\mathrm{O}}_{\mathrm{2}}}}}$) and fluorimetry (reactive oxygen species emission, JH2O2${J_{{{\mathrm{H}}_{\mathrm{2}}}{{\mathrm{O}}_{\mathrm{2}}}}}$) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin‐6, voltage‐dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α‐level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice. What is the central question of this study?Postnatal growth restriction (PGR) in early life is associated with cardiovascular disease: what are the mechanisms with regard to oxidative phosphorylation (OxPhos)?What is the main finding and its importance?PGR during development reduces cardiac metabolism through impairments in OxPhos. Our results show the PGR heart has higher electron leakage in the form of free radical production and reactive oxygen species emission. These findings are associated with an increased risk for cardiovascular disease in adulthood. Simply put, a brief period of growth restriction in early life has long‐lasting effects on cardiac metabolism in adulthood. [ABSTRACT FROM AUTHOR]

Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T‐cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD‐1, PD‐L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD‐L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD‐1+ immune cells (p = 0.0002) and CD8+ T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3+ (p = 0.0343) and CD8+ (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8+ (p = 0.0148), FOXP3+ (p = 0.0208), PD‐1+ (p = 0.0318) cells in PDAC, and FOXP3+ cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p < 0.0001), mass size (p = 0.0004), metastasis (p = 0.006), PD‐L1 (p < 0.0001), PD‐1 (p = 0.003) and CD8 (p = 0.0063) was significantly associated with OS in PDAC, and CD8 (p = 0.007) was statistically related to OS in BTC. In multivariate analysis, prognostic factors were operation after chemotherapy (p = 0.021) in PDAC and CD8 (p = 0.037) in BTC. Therefore, immunoprofile analysis of cells expressing CD8, FOXP3, PD‐1, and PD‐L1 might have prognostic values in patients with pancreaticobiliary tract cancers. [ABSTRACT FROM AUTHOR]

Background: Multi-segment foot models (MFMs) for assessing three-dimensional segmental foot motions are calculated via various analytical methods. Although validation studies have already been conducted, we cannot compare their results because the experimental environments in previous studies were different from each other. This study aims to compare the kinematics, repeatability, and reproducibility of five MFMs in the same experimental conditions. Methods: Eleven healthy males with a mean age of 26.5 years participated in this study. We created a merged 29-marker set including five MFMs: Oxford (OFM), modified Rizzoli (mRFM), DuPont (DFM), Milwaukee (MiFM), and modified Shriners Hospital for Children Greenville (mSHCG). Two operators applied the merged model to participants twice, and then we analysed two relative angles of three segments: shank-hindfoot (HF) and hindfoot-forefoot (FF). Coefficients of multiple correlation (CMC) and mean standard errors were used to assess repeatability and reproducibility, and statistical parametric mapping (SPM) of the t-value was employed to compare kinematics. Results: HF varus/valgus of the MiFM and mSHCG models, which rotated the segment according to radiographic or goniometric measurements during the reference frame construction, were significantly more repeatable and reproducible, compared to other models. They showed significantly more dorsiflexed HF and plantarflexed FF due to their static offset angles. DFM and mSHCG showed a greater range of motion (ROM), and some models had significantly different FF points of peak angle. Conclusions: Under the same conditions, rotating the segment according to the appropriate offset angle obtained from radiographic or goniometric measurement increased reliability, but all MFMs had clinically acceptable reliability compared to previous studies. Moreover, in some models, especially HF varus/valgus, there were differences in ROM and points of peak angle even with no statistical difference in SPM curves. Therefore, based on the results of this study, clinicians and researchers involved in the evaluation of foot and ankle dysfunction need an understanding of the specific features of each MFM to make accurate decisions. [ABSTRACT FROM AUTHOR]

Background: Hypervascular hyperplastic nodules (HHNs) occasionally develop in patients with alcoholic liver cirrhosis (ALC) and show arterial enhancement, thus mimicking hepatocellular carcinoma (HCC). Importantly, HHN as a benign lesion should be distinguished from HCC.Purpose: To evaluate the value of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) and diffusion-weighted imaging (DWI) in distinguishing HHN from small (<3 cm) hypervascular HCC (hHCC) in patients with ALC.Study Type: Retrospective case-control study.Field Strength/sequence: 3.0T/in- and out-of-phase, T1 -weighted, T2 -weighted, diffusion-weighted, apparent diffusion coefficient, and dynamic gadoxetic acid-enhanced images.Population: Among 560 patients with ALC who underwent Gd-EOB-MRI and DWI, 12 patients with 28 HHNs and 22 patients with 29 hHCCs smaller than 3 cm were included.Assessment: The following MRI features were evaluated by three independent radiologists: signal intensity (SI) on T1 -weighted, T2 -weighted, diffusion-weighted, and hepatobiliary phase (HBP) images; shape, homogeneity, and margin on HBP; diffusion restriction; intralesional fat; necrosis; hemorrhage; washout on portal venous phase (PVP) and/or transitional phase (TP); and capsular enhancement. Quantitative analysis was also conducted.Statistical Tests: Univariate and multivariate analyses were performed to determine the significant MRI findings, and their diagnostic performance for the prediction of HHN was analyzed.Results: Lesion size of ≤16 mm (odds ratio [OR], 24.41; P = 0.007), low-to-iso SI on DWI (OR, 26.92; P = 0.007), and absence of washout on PVP and/or TP (OR, 31.84; P = 0.009) were significant independent factors for predicting HHN. When all three criteria were satisfied, the specificity was 100%. Compared with hHCCs, HHNs showed significantly smaller size (mean, 13.8 mm vs. 19.9 mm; P < 0.001) and higher mean SI value (994.0 vs. 669.5) and lesion-to-liver SI ratio (1.045 vs. 0.806) on HBP (P < 0.001, respectively).Data Conclusion: Gd-EOB-MRI and DWI may be helpful in differentiating HHN from small hHCC in patients with ALC.Level Of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:70-80. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of rectal MRI in predicting candidates for local excision (LE; ypT0-1N0) after neoadjuvant chemoradiation therapy (CRT) in patients with rectal cancer.Materials and Methods: The institutional review board approved our retrospective study and waived informed consent. Inclusion criteria were as follows: patients with pathologically confirmed mid to lower rectal cancer (cT3NxM0 before neoadjuvant CRT) who underwent neoadjuvant CRT and had MRI performed at 3T before and after neoadjuvant CRT. A total of 168 patients met the study criteria between 2011 and 2012. Two observers independently assessed tumor and nodal stages on MR images obtained after neoadjuvant CRT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying a candidate for LE (ypT0-1N0) were calculated. Interobserver agreement was assessed with kappa value. Predictive factors for ypT0-1N0 were evaluated by logistic regression models.Results: MRI had relatively high accuracy, specificity, and NPV (85.9%, 93.8%, and 88.9% for observer 1 and 85.3%, 96.1%, and 86.6% for observer 2), moderate PPV (71.4% and 76.2%), and relatively low sensitivity (57.1% and 45.7%) for predicting ypT0-1N0. The interobserver agreement was fair (kappa value = 0.593). Carcinoembryonic antigen levels after neoadjuvant CRT and the maximal extramural depth of tumor spread were significant predictors of ypT0-1N0 (P = 0.037 and 0.017, respectively).Conclusion: MRI after neoadjuvant CRT can predict a candidate for LE (ypT0-1N0) after neoadjuvant CRT with moderate PPV and relatively high NPV. J. Magn. Reson. Imaging 2016;44:471-477. [ABSTRACT FROM AUTHOR]

Apoptosis repressor with caspase-recruiting domain (ARC) is an apoptosis repressor that inhibits both intrinsic and extrinsic apoptosis signalling. Human ARC contains an N-terminal caspase-recruiting domain (CARD domain) and a C-terminal proline- and glutamic acid-rich (P/E-rich) domain. The CARD domain in ARC is the domain that is directly involved in inhibition of the extrinsic pathway. In this study, the N-terminal CARD domain of ARC was overexpressed, purified and crystallized. X-ray diffraction data were collected to a resolution of 2.1 Å and the crystals were found to belong to space group P61 or P65, with unit-cell parameters a = 98.28, b = 98.28, c = 51.86 Å, α = 90, β = 90, γ = 120°. [ABSTRACT FROM AUTHOR]

Purpose To determine the added value of 3 Tesla liver MR in patients with hepatocellular carcinoma (HCC) within the liver computed tomography (CT) -based Milan criteria. Materials and Methods Liver CT and MR images of 130 patients with HCC within the Milan criteria based on liver CT were retrospectively reviewed. The number of MR-diagnosed HCCs and that of high risk hypervascular nodules (HRHNs), the effect of obtaining MR on patient management and CT appearances of MR-diagnosed HCCs and those of HRHNs were evaluated. Independent predictor for diagnosing additional HCCs on liver MR was analyzed. Results A total of 18.5% (24/130) of patients had additional 39 HCCs on MR, with a 5.4% (7/130) dropout rate from the Milan criteria. 28.5% (37/130) of patients had additional 78 HRHNs. Overall, 39.2% (51/130) of patients required changes in management. The common CT appearances of MR-diagnosed HCCs were arterial enhancing lesions ≥ 0.5cm (38.4%, 15/39), low density nodules < 1.5 cm (30.8%, 12/39) and invisibility (28.2%, 11/39). For MR-diagnosed HRHNs, 55.1% (43/78) were invisible on CT. The presence of inconclusive lesions on CT was an independent predictor for diagnosing additional HCCs on MR. Conclusion For patients with HCCs within the Milan criteria on liver CT, liver MR may be necessary to detect additional HCCs and HRHNs. J. Magn. Reson. Imaging 2014;39:842-852. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy of diffusion-weighted imaging (DWI) in differentiating hepatic abscess from malignant mimickers with an emphasis on periphery of the lesions. Materials and Methods Thirty-nine patients with hepatic abscess and 74 patients with malignant hepatic tumors were included, who underwent gadoxetic acid-enhanced MRI. For qualitative and quantitative analysis, signal intensities and apparent diffusion coefficient (ADC) values of the periphery were assessed. Two observers reviewed DWI and ADC maps rated using a 5-point scale. Diagnostic performance was evaluated using the receiver operating characteristics (ROC) curve analysis. Results The periphery of hepatic abscesses was T1-hypointense, arterial hyperintense, and hypointense on hepatobiliary phase less frequently than that of malignant tumors ( P < 0.05). No hepatic abscesses showed peripheral washout on 3-min late phase compared with malignant tumors (59.5%) ( P < 0.001). Both groups showed hyperintense rims on DWI, but, 37(94.9%) abscesses revealed rims with high ADC values compared with one (1.4%) malignant tumor ( P < 0.001). Mean ADC values of abscesses (1.47 × 10−3 mm2/s ± 0.36 [standard deviation]) were significantly higher than those of malignancies (0.68 × 10−3 mm2/s ± 0.20). Diagnostic performance (area under the ROC curve [ Az]) of DWI in identifying hepatic abscess was 0.986 and 0.982 for each observer. Conclusion In addition to conventional MRI, DWI is helpful in differentiating hepatic abscess from malignant mimickers. J. Magn. Reson. Imaging 2013;38:1333-1341. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To compare the image quality between T1 high-resolution isotropic volume examination using the multi-echo Dixon technique (mDixon-eTHRIVE) and that using spectrally adiabatic inversion recovery (SPAIR-eTHRIVE) in gadoxetic acid-enhanced liver MRI, and to evaluate the detectability of hepatocellular carcinoma (HCC) on mDixon-eTHRIVE. Materials and Methods Seventy patients with 117 HCCs underwent gadoxetic acid-enhanced liver MRI using mDixon-eTHRIVE. All patients also underwent gadoxetic acid-enhanced MRI using SPAIR-eTHRIVE (mean interval of 96 days). Two radiologists performed a consensus review of MRIs for image quality, homogeneity of fat suppression, artifact, and anatomic sharpness using a four-point scale. The detectability for HCC with mDixon-eTHRIVE was assessed using alternative-free response receiver operating characteristic. Results All mDixon-eTHRIVE images received higher scores for homogeneity of fat suppression and image quality ( P < 0.05) compared with those for SPAIR-eTHRIVE. With respect to artifact and anatomic sharpness, there was no significant difference between two MRIs ( P > 0.05). Diagnostic accuracy (Az) and sensitivity for detecting HCCs with mDixon-eTHRIVE images were mean 0.954 and 93.2%, respectively. Conclusion For gadoxetic acid-enhanced liver MRI, mDixon-eTHRIVE showed improved homogeneity of fat suppression and overall image quality compared with SPAIR-eTHRIVE. J. Magn. Reson. Imaging 2013;38:401-410. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To compare enhancement of the liver and pancreas quantitatively on late hepatic arterial phase images among various gadolinium-based contrast agents (GBCAs) at 1.5 Tesla (T) MRI. Materials and Methods Patients underwent consecutive MR studies with the following GBCAs: gadopentetate dimeglumine (0.1 mmol/kg) gadobenate dimeglumine (0.05 mmol/kg), gadoxetic acid, and gadobutrol group. The enhancement of liver and pancreas was evaluated quantitatively on late hepatic arterial phase. Relative pancreas-to-liver enhancement ratio was also calculated. Results Mean % enhancement of the liver and the pancreas was 21.57 and 55.40, and mean relative pancreas to liver enhancement was 2.23. Mean % enhancement of the liver for gadopentetate, gadobenate, gadoxetic, and gadobutrol were 20.4 ± 12.3, 21.7 ± 7.1, 16.2 ± 6.1, 29.1 ± 21.9. Significant difference was observed for % enhancement of liver comparing gadobutrol and gadoxetic ( P = 0.048). Mean % enhancement of pancreas for gadopentetate, gadobenate, gadoxetic, and gadobutrol were 53.6 ± 12.6, 60.1 ± 13.7, 52.7 ± 10.6, 54.7 ± 19.5. No significant differences were observed for % enhancement of pancreas ( P > 0.05). No significant differences were observed for relative pancreas-to-liver enhancement ratio ( P > 0.05). Conclusion Our study describes % enhancement of liver and pancreas using various GBCAs. The data may provide reference material on relaxation properties of GBCAs in vivo. J. Magn. Reson. Imaging 2013;38:102-108. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relative enhancement of liver, pancreas, focal nodular hyperplasia (FNH), pancreas-to-liver index, and FNH-to-liver index in the hepatic arterial dominant phase (HADP) after injection of hepatocyte-specific MRI contrast agents, gadoxetic acid and gadobenate dimeglumine, on 3 and 1.5 Tesla (T) MRI in the same patient. Materials and Methods: The MRI database was retrospectively searched to identify consecutive patients who underwent abdominal MRI at 3T and 1.5T systems, using both 0.025 mmol/kg gadoxetic acid-enhanced and 0.05 mmol/kg gadobenate dimeglumine-enhanced MRI at the same magnetic strength field system. 22 patients were identified, 10 were scanned at 3T system and 12 at 1.5T system. The enhancement of liver, pancreas, and FNH was evaluated quantitatively on MR images. Results: The relative enhancement of liver in HADP in the gadobenate dimeglumine-enhanced group in all subjects was significantly higher than that in gadoxetic acid-enhanced group ( P = 0.023). The gadobenate dimeglumine-enhanced group in HADP had better relative enhancement of pancreas and FNH, pancreas-to-liver index, and FNH-to-liver index than gadoxetic acid-enhanced group, but the difference was not statistically significant. Conclusion: The 0.05 mmol/kg gadobenate dimeglumine-enhanced abdominal MRI studies at 3T and 1.5T MR systems are superior in relative enhancement of the liver in HADP to 0.025 mmol/kg gadoxetic acid-enhanced MRI. This type of assessment may provide comparative effectiveness data. J. Magn. Reson. Imaging 2013;37:903-908. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To examine the differential features of combined hepatocellular and cholangiocarcinoma (HCC-CC) from mass-forming intrahepatic cholangiocarcinoma (ICC) on gadoxetic acid-enhanced MRI. Materials and Methods: Forty patients with pathologically proven combined HCC-CC (n = 20) and ICCs (n = 20) who had undergone gadoxetic acid-enhanced MRI were enrolled in this study. MR images were analyzed for the shape of lesions, hypo- or hyperintense areas on the T2-weighted image (T2WI), rim enhancement during early dynamic phases, and central enhancement with hypointense rim (target appearance) on the 10-min and 20-min hepatobiliary phase (HBP). The significance of these findings was determined by the χ2 test. Results: Irregular shape and strong rim enhancement during early dynamic phases, and absence of target appearance on HBP favored combined HCC-CCs ( P < 0.05). Lobulated shape, weak peripheral rim enhancement, and the presence of complete target appearance on the 10-min and 20-min HBP favored ICCs ( P < 0.05). However, 10 CC-predominant type of combined HCC-CC showed complete or partial target appearance on 10-min HBP. Conclusion: The shape of tumors, degree of rim enhancement during early dynamic phases, and target appearance on HBP were valuable for differentiating between combined HCC-CC and mass-forming ICC on gadoxetic acid-enhanced MRI. J. Magn. Reson. Imaging 2012;36:881-889. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To determine histological and MR imaging differences between areas with Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid) uptake and without in hepatocellular carcinomas (HCCs) as seen on Gd-EOB-DTPA-enhanced hepatobiliary-phase MR images. Materials and Methods: This study included nine patients with nine histopathologically proven HCCs (mean size, 1.9 cm) that consisted of two portions of a non-hypointense (Gd-EOB-DTPA uptake) and hypointense area (no Gd-EOB-DTPA uptake) in one tumor as depicted on hepatobiliary-phase MR images. Two radiologists and one pathologist compared the histological and MR finding differences between the two portions in consensus. Results: In eight specimens, non-hypointense areas of six specimens showed a green color and two specimens did not show a green color. Microscopically, two of nine showed a higher percentage of bile pigments in the non-hypointense area as compared to the hypointense area and the remaining seven showed no difference. Six were homogeneous Edmondson-Steiner grade II, and one was grade I. In two, non-hypointense areas were grade II and hypointense areas were grade I. No difference between the two portions was found for necrosis, hemorrhage, fibrosis, and a fibrous capsule. Seven on T1/T2-weighted images and eight on arterial and portal phase images showed no different signal intensity between the two portions. Conclusion: Although macroscopically, a non-hypointense area of an HCC seen on GD-EOB-DTPA-enhanced hepatobiliary-phase images may be associated with the area with a green color, no definite microscopic and MR imaging findings that could discriminate a non-hypointense from a hypointense area of an HCC was found. J. Magn. Reson. Imaging 2010;32:719-725. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of gadoxetic acid-enhanced MRI with that of multi-phase 40- or 64-multidetector row computed tomography (MDCT) to evaluate viable tumors of hepatocellular carcinomas (HCCs) treated with image-guided tumor therapy. Materials and Methods: A total of 108 patients with 162 HCCs (56 lesions with viable tumor and 106 without viable tumor) treated by means of transcatheter arterial chemoembolization or radiofrequency ablation were retrospectively included in this study. All patients underwent multi-phase CT at 40- or 64-MDCT and gadoxetic acid-enhanced MRI using 3.0 Tesla (T). Two observers independently and randomly reviewed the CT and MR images of the treated lesions. The diagnostic performance of two techniques for the evaluation of the viable tumors in the treated lesions was assessed with a receiver operating characteristic (ROC) analysis. Results: For each observer, the areas under the ROC curve were 0.953 and 0.969 for MRI, and 0.870 and 0.888 for MDCT ( P < 0.05). The diagnostic accuracies (96.3% for each observer) and sensitivities (92.9% and 96.4%) of MRI in two observers were significantly higher than those (82.7% and 80.9%, 53.6% for each observer, respectively) of MDCT ( P < 0.001). The negative predictive values (96.3% and 98.1%) of MRI in two observers were significantly higher than those (80.0% and 79.5%) of MDCT ( P < 0.001). For each observer, specificities and positive predictive values did not differ significantly between the two techniques ( P > 0.05). Conclusion: Gadoxetic acid-enhanced MRI shows better diagnostic performance than that of MDCT for evaluating the viable tumors of HCCs treated with image-guided tumor therapy. J. Magn. Reson. Imaging 2010;32:629-638. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum-like papillary dermal elastolysis is a rare acquired elastolytic disorder characterized by papules that resemble pseudoxanthoma elasticum, and it typically affects elderly women. Histopathological examination shows atrophic epidermis and band-like loss of elastic tissue in the papillary dermis. The pathogenesis is assumed to be related to intrinsic aging because it affects elderly people and shows the loss of elastic tissue. We report a case of pseudoxanthoma elasticum-like papillary dermal elastolysis in early middle age presenting typical clinical and histopathological findings. The patient was a 41-year-old woman who had had her lesions for 10 years. We propose that younger patients, hitherto unknown, can be affected by this disorder and suggest that mechanisms other than intrinsic aging are involved in its pathogenesis. [ABSTRACT FROM AUTHOR]