A novel high power vacuum diode with a focusing electrode for effective operation in a low guiding magnetic field.

A novel diode featuring an annular cathode and a ring-shaped focusing electrode and operating in a low guiding magnetic field (GMF) has been developed. It was found that the breakdown threshold for a focusing electrode made of titanium was 140 kV/cm higher than a stainless steel electrode for the same operating conditions. Comparison of the diode current measured by a Rogowski coil and the beam current measured by a Faraday cup at the collector indicated that an intense relativistic electron beam was transmitted effectively even in a GMF of as low as 0.21 T. In addition, a photo of the cathode plasma and the targeting results indicated that the emission uniformity of the graphite cathode was satisfactory.

Standardized MRI assessment of high-grade glioma response: a review of the essential elements and pitfalls of the RANO criteria.

Accurately evaluating response in the treatment of high-grade gliomas presents considerable challenges. This review looks at the advancements made in response criteria while critically outlining remaining weaknesses, and directs our vision toward promising endpoints to come. The 2010 guidelines from the Response Assessment in Neuro-Oncology (RANO) working group have enhanced interpretation of clinical trials involving novel treatments for high-grade glioma. Yet, while the criteria are considered clinically applicable to high-grade glioma trials, as well as reasonably accurate and reproducible, RANO lacks sufficient detail for consistent implementation in certain aspects and leaves some issues from the original Macdonald guidelines unresolved. To provide the most accurate assessment of response to therapeutic intervention currently possible, it is essential that trial oncologists and radiologists not only have a solid understanding of RANO guidelines, but also proper insight into the inherent limitations of the criteria. With the expectation of improved data collection as a standard, the author anticipates that the next high-grade glioma response criteria updates will incorporate advanced MRI methods and quantitative tumor volume measurements, availing a more accurate interpretation of response in the future.

Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials.

A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR systems.

Volumetric MRI and MRS provide sensitive measures of Alzheimer's disease neuropathology in inducible Tau transgenic mice (rTg4510).

The purpose of this study was to determine if in vivo high resolution 3D MRI and localized (1)H MR spectroscopy (MRS) can detect brain findings resembling Alzheimer's disease in a transgenic mouse model of Tau pathology. Seven double transgenic rTg4510 female mice and 7 age-matched wild-type (wt) female mice were evaluated at 5 months of age. To confirm the usefulness and consistency of in vivo MRI/S, we also scanned the brains of 14 male mice (7 rTg4510 and 7 age-matched wt) at 8 months of age. Mean hippocampal and cerebral cortex volumes in the female rTg4510 mice were 26.7% and 20.6% smaller than that in the wt controls (p<0.0001), respectively. Mean hippocampal and cerebral cortex volumes in the male rTg4510 mice were 18.4% and 16.9% smaller than that in the wt controls (p<0.00005), respectively. The mean volumes of the cerebellum were not statistically different between the rTg4510 and the wt groups. MRS assessment revealed that the myo-inositol to total creatine ratios (mIns/tCr), a measure of gliosis, were significantly higher in the hippocampus of rTg4510 mice relative to wt mice (p=0.03 for the females; p=0.005 for the males). Immunohistochemistry and histology in the same animals verified previously published data showing elevation of hyperphosphorylated Tau, glial activation and cortical and hippocampal neuronal loss. This study demonstrates that in vivo MRI/S can be a non-invasive biomarker to assess brain atrophy and related biochemical changes in the rTg4510 mouse model.

Characterizing the regional structural difference of the brain between tau transgenic (rTg4510) and wild-type mice using MRI.

rTg4510 transgenic mouse model demonstrates features resembling Alzheimer's disease including neurofibrillary degeneration and progressive neuronal loss. We investigated the volumetric differences of brain structures between transgenic and wild-type mice using MR images of fourteen 5.5 month old female mice. Tensor-based morphometry and atlas-based segmentation were applied to MRI images. Severe atrophy of hippocampus and neocortex as well as ventricular dilatation were observed in the transgenic mice. These findings were confirmed by histopathologic evaluation of the same mice. The results suggest that MRI should be useful for evaluating disease-modifying therapies for Alzheimer's disease in the rTg4510 model and comparing treatment responses in mice and humans.

Selective PPARdelta agonist treatment increases skeletal muscle lipid metabolism without altering mitochondrial energy coupling: an in vivo magnetic resonance spectroscopy study.

Peroxisome proliferator-activated receptor-delta (PPARdelta) activation results in upregulation of genes associated with skeletal muscle fatty acid oxidation and mitochondrial uncoupling. However, direct, noninvasive assessment of lipid metabolism and mitochondrial energy coupling in skeletal muscle following PPARdelta stimulation has not been examined. Therefore, in this study we examined the response of a selective PPARdelta agonist (GW610742X at 5 or 100 mg.kg(-1).day(-1) for 8 days) on skeletal-muscle lipid metabolism and mitochondrial coupling efficiency in rats by using in vivo magnetic resonance spectroscopy (MRS). There was a decrease in the intramyocellular lipid-to-total creatine ratio as assessed by in vivo (1)H-MRS in soleus and tibialis anterior muscles by day 7 (reduced by 49 and 46%, respectively; P < 0.01) at the high dose. Following the (1)H-MRS experiment (day 8), [1-(13)C]glucose was administered to conscious rats to assess metabolism in the soleus muscle. The relative fat-vs.-carbohydrate oxidation rate increased in a dose-dependent manner (increased by 52 and 93% in the 5 and 100 mg.kg(-1).day(-1) groups, respectively; P < 0.05). In separate experiments where mitochondrial coupling was assessed in vivo (day 7), (31)P-MRS was used to measure hindlimb ATP synthesis and (13)C-MRS was used to measure the hindlimb tricarboxylic acid cycle flux (V(tca)). There was no alteration, at either dose, in mitochondrial coupling efficiency measured as the ratio of unidirectional ATP synthesis flux to V(tca). Soleus muscle GLUT4 expression was decreased by twofold, whereas pyruvate dehydrogenase kinase 4, carnitine palmitoyl transferase 1a, and uncoupling protein 2 and 3 expression was increased by two- to threefold at the high dose (P < 0.05). In summary, these are the first noninvasive measurements illustrating a selective PPARdelta-mediated decrease in muscle lipid content that was consistent with a shift in metabolic substrate utilization from carbohydrate to lipid. However, the mitochondrial-energy coupling efficiency was not altered in the presence of increased uncoupling protein expression.

Correlation of CT analysis and audiometry in Japanese otosclerosis.

OBJECTIVE: To determine the extent of audiometric correlation with CT findings. METHODS: Forty-four patients (82 ears) with surgically confirmed otosclerosis underwent preoperative CT examination. Based on the computed tomography (CT) findings, the ears were classified into five groups as follows: Group A, the group with no pathological CT findings; Group B1, the group with demineralization localized in the region of the fissula antefenestram; Group B2, the group with demineralization extending towards the cochleariform process from the anterior region of the oval window; Group B3, the group with extensive demineralization surrounding the cochlea; and Group C, the group with thick anterior and posterior calcified plaques. RESULTS: There were 32 ears (39.0%) in Group A, 21 ears (25.6%) in Group B1, 16 ears (19.5%) in Group B2, 7 ears (8.5%) in Group B3, and 6 ears (7.3%) in Group C. The mean bone conduction levels were greater in the order of the extent of demineralization: Groups A, B1-B3 suggesting positive relationship between the cochlear function and the degree of labyrhinthine otosclerosis. CONCLUSION: A good correlation between the preoperative CT findings and audiometry findings suggests that CT with a slice intervals between 0.5 and 1mm could provide useful informations in assuming the extent of otosclerosis in the inner ear.

Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.

PURPOSE: To investigate the feasibility of obtaining reproducible apparent diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory-triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to investigate the sensitivity of ADC maps in the evaluation of renal blood flow, and to use this technique to monitor acute graft rejection in transplanted rat kidneys. MATERIALS AND METHODS: Spin-echo diffusion-weighted MR imaging measurements were performed in 20 normal rats and nine rats that had undergone transplantation (six rats had received allografts; three had received isografts) at 7 T. To evaluate the effect of alteration in blood flow and water transport function, angiotensin II was infused in six normal rats and a series of spin-echo diffusion-weighted MR images was obtained at five time points. Transplanted kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and gradient-echo MR images every 2 hours for 8 hours on postoperative day 4. Statistical analysis was performed with repeated-measures multivariate analysis of variance and the paired t test. RESULTS: No significant differences in ADC values were observed between right and left kidneys in all three orthogonal directions; however, a small difference was observed between the cortex and medulla. ADC values in the cephalocaudal and mediolateral directions were higher than those in the anteroposterior direction (P <.01 for all). ADC values in the cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin II-induced reduction in renal blood flow. No significant signal intensity change was observed between native and transplanted kidneys on gradient-echo MR images. Allografts exhibited decreased ADC values (P <.01) and isografts exhibited similar ADC values compared with native kidneys. CONCLUSION: These findings suggest that reproducible renal ADC maps can be obtained in rats by using spin-echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR imaging may have potential as a noninvasive tool for monitoring early graft rejection after kidney transplantation.

Improving spatiotemporal resolution of USPIO-enhanced dynamic imaging of rat kidneys.

This paper addresses the problem of enhancing spatiotemporal resolution of ultra-small superparamagnetic iron oxide (USPIO)-enhanced dynamic MRI of rat kidneys. To alleviate the limited resolution problem of conventional full-scan Fourier imaging methods, we use a generalized series-based imaging scheme to reduce coverage of kappa-space. Experimental results demonstrate that the generalized series imaging method with basis functions constructed using two references (pre- and post-contrast) can reduce the number of phase encodings measured during the dynamic contrast wash-in process by a factor of 4 with a negligible or minimal loss of image quality. The method is expected to make 3D studies possible using USPIO-enhanced dynamic imaging of rat kidneys, and prove valuable for early detection of renal rejection after kidney transplantation.

In vivo detection of acute rat renal allograft rejection by MRI with USPIO particles.

BACKGROUND: Magnetic resonance imaging (MRI) for non-invasively detecting renal rejection was developed by monitoring the accumulation of macrophages labeled with dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles at the rat renal allografts during acute rejection. METHODS: Five groups of male rats with DA-->BN renal allografts and one group with BN-->BN renal isografts were investigated by MRI before, immediately after, and 24 hr after intravenous infusion with different doses of USPIO particles. All infusions were done on post-operative day 4. MRI experiments were carried out in a 4.7-Tesla instrument using a gradient echo sequence. RESULTS: MR signal intensity (MRSI) of the cortex was found to decrease with higher dosages of USPIO particles. In the absence of USPIO infusion, a decrease in MRSI was seen in the medulla region, presumably due to hemorrhage associated with renal graft rejection, while no significant change was observed in the cortex. The optimal dose of USPIO particles for visualizing rejection-associated changes in our rat kidney model appears to be 6 mg Fe/kg body weight. Iron staining results correlated with the MRSI data, indicating that the signal reduction in the MR images was due to the presence of iron. Immunohistochemical results indicated that USPIO particles were mostly taken up by infiltrating macrophages in the rejecting grafts. CONCLUSIONS: Our results suggest that MRI with intravenous administration of dextran-coated USPIO particles appears to be a valuable and promising tool that can be used as a non-invasive and sensitive method to detect graft rejection in renal transplantation.