Gestational Ectopic Hyperparathyroidism: A Case Report of Perioperative and Perinatal Outcomes.

In the realm of obstetric care, discerning the subtle signs of primary hyperparathyroidism (PHPT) amidst common pregnancy symptoms remains a formidable challenge. Our exploration into a case of gestational hypercalcemia peels back the layers of this complexity, revealing the clinical conundrum posed by overlapping gastrointestinal manifestations. The journey from diagnosis through surgical intervention to the resolution of symptoms underscores the importance of vigilance for PHPT in pregnant patients. This case further prompts consideration of gamma-aminobutyric acid (GABA) as a potential piece in the puzzle of persistent symptoms post-calcium normalization, inviting a broader dialogue on the intricacies of parathyroid pathology in pregnancy.

Functional Connectivity Pattern Using Resting-state fMRI as an Assessment Tool for Spatial Neglect during the Recovery Stage of Stroke: A Pilot Study.

PURPOSE: To determine if functional connectivity measured with resting-state functional MRI could be used as a tool to assess unilateral spatial neglect during stroke recovery. METHODS: Resting-state functional MRI was performed on 13 stroke patients with lesions in the right cerebral hemisphere and 31 healthy subjects. The functional connectivity score was defined as a correlation of a target region with the right inferior parietal lobule. Spatial neglect was measured with a behavioral inattention test. RESULTS: First, the functional connectivity scores between the right inferior parietal lobule and right inferior frontal gyrus, including the opercular and triangular parts, were significantly decreased in stroke patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Second, the functional connectivity scores between the bilateral inferior parietal lobules were also significantly decreased in patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Third, negative functional connectivity scores between the right inferior parietal lobule and bilateral medial orbitofrontal cortexes, which are related to the default mode network, were detected in patients without unilateral spatial neglect in contrast to a reduction of this negative tendency in patients with unilateral spatial neglect. The functional connectivity scores between these regions were significantly different between patients with and without unilateral spatial neglect and were negatively correlated with the behavioral inattention test score. CONCLUSION: Though still in the pilot research stage and using a small number of cases, our findings are consistent with the hypothesis that functional connectivity maps generated with resting-state functional MRI may be used as a tool to evaluate unilateral spatial neglect during stroke recovery.

Black-blood magnetic resonance imaging suggesting central nervous system vasculitis in moyamoya syndrome associated with systemic lupus erythematosus.

Moyamoya syndrome is a cerebrovascular disorder characterized by bilateral stenosis and occlusion of the internal carotid arteries and their branches. A 45-year-old woman with a history of systemic lupus erythematosus was admitted for recurrent ischemic strokes. Magnetic resonance (MR) angiography revealed moyamoya-like vasculopathy. Black-blood gadolinium-based contrast-enhanced MR images showed strong, concentric enhancement along the occluded arteries, which suggested vasculitis as the etiology of moyamoya-like vasculopathy. Intensive immunosuppressive therapy combined with anticoagulation therapy and rehabilitation led to a favorable outcome in this case. Black-blood MR imaging can be a non-invasive and prompt imaging modality when central nervous system vasculitis is suspected.

Visualization of carotid vessel wall and atherosclerotic plaque: T1-SPACE vs. compressed sensing T1-SPACE.

OBJECTIVES: To compare visualization of carotid plaques and vessel walls between 3D T1-fast spin echo imaging with conventional SPACE (T1-SPACE) and with a prototype compressed sensing T1-SPACE (CS-T1-SPACE) METHODS: This retrospective study was approved by the institutional review board. Participants comprised 43 patients (36 males, 7 females; mean age, 71 years) who underwent carotid MRI including T1-SPACE and CS-T1-SPACE. The quality of visualization for carotid plaques and vessel walls was evaluated using a 5-point scale, and signal intensity ratios (SRs) of the carotid plaques were measured and normalized to the adjacent sternomastoid muscle. Scores for the quality of visualization were compared between T1-SPACE and CS-T1-SPACE using the Wilcoxon signed-rank test. Statistical differences between SRs of plaques with T1-SPACE and CS-T1-SPACE were also evaluated using the Wilcoxon signed-rank test, and Spearman's correlation coefficient was calculated to investigate correlations. RESULTS: Visualization scores were significantly higher for CS-T1-SPACE than for T1-SPACE when evaluating carotid plaques (p = 0.0212) and vessel walls (p < 0.001). The SR of plaques did not differ significantly between T1-SPACE and CS-T1-SPACE (p = 0.5971). Spearman's correlation coefficient was significant (0.884; p < 0.0001). CONCLUSIONS: CS-T1-SPACE allowed better visualization scores and sharpness compared with T1-SPACE in evaluating carotid plaques and vessel walls, with a 2.5-fold accelerated scan time with comparable image quality. CS-T1-SPACE appears promising as a method for investigating carotid vessel walls, offering better image quality with a shorter acquisition time. KEY POINTS: • CS-T1-SPACE allowed better visualization compared with T1-SPACE in evaluating carotid plaques and vessel walls, with a 2.5-fold accelerated scan time with comparable image quality. • CS-T1-SPACE offers a promising method for investigating carotid vessel walls due to the better image quality with shorter acquisition time. • Physiological movements such as swallowing, arterial pulsations, and breathing induce motion artifacts in vessel wall imaging, and a shorter acquisition time can reduce artifacts from physiological movements.

Clinical evaluation of time-of-flight MR angiography with sparse undersampling and iterative reconstruction for cerebral aneurysms.

Compressed sensing (CS) MRI has just been introduced to research areas as an innovative approach to accelerate MRI. CS is expected to achieve higher k-space undersampling by exploiting the underlying sparsity in an appropriate transform domain. MR angiography (MRA) provides high spatial resolution information on arteries; however, a relatively long acquisition time is necessary to cover a wide volume. Reduction of acquisition time by CS for time-of-flight (TOF) MR angiography (Sparse-TOF) is beneficial in clinical examinations; therefore, the clinical validity of Sparse-TOF needs to be investigated. The aim of this study was to compare the diagnostic capability of TOF MRA between parallel imaging (PI)-TOF with an acceleration factor of 3 (annotated as 3×) and Sparse-TOF (3× and 5×) in patients with cerebral aneurysms. PI-TOF (3×) and Sparse-TOF (3× and 5×) imaging were performed in 20 patients using a 3 T MRI system. Aneurysms in PI-TOF (3×) and Sparse-TOF (3× and 5×) were blindly rated as visible or scarcely visible by neuroradiologists. The neck, height and width of aneurysms were also measured. Twenty-six aneurysms were visualized and rated as visible in PI-TOF (3×) and Sparse-TOF (3× and 5×), with excellent agreement between two raters. No significant differences were found in measured neck, height or width of aneurysms among them. Sparse-TOF (3× and 5×) were acquired and reconstructed within 6 min, and cerebral aneurysms were visible in both of them with equivalent quality to PI-TOF (3×). Sparse-TOF (5×) is a good alternative to PI-TOF (3×) to visualize cerebral aneurysms.

Differential diagnosis of posterior fossa brain tumors: Multiple discriminant analysis of Tl-SPECT and FDG-PET.

This study investigated the combined capability of thallium-201 (Tl)-SPECT and fluorine-18-fluoro-deoxy-glucose (FDG)-PET for differential diagnosis of posterior fossa brain tumors using multiple discriminant analysis.This retrospective study was conducted under approval of the institutional review board. In the hospital information system, 27 patients with posterior fossa intra-axial tumor between January 2009 and June 2015 were enrolled and grouped as the following 7 entities: low grade glioma (LGG) 6, anaplastic astrocytoma (AA) 2, glioblastoma (GBM) 3, medulloblastoma (MB) 3, hemangioblastoma (HB) 6, metastatic tumor (Mets) 3, and malignant lymphoma (ML) 4. Tl and FDG uptakes were measured at the tumors and control areas, and several indexes were derived. Using indexes selected by the stepwise method, discriminant analysis was conducted with leave-one-out cross-validation.The predicted accuracy for tumor classification was 70.4% at initial analysis and 55.6% at cross-validation to differentiate 7 tumor entities. HB, LGG, and ML were well-discriminated, but AA was located next to LGG. GBM, MB, and Mets largely overlapped and could not be well distinguished even applying multiple discriminant analysis. Correct classification in the original and cross-validation analyses was 44.4% and 33.3% for Tl-SPECT and 55.6% and 48.1% for FDG-PET.

Relationship between aging and T1 relaxation time in deep gray matter: A voxel-based analysis.

PURPOSE: To investigate age-related changes in T1 relaxation time in deep gray matter structures in healthy volunteers using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE). MATERIALS AND METHODS: In all, 70 healthy volunteers (aged 20-76, mean age 42.6 years) were scanned at 3T magnetic resonance imaging (MRI). A MP2RAGE sequence was employed to quantify T1 relaxation times. After the spatial normalization of T1 maps with the diffeomorphic anatomical registration using the exponentiated Lie algebra algorithm, voxel-based regression analysis was conducted. In addition, linear and quadratic regression analyses of regions of interest (ROIs) were also performed. RESULTS: With aging, voxel-based analysis (VBA) revealed significant T1 value decreases in the ventral-inferior putamen, nucleus accumbens, and amygdala, whereas T1 values significantly increased in the thalamus and white matter as well (P < 0.05 at cluster level, false discovery rate). ROI analysis revealed that T1 values in the nucleus accumbens linearly decreased with aging (P = 0.0016), supporting the VBA result. T1 values in the thalamus (P < 0.0001), substantia nigra (P = 0.0003), and globus pallidus (P < 0.0001) had a best fit to quadratic curves, with the minimum T1 values observed between 30 and 50 years of age. CONCLUSION: Age-related changes in T1 relaxation time vary by location in deep gray matter. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:724-731.

Quantitative assessment of gadolinium deposition in dentate nucleus using quantitative susceptibility mapping.

PURPOSE: Gadolinium deposition in dentate nucleus (DN) has been reported after serial administration of gadolinium-based contrast agents (GBCAs). Gadolinium complexes have paramagnetic properties; therefore, we evaluated susceptibility changes of gadolinium deposition in DN using quantitative susceptibility mapping (QSM) for patients after serial administration of GBCAs. MATERIALS AND METHODS: In all, 48 patients with brain tumors, who had had serial GBCA administrations (GBCA group), and 48 healthy volunteers without any history of GBCA administrations (non-GBCA group) were enrolled in this study. Susceptibility values in DN on QSM and DN-to-cerebellum signal intensity ratios on unenhanced T1 -weighted images (T1 ratios) on 3T were analyzed. The relationship between the number of times of GBCA administrations and susceptibility values or T1 ratios were evaluated in the GBCA group. RESULTS: Susceptibility values at DN in the GBCA group were 0.107 ± 0.029 ppm, and significantly higher than those of the non-GBCA group (0.079 ± 0.025 ppm) (P < 0.0001). T1 ratios in DN of the GBCA group were 1.059 ± 0.070, and also significantly higher than that of the non-GBCA group (0.993 ± 0.016) (P < 0.0001). Spearman rank correlation coefficients between susceptibility values and the number of times of linear GBCA administration showed a modest significant correlation (ρ = 0.45, P = 0.0015). There was good correlation between T1 ratios and the number of times of linear GBCA administration, as reported previously (ρ = 0.76, P < 0.0001). CONCLUSION: Susceptibility values on QSM in DN of the GBCA group, after serial administration of GBCAs, were significantly higher than those of the non-GBCA group. Evidence Level: 3 J. MAGN. RESON. IMAGING 2017;45:1352-1358.

T1-weighted MR imaging of glioma at 3T: a comparative study of 3D MPRAGE vs. conventional 2D spin-echo imaging.

PURPOSE: This study aims to investigate difference between magnetization-prepared rapid gradient-echo imaging (MPRAGE) and spin-echo (SE) imaging for evaluating glioma on pre-contrast-enhanced (CE) and post-CE T1-weighted images at 3 T. MATERIALS AND METHODS: We retrospectively assessed pre-CE and post-CE T1-weighted images for tumor contrast in 64 consecutive glioma patients. RESULTS: In the nonenhancing tumors, the contrast was significantly clearer in MPRAGE than SE. In the enhancing tumors, post-CE contrast ratio was significantly higher in SE than MPRAGE, but when subtraction images are evaluated, the difference got smaller. CONCLUSION: MPRAGE can be a good substitute of SE for T1-weighted imaging of glioma.

Use of the sit-to-stand task to evaluate motor function of older adults using telemetry.

BACKGROUND: Physical exercises are widely used in community programs, but not all older adults are willing to participate. Information and communication technology may solve this problem by allowing older people to participate in fitness programs at home. Use of remote instruction will facilitate physical exercise classes without requiring that participants gather at one place. The aim of this study was to examine use of a sit-to-stand task in evaluating motor function using conventional video communication in a telemetry system to enable real-time monitoring, and evaluation in physical performance of older adults at home. METHODS: The participants were 59 older individuals and 81 university students. Three physical exercise batteries were used: arm curl, figure-of-eight walk test, and functional reach. The knee extension maximum angular velocity (KEMAV) and the iliac elevation maximum velocity (IEMV) during standing up from a chair and the heel rise frequency were used in the motion-capture measurements. The results were assessed using multi-group structural equation modeling (SEM) for the young and older groups. RESULTS: Young participants consistently performed better than their older counterparts on all items. Analyses with multi-group SEM based on correlations between items yielded a good model-fit for the data. Among all path diagrams for IEMV and KEMAV in the older and young groups, paths from muscular strength to skillfulness showed significant effects. The path from the IEMV to muscular strength was also significant in the older group. CONCLUSIONS: Multi-group SEM suggested that video-based measurements of IEMV during sit-to-stand motion can estimate muscular strength, which suggests that remote monitoring of physical performance can support wellness of community-dwelling older adults.

The soluble form of BMPRIB is a novel therapeutic candidate for treating bone related disorders.

Bone morphogenetic proteins (BMPs) are multi-functional growth factors that belong to the TGF-beta superfamily. Recently, several soluble BMP receptors, such as ActRIIA-Fc, ActRIIB-Fc, and ALK1-Fc, are undergoing clinical trials. Both BMPRIA and BMPRIB are type I BMP receptors, and while BMPRIA-Fc has been reported to have bone-increasing properties, there have been no investigations concerning the biological functions of BMPRIB-Fc. Therefore, comparing the effects of BMPRIA-Fc and BMPRIB-Fc in vivo should be helpful in revealing the differences in biological function between BMPRIA and BMPRIB, and would also aid in the evaluation of BMPRIB-Fc as a therapeutic agent. Here, we produced Tg chimeras in which BMPRIA-Fc and BMPRIB-Fc proteins circulated at high concentrations (36.8-121.4 µg/mL). Both Tg chimeras showed a significant increase of bone volume and strength. Using histological analysis, adenoma of the glandular stomach was observed only in BMPRIA-Fc chimeras suggesting the tumorigenic activity of this protein. Administration of recombinant BMPRIB-Fc protein to normal mice also increased bone volumes. Finally, treatment with BMPRIB-Fc decreased the area of osteolytic regions in a mouse model of breast cancer metastasis. In conclusion, our data suggest that BMPRIB-Fc can be used for the treatment of bone-related disorders with a lower risk than BMPRIA-Fc.

MP2RAGE for deep gray matter measurement of the brain: A comparative study with MPRAGE.

BACKGROUND: To compare magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) imaging with conventional MPRAGE imaging for deep gray matter (GM) segmentation, reproducibility, contrast ratio (CR) and contrast-to-noise ratio (CNR), and to evaluate reproducibility of T1 maps derived from MP2RAGE. METHODS: MP2RAGE and MPRAGE imaging were conducted twice for each of 20 volunteers on a 3 Tesla MRI scanner. Images were normalized and segmented using SPM12 with the DARTEL algorithm. Reproducibility of segmentation was evaluated using coefficients of variation (COVs) of deep GM probability maps between first and second scans, which was compared between MP2RAGE and MPRAGE. Differences in deep GM probability were compared voxel-wise. CR and CNR analyses were conducted using regions of interest. COVs of T1 maps were also evaluated. RESULTS: Comparison of GM probability maps demonstrated that putamen, caudate nucleus and thalamus were segmented significantly larger in MP2RAGE than in MPRAGE, and MP2RAGE was inferior only at some areas of globus pallidus and lateral thalamus (P < 0.05; false discovery rate, FDR). CRs of deep GM structures were significantly better in MP2RAGE (P < 0.0001). COVs of deep GM probability maps were significantly higher at large areas of the deep GM in MPRAGE (P < 0.05, FDR). COVs ranged from 0.50 to 3.31% in MP2RAGE and from 0.62 to 4.12% in MPRAGE. COVs of the T1 map were around 2%. CONCLUSION: MP2RAGE yields greater reproducibility and better tissue contrast than MPRAGE in deep GM. T1 maps derived from MP2RAGE were highly reliable. MP2RAGE is useful for measurement and analysis of deep GM.

Quantitative Susceptibility Mapping at 3 T and 1.5 T: Evaluation of Consistency and Reproducibility.

OBJECTIVES: The aim of this study was to assess the consistency and reproducibility of quantitative susceptibility mapping (QSM) at 3-T and 1.5-T magnetic resonance (MR) scanners. MATERIALS AND METHODS: This study was approved by institutional ethics committee, and written informed consent was obtained. Twenty-two healthy volunteers underwent 2 examinations on different days. Each examination consisted of MR imaging on both 3-T and 1.5-T MR scanners. The data from both scanners and examination days were obtained, and QSM was calculated with STI Suite using 2 different algorithms--harmonic phase removal using laplacian operator (HARPERELLA) and a sophisticated harmonic artifact reduction for phase data (SHARP) method with a variable radius of the spherical kernel at the brain boundary (V-SHARP). We evaluated consistency of QSM between 3 T and 1.5 T and the reproducibility between the first and second examinations using 2-phase processing methods (HARPERELLA and V-SHARP). RESULTS: Susceptibility values of regions of interests at 3 T were highly correlated with those at 1.5 T with good agreement (HARPERELLA, R2 = 0.838; V-SHARP, R2 = 0.898) (average difference, ±1.96 SD; HARPERELLA, -0.012 ± 0.046; V-SHARP, -0.002 ± 0.034). Reproducibility analysis demonstrated excellent correlation between the first and second examination at both 3 T and 1.5 T for both algorithms (HARPERELLA at 3 T, R2 = 0.921; 1.5 T, R2 = 0.891; V-SHARP at 3 T, R2 = 0.937; 1.5 T, R2 = 0.926). Bland-Altman analysis showed excellent reproducibility for HARPERELLA (3 T, -0.003 ± 0.032; 1.5 T, -0.003 ± 0.038) and V-SHARP (3 T, -0.003 ± 0.027; 1.5 T, -0.003 ± 0.029). Susceptibility values of these 2 algorithms were highly correlated with good agreement (3T, R2 = 0.961; 1.5 T, R = 0.931) (3 T, 0.009 ± 0.023; 1.5 T, -0.003 ± 0.049). CONCLUSIONS: Quantitative susceptibility mapping with HARPERELLA and V-SHARP demonstrated good reproducibility at 3 T and 1.5 T, and QSM with V-SHARP demonstrated good consistency at 3 T and 1.5 T.

Grading meningioma: a comparative study of thallium-SPECT and FDG-PET.

The purpose was to compare capability of fluorine-18 fluorodeoxyglucose (FDG)-PET and thallium-201 (Tl)-SPECT for grading meningioma.This retrospective study was conducted as a case-control study under approval by the institutional review board. In the hospital information system, 67 patients (22 men and 45 women) who had both FDG-PET and Tl-SPECT preoperative examinations were found with histopathologic diagnosis of meningioma. The maximum FDG uptake values of the tumors were measured, and they were standardized to the whole body (SUVmax) and normalized as gray matter ratio (SUVRmax). Mean and maximum Tl uptake ratios (TURmean and TURmax, respectively) of the tumors were measured and normalized as ratios to those of the contralateral normal brain. Receiver-operating characteristic curve analyses of the 4 indexes were conducted for differentiation between low- and high-grade meningiomas, and areas under the curves (AUCs) were compared. Correlation coefficients were calculated between these indexes and Ki-67.Fifty-six meningiomas were classified as grade I (low grade), and 11 were grade II or III (high grade). In all 4 indexes, a significant difference was observed between low- and high-grade meningiomas (P < 0.05). AUCs were 0.817 (SUVmax), 0.781 (SUVRmax), 0.810 (TURmean), and 0.831 (TURmax), and no significant difference was observed among the indexes. Their sensitivity and specificity were 72.7% to 90.9% and 71.4% to 87.5%, respectively. Correlation of the 4 indexes to Ki-67 was statistically significant, but coefficients were relatively low (0.273-0.355).Tl-SPECT, which can be used at hospitals without a cyclotron or an FDG distribution network, has high diagnostic capability of meningioma grades comparable to FDG-PET.

Grading glial tumors with amide proton transfer MR imaging: different analytical approaches.

Amide proton transfer (APT) magnetic resonance imaging is gaining attention for its capability for grading glial tumors. Usually, a representative slice is analyzed. Different definitions of tumor areas have been employed in previous studies. We hypothesized that the accuracy of APT imaging for brain tumor grading may depend upon the analytical methodology used, such as selection of regions of interest (ROIs), single or multiple tumor slices, and whether or not there is normalization to the contralateral white matter. This study was approved by the institutional review board, and written informed consent was waived. Twenty-six patients with histologically proven glial tumors underwent preoperative APT imaging with a three-dimensional gradient-echo sequence. Two neuroradiologists independently analyzed APT asymmetry (APTasym) images by placing ROIs on both a single representative slice (RS) and all slices including tumor (i.e. whole tumor: WT). ROIs indicating tumor extent were separately defined on both FLAIR and, if applicable, contrast-enhanced T1-weighted images (CE-T1WI), yielding four mean APTasym values (RS-FLAIR, WT-FLAIR, RS-CE-T1WI, and WT-CE-T1WI). The maximum values were also measured using small ROIs, and their differences among grades were evaluated. Receiver operating characteristic (ROC) curve analysis was also conducted on mean and maximum values. Intra-class correlation coefficients for inter-observer agreement were excellent. Significant differences were observed between high- and low-grade gliomas for all five methods (P < 0.01). ROC curve analysis found no statistically significant difference among them. This study clarifies that single-slice APT analysis is robust despite tumor heterogeneity, and can grade glial tumors with or without the use of contrast material.

Magnetic resonance imaging relaxation times of female reproductive organs.

BACKGROUND: Relaxation time of female reproductive organs affects the tissue contrast of magnetic resonance image (MRI), and is used for quantitative analysis. PURPOSE: To evaluate the relaxation times of normal female reproductive organs in the luteal phase of the menstrual cycle. MATERIAL AND METHODS: On a 1.5-T MRI, relaxation times were measured in pelvic tissues (endometrium, junctional zone, myometrium, follicle, and stroma) of 32 female healthy volunteers (33.5 ± 6.8 years). The Look-Locker sequence was used to measure T1 relaxation times. Furthermore, a multiple spin-echo method with 32 different echo times was used to measure T2 relaxation times. The images were obtained in the luteal phase of each volunteer's menstrual cycle. RESULTS: The measured relaxation times (means ± standard deviations) were as follows: endometrium (T1, 1703 ± 147 ms; T2, 214 ± 35 ms), junctional zone (T1, 1168 ± 63 ms; T2, 72 ± 12 ms), myometrium (T1, 1314 ± 103 ms; T2, 138 ± 20 ms), follicle (T1, 2267 ± 49 ms; T2, 603 ± 68 ms), and stroma (T1, 1481 ± 129 ms; T2, 126 ± 29 ms). CONCLUSION: Reliable MRI measurements of T1 and T2 relaxation times of normal female reproductive organs in the luteal phase of the menstrual cycle are useful as references to recognize the normal value.

Primary central nervous system lymphoma and glioblastoma: differentiation using dynamic susceptibility-contrast perfusion-weighted imaging, diffusion-weighted imaging, and (18)F-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: The objective was to evaluate diagnostic performance of dynamic susceptibility-contrast perfusion-weighted imaging, diffusion-weighted imaging, and (18)F-fluorodeoxyglucose positron emission tomography in differentiating primary central nervous system lymphoma (PCNSL) and glioblastoma. MATERIALS AND METHODS: Twenty-three glioblastomas and 11 PCNSLs were analyzed with uncorrected cerebral blood volume (CBV) ratio, fifth percentile value of cumulative apparent diffusion coefficient histogram (ADC5%), and maximum standardized uptake value (SUVmax) using regions of interest created semiautomatically on enhancing areas. RESULTS: Uncorrected CBV ratio was highly capable of differentiating PCNSL from glioblastoma, as well as SUVmax and ADC5%. CONCLUSIONS: Uncorrected CBV ratio demonstrates high diagnostic performance comparable to SUVmax.

Adult-specific systemic over-expression reveals novel in vivo effects of the soluble forms of ActRIIA, ActRIIB and BMPRII.

Bone morphogenetic proteins (BMPs)/growth differentiation factors (GDFs), which belong to the TGF-beta superfamily, are pleiotropic factors that play a role in regulating the embryonic development and postnatal homeostasis of various organs and tissues by controlling cellular differentiation, proliferation and apoptosis. Conventional transgenic and knockout (KO) mouse approaches have provided only limited information regarding the in vivo functions of BMP signaling in adult animals due to the effects on prenatal development and the difficulty in manipulating multiligand signals simultaneously. We recently produced transgenic chimeric mice(Tg chimeras) in which the soluble IgG1-Fc fusion protein of three BMP type II receptors (ActRIIA, ActRIIB, BMPRII) was highly circulated (281-709 µg/ml), specifically in adult mouse blood. Since each BMP receptor can bind to multiple BMP ligands, these Tg chimeras should be useful to investigate the effects of trapping multiple BMP ligands. Remarkably, some phenotypes were unexpected based on previous studies, such as KO mouse analyses, presumably representing the effects of the multiple ligand trapping. These phenotypes included increased red blood cells (RBCs) and decreased viability in adults. In a further study, we focused on the phenotype of increased RBCs and found that extramedullary hematopoiesis in the spleen, not in the bone marrow, was increased using histological and flow cytometric analyses. Although it remains to be elucidated whether the transgene products affect the tissues directly or indirectly, our data provide novel and important insight into the biological functions of the soluble IgG1-Fc fusion protein of three BMP type II receptors in adults, and our approach should have broad applications to research on other ligand receptor families and studies involving mouse models.

Cancer-testis antigen BORIS is a novel prognostic marker for patients with esophageal cancer.

Esophageal squamous cell cancer (ESCC) is one of the most common lethal tumors in the world, and development of new diagnostic and therapeutic methods is needed. In this study, cancer-testis antigen, BORIS, was isolated by functional cDNA expression cloning using screening technique with serum IgG Abs from ESCC patients. BORIS was previously reported to show cancer-testis antigen like expression, but its immunogenicity has remained unclear in cancer patients. BORIS was considered to be an immunogenic antigen capable of inducing IgG Abs in patients with various cancers, including four of 11 ESCC patients. Immunohistochemical study showed that the BORIS protein was expressed in 28 of 50 (56%) ESCC tissues. The BORIS expression was significantly associated with lymph node metastasis in ESCC patients with pT1 disease (P = 0.036). Furthermore, the patients with BORIS-positive tumors had a poor overall survival (5-year survival rate: BORIS-negative 70.0% vs BORIS-positive 29.9%, log-rank P = 0.028) in Kaplan-Meier survival analysis and log-rank test. Multivariate Cox proportional hazard model demonstrated that BORIS expression was an independent poor prognostic factor (hazard ratio = 4.158 [95% confidence interval 1.494-11.57], P = 0.006). Downregulation of BORIS with specific siRNAs resulted in decreased cell proliferation and invasion ability of ESCC cell lines. BORIS may be a useful biomarker for prognostic diagnosis of ESCC patients and a potential target for treatment including by BORIS-specific immunotherapy and molecular target therapy.