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Objective: The aim of the study was to evaluate the prognostic utility of computed tomography (CT) histogram analysis with an automated whole-brain extraction algorithm in patients with post-cardiac arrest syndrome (PCAS)., Methods: Computed tomography data from consecutive patients between January 2009 and February 2012 were obtained and retrospectively analyzed. All CT images were obtained using a 64-detector-row CT scanner with a slice thickness of 4.0 mm. A brain region was extracted from the whole-brain CT images using our original automated algorithm and used for the subsequent histogram analysis. The obtained histogram statistics (mean brain tissue CT value, kurtosis, and skewness), as well as clinical parameters, were compared between the good and poor outcome groups using the Student t test. In addition, receiver operating characteristic curve analysis was performed for the discrimination between the 2 groups for each parameter., Results: One hundred thirty-eight consecutive PCAS patients were enrolled. The patients were classified into good (n = 47) and poor (n = 91) outcome groups. The mean brain tissue CT value was significantly higher in the good outcome group than in the poor outcome group (P < 0.05). Kurtosis, skewness, and age were significantly lower in the good outcome group than in the poor outcome group (P < 0.0001, P < 0.05, and P < 0.05, respectively). The area-under-the-curve values for kurtosis, mean brain tissue CT value, skewness, and age were 0.751, 0.639, 0.623, and 0.626, respectively. A combination of the 4 parameters increased the diagnostic performance (area under the curve = 0.814)., Conclusions: Histogram analysis of whole-brain CT images with our automated extraction algorithm is useful for assessing the outcome of PCAS patients.

Objective: Correction of contrast leakage is recommended when enhancing lesions during perfusion analysis. The purpose of this study was to assess the diagnostic performance of computed tomography perfusion (CTP) with a delay-invariant singular-value decomposition algorithm (SVD+) and a Patlak plot in differentiating glioblastomas from lymphomas., Materials and Methods: This prospective study included 17 adult patients (12 men and 5 women) with pathologically proven glioblastomas (n=10) and lymphomas (n=7). CTP data were analyzed using SVD+ and a Patlak plot. The relative tumor blood volume and flow compared to contralateral normal-appearing gray matter (rCBV and rCBF derived from SVD+, and rBV and rFlow derived from the Patlak plot) were used to differentiate between glioblastomas and lymphomas. The Mann-Whitney U test and receiver operating characteristic (ROC) analyses were used for statistical analysis., Results: Glioblastomas showed significantly higher rFlow (3.05±0.49, mean±standard deviation) than lymphomas (1.56±0.53; P<0.05). There were no statistically significant differences between glioblastomas and lymphomas in rBV (2.52±1.57 vs. 1.03±0.51; P>0.05), rCBF (1.38±0.41 vs. 1.29±0.47; P>0.05), or rCBV (1.78±0.47 vs. 1.87±0.66; P>0.05). ROC analysis showed the best diagnostic performance with rFlow (Az=0.871), followed by rBV (Az=0.771), rCBF (Az=0.614), and rCBV (Az=0.529)., Conclusion: CTP analysis with a Patlak plot was helpful in differentiating between glioblastomas and lymphomas, but CTP analysis with SVD+ was not., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: To document long-term morphological changes of Chiari type II malformation (CM-II) following closure of spina bifida manifesta (SBM)., Methods: We retrospectively evaluated postnatal magnetic resonance images of the CM-II and posterior fossa (PF) in 28 consecutive cases. We measured changes in vertebral level and length of the cerebellar peg (CP), cerebrospinal fluid (CSF) spaces anterior and posterior to the cerebrospinal junction, PF area, and the anteroposterior diameters of the foramen magnum (FM) and C1 vertebra. We examined the morphological differences between the cases with and without ventriculoperitoneal (VP) shunting and derived predicted means by nonlinear mixed-effect modeling., Results: At birth, there were significant differences in CP length, PF area, and FM and C1 diameters between those who underwent VP shunting and those who did not. In cases with a CP below C1, VP shunting was required in every case but one. In those with visible CSF space at birth, VP shunts were not required. In 17 of 18 cases with a CP below C1, the vertebral level ascended by mean two vertebral levels (range 0-5 levels) within 4-6 months of delivery. In the remaining case, slowly progressive hydrocephalus and delayed CP descent required VP shunting at 8 months. Predicted mean CP length and FM and C1 diameters were greater in those who underwent VP shunting, but there was no difference in predicted mean PF area., Conclusion: The morphology of CM-II and the presence of hydrocephalus influence each other in children who have undergone postnatal SBM repair.

In this study, we evaluated the dependence of saturation pulse length on APT imaging of diffuse gliomas using a parallel transmission-based technique. Twenty-two patients with diffuse gliomas (9 low-grade gliomas, LGGs, and 13 high-grade gliomas, HGGs) were included in the study. APT imaging was conducted at 3T with a 2-channel parallel transmission scheme using three different saturation pulse lengths (0.5 s, 1.0 s, 2.0 s). The 2D fast spin-echo sequence was used for imaging. Z-spectrum was obtained at 25 frequency offsets from -6 to +6 ppm (step 0.5 ppm). A point-by-point B0 correction was performed with a B0 map. Magnetization transfer ratio (MTRasym) and ΔMTRasym (contrast between tumor and normal white matter) at 3.5 ppm were compared among different saturation lengths. A significant increase in MTRasym (3.5 ppm) of HGG was found when the length of saturation pulse became longer (3.09 ± 0.54% at 0.5 s, 3.83 ± 0.67% at 1 s, 4.12 ± 0.97% at 2 s), but MTRasym (3.5 ppm) was not different among the saturation lengths in LGG. ΔMTRasym (3.5 ppm) increased with the length of saturation pulse in both LGG (0.48 ± 0.56% at 0.5 s, 1.28 ± 0.56% at 1 s, 1.88 ± 0.56% at 2 s and HGG (1.72 ± 0.54% at 0.5 s, 2.90 ± 0.49% at 1 s, 3.83 ± 0.88% at 2 s). In both LGG and HGG, APT-weighted contrast was enhanced with the use of longer saturation pulses.

Our goals were to develop and establish nanoparticle (NP)-facilitated inhalational gene delivery, and to validate its biomedical application by testing the hypothesis that targeted upregulation of pulmonary erythropoietin receptor (EpoR) expression protects against lung injury. Poly-lactic-co-glycolic acid (PLGA) NPs encapsulating various tracers were characterized and nebulizated into rat lungs. Widespread NP uptake and distribution within alveolar cells were visualized by magnetic resonance imaging, and fluorescent and electron microscopy. Inhalation of nebulized NPs bearing EpoR cDNA upregulated pulmonary EpoR expression and downstream signal transduction (ERK1/2 and STAT5 phosphorylation) in rats for up to 21 days, and attenuated hyperoxia-induced damage in lung tissue based on apoptosis, oxidative damage of DNA, protein and lipid, tissue edema, and alveolar morphology compared to vector-treated control animals. These results establish the feasibility and therapeutic efficacy of NP-facilitated cDNA delivery to the lung, and demonstrate that targeted pulmonary EpoR upregulation mitigates acute oxidative lung damage., From the Clinical Editor: Acute lung injury often results in significant morbidity and mortality, and current therapeutic modalities have proven to be ineffective. In this article, the authors developed nanocarrier based gene therapy in an attempt to upregulate the expression of pulmonary erythropoietin receptor in an animal model. Inhalation delivery resulted in reduction of lung damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To test the validity of diffusion tensor imaging (DTI) measures of tissue injury by examining such measures in a white matter structure with well-defined function, the medial longitudinal fasciculus (MLF). Injury to the MLF underlies internuclear ophthalmoparesis (INO)., Methods: 40 MS patients with chronic INO and 15 healthy controls were examined under an IRB-approved protocol. Tissue integrity of the MLF was characterized by DTI parameters: longitudinal diffusivity (LD), transverse diffusivity (TD), mean diffusivity (MD) and fractional anisotropy (FA). Severity of INO was quantified by infrared oculography to measure versional disconjugacy index (VDI)., Results: LD was significantly lower in patients than in controls in the medulla-pons region of the MLF (p < 0.03). FA was also lower in patients in the same region (p < 0.0004). LD of the medulla-pons region correlated with VDI (R = -0.28, p < 0.05) as did FA in the midbrain section (R = 0.31, p < 0.02)., Conclusions: This study demonstrates that DTI measures of brain tissue injury can detect injury to a functionally relevant white matter pathway, and that such measures correlate with clinically accepted evaluation indices for INO. The results validate DTI as a useful imaging measure of tissue integrity.

Background: Our aim was to assess the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs)., Methods: Forty-five patients with diffuse glioma (age 50.9 ± 20.4 y; 26 males, 19 females) were assessed with IVIM imaging using 13 b-values (0-1000 s/mm(2)) at 3T. The perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were calculated by fitting the bi-exponential model. The apparent diffusion coefficient (ADC) was obtained with 2 b-values (0 and 1000 s/mm(2)). Relative cerebral blood volume was measured by the dynamic susceptibility contrast method. Two observers independently measured D, ADC, D*, and f, and these measurements were compared between the LGG group (n = 16) and the HGG group (n = 29)., Results: Both D (1.26 ± 0.37 mm(2)/s in LGG, 0.94 ± 0.19 mm(2)/s in HGG; P < .001) and ADC (1.28 ± 0.35 mm(2)/s in LGG, 1.03 ± 0.19 mm(2)/s in HGG; P < .01) were lower in the HGG group. D was lower than ADC in the LGG (P < .05) and HGG groups (P < .0001). D* was not different between the groups. The f-values were significantly larger in HGG (17.5 ± 6.3%) than in LGG (5.8 ± 3.8%; P < .0001) and correlated with relative cerebral blood volume (r = 0.85; P < .0001). Receiver operating characteristic analyses showed areas under curve of 0.95 with f, 0.78 with D, 0.73 with ADC, and 0.60 with D*., Conclusion: IVIM imaging is useful in differentiating HGGs from LGGs., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Glioblastoma multiforme is highly aggressive and the most common type of primary malignant brain tumor in adults. Imaging biomarkers may provide prognostic information for patients with this condition. Patients with glioma with isocitrate dehydrogenase 1 (IDH1) mutations have a better clinical outcome than those without such mutations. Our purpose was to investigate whether the IDH1 mutation status in glioblastoma multiforme can be predicted by using MR imaging., Materials and Methods: We retrospectively studied 55 patients with glioblastoma multiforme with wild type IDH1 and 11 patients with mutant IDH1. Absolute tumor blood flow and relative tumor blood flow within the enhancing portion of each tumor were measured by using arterial spin-labeling data. In addition, the maximum necrosis area, the percentage of cross-sectional necrosis area inside the enhancing lesions, and the minimum and mean apparent diffusion coefficients were obtained from contrast-enhanced T1-weighted images and diffusion-weighted imaging data. Each of the 6 parameters was compared between patients with wild type IDH1 and mutant IDH1 by using the Mann-Whitney U test. The performance in discriminating between the 2 entities was evaluated by using receiver operating characteristic analysis., Results: Absolute tumor blood flow, relative tumor blood flow, necrosis area, and percentage of cross-sectional necrosis area inside the enhancing lesion were significantly higher in patients with wild type IDH1 than in those with mutant IDH1 (P < .05 each). In contrast, no significant difference was found in the ADC(minimum) and ADC(mean). The area under the curve for absolute tumor blood flow, relative tumor blood flow, percentage of cross-sectional necrosis area inside the enhancing lesion, and necrosis area were 0.850, 0.873, 0.739, and 0.772, respectively., Conclusions: Tumor blood flow and necrosis area calculated from MR imaging are useful for predicting the IDH1 mutation status., (© 2016 by American Journal of Neuroradiology.)

Amide proton transfer (APT) contrast imaging is based on the chemical exchange saturation transfer (CEST) of protons between the amide groups and bulk water. Here, we demonstrate the effect of the saturation pulse duration on CEST in APT imaging with use of a clinical MR scanner. Four samples were prepared from chicken egg white diluted with H2O. Experiments were performed on a 3T clinical MR scanner with use of a body coil for two-channel parallel radiofrequency transmission. APT images were acquired at six frequency offsets (± 3.0, ± 3.5, ± 4.0 ppm) with respect to the water resonance as well as one far off-resonant frequency (-160 ppm) for signal normalization. The CEST effect was defined as asymmetry of the magnetization transfer ratio at 3.5 ppm. We measured the CEST effects in the egg white samples with different concentrations at seven saturation pulse durations. The influence of the extension of repetition time (TR) on the CEST effect was also evaluated. The CEST effect was not influenced by the change in TR. The CEST effect was increased significantly with the concentration when the duration was ≥1.0 s (P < 0.01). The CEST effect was highly correlated with the concentration at all saturation pulse durations, and its increase ratio was higher at longer saturation pulse durations. In conclusion, a long saturation pulse duration is useful for the sensitive detection of mobile proteins and peptides in APT imaging.

The aim of the study was to assess the feasibility of high-resolution three-dimensional diffusion-weighted images (HR3D-DWIs)/multi-detector row CT (MDCT) images' data fusion for surgical planning for cholesteatoma. A total of 12 patients (7 male and 5 female; age range 11-72 years; mean 38.1 years) with cholesteatoma underwent preoperative MRI using a 3.0-T clinical unit and an 8-channel array-head coil. For each subject, HR3D-DWIs were obtained using a turbo field-echo with diffusion-sensitized driven-equilibrium preparation with 1.5 mm iso-voxel dimension. These patients also underwent MDCT with a slice thickness of 0.5 mm. Fusion of the HR3D-DWIs and MDCT images was performed using an automated rigid registration and subsequent manual fine-tuning by a board-certified neuroradiologist on a workstation. Fused images were compared to CT and findings confirmed based on operation reports. On the fused images, the extent of the cholesteatoma, which was depicted as a conspicuous high-intensity lesion could be easily evaluated with background bony structures. In all patients, the location and extent of the cholesteatoma on the fused images corresponded well with the intraoperative findings. Image fusion between HR3D-DWIs and MDCT images is feasible, and provides valuable preoperative information for surgical planning to otorhinolaryngologists.

Purpose: To evaluate the reproducibility of amide proton transfer (APT) imaging of brain tumors using a parallel transmission-based technique., Materials and Methods: Thirteen patients with brain tumors (four low-grade gliomas, three glioblastoma multiforme, five meningiomas, and one malignant lymphoma) were included in the study. APT imaging was conducted at 3T using a 2-channel parallel transmission scheme with a saturation time of 2 seconds and B1 amplitude of 2 μT. A 2D fast spin-echo sequence with driven-equilibrium refocusing was used for imaging. Z-spectra were obtained at 25 frequency offsets from -6 to +6 ppm (step 0.5 ppm). A point-by-point B0 correction was performed with a B0 map. A scan-rescan reproducibility test was performed in two sessions on separate days for each patient. The interval between the two sessions was 4.8 ± 3.5 days. Regions-of-interest (ROIs) were placed to include the whole tumor for each case. A mean and 90-percentile value of APT signal for the whole tumor histogram was calculated for each session. The between-session and within-session reproducibility was evaluated using linear regression analysis, intraclass correlation coefficient (ICC), and a Bland-Altman plot., Results: The mean and 90-percentile values of the APT signal for whole tumor ROI showed excellent agreements between the two sessions, with R(2) of 0.91 and 0.96 in the linear regression analysis and ICC of 0.95 and 0.97, respectively., Conclusion: Parallel transmission-based APT imaging of brain tumors showed good reproducibility., (© 2015 Wiley Periodicals, Inc.)

Background: Pure dysarthria (PD) and dysarthria-facial paresis syndrome (DFP) mainly result from lenticulostriate artery territory infarction. PD and DFP are rare clinical entities, often grouped without distinction. The purpose of this study was to examine clinical and radiographic differences between PD and DFP due to unilateral internal capsule and/or corona radiata infarction., Methods: Using a database that included consecutive patients with ischemic stroke admitted to the neurological stroke units of three hospitals within 7 days from onset between September 2011 and April 2014, we retrospectively extracted first-ever stroke patient data, who presented with PD or DFP with a single ischemic lesion localized in the internal capsule and/or corona radiata. Patients with weakness, ataxia, sensory deficit, or cortical symptoms were excluded. Ischemic lesion volume was calculated by the ABC/2 method on diffusion-weighted imaging (DWI). DWI images were normalized and superimposed to the template for PD and DFP. We compared patients' characteristics between PD and DFP., Results: A total of 2126 patients, including 65 patients (3.1%) with PD or DFP, were registered. Of these, 13 PD patients and 18 patients with DFP due to unilateral internal capsule and/or corona radiata infarction were included for analysis. Compared with DFP patients, PD patients had longer onset-to-door time (median 37.5 vs. 10.8 h, p = 0.031), shorter vertical length (C component) of ischemic lesions (median 12.0 vs. 18.8 mm, p = 0.007), and smaller ischemic lesion volume (median 285 vs. 828 mm(3), p = 0.023). Ischemic lesions causing PD were located more frequently in the left hemisphere than DFP (92% vs. 56%, p = 0.045). The superimposed lesion pattern indicated that DFP had lesions more medial and involving posterior portions of the putamen and the caudate body, as well as more of the genu and posterior limb of the internal capsule, than PD. Ninety days after onset, symptoms disappeared in 21 (72%) out of 29 patients., Conclusions: In cerebral infarction limited to the internal capsule and/or corona radiata, PD is derived from smaller and left-sided lesions with delay in diagnosis compared with DFP. The clinical course of those with PD and DFP might be benign.

Aim: Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype., Methods: Magnetic resonance imaging examinations of 37 OCD patients and 37 matched healthy controls were conducted using a 3.0-Tesla scanner. In the voxel-based morphometric procedure, preprocessed GM structural images were used to compare the two groups, and multiple regression analysis was used to investigate the correlation between regional GM volume in OCD patients and the OCD symptom dimension type assessed by using the Dimensional Yale-Brown Obsessive-Compulsive Scale., Results: We found significant reductions in GM volume in broad areas of the left prefrontal, right orbitofrontal, right parietal, right temporal, and right posterior cingulate cortex in the OCD patients compared to healthy controls. In addition, we found specific negative correlations between symptomatic dimension scores and regional GM volumes, mainly as decreased right cerebellum in 'aggression/checking' and decreased right insula in 'contamination/washing'., Conclusion: The pathophysiology of OCD may involve widely distributed neural systems. Moreover, there are distinct correlations among symptomatic dimensions and structural abnormalities., (© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.)

Objective: Volume isotropic simultaneous interleaved bright- and black-blood examination (VISIBLE) is a recently developed 3D MR sequence that provides simultaneous acquisitions of images with blood vessel suppression (Black) and images without it (Bright). Our purpose was to evaluate the usefulness of VISIBLE in detecting brain metastases., Methods: This prospective study included patients with suspected brain metastasis imaged with both VISIBLE and MPRAGE. From a data set, we compared the number of visualized blood vessels and the lesion-to-normal contrast-to-noise ratio (CNR) in 60 patients. We also performed an observer test to compare their diagnostic performance with VISIBLE, MPRAGE and only Black in 34 patients. Diagnostic performance was evaluated using a figure of merit (FOM), sensitivity, false-positive results per case (FPs/case) and reading time., Results: The number of vessels was significantly fewer in Black compared to MPRAGE and Bright (P < 0.0001). CNR was significantly higher with both Black and Bright than with MPRAGE (P < 0.005). In the observer test, significantly higher sensitivity (P < 0.0001) and FOM (P < 0.0001), significantly shorter reading time (P = 0.0001) and similar FPs/case were achieved with VISIBLE compared to MPRAGE. Compared to only Black, VISIBLE resulted in comparable sensitivity, but significantly fewer FPs/case (P = 0.0008)., Conclusion: VISIBLE can improve radiologists' diagnostic performance for brain metastasis., Key Points: • VISIBLE can achieve higher sensitivity and shorter reading time than MPRAGE. • VISIBLE can achieve lower false-positive rates than blood vessel suppressed images. • Compared to MPRAGE, VISIBLE can improve diagnostic performance for brain metastasis.

The recent development in magnetic resonance(MR)hardware and techniques allows the acquisition of functional information, such as perfusion or metabolism, in addition to conventional anatomical information in of cancers.In this review article, various molecular imaging methods based on MR are introduced and their application and usefulness for diagnosis of cancer are discussed.Diffusion weighted image (DWI) is believed to correlate cell density and reflect malignancy of tumor. DWI has been widely used for the diagnosis and evaluation of responses to cancer treatment.Arterial spin labeling (ASL) allows acquisition of perfusion data without the use of any contrast agent and is expected to be an alternative or complementary method to dynamic contrast enhanced MR imaging.Amide proton transfer (APT) imaging reflects the amount of mobile peptide and proteins in cancer tissue, and could be a useful tool for assessing tumor malignancy or evaluating treatment responses.More specific measurement of cancer metabolites is available at the cost of spatial resolution by MR spectroscopy (MRS). Finally, the positron emission tomography (PET)/MR hybrid system enables simultaneous acquisition of functional/ anatomical information from MR imaging and molecular/metabolic information from PET imaging.Combining various molecular MR imaging methods with PET tracers may have a huge potential for clinical diagnosis of cancer.

Bone density measurements using high-resolution CT have been reported to be useful to diagnose fenestral otosclerosis. However, small region of interest (ROI) chosen by less-experienced radiologists may result in false-negative findings. Semi-automatic analysis such as CT histogram analysis may offer improved assessment. The aim of this study was to evaluate the utility of CT histogram analysis in diagnosing fenestral otosclerosis. Temporal bone CT of consecutive patients with otosclerosis and normal controls was retrospectively analyzed. The control group consisted of the normal-hearing contralateral ears of patients with otitis media, cholesteatoma, trauma, facial nerve palsy, or tinnitus. All CT images were obtained using a 64-detector-row CT scanner with 0.5-mm collimation. AROI encompassing 10 × 10 pixels was placed in the bony labyrinth located anterior to the oval window. The mean CT value, variance and entropy were compared between otosclerosis patients and normal controls using Student's t test. The number of pixels below mean minus SD in the control (%Lowcont) and total subjects (%Lowtotal) were also compared. In addition, the area under the receiver operating characteristic curves (AUC) value for the discrimination between otosclerosis patients and normal controls was calculated. 51 temporal bones of 38 patients with otosclerosis and 30 temporal bones of 30 control subjects were included. The mean CT value was significantly lower in otosclerosis cases than in normal controls (p < 0.01). In addition, variance, entropy, %Lowcont and %Lowtotal were significantly higher in otosclerosis cases than in normal controls (p < 0.01, respectively). The AUC values for the mean CT value, %Lowcont and %Lowtotal were 0.751, 0.760 and 0.765, respectively. In conclusion, our results demonstrated that histogram analysis of CT image may be of clinical value in diagnosing otosclerosis.

Purpose: To evaluate the diagnostic performance of a double-dose administration of gadolinium for brain metastases at 3 T in a systematic observer test., Materials and Methods: Postcontrast MR images of 39 patients (total 104 metastases) were obtained by 3D T1-weighted sequences with both standard and cumulative double dose contrast administration. An observer test involving 9 radiologists (5 board-certified radiologists and 4 residents) was performed, and their diagnostic performance with the two doses was compared by means of sensitivity, false-positives, reading time, and a figure-of-merit., Results: Compared to the standard dose, the double dose showed higher sensitivity (P < 0.0001), higher false-positive/case (P < 0.05), longer reading time (P < 0.05), and higher figure-of-merit (P < 0.0001). Particularly in small lesions (< 5 mm), sensitivity with the double dose (61.5%, P < 0.0001) was approximately twice as high as that with the standard dose (29.5%). Artifacts and blood vessels were the most common imaging findings resulting in false-positives., Conclusions: The double dose improved detection for metastases smaller than 5 mm at 3 T and thus resulted in better diagnostic performance of radiologists. However, a higher dose might result in prolonged reading time and increased false-positives, presumably due to increased vessel signals and frequency of flow-related artifacts.

Aim: To reveal angiographic findings to predict the result of balloon test occlusion (BTO)., Methods: The cerebral angiograms of 42 consecutive patients who underwent cerebral angiography including both the Matas and Allcock maneuvers and BTO were retrospectively analyzed. Visualization of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) by the cross flow on the tested side during the Matas or Allcock maneuver was graded on a 5-point scale. Circle of Willis (COW) anatomy with respect to the presence/absence of a collateral path to reach the tested internal carotid artery (ICA) was classified into four categories. A univariate logistic analysis was used to analyze the associations between each angiographic finding and the BTO result. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for each finding were calculated., Results: Five patients (12%) were BTO-positive and the remaining 37 patients (88%) were BTO-negative. Visualizations of the ACA and MCA as well as the COW anatomy were significantly associated with the BTO result (P = 0.0051 for ACA, P = 0.0002 for MCA, and P < 0.0001 for COW anatomy). In particular, good MCA visualization and the presence of an anterior connection (collateral path to the tested ICA from the contralateral ICA via the anterior communicating artery) in the COW were highly predictive for negative BTO (negative predictive value = 100% for both)., Conclusion: A BTO result may be predicted by angiographic findings including ACA/MCA visualization and COW anatomy.

Glioblastoma multiforme (GBM), which account for more than 50% of all gliomas, is among the deadliest of all human cancers. Given the dismal prognosis of GBM, it would be advantageous to identify early biomarkers of a response to therapy to avoid continuing ineffective treatments and to initiate other therapeutic strategies. The present in vivo longitudinal study in an orthotopic mouse model demonstrates quantitative assessment of early treatment response during short-term chemotherapy with temozolomide (TMZ) by amide proton transfer (APT) imaging. In a GBM line, only one course of TMZ (3 d exposure and 4 d rest) at a dose of 80 mg/kg resulted in substantial reduction in APT signal compared with untreated control animals, in which the APT signal continued to increase. Although there were no detectable differences in tumor volume, cell density, or apoptosis rate between groups, levels of Ki67 (index of cell proliferation) were substantially reduced in treated tumors. In another TMZ-resistant GBM line, the APT signal and levels of Ki67 increased despite the same course of TMZ treatment. As metabolite changes are known to occur early in the time course of chemotherapy and precede morphologic changes, these results suggest that the APT signal in glioma may be a useful functional biomarker of treatment response or degree of tumor progression. Thus, APT imaging may serve as a sensitive biomarker of early treatment response and could potentially replace invasive biopsies to provide a definitive diagnosis. This would have a major impact on the clinical management of patients with glioma.

Objectives: 3D turbo field echo with diffusion-sensitised driven-equilibrium preparation (DSDE-TFE) is a novel non-echo planar technique for diffusion-weighted (DW) imaging. The purpose of this study was to differentiate intraorbital lymphoma from immunoglobulin G4-related disease (IgG4-RD) using the apparent diffusion coefficient (ADC) derived from DSDE-TFE., Methods: Fifteen patients with lymphomas and 8 with IgG4-RDs underwent imaging. ADC and signal intensities compared with normal grey matter on T1-weighted images, fat-suppressed T2-weighted images and fat-suppressed postcontrast T1-weighted images were measured. Statistical analyses were performed using the Mann-Whitney U test and receiver operating characteristic (ROC) analysis., Results: Intraorbital lesions were clearly visualised on DSDE-TFE without obvious geometrical distortion. The ADC of lymphoma (1.25 ± 0.50 × 10(-3) mm(2)/s; mean ± standard deviation) was significantly lower than that of IgG4-RD (1.67 ± 0.84 × 10(-3) mm(2)/s; P < 0.05). Conventional sequences could not separate lymphoma from IgG4-RD (0.93 ± 0.18 vs. 0.94 ± 0.21 on T1-weighted images, 0.92 ± 0.17 vs. 0.95 ± 0.14 on T2-weighted images and 2.03 ± 0.35 vs. 2.30 ± 0.58 on postcontrast T1-weighted images, for lymphoma and IgG4-RD, respectively; P > 0.05). ROC analysis showed the best diagnostic performance with ADC., Conclusion: The apparent diffusion coefficient derived from diffusion-sensitised driven-equilibrium preparation techniques may help to differentiate lymphoma from immunoglobulin G4-related disease., Key Points: • Distinguishing between orbital lymphoma and immunoglobulin G4-related disease can be difficult • Intraorbital lesions were clearly visualised on diffusion-sensitised driven-equilibrium preparation magnetic resonance techniques. • Variations in field homogeneity do not affect DSDE-TFE techniques all that much. • ADCs derived from DSDE-TFE may help differentiate lymphoma from IgG4-RD.

Background: Amide proton transfer (APT) imaging is a novel molecular MRI technique to detect endogenous mobile proteins and peptides through chemical exchange saturation transfer. We prospectively assessed the usefulness of APT imaging in predicting the histological grade of adult diffuse gliomas., Methods: Thirty-six consecutive patients with histopathologically proven diffuse glioma (48.1 ± 14.7 y old, 16 males and 20 females) were included in the study. APT MRI was conducted on a 3T clinical scanner and was obtained with 2 s saturation at 25 saturation frequency offsets ω = -6 to +6 ppm (step 0.5 ppm). δB0 maps were acquired separately for a point-by-point δB0 correction. APT signal intensity (SI) was defined as magnetization transfer asymmetry at 3.5 ppm: magnetization transfer ratio (MTR)asym = (S[-3.5 ppm] - S[+3.5 ppm])/S0. Regions of interest were carefully placed by 2 neuroradiologists in solid parts within brain tumors. The APT SI was compared with World Health Organization grade, Ki-67 labeling index (LI), and cell density., Results: The mean APT SI values were 2.1 ± 0.4% in grade II gliomas (n = 8), 3.2 ± 0.9% in grade III gliomas (n = 10), and 4.1 ± 1.0% in grade IV gliomas (n = 18). Significant differences in APT intensity were observed between grades II and III (P < .05) and grades III and IV (P < .05), as well as between grades II and IV (P < .001). There were positive correlations between APT SI and Ki-67 LI (P = .01, R = 0.43) and between APT SI and cell density (P < .05, R = 0.38). The gliomas with microscopic necrosis showed higher APT SI than those without necrosis (P < .001)., Conclusions: APT imaging can predict the histopathological grades of adult diffuse gliomas.

We introduced and optimized a novel sequence of fast (about 4 min), volumetric, high resolution, simultaneous bright- and black-blood imaging with sufficient T1 contrast between enhanced metastasis and surrounding brain parenchyma for their differentiation. This proposed sequence can be used for 3-dimensional volumetric T1-weighted bright- and black-blood imaging in contrast-enhanced studies and may be promising for detecting small brain metastases by improving differentiation between blood vessels and small brain metastases.

Background and Purpose: 3D turbo field echo with diffusion-sensitized driven-equilibrium preparation is a non-echo-planar technique for DWI, which enables high-resolution DWI without field inhomogeneity-related image distortion. The purpose of this study was to evaluate the feasibility of diffusion-sensitized driven-equilibrium turbo field echo in evaluating diffusivity in the normal pituitary gland., Materials and Methods: First, validation of diffusion-sensitized driven-equilibrium turbo field echo was attempted by comparing it with echo-planar DWI. Five healthy volunteers were imaged by using diffusion-sensitized driven-equilibrium turbo field echo and echo-planar DWI. The imaging voxel size was 1.5 × 1.5 × 1.5 mm(3) for diffusion-sensitized driven-equilibrium turbo field echo and 1.5 × 1.9 × 3.0 mm(3) for echo-planar DWI. ADCs measured by the 2 methods in 15 regions of interests (6 in gray matter and 9 in white matter) were compared by using the Pearson correlation coefficient. The ADC in the pituitary anterior lobe was then measured in 10 volunteers by using diffusion-sensitized driven-equilibrium turbo field echo, and the results were compared with those in the pons and vermis by using a paired t test., Results: The ADCs from the 2 methods showed a strong correlation (r = 0.79; P < .0001), confirming the accuracy of the ADC measurement with the diffusion-sensitized driven-equilibrium sequence. The ADCs in the normal pituitary gland were 1.37 ± 0.13 × 10(-3) mm(2)/s, which were significantly higher than those in the pons (1.01 ± 0.24 × 10(-3) mm(2)/s) and the vermis (0.89 ± 0.25 × 10(-3) mm(2)/s, P < .01)., Conclusions: We demonstrated that diffusion-sensitized driven-equilibrium turbo field echo is feasible in assessing ADC in the pituitary gland.

Objective: We report the clinical application of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging to diagnose a case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in the acute phase., Results: On IVIM MR Images of this patient, higher perfusion (f) and diffusion (D) values in the left occipital and temporal lobes were found compared to the contralateral areas., Conclusion: These findings imply a breakdown of autoregulation with hyperperfusion and vasogenic edema during the acute phase of MELAS, as described in previous reports. IVIM imaging is a valuable, noninvasive tool that simultaneously quantifies perfusion and diffusion parameters.

Background: Loeys-Dietz syndrome, also known as Marfan syndrome type II, is a rare connective tissue disorder caused by dominant mutations in transforming growth factor-beta receptors (TGFBR1 and 2)., Case Presentation: We report a 7-year-old Japanese boy with Loeys-Dietz syndrome who carried a novel, de novo missense mutation in TGFBR2 (c.1142g > c, R381P). He showed dysmorphic faces and skeletal malformations that were typical in previous cases with Loeys-Dietz syndrome. The cardiac studies disclosed the presence of markedly dilated aortic root and patent ductus aorteriosus. The cranial magnetic resonance imaging (MRI) and angiography (MRA) detected the tortuous appearances of the bilateral middle cerebral and carotid arteries., Conclusion: This study depicts the systemic vascular phenotypes of a child with Loeys-Dietz syndrome that were caused by a novel heterozygous mutation of TGFR2. A large cohort with serial imaging studies for vascular phenotypes will be useful for delineating the genotype-phenotype correlations of Loeys-Dietz syndrome.

Amide proton transfer (APT) imaging is one of the chemical exchange saturation transfer (CEST) imaging methods which images the exchange between protons of free tissue water and the amide groups (-NH) of endogenous mobile proteins and peptides. Previous work suggested the ability of APT imaging for characterization of the tumoral grade in the brain tumor. In this study, we tested the feasibility of in-vivo APT imaging of lung tumor and investigated whether the method could differentiate the tumoral types on orthotopic tumor xenografts from two malignant lung cancer cell lines. The results revealed that APT imaging is feasible to quantify lung tumors in the moving lung. The measured APT effect was higher in the tumor which exhibited more active proliferation than the other. The present study demonstrates that APT imaging has the potential to provide a characterization test to differentiate types or grade of lung cancer noninvasively, which may eventually reduce the need invasive needle biopsy or resection for lung cancer.

Objective: To prospectively evaluate the usefulness of a newly developed high-resolution three-dimensional diffusion-weighted imaging method, turbo field-echo with diffusion-sensitized driven-equilibrium (TFE-DSDE) in diagnosing middle-ear cholesteatoma by comparing it to conventional single-shot echo-planar diffusion-weighted imaging (SS-EP DWI)., Materials and Methods: Institutional review board approval and informed consent from all participants were obtained. We studied 30 patients with preoperatively suspected acquired cholesteatoma. Each patient underwent an MR examination including both SS-EP DWI and DSDE-TFE using a 3.0 T MR scanner. Images of the 30 patients (60 temporal bones including 30 with and 30 without cholesteatoma) were reviewed by two independent neuroradiologists. The confidence level for the presence of cholesteatoma was graded on a scale of 0-2 (0=definite absence, 1=equivocal, 2=definite presence). Interobserver agreement as well as sensitivity, specificity, and accuracy for detection were assessed for the two reviewers., Results: Excellent interobserver agreement was shown for TFE-DSDE (κ=0.821) whereas fair agreement was obtained for SS-EP DWI (κ=0.416). TFE-DSDE was associated with significantly higher sensitivity (83.3%) and accuracy (90.0%) compared to SS-EP DWI (sensitivity=35.0%, accuracy=66.7%; p<0.05). No significant difference was found in specificity (96.7% for TFE-DSDE, 98.3% for SS-EP DWI) CONCLUSION: With increased spatial resolution and reduced susceptibility artifacts, TFE-DSDE improves the accuracy in diagnosing acquired middle ear cholesteatomas compared to SS-EP DWI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We are the first to report a case that showed spontaneous resolution of epidural hematoma which was related to a steroid-induced osteoporotic compression fracture. The patient had a painful fracture with an intravertebral cleft at L1 accompanying an epidural hematoma posteriorly. Immediate pain relief was achieved after percutaneous vertebroplasty. Complete resolution of hematoma was noted three months after procedure. We theorized that intravertebral stability after treatment might have played a role in this patient.

Parkinson's disease (PD) reportedly includes altered connectivity of neural loops involving the basal ganglia and cerebellum, although little is known regarding any changes in the connectivity of motor loops. The goal of this study was to further understand the connectivity within the basal ganglia-thalamo-motor (BGTM) and cerebro-cerebellar (CC) loops in PD. Twelve PD patients and 12 age-matched control subjects performed a protocol involving self-initiated (SI) and externally-triggered (ET) finger movements, while being scanned with functional magnetic resonance imaging. Compared with the control subjects, the PD subjects showed hypo-activation in the bilateral putamen, right supplementary motor area and hyper-activation in the right premotor cortex. In the sensorimotor cortex and cerebellar hemisphere, PD subjects tended to show hyper-activation in a main effects analysis, but hypo-activation in a linear effects analysis. Analysis using structural equation modeling (SEM) revealed significant positive interactions within the right BGTM loop during the SI task and within the right (right cerebral hemisphere-left cerebellum) CC loop during the ET task. SEM also revealed task-related quantitative changes between the thalamus and the motor cortices in the control subjects. We found that the PD patients showed reduced connectivity in the right BGTM loop and inter-hemispheric connections in SEM, which is the first demonstration of this phenomenon. Interestingly, PD patients exhibited preserved connectivity within the right CC loop during the ET task. These results suggest disruption of cortico-striatal processing and preservation of relatively intact neural circuits that do not involve the basal ganglia in PD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Our purpose was to evaluate the diagnostic performance of arterial spin labeling (ASL) perfusion imaging, diffusion-weighted imaging (DWI), and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastoma multiformes (GBMs)., Methods: Fifty-six patients including 19 with PCNSL and 37 with GBM were retrospectively studied. From the ASL data, an absolute tumor blood flow (aTBF) and a relative tumor blood flow (rTBF) were obtained within the enhancing portion of each tumor. In addition, the minimum apparent diffusion coefficient (ADCmin) and the maximum standard uptake value (SUVmax) were obtained from DWI and FDG-PET data, respectively. Each of the four parameters was compared between PCNSLs and GBMs using Kruskal-Wallis test. The performance in discriminating between PCNSLs and GBMs was evaluated using the receiver-operating characteristics analysis. Area-under-the-curve (AUC) values were compared among the four parameters using a nonparametric method., Results: The aTBF, rTBF, and ADCmin were significantly higher in GBMs (mean aTBF ± SD = 91.6 ± 56.0 mL/100 g/min, mean rTBF ± SD = 2.61 ± 1.61, mean ADCmin ± SD = 0.78 ± 0.19 × 10(-3) mm(2)/s) than in PCNSLs (mean aTBF ± SD = 37.3 ± 10.5 mL/100 g/min, mean rTBF ± SD = 1.24 ± 0.37, mean ADCmin ± SD = 0.61 ± 0.13 × 10(-3) mm(2)/s) (p < 0.005, respectively). In addition, SUVmax was significantly lower in GBMs (mean ± SD = 13.1 ± 6.34) than in PCNSLs (mean ± SD = 22.5 ± 7.83) (p < 0.005). The AUC for aTBF (0.888) was higher than those for rTBF (0.810), ADCmin (0.768), and SUVmax (0.848), although their difference was not statistically significant., Conclusion: ASL perfusion imaging is useful for differentiating PCNSLs from GBMs as well as DWI and FDG-PET.

It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy., (Copyright © 2012 John Wiley & Sons, Ltd.)

The exchange of water molecules between the inner sphere of a paramagnetic chemical exchange saturation transfer (PARACEST) contrast agent and bulk water can shorten the bulk water T(2) through the T(2) -exchange (T(2ex) ) mechanism. The line-broadening T(2ex) effect is proportional to the agent concentration, the chemical shift of the exchanging water molecule, and is highly dependent on the water molecule exchange rate. A significant T(2ex) contribution to the bulk water linewidth can make the regions of agent uptake appear dark when imaging with conventional sequences like gradient-echo and fast spin-echo. The minimum echo times for these sequences (1-10 ms) are not fast enough to capture signal from the regions of shortened T(2) . This makes "Off" (saturation at -Δω) minus "On" (saturation at +Δω) imaging of PARACEST agents difficult, because the regions of uptake are dark in both images. It is shown here that the loss of bulk water signal due to T(2ex) can be reclaimed using the ultrashort echo times (<10 μs) achieved with the sweep imaging with Fourier transform pulse sequence. Modification of the sweep imaging with Fourier transform sequence for PARACEST imaging is first discussed, followed by parameter optimization using in vitro experiments. In vivo PARACEST studies comparing fast spin-echo to sweep imaging with Fourier transform were performed using EuDOTA-(gly) 4- uptake in healthy mouse kidneys. The results show that the negative contrast caused by T(2ex) can be overcome using the ultrashort echo time achieved with sweep imaging with Fourier transform, thereby enabling fast and sensitive in vivo PARACEST imaging., (Copyright © 2011 Wiley Periodicals, Inc.)

Introduction: Hemangioblastoma and metastatic tumors are the major differential diagnoses for the posterior fossa tumors in adults. Our purpose was to evaluate the efficacy of ASL in differentiating hemangioblastomas from metastatic brain tumors., Methods: A total of 19 patients including 5 with a hemangioblastomas and 14 with metastatic tumors (7 from lung cancer, 4 from breast cancer, 1 from RCC, 1 from gastric cancer, and 1 from unknown origin) were enrolled in this study. ASL was performed using a pulsed ASL method at a 3-T unit. aTBF was measured as a mean absolute blood flow value within a region of interest drawn in the tumor. In addition, rTBF was obtained by normalizing the aTBF by a blood flow measured in the normal-appearing cortical gray matter. The aTBF and rTBF values were compared between hemangioblastomas and metastatic tumors using Student's t test., Results: Both the aTBF and rTBF values were significantly higher in hemangioblastomas (mean aTBF ± SD = 437 ± 274 mL/100 g/min, mean rTBF ± SD = 7.96 ± 3.12) in comparison with metastatic brain tumors (mean aTBF ± SD = 125 ± 134 mL/100 g/min, mean rTBF ± SD = 2.98 ± 3.91; p < 0.05, respectively). However, a metastasis from RCC showed very high aTBF (559 mL/100 g/min) and rTBF (16.2)., Conclusion: Our results demonstrated that ASL provides useful information to differentiate between hemangioblastomas and metastatic brain tumors. Metastasis from RCC may mimic hemangioblastoma on ASL blood flow measurement.

Purpose: We investigated the time interval from labeling to peak (TLP) of perfusion-signal intensity (SIs) in normal brain using a multiphase arterial spin-labeling (ASL) magnetic resonance imaging (MRI) technique as a fundamental study to assess the temporal characteristics of perfusion SIs., Materials and Methods: Twenty temporal phases of a pulsed ASL-MRI [QUASAR, quantitative signal targeting by alternating radiofrequency pulses (STAR) labeling of arterial regions] in single-slice imaging were performed in 9 volunteers. Perfusion SIs were measured and TLPs were calculated in 14 regions of interest (ROIs), 7 in each hemisphere: thalamus, lentiform nucleus, medial frontal cortex in the anterior cerebral artery (ACA) territory, temporal cortex in the middle cerebral artery (MCA) territory, medial occipital cortex in the posterior cerebral artery (PCA) territory, anterior watershed region (AWR) and posterior watershed region (PWR)., Results: Mean TLP varied with ROI (region and mean ± standard deviation in seconds): thalamus, 1.60 ± 0.11; lentiform nucleus, 1.52 ± 0.11; ACA territory, 1.53 ± 0.16; MCA territory, 1.59 ± 0.18; PCA territory, 1.68 ± 0.20; AWR, 1.79 ± 0.14; PWR, 2.00 ± 0.20. TLP in the PWR was significantly longer than those in all other regions except the AWR, and TLP in the AWR was significantly longer than those in the lentiform nucleus and the ACA territory., Conclusion: Our results revealed regional differences in the temporal characteristics of perfusion SIs on ASL-MRI.

Purpose: To test the feasibility of ultra-short echo time (UTE) MRI for assessment of regional pulmonary ventilation/perfusion in a standard 3 Tesla clinical MRI system., Materials and Methods: MRI of the lungs was conducted with an optimized three-dimensional UTE sequence in normal rats and in a rat model of pulmonary embolism (PE) induced by a blood clot. Changes in signal intensities (SIs) due to inhalation of molecular oxygen or intravenous (i.v.) injection of Gd, which represents the distribution of ventilation and perfusion, respectively, were assessed in the lung parenchyma., Results: The UTE MRI with a TE of 100 μs could detect and map the changes in SI of the lung parenchyma due to the inhalation of 100% oxygen or i.v. injection of Gd in normal rats. Reduced T1 resulting from oxygen inhalation was also quantified. These changes were not observed on the images that were obtained simultaneously with a conventional range of TE (2.3 ms). Furthermore, the method could delineate the embolized lesions where the lung ventilation and perfusion were mismatched in a rat model with PE., Conclusion: These results show the feasibility and diagnostic potential of UTE MRI for the assessment of pulmonary ventilation and perfusion which is essential for the evaluation of a variety of lung diseases., (Copyright © 2011 Wiley-Liss, Inc.)

The medial longitudinal fasciculus (MLF) is a white matter pathway in the brainstem that plays a key role in coordinating eye movements. Injury to the MLF leads to abnormalities in eye movements that can be measured with high precision by oculography, making it an ideal eloquent pathway to study imaging/function correlates. Tractography is an emerging method for identifying white matter pathways and offers the tantalizing promise of noninvasive, quantitative characterization of tissue integrity underlying functional deficits. However, the small caliber of the MLF and partial volume averaging with signal from nearby cerebrospinal fluid pose severe technical challenges to tractography-based delineation of the MLF. We discuss progress toward the goal of imaging the MLF and potential benefits of achieving this goal. Initial work suggests that ultra-high field (7 tesla) may complement tractography for characterizing the MLF., (© 2011 New York Academy of Sciences.)

Nanoparticulate imaging probes have become an increasingly important arsenal in the visualization of molecular markers for early diagnosis and post-therapy assessment of diseases. Surface functionalization of these nanoparticles has led to the development of a variety of targeted nanoprobes for various imaging modalities (e.g. PET, MRI, optical). Despite these advances, detailed understanding of the nanoparticle targeting kinetics, particularly at the early time points immediately after injection, is still lacking. In this study, we report the combination of a T(2)*-weighted time-resolved-MRI (TR-MRI) method with ultra-sensitive superparamagnetic polymeric micelle (SPPM) nanoprobes to quantify the targeting kinetics of cyclic (RGDfK) (cRGD)-encoded SPPM to angiogenic endothelium in subcutaneous human tumor xenograft models in mice. TR-MRI analyses of the α(v)β(3)-targeted and non-targeted SPPMs allowed for the subtraction of blood volume and extravascular signal components from the cRGD-SPPM data, resulting in a specific measurement of the accumulation kinetics of nanoprobes in lung, breast and brain cancer preclinical models. In all three models, α(v)β(3)-specific accumulation of SPPM nanoprobes was observed in the first 5 mins after intravenous injection (first order rate constants were in the range of 0.22-0.24 min(-1)). Similar α(v)β(3)-targeting kinetics was observed for cRGD-SPPM nanoprobes in different tumor xenograft models, consistent with the targeting of mouse angiogenic endothelium despite tumor inoculation from different human cancer cell lines. Results from this study offer new opportunities in the quantitative characterization of the targeting kinetics of cancer-specific nanoparticles to their intended biological targets in an intact animal, which provides fundamental insights on molecular recognition processes in vivo for further development of these nanoprobes.

Fibrosis is a pathological process characterized by infiltration and proliferation of mesenchymal cells in interstitial space. A substantial portion of these cells is derived from residing non-epithelial and/or epithelial cells that have acquired the ability to migrate and proliferate. The mesenchymal transition is also observed in cancer cells to confer the ability to metastasize. Here, we show that renal fibrosis induced by unilateral ureteral obstruction and metastasis of human cancer xenografts are suppressed by administration of secreted Klotho protein to mice. Klotho is a single-pass transmembrane protein expressed in renal tubular epithelial cells. The extracellular domain of Klotho is secreted by ectodomain shedding. Secreted Klotho protein directly binds to the type-II TGF-β receptor and inhibits TGF-β1 binding to cell surface receptors, thereby inhibiting TGF-β1 signaling. Klotho suppresses TGF-β1-induced epithelial-to-mesenchymal transition (EMT) responses in cultured cells, including decreased epithelial marker expression, increased mesenchymal marker expression, and/or increased cell migration. In addition to TGF-β1 signaling, secreted Klotho has been shown to inhibit Wnt and IGF-1 signaling that can promote EMT. These results have raised the possibility that secreted Klotho may function as an endogenous anti-EMT factor by inhibiting multiple growth factor signaling pathways simultaneously.

Off-resonance saturation (ORS) is a new magnetic resonance imaging (MRI) method that has shown greatly improved contrast sensitivity for the detection of cancer-specific biomarkers by superparamagnetic nanoprobes in vivo. However, quantitative understanding of the ORS contrast mechanism and its dependence on the structural parameters of superparamagnetic nanoprobes are still lacking. Here we propose a quantitative model of ORS contrast and its experimental validation by superparamagnetic polymeric micelles (SPPM) with precisely controlled structural properties. Size selected, monodisperse Fe₃O₄ nanoparticles (6.1 ± 0.2 nm) were used to form a series of SPPM nanoprobes with specifically controlled corona thickness using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypoly(ethylene glycol) (DSPE-PEG) with different PEG molecular weights. Transmission electron microscopy and dynamic light scattering showed that SPPM were uniform in size. The average hydrodynamic diameters of SPPM with PEG lengths of 0.55, 1, 2, and 5 kD were 16.6 ± 2.8, 18.4 ± 2.9, 24.1 ± 3.4, and 28.9 ± 3.4 nm, respectively. MRI experiments at 7 T determined that r₂ values of SPPM with 0.55, 1, 2, and 5 kD PEG as corona were 201 ± 3, 136 ± 8, 107 ± 5, and 108 ± 8 FemM⁻¹s⁻¹, respectively. ORS intensity from Z-spectra of SPPM showed a significant correlation with the inverse of T₂ relaxation rates (1/T₂, s⁻¹) of the SPPM nanoprobes regardless of the PEG corona thickness. These data provide the fundamental understanding of the structure-property relationships between the SPPM nanostructures and ORS sensitivity, which offers useful mechanistic insights for the future improvement of SPPM nanoprobes in cancer molecular imaging applications., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: the purpose of this study was to examine interhemispheric asymmetry in volume of the caudate nucleus and its age dependency., Methods: high-resolution T1-weighted brain magnetic resonance (MR) images were obtained for each subject using a 3-dimensional fast field-echo pulse sequence. The volumes of the bilateral caudate nuclei on MR images were measured using an automated method. Right-to-left comparison was made using paired t-test. Age-related change of right-to-left volume ratio (R/L ratio) was examined using Pearson's correlation coefficient., Results: fifty healthy right-handed Japanese male subjects (age 12 to 67 years, mean 39.6 years) were involved in this study. The volume of right caudate nucleus was larger than the left in 48 of 50 subjects (P < .001). R/L ratio increased with age (r= .420, P < .01)., Conclusions: our results confirmed the rightward volumetric asymmetry of caudate nucleus in right-handed individuals, and revealed that this asymmetry becomes notable with age.

Previous functional neuroimaging studies found that the amygdala and other limbic regions may play a substantial role in social anxiety disorder (SAD). However, more widely distributed large-scale brain systems may be involved in cognitive processing in SAD patients when confronted with social situations. We employed functional MRI (fMRI) to investigate local brain activation of patients with SAD (n=6) and healthy controls (HC, n=9) during cognitive work. During fMRI scanning, subjects performed a social situation task using a block design paradigm in which the task and control trials were performed by turn. The patients with SAD showed higher anxiety levels during scanning in all social situations. The HC group showed greater common activation in the posterior cingulate cortex (PCC), cuneus, occipital gyrus, and cerebellum. Although the patients with SAD showed activation patterns similar to that of the HC group, they showed comparatively significant decreased activation in the left cerebellum, left precuneus, and bilateral PCC. The present study demonstrates that SAD may involve dysfunction of a broad neuronal network including the limbic system, parieto-posterior cortex and cerebellum. The findings contribute to previous findings that revealed abnormal activities of emotion-related regions including the amygdala and insular cortex during facial perception in SAD., (Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Nonuniform disruption of lung architecture is usually assessed by CT, which carries potential radiation risk. Here we report our use of a three-dimensional ultrashort echo time MR method to image the lungs of normal mice at different positive end-expiratory pressures in a 3-T clinical MR system. The ultrashort echo time sequence in conjunction with a projection acquisition of the free induction decay could reduce the echo time to 100 μsec and provide a more inherent MR signal intensity from the lung parenchyma, which is usually invisible due to its short T*(2) in conventional MRI methods. The signal intensity and T*(2) was reduced as the positive end-expiratory pressure became higher. Further, these parameters were highly correlated to the changes in lung volume (% lung expansion). The results indicated that the MR signal acquired at ultrashort echo time in the lung parenchyma represents interstitial tissue density including blood. The capability of acquiring sufficient MR signal would have implications for the direct assessment of parenchymal architecture in the lung. Therefore, ultrashort echo time imaging may have the potential to assist detection of early and localized pathological destruction of lung tissue architecture observed in various pulmonary disorders such as emphysema without incurring the risks of radiation exposure., (Copyright © 2010 Wiley-Liss, Inc.)

Previous studies have demonstrated both functional and structural abnormalities in the frontal-striatal-thalamic circuits in obsessive-compulsive disorder (OCD). The purpose of this study was to assess volume abnormalities not only of gray matter (GM), but also of white matter (WM) in patients with OCD using voxel-based morphometry (VBM). Subjects consisted of 23 patients with OCD and 26 normal control subjects. All patients were drug-free for at least 2 weeks before the study. Three-dimensional T1-weighed MR images were obtained in all subjects. Optimized voxel-based morphometry was performed to detect structural difference between the two groups. The patients with OCD demonstrated a significant reduction of GM volume in the bilateral medial prefrontal cortex, right premotor area, right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex, and bilateral temporal and occipital regions. The OCD patients also showed a significant WM volume increase in the right anterior limb of the internal capsule, right orbitofrontal region, and a significant WM volume reduction in the left anterior cingulate gyrus. Our findings are consistent with previous studies implicating dysfunction of the frontal cortex including the OFC. The results suggested that WM volume abnormalities in the orbitofrontal region, anterior limb of the internal capsule, and anterior cingulate gyrus would imply abnormalities in the pathways of frontal-striatal circuits., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Medulloblastoma is an aggressive childhood cerebellar tumor. We recently reported a mouse model with conditional deletion of Patched1 gene that recapitulates many characteristics of the human medulloblastoma. Qualitative symptoms observed in the mouse model include irregular stride length, impaired cranial nerve function and decreased motor coordination and performance. In our current study, several quantitative behavioral assays including a mouse rotarod, a forced air challenge, a screen inversion test, a horizontal wire test, and stride length analysis were evaluated to determine the most sensitive and cost-effective functional assay for impaired neuromotor behavior associated with disease progression. Magnetic resonance imaging (MRI) was used to confirm and monitor tumor growth and as an anatomical biomarker for therapeutic response. Wild type mice or medulloblastoma-prone, conditional Patched1 knockout mice were observed by behavioral assays and MRI from postnatal weeks 3-6. Bortezomib treatment was administered during this period and therapeutic response was assessed using cerebellar volumes at the end of treatment. Of the behavioral tests assessed in this study, stride length analysis was best able to detect differences between tumor-prone mice and wild type mice as early as postnatal day 37 (P=0.003). Significant differences between stride lengths of bortezomib treated and control tumor-bearing mice could be detected as early as postnatal day 42 (P=0.020). Cerebellar volumes measured by MRI at the end of treatment validated the therapeutic effects seen by behavioral tests (P=0.03). These findings suggest that stride length analysis may serve as one of the more sensitive and cost-effective method for assessing new therapeutic compounds in this and other preclinical model of brain tumors.

Purpose: To investigate the utility of ultra-short echo time (UTE) sequence as pulmonary MRI to detect non-uniform disruption of lung architecture that is typical of emphysema., Materials and Methods: MRI of the lungs was conducted with a three-dimensional UTE sequence in transgenic mice with severe emphysema and their wild-type littermates in a 3 Tesla clinical MR system. Measurements of the signal intensity (SI) and transverse relaxation time (T2*) of the lung parenchyma were performed with various echo times (TEs) ranging from 100 micros to 2 ms., Results: Much higher SI of the lung parenchyma was observed at an UTE of 100 micros compared with longer TEs. The emphysematous lungs had reduced SIs and T2* than the controls, in particular at end-expiratory phase. The results suggested that both SI and T2* in lung parenchyma measured with the method represent fractional volume of lung tissue., Conclusion: The UTE imaging provided MR signal from the lung parenchyma. Moreover, the UTE sequence was sensitive to emphysematous changes and may provide a direct assessment of lung parenchyma. UTE imaging has the potential to assist detection of localized pathological destruction of lung tissue architecture in emphysema., (2010 Wiley-Liss, Inc.)

The objective of this study was to develop and evaluate an alpha(v)beta(3)-specific nanoprobe consisting of fluorescent superparamagnetic polymeric micelles (FSPPM) for in vivo imaging of tumor angiogenesis. Spherical micelles were produced using poly(ethylene glycol)-b-poly(d,l-lactide) co-polymers conjugated with tetramethylrhodamine, a fluorescent dye, and loaded with superparamagnetic iron oxide nanoparticles. The resulting micelle diameter was 50-70 nm by dynamic light scattering and transmission electron microscopy measurements. Micelles were encoded with an alpha(v)beta(3)-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in alpha(v)beta(3)-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed alpha(v)beta(3)-specific FSPPM accumulation in human lung cancer subcutaneous tumor xenografts. Together with the histological validation, the three-dimensional gradient echo magnetic resonance imaging (MRI) data provide high spatial resolution mapping and quantification of angiogenic vasculature in an animal tumor model using targeted, ultrasensitive MRI nanoprobes.

We report a rare case of giant cell glioblastoma that was difficult to distinguish from cerebral metastasis. The MRI finding was a ring-enhancing well-circumscribed solitary brain tumor that was very similar to cerebral metastasis. Even when MRI results were considered together with the findings by magnet resonance spectroscopy and perfusion-weighted MRI, it was hard to distinguish between giant cell glioblastoma and cerebral metastasis before surgery. When we find a solitary ring-enhancing intracranial mass with little tendency of invasion, we need to consider the possibility of giant cell GBM as a differential diagnosis.

Purpose: To test, in a murine model of unilateral ureteral obstruction (UUO), whether the magnetic resonance (MR) imaging-derived apparent diffusion coefficient (ADC) changes during the progression of renal fibrosis and correlates with the histopathologic changes observed in renal fibrogenesis., Materials and Methods: This study was approved by the institutional animal care and use committee. A UUO was created in each of 14 mice. In five mice, longitudinal diffusion-weighted (DW) imaging was performed before the UUO (day 0) and on days 3 and 7 after the UUO and was followed by histopathologic analysis. The nine remaining mice were examined with cross-sectional studies on days 0 (n = 4) and 3 (n = 5). ADCs were measured with a spin-echo echo-planar sequence at five b values ranging from 350 to 1200 sec/mm(2). Differences in ADC among the time points and between the sides were assessed by using Tukey-Kramer and Student t tests, respectively. ADC was correlated with cell density and alpha-smooth muscle actin (alpha-SMA, a marker of myofibroblasts) expression at linear regression analysis., Results: Histopathologic examination revealed typical renal fibrosis on the side with UUO. The ADC decreased over time on the UUO side, from (1.02 +/- 0.06 [standard deviation]) x 10(-3) mm(2)/sec on day 0 to (0.70 +/- 0.08) x 10(-3) mm(2)/sec on day 3 (P < .001) and (0.57 +/- 0.10) x 10(-3) mm(2)/sec on day 7 (P < .001). The percentage change in ADC was greater on the UUO side than on the contralateral side on days 3 (29% +/- 9, P = .05) and 7 (44% +/- 11, P < .01). ADC correlated with both increased cell density and increased alpha-SMA expression (P < .001 for both correlations)., Conclusion: An ADC decrease in renal fibrosis is associated with an increased number of cells, including fibroblasts. ADC has the potential to serve as a sensitive noninvasive biomarker of renal fibrosis., (Copyright RSNA, 2010)

Recent neuroimaging studies suggest that the pathophysiology of obsessive-compulsive disorder (OCD) may involve more widely distributed large-scale brain systems, including the parietal, occipital, and cerebellar areas, rather than the conventional orbitofronto-striatal model. We hypothesized that not only orbitofrontal cortex and caudate nucleus activities but also posterior brain regions might be associated with subsequent treatment response to serotonin reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before treatment, fMRI images of the subjects were obtained in the context of a symptom-provocation paradigm. The percentage changes in total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the index of treatment response. Statistical Parametric Mapping was used to identify brain loci where pre-treatment brain activation significantly correlated with the subsequent treatment response. Fifteen of 17 patients completed the 12-week treatment. During the symptom provocation task, patients showed brain activation in the left superior temporal gyrus (STG), left precuneus, left frontal cortices, right cerebellum, and right frontal cortices. We found that pre-treatment activation in the right cerebellum (Z-score=5.10, x,y,z=22,-84,-18) and the left STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score. Our results suggest that pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity. There is every possibility that fMRI can be used as a tool to predict treatment response., (Copyright 2009 Elsevier Ltd. All rights reserved.)