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IntroductionAdministration of follicle-stimulating hormone (FSH) has been recommended to stimulate spermatogenesis in infertile men with hypogonadotropic hypogonadism, whose sperm counts do not respond to human chorionic gonadotropin alone. However, FSH has a short serum half-life requiring frequent administration to maintain its therapeutic efficacy. To improve its pharmacokinetic properties, we developed a unique albumin-binder technology, termed “anti-serum albumin Fab-associated” (SAFA) technology. We tested the feasibility of applying SAFA technology to create long-acting FSH as a therapeutic candidate for patients with hypogonadotropic hypogonadism.MethodsSAFA-FSH was produced using a Chinese hamster ovary expression system. To confirm the biological function, the production of cyclic AMP and phosphorylation of ERK and CREB were measured in TM4-FSHR cells. The effect of gonadotropin-releasing hormone agonists on spermatogenesis in a hypogonadal rat model was investigated.ResultsIn in vitro experiments, SAFA-FSH treatment increased the production of cyclic AMP and increased the phosphorylation of ERK and CREB in a dose-dependent manner. In animal experiments, sperm production was not restored by human chorionic gonadotropin treatment alone, but was restored after additional recombinant FSH treatment thrice per week or once every 5 days. Sperm production was restored even after additional SAFA-FSH treatment at intervals of once every 5 or 10 days.DiscussionLong-acting FSH with bioactivity was successfully created using SAFA technology. These data support further development of SAFA-FSH in a clinical setting, potentially representing an important advancement in the treatment of patients with hypogonadotropic hypogonadism.

Background: Inflammatory myofibroblastic tumors (IMTs) of the gastrointestinal (GI) tract are rare phenomena, and the computed tomography (CT) findings of GI IMTs are not well-established. Objectives: To describe the characteristics of CT scans, pathological specimens, and histological subtypes of GI IMTs in adults. Patients and Methods: The multidetector computed tomography (MDCT) scans of 11 adult patients (8 males, 3 females; age range, 19 - 76 years) with pathologically proven GI tract IMTs (stomach, small bowel, and colon) were retrospectively evaluated by two abdominal radiologists. The radiological features of IMTs were investigated. The imaging features were correlated with three microscopic IMT subtypes (myxoid vascular, spindle cell, and hypocellular fibrous). Immunohistochemistry was also performed on the specimens, including smooth muscle actin (SMA), vimentin, desmin, S-100, and anaplastic lymphoma kinase. Results: The tumor size ranged from 1.4 to 15 cm (mean, 5.7 cm). Two growth patterns were classified, namely, wall-thickening (n = 3) and solitary mass-forming (n = 8) patterns; each pattern was matched with a characteristic pathological subtype. All solitary, well-circumscribed masses corresponded to the spindle cell type. Low-attenuation wall thickening with perienteric infiltration was observed in three patients with a wall-thickening pattern. All solitary, well-circumscribed masses (n = 8) showed homogeneous enhancement with variable internal low attenuation, correlated with cystic degeneration, necrosis, myxoid change (n = 6), and hemorrhagic necrosis (n = 2). No patient showed bowel obstruction, while one patient showed regional lymphadenopathy. Immunophenotypes were not correlated with any growth pattern or histological subtype. Conclusion: The GI IMTs can be classified into two patterns, including wall-thickening and well-circumscribed masses, each matched with a characteristic pathological subtype, which can help explain the tumor behavior. Concomitant CT findings may also provide diagnostic clues for IMT.

BACKGROUND Arterial perforation has inevitably increased as endovascular treatments have become more common for intracranial large vessel occlusions, and even distal, medium vessel occlusions. A distal, medium vessel has a tortuous course and thinner wall compared to large arteries, making it more susceptible to damage. Here, we review the treatment strategies for arterial perforation during mechanical thrombectomy, and we report the case of a patient treated with gelfoam embolization. CASE SUMMARY A 63-year-old woman presented to the emergency department with sudden neurologic symptoms of right hemiparesis and global aphasia. The initial National Institutes of Health Stroke Scale score was 15. Computed tomography (CT) and CT angiography revealed hyperacute infarction and emergent arterial occlusion of the left middle cerebral artery M2-3 portion. During endovascular mechanical thrombectomy, arterial rupture occurred. The patient’s vital signs were stable, but delayed angiography showed persistent active bleeding. Therefore, selective embolization of the injured artery was performed using gelfoam. Subsequent left vertebral and internal carotid angiography was performed to confirm hemostasis. A localized subarachnoid hemorrhage (SAH) was confirmed on a follow-up CT scan. A repeated CT scan after 12 d showed resolution of the SAH, and rebleeding did not occur. CONCLUSION Rescue embolization with gelfoam could be considered an additional option in distal, medium vessel perforation.

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

Purpose Although endovascular treatment is currently thought to only be suitable for patients who have pial arterial filling scores >3 as determined by multiphase computed tomography angiography (mpCTA), a cut-off score of 3 was determined by a study, including patients within 12 hours after symptom onset. We aimed to investigate whether a cut-off score of 3 for endovascular treatment within 6 hours of symptom onset is an appropriate predictor of good functional outcome at 3 months. Materials and Methods From April 2015 to January 2016, acute ischemic stroke patients treated with mechanical thrombectomy within 6 hours of symptom onset were enrolled into this study. Pial arterial filling scores were semi-quantitatively assessed using mpCTA, and clinical and radiological parameters were compared between patients with favorable and unfavorable outcomes. Multivariate logistic regression analysis was then performed to investigate the independent association between clinical outcome and pial collateral score, with the predictive power of the latter assessed using C-statistics. Results Of the 38 patients enrolled, 20 (52.6%) had a favorable outcome and 18 had an unfavorable outcome, with the latter group showing a lower mean pial arterial filling score (3.6±0.8 vs. 2.4±1.2, P=0.002). After adjusting for variables with a P-value of 2 vs. ≤2. Conclusion A pial arterial filling cut-off score of 2 as determined by mpCTA appears to be more suitable for predicting clinical outcomes following endovascular treatment within 6 hours of symptom onset than the cut-off of 3 that had been previously suggested.

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found co-localized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206+ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68+ microglia/macrophages can therefore be used as a potential therapeutic target.

To evaluate the feasibility of using computed tomography texture analysis (CTTA) parameters for predicting malignant risk grade and mitosis index of gastrointestinal stromal tumors (GISTs), compared with visual inspection. CTTA was performed on portal phase CT images of 145 surgically confirmed GISTs (mean size: 42.9 ± 37.5 mm), using TexRAD software. Mean, standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis of CTTA parameters, on spatial scaling factor (SSF), 2–6 were compared by risk grade, mitosis rate, and the presence or absence of necrosis on visual inspection. CTTA parameters were correlated with risk grade. Diagnostic performance was evaluated with receiver operating characteristic curve analysis. Enhancement pattern, necrosis, heterogeneity, calcification, growth pattern, and mucosal ulceration were subjectively evaluated by two observers. Three to four parameters at different scales were significantly different according to the risk grade, mitosis rate, and the presence or absence of necrosis (p

Rationale: Sphenoid sinus pseudoaneurysm arising from the cavernous segment of the internal carotid artery (ICA) caused by traumatic vessel injury is rare, and rarer is a concomitant carotid-cavernous fistula (CCF). In particular, delayed subarachnoid hemorrhage (SAH) due to pseudoaneurysm rupture has not been reported to-date in literature. Here, we report a case of sphenoid sinus pseudoaneurysm with CCF presenting with delayed SAH. Patient concerns: A 73-year-old man presented with traumatic brain injury due to motorcycle accident. Diagnoses: Twenty-four days after admission, the patient's neurological status suddenly deteriorated. Brain computed tomography (CT) showed acute SAH along interhemispheric cisterns and suprasellar intracerebral hematoma. Brain CT angiography and digital subtraction angiography revealed giant sphenoid sinus pseudoaneurysm with CCF and the daughter sac of the pseudoaneurysm extended to the intracranial part via fracture in the superior wall of the sphenoid sinus. Interventions: As the sphenoid sinus pseudoaneurysm and CCF shared one rupture point, endovascular treatment with intraarterial approach using coil and liquid embolic material by balloon assisted technique was performed simultaneously. Outcomes: The origin of the pseudoaneurysmal sac and CCF was sufficiently blocked after injection of liquid embolic material and the lesions completely resolved immediately after endovascular treatment. Lessons: Sphenoid sinus pseudoaneurysm and CCF rarely occur following head trauma through a series of processes involving fracture of the lateral wall of the sphenoid sinus and ICA cavernous segment injury. Sphenoid sinus pseudoaneurysm may present as SAH through intracranial rupture with concomitant superior wall fracture of the sphenoid sinus. Therefore, early diagnosis using CT or magnetic resonance angiography and appropriate treatment through understanding the disease mechanism is necessary.

The neurovascular unit (NVU) comprises multiple types of brain cells, including brain endothelial cells, astrocytes, pericytes, neurons, microglia, and oligodendrocytes. Each cell type contributes to the maintenance of the molecular transport barrier and brain tissue homeostasis. Several disorders and diseases of the central nervous system, including neuroinflammation, Alzheimer’s disease, stroke, and multiple sclerosis, have been associated with dysfunction of the NVU. As a result, there has been increased demand for the development of NVU in vitro models. Here, we present a three-dimensional (3D) immortalized human cell-based NVU model generated by organizing the brain microvasculature in a collagen matrix embedded with six different types of cells that comprise the NVU. By surrounding a perfusable brain endothelium with six types of NVU-composing cells, we demonstrated a significant impact of the 3D co-culture on the maturation of barrier function, which is supported by cytokines secreted from NVU-composing cells. Furthermore, NVU-composing cells alleviated the inflammatory responses induced by lipopolysaccharides. Our human cell-based NVU in vitro model could enable elucidation of both physiological and pathological mechanisms in the human brain and evaluation of safety and efficacy in the context of high-content analysis during the process of drug development.

To evaluate feasibility of computer tomography texture analysis (CTTA) at different energy level using dual-energy spectral detector CT for liver fibrosis. Eighty-seven patients who underwent a spectral CT examination and had a reference standard of liver fibrosis (histopathologic findings, n = 61, or clinical findings for normal, n = 26) were included. Mean gray-level intensity, mean number of positive pixels (MPP), entropy, skewness, and kurtosis using commercially available software (TexRAD) were compared at different energy levels. Optimal CTTA parameter cutoffs to diagnose liver fibrosis were evaluated. CTTA parameters at different energy levels correlated with liver fibrosis. The association of CTTA parameters with energy level was evaluated. Mean gray-level intensity, skewness, kurtosis, and entropy showed significant differences between patients with and without clinically significant hepatic fibrosis (P

This study was conducted to evaluate the clinical effect of real-time magnetic resonance imaging (MRI)-navigated ultrasonography (US) for preoperative second-look examination in patients with breast cancer.Between October 2013 and February 2015, 232 patients with breast cancer underwent MRI for staging; second-look US was performed in 70 patients to evaluate additional lesions suspected to be disease detected using MRI. We retrospectively included 67 lesions in 55 patients. Lesions were classified as detected on conventional US (group 1), and not visible on conventional US, but detected on MRI-navigated US (group 2). The imaging features between groups 1 and 2 were compared using Student t, χHeterogeneous background echotexture (69.6% [16 of 23] vs. 34.1% [14 of 41]) and lesion isoechogenicity (65.2% [15 of 23] vs. 7.3% [3 of 41]) on US and middle or posterior lesion depth on MRI (78.3% [18 of 23] vs. 46.3% [19 of 41]) were more common in group 2 (P .05). More lesions were detected using MRI-navigated US (64 of 67; 95.5%) than conventional US (41 of 67; 61.2%; P .01). Using MRI-navigated US we found more high-risk or malignant lesions than conventional US (21 vs. 11; P .01). The optimal treatment plan was determined for 9 of 16 (56.3%) patients by virtue of MRI-navigated US.Real-time MRI-navigated US significantly improved the detection of additional high-risk or malignant lesions during second-look US in preoperative evaluation of patients with breast cancer and ultimately determined the optimal treatment plan.

To assess hyperacute focal cerebral ischemia in rats on 3.0-Tesla diffusion-weighted imaging (DWI), we developed a novel voxel-wise lesion segmentation technique that overcomes intra- and inter-subject variation in apparent diffusion coefficient (ADC) distribution. Our novel technique involves the following: (1) intensity normalization including determination of the optimal type of region of interest (ROI) and its intra- and inter-subject validation, (2) verification of focal cerebral ischemic lesions at 1 h with gross and high-magnification light microscopy of hematoxylin-eosin (H&E) pathology, (3) voxel-wise segmentation on ADC with various thresholds, and (4) calculation of dice indices (DIs) to compare focal cerebral ischemic lesions at 1 h defined by ADC and matching H&E pathology. The best coefficient of variation was the mode of the left hemisphere after normalization using whole left hemispheric ROI, which showed lower intra- (2.54 ± 0.72%) and inter-subject (2.67 ± 0.70%) values than the original. Focal ischemic lesion at 1 h after middle cerebral artery occlusion (MCAO) was confirmed on both gross and microscopic H&E pathology. The 83 relative threshold of normalized ADC showed the highest mean DI (DI = 0.820 ± 0.075). We could evaluate hyperacute ischemic lesions at 1 h more reliably on 3-Tesla DWI in rat brains.

Background Radiogenomic investigations for breast cancer provide an understanding of tumor heterogeneity and discover image phenotypes of genetic variation. However, there is little research on the correlations between US features of breast cancer and whole-transcriptome profiling. Purpose To explore US phenotypes reflecting genetic alteration relevant to breast cancer treatment and prognosis by comparing US images of tumor with their RNA sequencing results. Materials and Methods From January to October 2016, B-mode and vascular US images in 31 women (mean age, 49 years ± 9 [standard deviation]) with breast cancer were prospectively analyzed. B-mode features included size, shape, echo pattern, orientation, margin, and calcifications. Vascular features were evaluated by using microvascular US and contrast agent-enhanced US: vascular index, vessel morphologic features, distribution, penetrating vessels, enhancement degree, order, margin, internal homogeneity, and perfusion defect. RNA sequencing was conducted with total RNA obtained from a surgical specimen by using next-generation sequencing. US features were compared with gene expression profiles, and ingenuity pathway analysis was used to analyze gene networks, enriched functions, and canonical pathways associated with breast cancer. The P value for differential expression was extracted by using a parametric F test comparing nested linear models. Results Thirteen US features were associated with various patterns of 340 genes (P < .05). Nonparallel orientation at B-mode US was associated with upregulation of TFF1 (log twofold change [log2FC] = 4.0; P < .001), TFF3 (log2FC = 2.5; P < .001), AREG (log2FC = 2.6; P = .005), and AGR3 (log2FC = 2.6; P = .003). Complex vessel morphologic structure was associated with upregulation of FZD8 (log2FC = 2.0; P = .01) and downregulation of IGF1R (log2FC = -2.0; P = .006) and CRIPAK (log2FC = -2.4; P = .01). The top networks with regard to orientation or vessel morphologic structure were associated with cell cycle, death, and proliferation. Conclusion Compared with RNA sequencing, B-mode and vascular US features reflected genomic alterations associated with hormone receptor status, angiogenesis, or prognosis in breast cancer. © RSNA, 2020 Online supplemental material is available for this article.

Objective This study aimed to evaluate the relationship between biliary excreted contrast media in the stomach and the presence of bile reflux gastritis. Methods Consecutive 111 patients who underwent both gadoxetic acid-enhanced magnetic resonance cholangiography (gadoxetic MRC) and gastric endoscopy were included in this study. We performed a review of the gadoxetic-MRC image sets acquired 60 minutes after intravenous injection of contrast media and endoscopic images. We recorded amount of contrast media in the stomach. The sensitivity, specificity, and accuracy of duodenogastric bile reflux diagnosis were evaluated for the gadoxetic MRC. Statistical analysis was performed using the Fisher exact test and the linear-by-linear association test. Results Among the 111 patients, 39 had 60-minute delayed images showing the presence of contrast media in the stomach. Of these 39 patients, 13 had bile reflux gastritis and 5 showed bile in the stomach without evidence of erythematous gastritis. Of the 72 patients who did not show contrast media in the stomach, none had bile reflux gastritis and 2 patients showed bile staining in the stomach without evidence of erythematous gastritis. Bile reflux gastritis was significantly more frequent in patients with contrast media in the stomach on gadoxetic MRC than in those without. Patients with high-grade extension of contrast media in the stomach had significantly frequent bile reflux gastritis than did those with low-grade extension. Conclusion Biliary excreted contrast media in the stomach on 60-minute delayed gadoxetic MRC has a correlation with the presence of bile reflux gastritis on endoscopic examination.

The Sewol ferry disaster is one of the most tragic events in Korea’s modern history. Among the 476 people on board, which included Danwon High School students (324) and teachers (14), 304 passengers died in the disaster (295 recovered corpses and 9 missing) and 172 survived. Of the rescued survivors, 72 were attending Danwon High School, located in Ansan City, and residing in a residence nearby. Because the students were young, emotionally susceptible adolescents, both the government and the parents requested the students be grouped together at a single hospital capable of appropriate psychiatric care. Korea University Ansan Hospital was the logical choice, as the only third-tier university-grade hospital with the necessary faculty and facilities within the residential area of the families of the students. We report the experiences and the lessons learned from the processes of preparing for and managing the surviving young students as a community-based hospital. (Disaster Med Public Health Preparedness. 2017;11:389–393)

Although early diffusion lesion reversal after recanalization treatment of acute ischaemic stroke has been observed in clinical settings, the reversibility of lesions observed by diffusion-weighted imaging remains controversial. Here, we present consistent observations of sustained diffusion lesion reversal after transient middle cerebral artery occlusion in a monkey stroke model. Seven rhesus macaques were subjected to endovascular transient middle cerebral artery occlusion with in-bore reperfusion confirmed by repeated prospective diffusion-weighted imaging. Early diffusion lesion reversal was defined as lesion reversal at 3 h after reperfusion. Sustained diffusion lesion reversal was defined as the difference between the ADC-derived pre-reperfusion maximal ischemic lesion volume (ADCD-P Match) and the lesion on 4-week follow-up FLAIR magnetic resonance imaging. Diffusion lesions were spatiotemporally assessed using a 3-D voxel-based quantitative technique. The ADCD-P Match was 9.7 ± 6.0% (mean ± SD) and the final infarct was 1.2–6.0% of the volume of the ipsilateral hemisphere. Early diffusion lesion reversal and sustained diffusion lesion reversal were observed in all seven animals, and the calculated percentages compared with their ADCD-P Match ranged from 8.3 to 51.9% (mean ± SD, 26.9 ± 15.3%) and 41.7–77.8% (mean ± SD, 65.4 ± 12.2%), respectively. Substantial sustained diffusion lesion reversal and early reversal were observed in all animals in this monkey model of transient focal cerebral ischaemia.

Background and Purpose Recent advances in intra-arterial techniques and thrombectomy devices lead to high rate of recanalization. However, little is known regarding the effect of the evolvement of endovascular revascularization therapy (ERT) in acute basilar artery occlusion (BAO). We compared the outcome of endovascular mechanical thrombectomy (EMT) versus intra-arterial fibrinolysis (IAF)-based ERT in patients with acute BAO. Methods After retrospectively reviewed a registry of consecutive patients with acute ischemic stroke who underwent ERT from September 2003 to February 2015, 57 patients with acute BAO within 12 hours from stroke onset were enrolled. They were categorized as an IAF group (n=24) and EMT group (n=33) according to the primary technical option. We compared the procedural and clinical outcomes between the groups. Results The time from groin puncture to recanalization was significantly shorter in the EMT group than in the IAF group (48.5 [25.3 to 87.8] vs. 92 [44 to 179] minutes; P=0.02) The rate of complete recanalization was significantly higher in the EMT group than in the IAF group (87.9% vs 41.7%; P

Purpose The purpose was to evaluate characteristics of pancreatic cancer without main pancreatic duct (MPD) dilatation on dual-phase computed tomographic (CT) scans. Materials and methods We studied 16 patients with pancreatic head cancer without accompanying MPD dilatation and 39 patients with MPD dilatation Results Elevation of serum amylase level and peripancreatic fluid collection were more frequently seen in the MPD(−). Common bile duct dilatation and atrophy of the upstream pancreatic parenchyma were more frequently seen in MPD(+). Conclusion Pancreatic cancers without MPD dilatation were more frequently related to acute pancreatitis and had fewer secondary signs. Thus, early diagnosis of pancreatic cancer with these characteristics could be difficult.

The study aimed to establish a staining method that could delineate the macroscopic lesion boundary of a hyperacute infarction depicted by diffusion-weighted MRI (DWI) and to validate the infarction boundary by comparing different staining methods.Thirteen rats with 1 -h middle cerebral artery (MCA) infarction were included. Five different staining methods (Hematoxylin and eosin (HE), Nissl, 2,3,5-triphenyltetrazolium hydrochloride (TTC), microtubule associated protein 2 (MAP2), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stains) were used to identify whether the hyperacute infarction could be histopathologically identified. Dice indices were compared to evaluate similarities in the lesion area ascertained by DWI and the staining methods. Through macroscopic lesion delineation, each region was subdivided into abnormal regions in all three stains (ROIMean Dice indices of the HE stain were significantly higher than those of the Nissl- and MAP2-stained specimens (0.83 ± 0.052, 0.58 ± 0.107, and 0.56 ± 0.059, respectively; p = 0.000). Grading scores for ROIs in the DWI abnormal lesions varied by region: ROIHE stain allowed for the macroscopic delineation of the 1 h DWI-abnormal lesions, while MAP2 and Nissl stains could only partially depict lesions.

Parkinson’s disease (PD) comprises an age-related and the second most common disorders which is characterized by progressive motor symptoms such as bradykinesia, rigidity, akinesia, abnormal posture, and resting tremor. The pathology of PD involves the loss of dopaminergic (DA) neurons from the substantia nigra and the production α-synuclein-containing Lewy bodies and Lewy neurites. Current pharmacological treatments for PD target early symptoms by supplying dopamine precursors. These treatments regrettably have long-term side-effects, whereas stem cells-based therapies demonstrate safety and efficiency in preclinical studies through enhancement of dopamine uptake and motor symptoms. Therefore, stem cell transplantation shows great promise as a method to replace lost DA neurons; and for acquiring a better understanding of these neurodegenerative diseases mechanisms. In this review, we discuss recent preclinical studies of stem cell-based therapy for PD and important areas of future research.

The subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) technique is reportedly effective in severe peripheral vascular disease that cannot be treated with standard endovascular techniques including subintimal angioplasty. In this report, we used a target balloon with the Outback catheter to recanalize a thrombosed bypass graft that could not be treated successfully with SAFARI.

To investigate the utility of superb microvascular imaging (SMI) for evaluating the vascularity of breast masses in comparison with colour or power Doppler ultrasound (US) and the effect on diagnostic performance.A total of 191 biopsy-proven masses (99 benign and 92 malignant) in 166 women with greyscale, colour Doppler, power Doppler, and SMI images were enrolled in this retrospective study. Three radiologists analysed the vascular images using a three-factor scoring system to evaluate the number, morphology, and distribution of tumour vessels. They assessed the Breast Imaging-Reporting and Data System categories for greyscale US alone and combinations of greyscale US and each type of vascular US. The Kruskal-Wallis test was performed and the area under the receiver-operating characteristic curve (AUC) measured. On SMI, vascular scores were compared between benign and malignant masses and the optimal cut-off value for the overall score was determined.SMI showed higher vascular scores than colour or power Doppler US and malignant masses had higher scores than benign masses (p0.001). The diagnostic performance of the combination of greyscale US and SMI was higher than those of greyscale US alone and greyscale and colour or power Doppler US (AUC, 0.815 versus 0.774, 0.789, 0.791; p0.001). The optimal cut-off value of the overall vascular score was 5 with a sensitivity of 82.3% and a specificity of 65.3% (AUC, 0.808).SMI is superior to colour or power Doppler US for characterising the vascularity in breast masses and improving diagnostic performance.

Rationale: Schwannomas involving the thyroid gland are very rare and only a few cases have been reported in the literature. However, previous reports did not distinguish between thyroid bed schwannomas and intrathyroidal schwannomas. Here, we report a thyroid bed schwannoma mimicking a malignant thyroid nodule and review the literature on thyroid bed schwannomas. Patient concerns: A 33-year-old woman presented at our hospital with mild neck swelling. Diagnosis: Thyroid ultrasound revealed a well-defined, oval-shaped, markedly hypoechoic solid nodule with echogenic foci suggesting macro- and microcalcifications in the left thyroid gland. The lesion was considered a “highly suspicious” intrathyroidal nodule, based on the guidelines for the assessment of thyroid nodules. Fine needle aspiration was performed twice, but the cytological results were nondiagnostic. Interventions: Left thyroidectomy was performed, and schwannoma of the thyroid bed was confirmed on histopathologic analysis. Outcomes: The patient was in a stable condition after surgery, and the thyroid function test results were within the normal range. Lessons: Diagnosis of a schwannoma of the thyroid bed is challenging because its incidence is extremely low, and it is often misdiagnosed as an intrathyroidal nodule on ultrasonography. Therefore, it is advisable to adopt a diagnostic strategy to perform additional core needle biopsy in cases of thyroid nodules with nondiagnostic fine needle aspiration results and to consider the location of the lesion more carefully to determine the suitable therapy.

To achieve consistent target delineation in radiotherapy for hepatocellular carcinoma (HCC), image registration between simulation CT and diagnostic MRI was explored. Twenty patients with advanced HCC were included. The median interval between MRI and CT was 11 days. CT was obtained with shallow free breathing and MRI at exhale phase. On each CT and MRI, the liver and the gross target volume (GTV) were drawn. A rigid image registration was taken according to point information of vascular bifurcation (Method[A]) and pixel information of volume of interest only including the periphery of the liver (Method[B]) and manually drawn liver (Method[C]). In nine cases with an indefinite GTV on CT, a virtual sphere was generated at the epicenter of the GTV. The GTV from CT (V GTV [CT]) and MRI (V GTV [MR]) and the expanded GTV from MRI (V +GTV [MR]) considering geometrical registration error were defined. The underestimation (uncovered V[CT] by V[MR]) and the overestimation (excessive V[MR] by V[CT]) were calculated. Through a paired T -test, the difference between image registration techniques was analyzed. For method[A], the underestimation rates of V GTV [MR] and V +GTV [MR] were 16.4 ± 8.9% and 3.2 ± 3.7%, and the overestimation rates were 16.6 ± 8.7% and 28.4 ± 10.3%, respectively. For V GTV [MR] and V +GTV [MR], the underestimation rates and overestimation rates of method[A] were better than method[C]. The underestimation rates and overestimation rates of the V GTV [MR] were better in method[B] than method[C]. By image registration and additional margin, about 97% of HCC could be covered. Method[A] or method[B] could be recommended according to physician preference.

Previous reports revealed that middle cerebral artery occlusion (MCAO) models in rats were very diverse in nature, and experimental stroke of a more homogenous nature had not been previously documented. This paper aims to present our novel observations of experimental stroke in rats with similar MRI characteristics after MCAO. Immediately after MCAO, 19 rats were placed into a 4.7 T MRI scanner, and diffusion weighted imaging (DWI) of axial and coronal planes was repeated every 10 minutes up to post-occlusion 115 minutes. Apparent diffusion coefficient (ADC) values of the ischemic lesions were calculated and compared to those of the unaffected contra-lateral hemispheres. Successful MCAO was defined when the whole left MCA territory showed ADC abnormality on DWI. Percentage of hemispheric lesion volume (% HLV), relative ADC value (rADC), and relative DWI signal intensity (rDWI) were serially evaluated for quantitative analysis of ADC-derived lesion characteristics. Successful MCA territorial infarction was induced in nine rats (9/19, 47.4%). In quantitative analysis of ADC-derived lesion characteristics, lesion volumes of seven rats (group 1) were very similar, but larger than those of the other two rats (group 2): % HLV of initial MRI = 45.4 ± 2.5 / 19.1 ± 6.6. rADCs and rDWIs of group 1 showed similar patterns of temporal change, which was different from those of group 2. Using prospective diffusion MRI after MCAO in rats, we identified territorial hyperacute ischemic lesions with similar MRI characteristics. This observation would contribute to the establishment of more homogenous rodent models for ischemic stroke translational research.

Objectives The purpose of this study was to investigate the quality of ultrasound (US) imaging for hepatocellular carcinoma screening. Methods The investigation was performed at all medical institutes participating in the National Cancer Screening Program in Korea. For assessment of personnel, we inquired who was performing the US screenings. For phantom image evaluation, the dead zone, vertical and horizontal measurements, axial and lateral resolution, sensitivity, and gray scale/dynamic range were evaluated. For clinical image evaluation, US images of patients were evaluated in terms of the standard images, technical information, overall image quality, appropriateness of depth, foci, annotations, and the presence of any artifacts. Results Failure rates for phantom and clinical image evaluations at general hospitals, smaller hospitals, and private clinics were 20.9%, 24.5%, 24.1% and 5.5%, and 14.8% and 9.5%, respectively. No statistically significant difference was observed in the failure rates for the phantom images among groups of different years of manufacture. For the clinical image evaluation, the results of radiologists were significantly better than those of other professional groups (P = .0001 and .0004 versus nonradiology physicians and nonphysicians, respectively). The failure rate was also higher when the storage format was analog versus digital (P < .001). Conclusions Approximately 20% of US scanners failed the phantom image evaluation. The year of scanner manufacture was not significantly associated with the results of the phantom image evaluation. The quality of the clinical images obtained by radiologists was the best.

Subependymomas are rare benign tumors located in the ventricular system. Intraparenchymal subependymoma is extremely rare; only 6 cases have been reported, and all were located in the supratentorial region. We describe a case of infratentorial, intraparenchymal subependymoma in a 28-year-old man with intermittent headache. Imaging revealed a well-demarcated cystic and solid cerebellar mass near the fourth ventricle. The mass had a microcystic component and calcification without contrast enhancement. Complete surgical excision was performed, and histopathology confirmed a subependymoma.

In this paper, we propose a method for suppressing shaft voltage by modifying the shape of the rotor and the permanent magnets in interior permanent magnet-type-high-voltage motors. Shaft voltage, which is induced by parasitic components and the leakage flux in motor-driven systems, adversely affects their bearings. In order to minimize shaft voltage, we designed a magnet re- arrangement and rotor re-structuring of the motor. The shaft voltage suppression effect of the designed model was confirmed experimentally and by comparative finite element analysis.

Objective To investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD). Materials and Methods Ninety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed. Results Malignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, p < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, p < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, p = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, p < 0.001), hyperenhancement (95.1% vs. 70.2%, p = 0.005), centripetal enhancement (70.7% vs. 45.6%, p = 0.023), penetrating vessels (65.9% vs. 22.8%, p < 0.001), and perfusion defects (31.7% vs. 3.5%, p < 0.001) on CEUS (p ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively (p = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, p = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, p < 0.001). US vascular parameters associated with malignancy showed higher MVD (p ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD (p < 0.05). Conclusion US microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD.

Introduction Integral membrane protein 2A (ITM2A) is a type 2 transmenbrane protein. Expression of ITM2A was reported to be regulated by PAX-3, a transcription factor important for muscle, neural, and facial development in vertebrates. However, the biological mechanism of ITM2A is so far unknown. Material and methods The ITM2A protein expression was down-regulated in epithelial ovarian cancer tissue samples and cancer cells as compared to normal cells (p Results and discussions Over-expressing ITM2A in ovarian cancer cells inhibited cell growth through the G2/M cell cycle arrest. A matrigel invasion assay showed that ITM2A-transfected ovarian cancer cells reduced the colony formation and attenuated invasiveness of ovarian cancer cells. To assess the chemosensitivity of ITM2A, chemosensitizing effects of ovarian cancer cells were measured using paclitaxel or carboplatin. ITM2A was remarkably reduced the proliferative activities after chemotherapeutic agent treatments. Moreover, ITM2A upregulation in ovarian cancer cells increased protein expressions of PARP, cleaved caspase-3 and p53 after carboplatin treatment. Conclusion Taken together, our results showed that up-regulation of ITM2A could contribute to poor maintenance of epithelial ovarian cancer, affecting both cell growth and invasion. Furthermore, ITM2A expression leads to increase chemosensitivity to chemoagent, and has therapeutic potential for ovarian cancer.

Objective: Ultrasound-guided needle localization has been used prior to the surgical excision of nonpalpable breast lesions. The aim of the study was to assess the feasibility of the use of a saline immersion specimen ultrasound technique (immersion-US) to confirm the successful removal of breast lesions. Materials and Methods: The devised immersion-US technique was used to examine the excised tissues of 72 ultrasound-guided needle localized breast lesions of 58 patients (34 benign lesions, 30 high-risk lesions and 8 malignant lesions). Freshly excised specimens were placed in a container filled with saline and one radiologist scanned the surgically excised specimens using a high-frequency linear transducer. We evaluated successful lesion removal and the qualities of the immersion-US images. Miss rates were determined by the use of postoperative ultrasound during follow-up. Results: All 72 lesions were identified by the use of immersion-US and satisfactory or excellent quality images were obtained for most lesions (70/72, 97%). Five (7%) lesions were initially identified as incompletely excised, based on the immersion-US findings, and prompt re-excision was undertaken. Follow-up ultrasound examinations showed no residual mass in the surgical field in any patient. Conclusion: The immersion-US technique was found straightforward and efficient to perform. Immersion-US was able to determine whether nonpalpable breast lesions had been successfully excised after ultrasound-guided needle localization.

Cerebral angiography (CA) is the gold standard for moyamoya disease (MMD) staging and diagnosis, but CA findings are not well correlated with clinical symptoms. The purpose of this study was to establish novel cerebral-perfusion-based staging for MMD that is well correlated with clinical symptoms. From 2010 to 2015, regional cerebrovascular reserve (rCVR) was examined by single-photon emission computed tomography (SPECT) using NeuroGam® (Segamicorp, Houston, TX, USA) in 30 patients (17 women, 13 men; 60 hemispheres; mean 42.0 years old [range 5–60 years old]) with MMD, which was diagnosed by CA and magnetic resonance angiography (MRA). Brain CT or brain magnetic resonance imaging (MRI) was used to evaluate neurological conditions such as transient ischemic attack (TIA), cerebral hemorrhage, and cerebral infarction. A novel staging system for MMD was developed by combining findings from CA, MRI, and SPECT with NeuroGam®. Our novel staging system was strongly associated with clinical symptoms. Twenty-two hemispheres out of 60 were categorized as stage I, 24 hemispheres were categorized as stage II, and 14 hemispheres were categorized as stage III. Hemispheres with higher scores exhibited a higher incidence of clinical symptoms. These findings indicate that cerebral-perfusion-based staging is predictive of MMD clinical symptoms. Perfusion-based SPECT staging correlates well with clinical symptoms and may be a reliable alternative to the Suzuki staging by CA.

This report describes a case of pathologically proven traumatic arterial dissection, presenting as complete occlusion of the axillary artery with radial artery embolism. Occlusion of the axillary artery by traumatic dissection mimicked transection and radial artery embolism mimicked congenital absence of the radial artery on the initial angiogram, but these were correctly diagnosed with the following sonogram.

Neonatal maple syrup urine disease (MSUD) is associated with diffuse oedema and characteristic MSUD oedema. We present a newborn infant with two coexisting different types of oedema. The myelinated white matter showed a marked decrease in the water apparent diffusion coefficient (ADC) compatible with cytotoxic oedema. The unmyelinated white matter showed an increase in ADC, consistent with vasogenic-interstitial oedema. On follow-up studies, the cytotoxic oedema showed improvement, but the vasogenic-interstitial oedema progressed into brain atrophy.