[Ruptured mycotic cerebral aneurysm in an adult T-cell leukemia/lymphoma patient undergoing allogeneic stem cell transplantation].

A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.

Right ventricular strain and volume analyses through deep learning-based fully automatic segmentation based on radial long-axis reconstruction of short-axis cine magnetic resonance images.

OBJECTIVE: We propose a deep learning-based fully automatic right ventricle (RV) segmentation technique that targets radially reconstructed long-axis (RLA) images of the center of the RV region in routine short axis (SA) cardiovascular magnetic resonance (CMR) images. Accordingly, the purpose of this study is to compare the accuracy of deep learning-based fully automatic segmentation of RLA images with the accuracy of conventional deep learning-based segmentation in SA orientation in terms of the measurements of RV strain parameters. MATERIALS AND METHODS: We compared the accuracies of the above-mentioned methods in RV segmentations and in measuring RV strain parameters by Dice similarity coefficients (DSCs) and correlation coefficients. RESULTS: DSC of RV segmentation of the RLA method exhibited a higher value than those of the conventional SA methods (0.84 vs. 0.61). Correlation coefficient with respect to manual RV strain measurements in the fully automatic RLA were superior to those in SA measurements (0.5-0.7 vs. 0.1-0.2). DISCUSSION: Our proposed RLA realizes accurate fully automatic extraction of the entire RV region from an available CMR cine image without any additional imaging. Our findings overcome the complexity of image analysis in CMR without the limitations of the RV visualization in echocardiography.

Epiregulin is critical for the acinar cell regeneration of the submandibular gland in a mouse duct ligation model.

Acinar cell regeneration from tubular structures has been reported to occur in duct-deligated salivary glands. However, the detailed process of acinar cell regeneration has not been clarified. We have developed a mouse duct ligation model to clarify the mechanisms underlying acinar cell regeneration, and we analyzed the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) ligands using the model. We studied these ligands expressions in the course of acinar cell regeneration using immunohistochemistry and RT-PCR methods. In the duct-ligated portion of the submandibular gland (SMG) that underwent atrophy, newly formed acinar cells were observed arising from the tubular structures after the release of the duct obstruction. The constitutive expression of EGFR was observed by immunohistochemistry in both the duct-ligated and duct-deligated animals as well as in normal controls. The EGFR phosphorylation detected on the tubular structures after duct ligation paralleled the acinar cell regeneration. RT-PCR showed an increase in the epiregulin and heparin-binding EGF levels from day 0 to day 3 after the release of the duct obstruction. The EGF level was increased only after day 7. In vitro, cultured cells isolated from ligated SMGs proliferated and produced EGF ligands following the addition of epiregulin to the culture medium. These findings suggest that the tubular structures localized in an atrophic gland are the source of acinar cell regeneration of the salivary gland. The induction of EGF ligands, in particular epiregulin, may play an important role in acinar cell regeneration in this model.

Relevance of increased negative T waves in apical hypertrophic cardiomyopathy with progressive myocardial damage: Insights from repeat cardiac magnetic resonance studies.

In patients with apical hypertrophic cardiomyopathy (HCM), progressive electrocardiographic changes are observed during long-term follow-up. However, it is difficult to correspond these changes to the specific myocardial changes. Cardiac magnetic resonance (CMR) imaging can elucidate myocardial changes by late gadolinium enhancement. Here, we present the long-term follow-up (>18 years) on a patient with apical HCM, whereupon, precise and continuous changes in the myocardium, causing ST segment and T wave changes on electrocardiography, were observed on CMR images. The combination of electrocardiography and CMR facilitates management of patients with apical HCM because it helps explain and understand the nature of electrocardiography changes over time.

Transforming growth factor-α activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation.

The role that transforming growth factor-α (TGF-α) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-α on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-α and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-α stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and α1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-α-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-α-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-α increased proliferation and migration of PSCs. TGF-α-induced migration of cells may be partly due to upregulation of MMP-1. TGF-α and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.

Differentiation between mild and severe myocarditis using multiparametric cardiac magnetic resonance.

The pathophysiology of myocarditis is associated with mild inflammation and may progress silently, or in severe cases such as fulminant myocarditis, may lead to sudden hemodynamic compromise. An invasive myocardial biopsy is generally required for a definitive myocarditis diagnosis. Alternatively, cardiac magnetic resonance (CMR), which evaluates myocardial characteristics and cardiac function, can be used as a noninvasive tool for diagnosing myocarditis. We describe the cases of a 49-year-old woman with mild acute eosinophilic myocarditis and a 48-year-old man with severe acute lymphocytic myocarditis. CMR was performed during the acute and convalescent phases in both cases. Compared with mild myocarditis, CMR in severe myocarditis showed higher T2 values and decreased left ventricular and atrial volumes and strains; however, the right ventricular strain was preserved. Late gadolinium enhancement showed faint contrast enhancement in the whole and strong enhancement in the local myocardium. Follow-up CMR showed recovery from myocardial inflammation and cardiac function. Some late gadolinium enhancement persisted whereas acute inflammation-associated enhancement disappeared. This case report highlights the differences between the cardiac parameters of patients with mild and severe myocarditis. Severe myocardial inflammation can be caused by severe heart failure owing to the concurrent reduction of cardiac function and compliance. Additionally, preserved right ventricular strain may predict cardiac function recovery in acute myocarditis. Noninvasive and repeatable CMR provides information on myocardial characteristics, cardiac function, and hemodynamics in a single scan at that time, which is useful not only for diagnosis but also for severity assessment and patient management in acute myocarditis.

Preoperative Novel Magnetic Resonance Fusion Imaging for Carotid Endarterectomy Patients with Contrast Contraindications: A Pilot Study.

OBJECTIVE: For carotid endarterectomy (CEA) patients with renal dysfunction and allergies to contrast media, we developed a preoperative novel method of noncontrast 3-dimensional magnetic resonance fusion imaging (NC-3DMRFI) which could describe well blood vessels, plaques, and bony structures even in surgical position. In this study, we examined the usefulness of this method. METHODS: We extracted noncontrast magnetic resonance images of bones, blood vessels, and plaques to create a 3-dimensionalusion image. An image acquired in the normal position and another in the surgical position during CEA were used to create a fusion image. We compared the fusion imaging results with the intraoperative findings of 6 patients with contrast contraindications received CEA. RESULTS: Preoperative NC-3DMRFI could clearly show the positions of the carotid bifurcation, the distal end of plaque, and the bony structure in 5 of the 6 cases. Intraoperative findings and preoperative fusion imaging results were comparable in all cases where fusion images could be created. The fusion imaging in the surgical position during CEA was useful for preoperative examination, and the surgical space could be secured in the case of a high cervical location. CONCLUSIONS: This pilot study showed our novel NC-3DMRFI method is useful for preoperative simulation in CEA, especially in patients with renal dysfunction and allergies to contrast media.

Cardiac Disease Classification Using Two-Dimensional Thickness and Few-Shot Learning Based on Magnetic Resonance Imaging Image Segmentation.

Cardiac cine magnetic resonance imaging (MRI) is a widely used technique for the noninvasive assessment of cardiac functions. Deep neural networks have achieved considerable progress in overcoming various challenges in cine MRI analysis. However, deep learning models cannot be used for classification because limited cine MRI data are available. To overcome this problem, features from cine image settings are derived by handcrafting and addition of other clinical features to the classical machine learning approach for ensuring the model fits the MRI device settings and image parameters required in the analysis. In this study, a novel method was proposed for classifying heart disease (cardiomyopathy patient groups) using only segmented output maps. In the encoder-decoder network, the fully convolutional EfficientNetB5-UNet was modified to perform the semantic segmentation of the MRI image slice. A two-dimensional thickness algorithm was used to combine the segmentation outputs for the 2D representation of images of the end-diastole (ED) and end-systole (ES) cardiac volumes. The thickness images were subsequently used for classification by using a few-shot model with an adaptive subspace classifier. Model performance was verified by applying the model to the 2017 MICCAI Medical Image Computing and Computer-Assisted Intervention dataset. High segmentation performance was achieved as follows: the average Dice coefficients of segmentation were 96.24% (ED) and 89.92% (ES) for the left ventricle (LV); the values for the right ventricle (RV) were 92.90% (ED) and 86.92% (ES). The values for myocardium were 88.90% (ED) and 90.48% (ES). An accuracy score of 92% was achieved in the classification of various cardiomyopathy groups without clinical features. A novel rapid analysis approach was proposed for heart disease diagnosis, especially for cardiomyopathy conditions using cine MRI based on segmented output maps.

Assessment of Bi-Ventricular and Bi-Atrial Areas Using Four-Chamber Cine Cardiovascular Magnetic Resonance Imaging: Fully Automated Segmentation with a U-Net Convolutional Neural Network.

Four-chamber (4CH) cine cardiovascular magnetic resonance imaging (CMR) facilitates simultaneous evaluation of cardiac chambers; however, manual segmentation is time-consuming and subjective in practice. We evaluated deep learning based on a U-Net convolutional neural network (CNN) for fully automated segmentation of the four cardiac chambers using 4CH cine CMR. Cine CMR datasets from patients were randomly assigned for training (1400 images from 70 patients), validation (600 images from 30 patients), and testing (1000 images from 50 patients). We validated manual and automated segmentation based on the U-Net CNN using the dice similarity coefficient (DSC) and Spearman's rank correlation coefficient (ρ); p < 0.05 was statistically significant. The overall median DSC showed high similarity (0.89). Automated segmentation correlated strongly with manual segmentation in all chambers-the left and right ventricles, and the left and right atria (end-diastolic area: ρ = 0.88, 0.76, 0.92, and 0.87; end-systolic area: ρ = 0.81, 0.81, 0.92, and 0.83, respectively; p < 0.01). The area under the curve for the left ventricle, left atrium, right ventricle, and right atrium showed high scores (0.96, 0.99, 0.88, and 0.96, respectively). Fully automated segmentation could facilitate simultaneous evaluation and detection of enlargement of the four cardiac chambers without any time-consuming analysis.

A Case of Adenomyoepithelioma With a Pleomorphic Adenoma-Like Component of the Male Breast.

Adenomyoepithelioma (AME) of the male breast is a rare tumor characterized by biphasic proliferation of gland epithelial cells and myoepithelial cells. Though pleomorphic adenoma (PA) is also known to be an epithelial-myoepithelial tumor in the breast, and these tumors are considered to exist on the same spectrum by some authors, to the best of our knowledge, there have been no reports of a clear transition from AME to PA in the male breast. Therefore, the case of an 85-year-old man with AME with PA-like components is presented.

Assessing myocardial circumferential strain using cardiovascular magnetic resonance after magnetic resonance-conditional cardiac resynchronization therapy.

Nondrug therapy for arrhythmia patients had been developed dramatically until recent years. Cardiac resynchronization therapy (CRT), a nondrug therapy for arrhythmia, is especially utilized for the treatment of left ventricular (LV) severe heart failure caused by cardiac dyssynchrony. Prolonged QRS duration (≧130 ms) is strongly used as a CRT indication criterion, but QRS is not the direct clinical index of mechanical contraction delay of the LV myocardium. Therefore, identifying the presence of dyssynchrony by diagnostic imaging is necessary. Echocardiography is widely used for the assessment of dyssynchrony as a standard diagnostic imaging. Several studies have addressed the efficacy of cardiovascular magnetic resonance feature tracking (CMR-FT) in the diagnosis of dyssynchrony for arrythmia patients. In addition, cardiac implantable electronic devices (CIEDs) were not available to examine CMR until recent years; however, new MR-conditional CIEDs have become available for use before and after CRT. Recently, diagnostic imaging using CMR-FT has been attracting attention for the assessment of dyssynchrony. However, a strong metal artifact caused by CIEDs may make the analysis difficult after CRT implantation. Strain analysis using short-axis (SA) cine CMR overcame this issue of artifact by enabling slice selection by avoiding artifact. Moreover, circumferential strain has superiority over other strain methods with respect to sensitivity, and we focused on these advantages. This case illustrates that circumferential strain with CMR-FT using SA cine CMR is useful in the assessment of improvement of myocardial motion after CRT and can provide useful additional information with imaging to determine the responders of CRT.

Quantification of intramyocardial hemorrhage volume using magnetic resonance imaging with three-dimensional T1-weighted sequence in patients with ischemia-reperfusion injury: a semi-automated image processing technique.

Although intramyocardial hemorrhage (IMH) is a poor prognostic factor caused by ischemia reperfusion injury, little evidence is available regarding the association between IMH volume and biomarkers. In the present study, we measured IMH volume using three-dimensional (3D) T1-weighted magnetic resonance imaging (T1-MRI) and investigated its association with biomarkers. Moreover, the accuracy of semi-automatic measurement of IMH volume was validated. We retrospectively enrolled 33 consecutive patients (mean age 67 ± 11 years) who underwent cardiac MRI after reperfusion therapy for acute myocardial infarction. IMH was observed in 4 patients (12.1%). Receiver operating characteristics (ROC) analysis of creatine kinase (CK) and CK-muscle/brain (CK-MB) tests for detecting IMH were performed. IMH volume measured using semi-automatic methods by a 2 standard deviation (SD) threshold was compared to manual measurements using the Spearman's correlation coefficient (ρ) and Bland-Altman analyses. ROC analysis revealed optimal cutoff values of CK: 2460 IU/l and CK-MB: 231 IU/l (area under the curve: 0.95 and 0.91; sensitivity: 86% and 79%; specificity: 100% for both). IMH volume with the 2SD threshold correlated with that of the manual measurement [5.84 g (3.30 to 9.00) g vs. 8.07 g (5.37 to 9.33); ρ: 0.85, p < 0.01; bias (limit of agreement): - 0.01 g (- 0.51 to 0.49); intraclass correlation coefficients 0.84 (0.75 to 0.90)]. Our findings could help identify the risk of IMH after reperfusion therapy with biomarkers. 3D T1-MRI can semi-automatically provide accurate IMH volume without being time-consuming.

Comparative genome-wide analysis of gastric adenocarcinomas with hyperplastic polyp components.

Gastric hyperplastic polyps are common and generally regarded as benign lesions, whereas gastric adenocarcinomas infrequently occur from gastric hyperplastic polyps. Although gastric hyperplastic polyps have received a lot of attention because of their association with malignant transformation, it remains unclear whether gastric hyperplastic polyps are neoplastic lesions that have sporadic genetic changes similar to colorectal hyperplastic polyps. We performed genome-wide analyses of two gastric adenocarcinomas with hyperplastic polyp components. The interface between "adenocarcinoma" and "hyperplastic polyp" components was fairly sharp, and the adenocarcinoma components had copy number alterations and TP53 mutations, whereas the hyperplastic polyp components had only single nucleotide polymorphisms, which were also found in adenocarcinoma components. We did not detect any somatic changes in the hyperplastic polyp components, even in genome-wide analyses, which was in contrast to the adenocarcinoma components. However, due to the small number of cases examined herein, further genetic analyses of more cases are needed.

IL-6/sIL-6R enhances cathepsin B and L production via caveolin-1-mediated JNK-AP-1 pathway in human gingival fibroblasts.

Interleukin (IL)-6 has an important role in inflammatory diseases. Lysosomal enzymes cathepsins are widely expressed as cysteine proteases regulating inflammatory process. Caveolin-1 (Cav-1) is a scaffolding/regulatory membrane protein that interacts with signaling molecules. In this study, we investigated the role of Cav-1 on (1) the productivity, and (2) the enzymatic activity of cathepsin B and L in human gingival fibroblasts (HGFs) treated with IL-6 in the presence of soluble form of IL-6 receptor (sIL-6R). At first, we established the siRNA-mediated Cav-1 down-regulating in vitro systems by transient transfection of Cav-1 siRNA. The siRNA-mediated Cav-1 down-regulated cells were treated with IL-6/sIL-6R for indicated times. Then, cell lysates were collected, and examined the IL-6-induced signaling pathway, cathepsin B and L production, and measurement of cathepsins activity. To investigate the cathepsin L activity, cathepsin-(B + L) activity was measured after pretreatment with CA-074Me, a specific inhibitor for cathepsin B. We found that IL-6/sIL-6R enhanced significantly both production and activity of cathepsin B and L in HGFs. Interestingly, IL-6-mediated phosphorylation of both p44/42 MAPK and JNK was dramatically suppressed in Cav-1 down-regulated HGFs treated with IL-6/sIL-6R. In addition, both production and activity of cathepsin B and L were also significantly suppressed. Importantly, we demonstrated that JNK inhibition, but not p44/42 MAPK inhibition, significantly diminished IL-6/sIL-6R-induced cathepsin B and L production. Taken together, we concluded that IL-6/sIL-6R enhances cathepsin B and L production via IL-6/sIL-6R-mediated Cav-1-JNK-AP-1 pathway in HGFs. Our findings indicate that Cav-1 might be a therapeutic target for IL-6-mediated tissue degradation in periodontitis.

Accurate and robust systolic myocardial T1 mapping using saturation recovery with individualized delay time: comparison with diastolic T1 mapping.

T1 mapping data are generally acquired in patients' diastolic phase, wherein their myocardium is the thinnest in the cardiac cycle. However, the analysis of the thin myocardium may cause errors in image registrations and settings related to the region of interest. In this study, we validated systolic T1 mapping using the saturation recovery with individualized delay time (SR-IDT) method and compared it with conventional diastolic T1 mapping. Both diastolic and systolic T1 mappings were performed in the mid-ventricular plane in 10 healthy volunteers (35 ± 9 years, 9 males) and 29 consecutive patients with cardiac diseases (68 ± 14 years, 19 males). Comparison of the myocardial T1 value at diastole and systole was performed with both the Pearson correlation coefficient (r) and the Bland-Altman analysis. Additionally, the systolic myocardial T1 value was compared between the volunteers and patients by using Tukey's test. Pearson correlation analysis demonstrated a strong positive correlation between diastolic and systolic T1 values (r = 0.88, P < 0.001). The Bland-Altman plot suggested that left ventricular T1 values in the diastole and systole showed high agreement (mean difference and 95% limits of agreement = 17 ± 104 ms). Further, systolic T1 values with SR-IDT in patients in the late gadolinium enhancement (LGE) group were significantly higher than those in the control group (1585 ± 118 ms vs 1469 ± 69 ms; P = 0.024). Therefore, the proposed systolic T1 mapping with the SR-IDT, which was validated with respect to the conventional diastolic method, is a useful clinical tool for the quantitative characterization of the myocardium.

Oligonucleotide array analysis of cyclic tension-responsive genes in human periodontal ligament fibroblasts.

Mechanical stress results in differential gene expression that is critical to convert the stimulus into biochemical signals. Under physiological stress such as occlusal force, human periodontal ligament fibroblasts (HPLF) are associated with homeostasis of periodontal tissues however the changes in response to mechanotransduction remain uncharacterized. We hypothesized that cyclic tension-responsive (CT) genes may be used to identify a set of fundamental pathways of mechanotransduction. Our goal was to catalogue CT genes in cultured HPLF. HPLF were subjected to cyclic tension up to 16h, and total RNA was isolated from both tension-loaded and static HPLF. The oligonucleotide arrays analysis revealed significant changes of mRNA accumulation for 122 CT genes, and their kinetics were assigned by the K-means clustering methods. Ingenuity Pathway Analysis was completed for HPLF mechanotransduction using 50 CT genes. This analysis revealed that cyclic tension immediately down-regulated all nuclear transcription factors except v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) reacting as an early responsive gene. In turn, transcription factors such as tumor protein p53 binding protein 2 (TP53BP2), and extra-nuclear molecules such as adrenergic receptor beta2 (ADRB2) were up-regulated after 1-2h, which may result in fundamental HPLF functions to adapt to cyclic tension. Subsequent inhibition assays using Y27632, a pharmacologic inhibitor of Rho-associated kinase (ROCK), suggested that HPLF has both ROCK-dependent and ROCK-independent CT genes. Mechanical stress was found to effect the expression of numerous genes, in particular, expression of an early responsive gene; FOS initiates alteration of HPLF behaviors to control homeostasis of the periodontal ligament.