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The spatial complexity of neuronal circuits in the central nervous system is a hurdle in understanding and treating brain and spinal cord injury (SCI). Although several methods have recently been developed to render the spinal cord transparent and label specific neural circuits, three-dimensional visualization of long segments of spinal cord with high resolution remains challenging for SCI researchers. We present a method that combines tissue staining of neuronal tracts traced with biotinylated dextran amine (BDA) and a modified passive clarity clearing protocol to describe individual fibers in long segments of mouse spinal cord. Corticospinal tract was traced with BDA with a mouse model of thoracic spinal cord injury. The spinal cord was stained and cleared in two weeks with four solutions: staining solution, hydrogel solution, clearing solution, and observation solution. The samples were observed with a light-sheet microscope, and three-dimensional reconstruction was performed with ImageJ software. High resolution-images comparable with tissue sections were obtained continuously and circumferentially. By tiling, it was possible to obtain high-resolution images of long segments of the spinal cord. The tissue could be easily re-stained in case of fading. The present method does not require special equipment such as vacuum devices, can label specific circuits without genetic technology, and re-staining rounds can be easily implemented. By using simple neural staining and clearing methods, it was possible to acquire a wide range of high-resolution three-dimensional images of the spinal cord. • No special devices or genetic tracers are required for a modified clearing method. • Neuronal fibers are individually depicted in long segments of mouse spinal cord. • Re-staining of neuronal fiber is possible. • Stereotaxic observation is achieved by 3-D reconstruction with open-source software. [ABSTRACT FROM AUTHOR]

Abstract: We have isolated and characterized a novel cDNA encoding a small neuronal membrane protein showing high sequence homology to Neuro-p24/Neurensin-1, a protein containing a microtubule-associated domain at the carboxyl-terminus and exclusively localized to small vesicles of neurons. The newly identified Neurensin-2 constitutes two-membrane spanning domains but not the microtubule-binding domain, with a molecular mass of 28 kDa. Neurensin-2 mRNA is expressed only in brain, whereas the protein expressed in various neurons including those of the thalamus/hypothalamus and hippocampus, of postnatally developing mice. While the levels of Neurensin-1 mRNA and protein in retinoic acid-exposed mouse neuroblastoma Neuro2a cells increased, those of Neurensin-2 mRNA and protein remained unchanged. When the Neurensin-2 cDNA was transfected into Neuro2a cells, Neurensin-2 was expressed in small vesicles including lysosomes in the perinuclear region. On the cotransfection of Neurensin-1 and -2 cDNA into Neuro2a cells, Neurensin-2 was mainly found in small vesicles of the cell body and Neurensin-1 in those of growth cones. In nerve growth factor-stimulated PC12 cells, the intracellular localization of these proteins also differed. Furthermore, immunochemical staining of mouse brain revealed that Neurensin-1 and -2 had a similar distribution in many regions such as the Diagonal band, hippocampus, amygdaloid nucleus, and habenula nucleus, but differed in the intracellular localization as follows: Neurensin-1 was found mainly in neuritic processes, while Neurensin-2 was found in cell bodies. Thus, both Neurensin-1, and -2 are localized in small vesicles in neural cells, but their localizations of the vesicles are not always the same by each other, suggesting that they are under separate regulation. [Copyright &y& Elsevier]

A 57-year-old man with a 15-year history of a right chest wall mass lesion without follow-up for 5 years was admitted to our hospital without any symptoms or evidence of malignancy. On MRI, an additional small subcutaneous mass lesion was found. Histology of both lesions revealed marginal zone B-cell lymphomas. Primary chest wall marginal zone B-cell lymphomas are rare; this report discusses the case and the literature on chest wall lymphomas. [ABSTRACT FROM AUTHOR]

Various locoregional treatments for localized hepatocellular carcinoma (HCC) have been developed. This retrospective study investigated the safety and feasibility of combining on-demand selective locoregional treatment for residual lesions after tumor shrinkage (complete response [CR] oriented) or for solitary or few drug-resistant lesions (progressive disease (PD) salvage) with first-line atezolizumab plus bevacizumab (atezo/bev) for unresectable HCC. Twenty-nine patients with unresectable HCC were included. Fourteen locoregional treatments were performed (CR oriented, 7; PD salvage, 7) in ten patients in the combination-therapy group. All patients in the combination-therapy group successfully achieved a CR or PD salvage status after the planned locoregional treatment. The objective response rate of the combination-therapy group (80.0%) was higher than that of the atezo/bev alone group (21.1%; p = 0.005). Progression-free survival (PFS) and overall survival (OS) were longer in the combination group (medians for PFS and OS not reached) than in the atezo/bev alone group (median PFS, 7.4 months; median OS, 19.8 months) (PFS, p = 0.004; OS, p < 0.001). The albumin–bilirubin score did not change, and no severe complications occurred after locoregional treatment. When performed in a minimally invasive manner, on-demand selective locoregional treatment combined with first-line atezo/bev could be safe and feasible for unresectable HCC. [ABSTRACT FROM AUTHOR]

Glioblastomas are highly infiltrative tumors, and differentiating between non-enhancing tumors (NETs) and vasogenic edema (Edemas) occurring in the non-enhancing T2-weighted hyperintense area is challenging. Here, we differentiated between NETs and Edemas in glioblastomas using neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI). Data were collected retrospectively from 21 patients with primary glioblastomas, three with metastasis, and two with meningioma as controls. MRI data included T2 weighted images and contrast enhanced T1 weighted images, NODDI, and DTI. Three neurosurgeons manually assigned volumes of interest (VOIs) to the NETs and Edemas. The DTI and NODDI-derived parameters calculated for each VOI were fractional anisotropy (FA), apparent diffusion coefficient (ADC), intracellular volume fraction (ICVF), isotropic volume fraction (ISOVF), and orientation dispersion index. Sixteen and 14 VOIs were placed on NETs and Edemas, respectively. The ICVF, ISOVF, FA, and ADC values of NETs and Edemas differed significantly (p < 0.01). Receiver operating characteristic curve analysis revealed that using all parameters allowed for improved differentiation of NETs from Edemas (area under the curve = 0.918) from the use of NODDI parameters (0.910) or DTI parameters (0.899). Multiple logistic regression was performed with all parameters, and a predictive formula to differentiate between NETs and Edemas could be created and applied to the edematous regions of the negative control-group images; the tumor prediction degree was well below 0.5, confirming differentiation as edema. Using NODDI and DTI may prove useful in differentiating NETs from Edemas in the non-contrast T2 hyperintensity region of glioblastomas. [ABSTRACT FROM AUTHOR]

The current study aimed to test whether the ratio of T1-weighted to T2-weighted signal intensity (T1W/T2W ratio: rT1/T2) derived from conventional MRI could act as a surrogate relaxation time predictive of IDH mutation status in histologically lower-grade gliomas. Strong exponential correlations were found between rT1/T2 and each of T1- and T2-relaxation times in eight subjects (rT1/T2 = 1.63exp−0.0005T1-relax + 0.30 and rT1/T2 = 1.27exp−0.0081T2-relax + 0.48; R2 = 0.64 and 0.59, respectively). In a test cohort of 25 patients, mean rT1/T2 (mrT1/T2) was significantly higher in IDHwt tumors than in IDHmt tumors (p < 0.05) and the optimal cut-off of mrT1/T2 for discriminating IDHmt was 0.666–0.677, (AUC = 0.75, p < 0.05), which was validated in an external domestic cohort of 29 patients (AUC = 0.75, p = 0.02). However, this result was not validated in an external international cohort derived from TCIA/TCGA (AUC = 0.63, p = 0.08). The t-Distributed Stochastic Neighbor Embedding analysis revealed a greater diversity in image characteristics within the TCIA/TCGA cohort than in the two domestic cohorts. The failure of external validation in the TCIA/TCGA cohort could be attributed to its wider variety of original imaging characteristics. [ABSTRACT FROM AUTHOR]

The transcription factor Bach1 heterodimerizes with small Maf proteins to repress Maf recognition element (MARE)-dependent gene expression. The repressor activity of Bach1 is inhibited by the direct binding of heme. To investigate the involvement of Bach1 in the heme-dependent regulation of the expression of the β-globin gene, mouse erythroleukemia (MEL) cells were cultured with succinylacetone (SA), a specific inhibitor of heme biosynthesis, and the level of β-globin mRNA was examined. A marked decrease of β-globin mRNA in SA-treated cells was observed, and this decrease was reversed by the addition of hemin. An iron chelator, desferrioxamine, also lowered the level of β-globin mRNA. The heme-dependent expression of β-globin is a transcriptional event since the expression of the human β-globin gene promoter-reporter gene containing the microlocus control region (µLCR) was inhibited when human erythroleukemia K562 cells and MEL cells were cultured with SA. Hemin treatment restored the decrease in promoter activity caused by SA. The control of the µLCR-β-globin promoter reporter gene by heme was dependent on DNase I-hypersensitive site 2 (HS2), which contains MARE. The MARE binding activity of Bach1 in K562 and MEL cells increased upon SA treatment, and the increase was diminished by the treatment with hemin. Transient expression of Bach1 suppressed the µtLCR activity, and this repressor activity was cancelled by treatment with hemin. The expression of a mutated Bach1 lacking hemeobinding sites led to a loss in the heme responsiveness of the µLCR. Furthermore, chromatin immunoprecipitation experiments revealed that Bach1 bound to the MARE of HS2 increased by the treatment of MEL cells with SA, and this was cancelled by hemin. We propose that heine positively regulates the β-globin gene expression by blocking the interaction of Bach1 with the MARE in the LCR. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the utility and limitation of gadopentetate (Gd)-enhanced MRI as a method for evaluating the anterior cruciate ligament (ACL) in the rheumatoid arthritis (RA) knee, using both surgical macro findings and histological findings to ascertain the pathological condition of the affected knee. Thirty-six knees of 25 RA patients were studied in this study. Four imaging protocols were employed: protocol A, T1-weighted and T2-weighted sagittal images; protocol B, T1-weighted sagittal image, after infusion of Gd-DTPA (0.2 mmol/kg, i.v.); protocol C, T1-weighted angled coronal image, parallel to the ACL; and protocol D, T1-weighted angled coronal image, parallel to the ACL, after infusion of Gd-DTPA. Sagittal image was determined as previously described. Angle coronal image was newly determined as coronal image parallel to the ACL. Surgical and MRI findings of the ACL were classified into four types: Type I (normal group) indicated that the thickness of the ACL was almost normal, adequate tension was maintained (surgical findings),and the ACL had thick and a more complex appearance with a homogeneous signal intensity and well-defined borders (MRI findings). Type II (degenerated group): the ACL had degenerated and tension was reduced (surgical findings), and the ACL had thin and a more complex appearance with a less homogeneous signal intensity and less well-defined borders. This appearance was more evident on Type II than Type I (MRI findings). Type III (ruptured group): the parenchyma of the ACL remained but lacked continuity (surgical findings), and the ACL appeared as partial lack of low signal intensity (MRI findings). Type IV (absent group): the parenchyma of the ACL was practically absent (surgical findings), and the ACL appeared as complete lack of signal low signal intensity (MRI findings). The concordance rate between surgical and MRI findings was investigated. Moreover, we investigated the extent to which histological changes of the ACL could be discriminated using MRI. In RA knees, the overall concordance rate between surgical and MRI findings was 41.7% under imaging protocol A. The overall rate improved up to 69.4% under imaging protocol B. But the overall rate dropped to 36.1% under imaging protocol C. The overall rate improved up to 83.3% under imaging protocol D. Especially, significant differences between imaging protocols A and B ( p<0.05), and imaging protocols C and D ( p<0.01), with respect to ACL degenerated group, were recognized. But significant differences between imaging protocols A and C, and imaging protocols B and D, with respect to ACL degenerated group, were not recognized. The concordance rate between histological and MRI findings was 41.7% in ACL normal group, and 61.5% in ACL degenerated group. The concordance rate between surgical and MRI findings was 100% in ACL normal group, and 78.9% in ACL degenerated group. There was a significant difference in the concordance rates between histological, surgical, and MRI findings in normal group ( p<0.05). The results of this study suggested that with Gd-enhanced MRI, the degree of synovial proliferation around the ACL and the degree of degradation of the ACL in the RA knee can be evaluated more accurately than with conventional MRI; however, in RA knees with severe synovial proliferation, it may be difficult to discriminate between the invasive synovium going into the ligament from synovium surrounding the ligament. This may be a limitation of Gd-enhanced MRI at present. In the clinical setting, the present imaging technique does allow the ligament to be evaluated to a certain degree, and may prove useful in the evaluation of temporal changes in the RA knee. [ABSTRACT FROM AUTHOR]

Objective: To report clinical features of bone metastases (BM) from head and neck squamous cell carcinoma (HNSCC).Methods: Among 772 patients with HNSCC diagnosed at our hospital over 9 years, 30 patients (3.9%) had clinical evidence of BM (24 men and 6 women; mean age: 63 years). We assessed the time interval from the primary diagnosis to BM development, symptoms attributable to BM, presence of distant metastases to other organs, number of BM, sites of BM, morphologic changes on computed tomography (CT) images, treatment for BM, and overall survival (OS).Results: BM at the initial stage were found in 9 patients with HNSCC (30%), and in 21 patients (70%) with HNSCC during the course of the disease. In the later patients, the median time interval from the primary diagnosis was 11.5 months. Nineteen patients (63%) did not have BM-related symptoms, 6 (20%) had pain, 3 (10%) had neurologic symptoms resulting from vertebral or skull metastases, and 2 (7%) had hypercalcemia. Seventeen patients (57%) showed bone-exclusive metastases, and 13 (43%) had distant metastases in other organs. Eleven patients (37%) had monostotic metastases (solitary BM), and 19 patients (63%) had polyostotic metastases (multiple BM). When combined, 9 patients (30%) showed bone-exclusive and monostotic metastases. The most commonly affected site was the thoracolumbar spine, accounting for 34% of total BM, followed by the pelvis (24%), shoulder and thorax (21%), and the extremities (17%). Notably, metastases to bones above the clavicle (craniofacial bones and cervical spine) accounted for only 3% of all bone lesions. CT images showed variable morphologic patterns with osteolytic type in 17 patients (57%), intertrabecular in 7 (23%), osteoblastic in 4 (13%), and mixed in 2 (7%). Systematic chemotherapy for BM was performed in 19 patients and radiotherapy in 18. The median survival time for patients with bone-exclusive and monostotic metastases was significantly longer than that for patients with multi-organ metastases or polyostotic metastases at 18.2 months vs. 5.7 months (p=0.02). Neither chemotherapy nor radiotherapy extended OS.Conclusion: Thirty percent of BM cases from HNSCC showed bone-exclusive and monostotic metastases. These patients tended to show a more favorable prognosis than patients with multi-organ metastases or polyostotic metastases. [ABSTRACT FROM AUTHOR]

Brain Tumor Image Analysis (BraTumIA) is a fully automated segmentation tool dedicated to detecting brain tumors imaged by magnetic resonance imaging (MRI). BraTumIA has recently been applied to several clinical investigations; however, the validity of this novel method has not yet been fully examined. The present study was conducted to validate the quality of tumor segmentation with BraTumIA in comparison with results from 11C-methionine positron emission tomography (MET-PET). A total of 45 consecutive newly diagnosed high-grade gliomas imaged by MRI and MET-PET were analyzed. Automatic tumor segmentation was conducted by BraTumIA and the resulting segmentation images were registered to MET-PET. Three-dimensional conformal association between these two modalities was calculated, considering MET-PET as the gold standard. High underestimation and overestimation errors were observed in tumor segmentation calculated by BraTumIA compared with MET-PET. Furthermore, when the tumor/normal ratio threshold was set at 1.3 from MET-PET, the BraTumIA false-positive fraction was ~0.4 and the false-negative fraction was 0.9. By tightening this threshold to 2.0, the BraTumIA false-positive fraction was 0.6 and the false-negative fraction was 0.6. Following comparison of segmentation performance with BraTumIA with regard to glioblastoma (GBM) and World Health Organization (WHO) grade III glioma, GBM exhibited better segmentation compared with WHO grade III glioma. Although BraTumIA may be able to detect enhanced tumors, non-enhancing tumors and necrosis, the spatial concordance rate with MET-PET was relatively low. Careful interpretation is therefore required when using this technique. [ABSTRACT FROM AUTHOR]

While rapid advancements in regenerative medicine strategies for spinal cord injury (SCI) have been made, most research in this field has focused on the early stages of incomplete injury. However, the majority of patients experience chronic severe injury; therefore, treatments for these situations are fundamentally important. Here, we hypothesized that environmental modulation via a clinically relevant hepatocyte growth factor (HGF)-releasing scaffold and human iPS cell-derived neural stem/progenitor cells (hNS/PCs) transplantation contributes to functional recovery after chronic complete transection SCI. Effective release of HGF from a collagen scaffold induced progressive axonal elongation and increased grafted cell viability by activating microglia/macrophages and meningeal cells, inhibiting inflammation, reducing scar formation, and enhancing vascularization. Furthermore, hNS/PCs transplantation enhanced endogenous neuronal regrowth, the extension of graft axons, and the formation of circuits around the lesion and lumbar enlargement between host and graft neurons, resulting in the restoration of locomotor and urinary function. This study presents an effective therapeutic strategy for severe chronic SCI and provides evidence for the feasibility of regenerative medicine strategies using clinically relevant materials. [ABSTRACT FROM AUTHOR]

Purposes: The aim of this study was to evaluate the association between the mesorectal extensions on high-resolution magnetic resonance imaging (MRI) and the prognosis of patients with clinical T3 lower rectal cancer. Methods: Fifty-eight patients with clinical T3 lower rectal cancer were investigated using high-resolution MRI. One radiologist who was blinded to the clinicopathological findings retrospectively examined the MRI-predicted circumferential resection margin (mrCRM) and the distance of mesorectal extension (mrDME) on the scans. If the imaging showed a tumor ≤1 mm from the mesorectal fascia, then the mrCRM involvement was defined as potentially present. The tumors were divided into two groups: mrDME ≤4 mm and mrDME >4 mm. Results: A survival analysis showed that mrCRM-positive patients had a significantly poorer prognosis in the RFS ( p < 0.01) and LRFS ( p < 0.01). Patients with mrDME >4 mm revealed a significantly poorer prognosis than those with mrDME ≤4 mm in the OS ( p = 0.04), RFS ( p < 0.01), and LRFS ( p = 0.04). A multivariate analysis revealed that both mrCRM and mrDME on MRI had a significant impact on the RFS ( p = 0.01 and 0.03, respectively). Conclusion: The mrDME, as well as the mrCRM, may be an important preoperative prognostic factor for patients with clinical T3 lower rectal cancer. [ABSTRACT FROM AUTHOR]

Reports have suggested that tumor textures presented on T2-weighted images correlate with the genetic status of glioma. Therefore, development of an image analyzing framework that is capable of objective and high throughput image texture analysis for large scale image data collection is needed. The current study aimed to address the development of such a framework by introducing two novel parameters for image textures on T2-weighted images, i.e., Shannon entropy and Prewitt filtering. Twenty-two WHO grade 2 and 28 grade 3 glioma patients were collected whose pre-surgical MRI and IDH1 mutation status were available. Heterogeneous lesions showed statistically higher Shannon entropy than homogenous lesions (p = 0.006) and ROC curve analysis proved that Shannon entropy on T2WI was a reliable indicator for discrimination of homogenous and heterogeneous lesions (p = 0.015, AUC = 0.73). Lesions with well-defined borders exhibited statistically higher Edge mean and Edge median values using Prewitt filtering than those with vague lesion borders (p = 0.0003 and p = 0.0005 respectively). ROC curve analysis also proved that both Edge mean and median values were promising indicators for discrimination of lesions with vague and well defined borders and both Edge mean and median values performed in a comparable manner (p = 0.0002, AUC = 0.81 and p < 0.0001, AUC = 0.83, respectively). Finally, IDH1 wild type gliomas showed statistically lower Shannon entropy on T2WI than IDH1 mutated gliomas (p = 0.007) but no difference was observed between IDH1 wild type and mutated gliomas in Edge median values using Prewitt filtering. The current study introduced two image metrics that reflect lesion texture described on T2WI. These two metrics were validated by readings of a neuro-radiologist who was blinded to the results. This observation will facilitate further use of this technique in future large scale image analysis of glioma. [ABSTRACT FROM AUTHOR]

Background: Information of tumor vascular architecture and hemodynamics is important in treating patients with head and neck tumors (HNTs). The purpose of this study is to investigate the feasibility of non-contrast-enhanced four-dimensional magnetic resonance angiography (non-CE 4DMRA) using arterial spin labeling for anatomical and hemodynamic evaluation of vascularity of head and neck tumors. Results: Non-CE 4DMRA images of 15 patients with HNTs were compared with those of contrast-enhanced 4DMRA (CE 4DMRA) by two independent observers. For qualitative evaluation, overall image quality, visualization of arterial branches and main arterial tumor feeders were assessed. For hemodynamic evaluation, signal-intensity-over-time curves within the tumors were compared. The sensitivity of non-CE 4DMRA for the identification of arterial branches and the main arterial tumor feeders was 75 and 20 %, respectively (interobserver agreement, κ = 0.56 and 0.54, respectively), while that of CE 4DMRA was 99 and 95 %, respectively (interobserver agreement, κ = 0.62 and 0.70, respectively). All three arterial/hypervascularized tumors determined on CE 4DMRA showed distinct signal-intensity-over-time curve pattern on non-CE 4DMRA, with distinct peak and wash out phases. Other tumors showed no wash out on non-CE 4DMRA. Conclusions: Use of non-CE 4DMRA for the anatomical and hemodynamic evaluation of vascularity of head and neck tumors is feasible, although the technique needs to be improved. [ABSTRACT FROM AUTHOR]

Purpose: A major drawback of magnetic resonance imaging (MRI) is its limited imaging speed. This study proposed an ultrafast cervical spine MRI protocol (2 min 57 s) using deep learning-based reconstruction (DLR) and compared the diagnostic results to those of conventional MRI protocols (12 min 54 s).Methods: Fifty patients who underwent cervical spine MRI using both conventional and ultrafast protocols, including sagittal T1-weighted, T2-weighted, short-TI inversion recovery, and axial T2*-weighted imaging were included in this study. The ultrafast protocol shortened the acquisition time to approximately-one-fourth of that of the conventional protocol by reducing the phase matrix, oversampling rate, and number of excitations, and by applying compressed sensing. To compensate for the decreased signal-to-noise ratio caused by acceleration, noise reduction using DLR was performed. For image interpretation, three neuroradiologists graded or classified degenerative changes, including central canal stenosis, foraminal stenosis, endplate degeneration, disc degeneration, and disc hernia. The presence of other pathologies was also recorded. Given the absence of a reference standard, we tested the interchangeability of the two protocols by calculating the 95% confidence interval (CI) of the individual equivalence index. We also assessed the inter-protocol intra-reader agreement using kappa statistics.Results: Except for endplate degeneration, the 95 % CI of the individual equivalence index for all variables did not exceed 5 %, indicating interchangeability between the two protocols. The kappa values ranged from 0.600 to 0.977, indicating substantial to almost perfect agreement.Conclusions: The proposed ultrafast MRI protocol yielded almost equivalent diagnostic results compared as the conventional protocol. [ABSTRACT FROM AUTHOR]

Study Design: This is a retrospective, single-institute, radiographical study. Objective: The study aimed to determine the correlation of magnetic resonance imaging (MRI) findings observed in metastatic spinal cord compression (MSCC) with post-treatment ambulatory status. Summary Of Background Data: Previous studies have reported various predictors of ambulatory outcome in patients with MSCC, but the relationship between the MRI features and post-treatment ambulatory function remains to be elucidated. Methods: Fifty-six hospitalized patients with MSCC and risk of MSCC were examined using MRI before therapeutic intervention. Circumferential ratio of cord compression (CRCC), clock position of compression, cross-sectional area (CSA), and change in signal intensity of the spinal cord were recorded. Each imaging feature was analyzed statistically regarding unassisted ambulatory status at the time of hospital discharge as the endpoint. Results: CRCC showed a prognostic value for post-treatment ambulatory function. More than half of CRCC predicted poor functional prognosis with statistical significance. However, the site of cord compression expressed by clock position on axial plane showed no relationship with functional prognosis. CSA of the spinal cord was enlarged in 23% of patients at the level of MSCC, which indicated that cord compression could also be formed by a relative relationship between cord swelling and surrounding mass effect. The said patients showed a better functional outcome. High intensity of the spinal cord on T2-weighted sagittal image was not useful because of lack of inter-rater reliability. Conclusion: CRCC on axial T2 image can guide clinicians to identify cancer patients at risk of paraplegia because of MSCC. More than half of CRCC entails urgent treatment despite preserved ambulatory function. Furthermore, some cases of MSCC accompany increased cord CSA. The measurement is also a useful guide to balance the risk and benefit of systemic steroid therapy. MRI is the key imaging modality in the risk assessment of MSCC. Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Aim This study aimed to determine the role of morphological patterns seen on imaging in predicting hepatocellular carcinoma recurrence following transarterial chemoembolization therapy. Methods Forty-seven patients from a single center who underwent transarterial chemoembolization to treat unresectable hepatocellular carcinomas between January 2011 and June 2012 were included in this study. We investigated whether the two pretreatment findings on computed tomography during hepatic arteriography (pattern 1, the single nodule pattern; pattern 2, at least one nodule showing the contiguous multinodular pattern) and other factors (age, sex, etiology, serum total bilirubin, serum albumin, prothrombin time, platelet count, serum level of protein induced by vitamin K absence/antagonist- II, serum α-fetoprotein, number of previous treatments for hepatocellular carcinoma, tumor number and maximum tumor size, presence of hypovascular lesions) could predict post-treatment recurrence. Results In a univariate analysis using Cox's proportional hazards model, serum total bilirubin, the serum level of protein induced by vitamin K absence/antagonist- II (≤100 vs ≥101 mAU/mL), tumor morphology (pattern 1 vs 2) and tumor number (≤3 vs ≥4) showed statistical significance (≤0.05). In a multivariate analysis of these factors, morphology and tumor number showed significance. According to Kaplan- Meier estimation, the cumulative disease-free survival rates were significantly lower in patients with four or more lesions than in those with three or less lesions and in patients showing pattern 2 than in those showing pattern 1. Conclusion Patients with pattern 2 hepatocellular carcinoma and/or four or more lesions may have a relatively high recurrence rate after transarterial chemoembolization. [ABSTRACT FROM AUTHOR]

One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively. The data of thirty-four histologically confirmed GBM patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11C-methionine positron emission tomography (Met-PET) were available were collected for analysis. Two of them also underwent MR relaxometry with rT1/T2 reconstructed for all cases. Met-PET was used as ground truth with T2-FLAIR hyperintense lesion, with >1.5 in tumor-to-normal tissue ratio being NET. rT1/T2 values were compared with MR relaxometry and Met-PET. rT1/T2 values significantly correlated with both T1- and T2-relaxation times in a logarithmic manner (p < 0.05 for both cases). The distributions of rT1/T2 from Met-PET high and low T2-FLAIR hyperintense lesions were different and a novel metric named Likeliness of Methionine PET high (LMPH) deriving from rT1/T2 was statistically significant for detecting Met-PET high T2-FLAIR hyperintense lesions (mean AUC = 0.556 ± 0.117; p = 0.01). In conclusion, this research study supported the hypothesis that rT1/T2 could be a promising imaging marker for NET identification. [ABSTRACT FROM AUTHOR]

Background: Many studies have reported that transverse computed tomography (CT) imaging findings correlate with prognosis of patients with small peripheral lung neoplasm with lepidic growth. However, no studies have examined this correlation with the aid of three-dimensional (3D) CT data. Purpose: To determine the most efficacious imaging factor for differentiation of lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. Material and Methods: We evaluated CT findings, nodule patterns, SUVmax on FDG-PET/CT, as well as nodule volume and ratios of solid parts to nodule volume that were semi-automatically measured on CT images of 64 pulmonary nodules of ≤ 2 cm in 60 consecutive patients (24 men and 36 women; mean age, 65 years). For logistic modeling, we used all of the significant factors observed between the neoplasms with good and with poor prognosis as independent variables to estimate the statistically significant factors for discriminating invasive adenocarcinomas with lepidic growth (lesions with poor prognosis, n=42) from the other neoplasms, including preinvasive lesions (lesions with good prognosis, n=22), resulting in a recommendation for the optimal criterion for predicting lesions with poor prognosis. Results: The logistic regression model identified the ratio of the solid part to the whole volume of a pulmonary nodule as the only significant factor (P=0.04) for differentiating lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. A ratio of 0.238 or more showed the highest discriminatory accuracy of 84% with 91% sensitivity and 76% specificity. Conclusion: Computer-aided analyses of pulmonary nodules proved most useful for establishing the optimal criterion for differentiation of lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Ground-glass opacity (GGO) is reported to be characteristic to lepidic growth of neoplasm in subsolid nodules. In solid nodules of lung cancer, however, there is no characteristic feature to be reported. Purpose: To study if there are any thin-section CT findings characteristic to tumor histology or if they are only related to tumor size in solid nodules of the lung cancer. Material and Methods: This study included 106 solid peripheral lung cancers of 3 cm or smaller (56 adenocarcinomas, 33 squamous cell carcinomas, and 17 small cell carcinomas) in which 16-slice CT with 1 mm collimation was performed before surgery. Six morphologic findings (presence or absence of lobulation, coarse spiculation, air bronchogram, cavity, pleural tag, and pleural-based lesion) and four measurements (ratio of the greatest transverse and vertical diameter to the shortest transverse diameter and density of lobulation and coarse spiculation) on thin-section CT images were evaluated. Density of lobulation (coarse spiculation) was defined as the ratio of lobulation (coarse spiculation) number to the greatest transverse diameter of a nodule. Results: Air bronchogram (P < 0.01) was the only significant factor for predicting lung adenocarcinoma. The prevalence of air bronchogram was significantly greater in adenocarcinoma than in squamous cell carcinoma (P < 0.01) or small cell carcinoma (P < 0.01). As the tumor size advanced, significantly positive linear trends were seen in the prevalence of lobulation (P < 0.01), coarse spiculation (P < 0.01), and pleural tag (P < 0.01), and the mean values of density of lobulation (P < 0.01) and coarse spiculation (P < 0.01), while the significant negative linear trend was seen in the ratio of vertical diameter to the shortest transverse (P = 0.02). Conclusion: Air bronchogram on thin-section CT is characteristic feature of solid adenocarcinoma of the lung. However, other thin-section CT findings are irrelevant to tumor histology and related only to tumor size. [ABSTRACT FROM AUTHOR]

Background: Radiological discrimination of histologic subtypes of small peripheral adenocarcinoma of the lung is clinically important. Although there are many articles in which CT findings were used for this purpose, there are only a few reports on the capability of FDG PET-CT findings for histologic classification of this tumor. Purpose: To investigate the correlation between visual assessment or maximum standard uptake values (SUVmax) on F18-FDG PET-CT and histology grading of small peripheral adenocarcinoma of the lung. Material and Methods: Proportions of positive PET-CT diagnoses and SUVmax were retrospectively reviewed on 96 solitary pulmonary nodules of ≤2 cm in 90 consecutive patients. Tumors were classified into four groups according to Noguchi's classification (group 1 [n = 10], atypical adenomatous hyperplasia and type A tumors; group 2 [n = 12], type B tumors; group 3 [n = 42], type C tumors; group 4 [n = 32], types D, E, and F tumors). Proportions of positive PET-CT diagnoses and mean SUVmax of lesions among four groups were compared using trend tests to examine if there is a significant linear correlation with the progression of the histology grading of tumors. Then, an optimal threshold of SUVmax was proposed to best discriminate tumors of poor (groups 3 and 4) from good (groups 1 and 2) prognosis. Results: There was a significant linear trend for both visual assessment (P < 0.01) and SUVmax (P < 0.01). A SUVmax of 0.42 showed the highest accuracy of 84% with 95% sensitivity and 50% specificity for predicting tumors of poor prognosis. A SUVmax of 2.05 showed 100% specificity with 49% sensitivity, and 60% accuracy. Positive visual diagnoses showed accuracy of 83% with 90% sensitivity and 59% specificity. Conclusion: Visual assessment and SUVmax on PET-CT correlated well with the histology grading of small peripheral adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare aggressive epithelial malignancy arising from a primary or recurrent benign mixed tumor. Only a few case reports describing the radiologic features of CXPA have been published. Purpose: To describe and characterize the magnetic resonance (MR) imaging findings of CXPA in the parotid gland and correlate them with pathologic findings. Material and Methods: The MR images of surgically proven CXPA in the parotid gland of five men and five women ranging in age from 28 to 75 years (mean 52 years) were retrospectively reviewed. All MR images were evaluated with emphasis on the size, margin characteristics, extraparotid infiltration, the presence of an encapsulated component, and signal intensity on T2-weighted or short-inversion-time inversion recovery (STIR) images. Results: The average maximal diameter was 4.3 cm. All 10 tumors had ill-defined boundaries, and seven tumors showed extraparotid infiltration, reflecting invasive growth of the malignant component identified on histological examination. Eight tumors had a round encapsulated component and seven of those signal intensities were a mixture of hypo- and hyperintensity on T2-weighted or STIR images. Histological correlation of these components revealed fibrously encapsulated tumors containing hyalinization and myxoid tissue, suggesting degenerated pleomorphic adenoma. Invasive malignant components had non-specific and various signal intensities. Conclusion: An invasive parotid mass co-existing with a round encapsulated component is suggestive of carcinoma ex pleomorphic adenoma. [ABSTRACT FROM AUTHOR]

Abstract: We present a case of malignant mesothelioma of the peritoneum with massive direct invasion to the liver in a 58-year-old Japanese woman. She had no history of asbestos exposure or other malignancies. Abdominal computed tomography revealed one 8-cm intrahepatic mass adjacent to the abdominal wall with peritoneal thickening, multiple smaller nodules in the peritoneal cavity, and intra-abdominal lymphadenopathy. Liver biopsy showed a small cluster of atypical cells similar to epithelial neoplasm, which formed a tubulopapillary structure. The tumor cells were positive for calretinin with strong nuclear and cytoplasmic expression together with podoplanin (D2-40) and some cytokeratins, but were negative for hepatocyte paraffin 1 and other adenocarcinoma markers. We confirmed a diffuse peritoneal mesothelioma with direct invasion to the liver. Liver masses with other peritoneal nodules are mostly encountered as metastatic diseases. However, the possibility of mesothelioma should be considered, even in women without an apparent history of asbestos exposure. [Copyright &y& Elsevier]

Chondrosarcomas are the most frequently occurring primary malignant chest wall tumors. Furthermore, the lungs serve as the most frequent sites for metastases. Pulmonary metastases from sarcomas usually appear as round nodules of varying sizes on roentgenograms. Here, we report an unusual clinical and radiographic presentation of pulmonary metastasis from a costal chondrosarcoma. Bilateral pulmonary metastases developed soon after wide surgical resection. Thoracic computed tomography revealed unusual radiological findings: consolidation accompanied with ground-glass opacity. To confirm the metastasis, we recommend a transbronchial biopsy in cases where unusual pulmonary findings are detected. [ABSTRACT FROM AUTHOR]

Aim: Two new imaging modalities have been developed recently that are directed at the focal liver lesions: gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and Sonazoid contrast-enhanced ultrasonography (CEUS). We investigated the usefulness of these modalities for the diagnosis of small (<2 cm), well-differentiated hepatocellular carcinoma (HCC). Methods: A total of 15 nodules from 13 patients, which were histologically diagnosed as well-differentiated HCC, were subjected to this study. Lesions that showed hypervascularity in the arterial phase and washout in the portal or late non-hemodynamic phase were regarded as HCC in the dynamic studies of all imaging modalities. Results: By multidetector computed tomography (MDCT), six of 15 (40%) nodules were diagnosed as HCC. Gd-EOB-DTPA-enhanced MRI diagnosed HCC in nine of the 15 (60%) nodules. Of the nine nodules that were not diagnosed by MDCT, four could be diagnosed by Gd-EOB-DTPA-enhanced MRI. In Sonazoid CEUS, 10 of 15 nodules (67%) were diagnosed as HCC. Four of nine nodules that could not be diagnosed as HCC by MDCT, were diagnosed by Sonazoid CEUS. A total of 11 of the 15 (73%) nodules were diagnosed as HCC by Gd-EOB-DTPA-enhanced MRI and Sonazoid CEUS in addition to MDCT. Conclusion: Gd-EOB-DTPA-enhanced MRI and Sonazoid CEUS had greater diagnostic value for small, well-differentiated HCC than did conventional MDCT. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to investigate the hypothesis that the spatial distribution of brain metastases could be affected by the biological subtypes of breast cancer. CT (n=1) or MRI (n=66) images of 67 patients with a total of 437 treatment-naive brain metastases from breast cancer were retrospectively reviewed. Patients were grouped according to the biological subtype of the tumor [luminal A, 28; luminal B, 9; human epidermal growth factor receptor 2 (HER2) positive, 14; triple-negative breast cancer (TNBC), 16]. All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. The distribution pattern of brain metastases after image standardization was analyzed. The cerebellum and the frontal lobe were more commonly affected by breast cancer brain metastases. Brain metastases from luminal A and B types of breast cancer arose more often in the cerebellum. Brain metastases from HER2-positive type breast cancer occurred more often in the putamen and the thalamus and less frequently in the cerebellum than other types (P=0.0057). The subtypes of breast cancer are related to differences in the spatial distributions of their brain metastases. These differences may be utilized to plan different cranial irradiation strategies according to the breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Simple Summary: To test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. A T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated high MET uptake. The stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850–3200 ms significantly indicated higher TCD while the T2-relaxation time and ADC did not significantly correlate with the stereotactic tissue sampling findings. However, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET. One of the most crucial yet challenging issues for glioma patient care is visualizing non-contrast-enhancing tumor regions. In this study, to test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared the T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. Regions that presented a T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated a high MET uptake. In addition, the stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850–3200 ms significantly indicated a higher TCD (p = 0.04). However, ADC was unable to show a significant correlation with MET uptake or with TCD. Finally, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET. [ABSTRACT FROM AUTHOR]

Measuring the thickness of sheet-like thin anatomical structures, such as articular cartilage and brain cortex, in three-dimensional (3-D) magnetic resonance (MR) images is an important diagnostic procedure. This paper investigates the fundamental limits on the accuracy of thickness determination in MR images. We defined thickness here as the distance between the two sides of boundaries measured at the subvoxel resolution, which are the zero-crossings of the second directional derivatives combined with Gaussian blurring along the normal directions of the sheet surface. Based on MR imaging and computer postprocessing parameters, characteristics for the accuracy of thickness determination were derived by a theoretical simulation. We especially focused on the effects of voxel anisotropy in MR imaging with variable orientation of sheet-like structure. Improved and stable accuracy features were observed when the standard deviation of Gaussian blurring combined with thickness determination processes was around √2/2 times as large as the pixel size. The relation between voxel anisotropy in MR imaging and the range of sheet normal orientation within which acceptable accuracy is attainable was also clarified, based on the dependences of voxel anisotropy and the sheet normal orientation obtained by numerical simulations. Finally, in vitro experiments were conducted using an acrylic plate phantom and a resected femoral head to validate the results of theoretical simulation. The simulated thickness was demonstrated to be well-correlated with the actual in vitro thickness. [ABSTRACT FROM AUTHOR]

The purpose of this investigation is to evaluate the diagnostic ability of three-dimensional spoiled gradient-echo (3D SPGR) magnetic resonance (MR) imaging in cases of osteonecrosis of the femoral head (ONFH), and to determine the accuracy of 3D SPGR imaging in area and volume measurement of ONFH. T1-weighted spin-echo (SE) and 3D SPGR imaging were performed on 20 femoral heads obtained from patients with ONFH. After MR imaging, the femoral heads were cut parallel to the imaging plane and were evaluated histologically. Areas and volumes of necrotic lesions were measured with a computer program and the deviation between MR images and anatomical measurements was evaluated. A low signal intensity band on 3D SPGR MR images was observed in all femoral heads and corresponded histologically to repaired marrow with viable fibrous mesenchymal tissue. The area proximate to the low band area coincided with the necrotic region. Both area and volume measurements by T1-weighted SE and 3D SPGR images showed a strong correlation to histological measurements. The discrepancies between histological and imaging results were minimal in 3D SPGR imaging, especially at the anterior and posterior portions of the femoral head. Three-dimensional SPGR imaging provides more accurate measurements of the area and volume of a necrotic lesion than T1-weighted SE imaging. [Copyright &y& Elsevier]

Ascending pharyngeal-vertebral anastomosis has been identified by angiography of the carotid artery in several cases. We present a case of ascending pharyngeal-vertebral anastomosis that was found incidentally in computed tomography angiography of the ascending pharyngeal artery. Images revealed that the anastomosis formed through the hypoglossal branch of the neuromeningeal trunk. The anastomosis seemed to be associated with hypoplasia of the right vertebral artery. Interventional radiologists should be aware of this dangerous anastomotic route of the APA to the VA. Discovery of hypoplasia of the major intracranial arteries before intra-arterial chemotherapy or embolization in head and neck area may avoid subsequent complications. [ABSTRACT FROM AUTHOR]

Background: Low-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, recently specified as harboring JAZF1–SUZ12 rearrangement. Typical JAZF1–SUZ12 ESS is slow growing, in which high uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET) and subserosal masses are quite unusual. Case presentation: A 69-year-old Japanese woman complained of urinary incontinence. Pelvic magnetic resonance imaging showed uterine lesions composed of (1) a 9 × 8 × 7-cm mass protruding from the right-anterior wall, (2) a 4.5-cm mass attached to the right-posterior wall, and (3) a 6.5-cm intramural mass in the fundus. FDG-PET demonstrated maximum standardized uptake value of 13.28 confined to the two subserosal masses (1 & 2) in contrast to no uptake of the intramural mass (3). She was diagnosed with a high-grade uterine sarcoma concomitant with leiomyomas and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The removed uterus had three tumors—two in the right-anterior and right-posterior subserosa, respectively, and the remaining in the fundal myometrium. Microscopically, the three tumors shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which neither round-cell component, pleomorphism, nor high mitotic activity was recognized. Nuclear cyclin D1 immunostaining was identified 50% of neoplastic cells in the two subserosal tumors (1 &2) whereas < 1% positive cells in the intramural component (3). Reverse transcriptase-polymerase chain reaction showed the same-sized electrophoretic bands indicating JAZF1–SUZ12 gene fusion shared by the three uterine tumors and a focal tumor extension into the extrauterine vein. The patient is alive without evidence of recurrence at 14 months after surgery. Conclusions: Pathologists and clinicians should not exclude the possibility of JAZF1–SUZ12 ESS even when uterine subserosal masses demonstrate extraordinary FDG uptake on PET. Molecular analysis is helpful for diagnostic confirmation of JAZF1–SUZ12 ESS with a complex growth pattern. [ABSTRACT FROM AUTHOR]

Background: Ovarian serous borderline tumor/atypical proliferative serous tumor (SBT/APST) is characterized by presenting at an early stage and much longer survival than high-grade serous carcinoma. Given that the prognosis of ovarian SBT/APST with no invasive features is excellent, remote relapse after surgery can pose a diagnostic pitfall. Bone metastasis as transformed low-grade carcinoma is an extremely rare initial presentation of recurrence in patients whose primary tumor was confined to the ovaries. Case presentation: A 55-year-old Japanese woman who had undergone surgery for a right ovarian tumor 13 years previously presented with right-lateral chest pain and neurologic abnormalities in the lower limbs. Computed tomography (CT) scan and magnetic resonance imaging revealed an irregular mass in the right arch of the 12th thoracic vertebra, extending through the intervertebral foramen and into surrounding soft tissue, the maximum diameter of the whole mass being 78 mm. Pathological examination of a CT-guided needle biopsy of the paraspinal lesion demonstrated papillary cell clusters with blunt nuclear atypia and psammomatous calcification that were positive for PAX8, estrogen receptor, and WT1, but negative for thyroglobulin on immunohistochemical testing, and of a P53 non-mutational pattern. On clinicopathologic review, the previous 13- × 11- × 9-cm ovarian tumor was an intracystic and exophytic papillary growth without surface involvement; it had ruptured intraoperatively. Microscopically there was serous epithelium with minimal cytologic atypia proliferating in hierarchical branches with no invasive foci or micropapillary components. The tumor was confined to the right ovary with no peritoneal implants. Neither primary nor metastatic tumor harbored KRAS/BRAF mutations according to polymerase chain reaction using formalin-fixed paraffin-embedded tissues. We concluded that, after a 13-year disease-free interval, the paraspinal lesion was bone metastasis of low-grade carcinoma originating from the ovarian SBT/APST. The patient received radiotherapy for the paraspinal lesion followed by administration of paclitaxel and carboplatin plus bevacizumab and remains alive 168 months after the initial surgery. Conclusions: Pathologists and radiologists should not exclude late recurrence of ovarian SBT/APST when bone metastases are suspected, even when neither peritoneal nor lymph node involvement are detected. Long-term surveillance of women with ovarian serous tumors with no invasive features is recommended. [ABSTRACT FROM AUTHOR]

Background Context: Giant cell tumor of the tendon sheath (GCTTS) is a common, benign lesion of the synovial membrane that occurs more often in large joints than in digits. Giant cell tumor of the tendon sheath rarely arises in close proximity to the axial skeleton.Purpose: The purpose of the study was to report a rare case of GCTTS arising from the membrane surrounding the posterior arch of the atlas (C1).Study Design/setting: This is a case report.Methods: The methods involve clinical findings and review of current literature.Results: In this report, we describe a rare case of GCTTS arising from the membrane surrounding the posterior arch of C1, with no apparent continuity with the facet joint. Here we show the radiographic features, with particular emphasis on positron emission tomography-computerized tomography scans, which have not been previously reported.Conclusions: We experienced an extremely rare case of GCTTS arising from the membrane surrounding the posterior arch of the C1 vertebra. In spite of the rarity of this disease, GCTTS should be considered in the differential diagnosis of the axial skeletal lesion. Awareness of GCTTS is important because its radiographic features may simulate other neoplastic lesions in the spine. [ABSTRACT FROM AUTHOR]