Numerical modelling of thermal effects in rats due to high-field magnetic resonance imaging (0.5-1 GHz)

A finite-difference time-domain (FDTD) thermal model has been developed to compute the temperature elevation in the Sprague Dawley rat due to electromagnetic energy deposition in high-field magnetic resonance imaging (MRI). The field strengths examined ranged from 11.75-23.5 T (corresponding to H-1 resonances of 0.5-1 GHz) and an N-stub birdcage resonator was used to both transmit radio-frequency energy and receive the MRI signals. With an in-plane resolution of 1.95 mm, the inhomogeneous rat phantom forms a segmented model of 12 different tissue types, each having its electrical and thermal parameters assigned. The steady-state temperature distribution was calculated using a Pennes 'bioheat' approach. The numerical algorithm used to calculate the induced temperature distribution has been successfully validated against analytical solutions in the form of simplified spherical models with electrical and thermal properties of rat muscle. As well as assisting with the design of MRI experiments and apparatus, the numerical procedures developed in this study could help in future research and design of tumour-treating hyperthermia applicators to be used on rats in vivo.

Electromagnetic fields inside a lossy, multilayered spherical head phantom excited by MRI coils: models and methods

The precise evaluation of electromagnetic field (EMF) distributions inside biological samples is becoming an increasingly important design requirement for high field MRI systems. In evaluating the induced fields caused by magnetic field gradients and RF transmitter coils, a multilayered dielectric spherical head model is proposed to provide a better understanding of electromagnetic interactions when compared to a traditional homogeneous head phantom. This paper presents Debye potential (DP) and Dyadic Green's function (DGF)-based solutions of the EMFs inside a head-sized, stratified sphere with similar radial conductivity and permittivity profiles as a human head. The DP approach is formulated for the symmetric case in which the source is a circular loop carrying a harmonic-formed current over a wide frequency range. The DGF method is developed for generic cases in which the source may be any kind of RF coil whose current distribution can be evaluated using the method of moments. The calculated EMFs can then be used to deduce MRI imaging parameters. The proposed methods, while not representing the full complexity of a head model, offer advantages in rapid prototyping as the computation times are much lower than a full finite difference time domain calculation using a complex head model. Test examples demonstrate the capability of the proposed models/methods. It is anticipated that this model will be of particular value for high field MRI applications, especially the rapid evaluation of RF resonator (surface and volume coils) and high performance gradient set designs.

Concurrent binding of anti-EphA3 antibody and ephrin-A5 amplifies EphA3 signaling and downstream responses: Potential as EphA3-specific tumor-targeting reagents

The Eph receptor tyrosine kinases and their membrane-bound ephrin ligands form a unique cell-cell contact-mediated system for controlling cell localization and organization. Their high expression in a wide variety of human tumors indicates a role in tumor progression, and relatively low Eph and ephrin levels in normal tissues make these proteins potential targets for anticancer therapies. The monoclonal antibody IIIA4, previously used to isolate EphA3, binds with subnanomolar affinity to a conformation-specific epitope within the ephrin-binding domain that is closely adjacent to the low-affinity ephrin-A5 heterotetramerization site. We show that similar to ephrin-A5, preclustered IIIA4 effectively triggers EphA3 activation, contraction of the cytoskeleton, and cell rounding. BIAcore analysis, immunoblot, and confocal microscopy of wild-type and mutant EphA3 with compromised ephrin-A5 or IIIA4-binding capacities indicate that IIIA4 binding triggers an EphA3 conformation which is permissive for the assembly of EphA3/ephrin-A5-type signaling clusters. Furthermore, unclustered IIIA4 and ephrin-A5 Fc applied in combination initiate greatly enhanced EphA3 signaling. Radiometal conjugates of ephrin-A5 and IIIA4 retain their affinity, and in mouse xenografts localize to, and are internalized rapidly into EphA3-positive, human tumors. These findings show the biological importance of EphA3/ ephrin-A5 interactions and that ephrin-A5 and IIIA4 have great potential as tumor targeting reagents.

Novel markers for poor prognosis in head and neck cancer

Head and neck cancer (HNSCC) is one of the most distressing human cancers, causing pain and affecting the basic survival functions of breathing and swallowing. Mortality rates have not changed despite recent advances in radiotherapy and surgical treatment. We have compared the expression of over 13,000 unique genes in 7 cases of matched HNSCC and normal oral mucosa. Of the 1,260 genes that showed statistically significant differences in expression between normal and tumor tissue at the mRNA level, the three top ranking of the top 5% were selected for further analysis by immunohistochemistry on paraffin sections,. along with the tumor suppressor genes p16 and p53, in a total of 62 patients including 55 for whom >4-year clinical data was available. Using univariate and multivariate survival analysis, we identified SPARC/osteonectin as a powerful independent prognostic marker for short disease-free interval (DFI) (p < 0.002) and poor overall survival (OS) (p = 0.018) of HNSCC patients. In combination with other ECM proteins found in our analysis, PAI-1 and uPA, the association with DFI and OS became even more significant (p < 0.001). Our study represents the first instance of SPARC as an independent prognostic marker in HNSCC.

Focused, eight-element transceive phased array coil for parallel magnetic resonance imaging of the chest-theoretical considerations

A new transceive system for chest imaging for MRI applications is presented. A focused, eight-element transceive torso phased array coil is designed to investigate transmitting a focused radiofrequency field deep within the torso and to enhance signal homogeneity in the heart region. The system is used in conjunction with the SENSE reconstruction technique to enable focused parallel imaging. A hybrid finite-difference-time-domain/method-of-moments method is used to accurately predict the radiofrequency behavior inside the human torso. The simulation results reported herein demonstrate the feasibility of the design concept, which shows that radiofrequency field focusing with SENSE reconstruction is theoretically achievable. (c) 2005 Wiley-Liss, Inc.

Multiple-acquisition parallel imaging combined with a transceive array for the amelioration of high-field RF distortion: a modeling study

A new method for ameliorating high-field image distortion caused by radio frequency/tissue interaction is presented and modeled, The proposed method uses, but is not restricted to, a shielded four-element transceive phased array coil and involves performing two separate scans of the same slice with each scan using different excitations during transmission. By optimizing the amplitudes and phases for each scan, antipodal signal profiles can be obtained, and by combining both images together, the image distortion can be reduced several-fold. A hybrid finite-difference time-domain/method-of-moments method is used to theoretically demonstrate the method and also to predict the radio frequency behavior inside the human head. in addition, the proposed method is used in conjunction with the GRAPPA reconstruction technique to enable rapid imaging. Simulation results reported herein for IIT (470 MHz) brain imaging applications demonstrate the feasibility of the concept where multiple acquisitions using parallel imaging elements with GRAPPA reconstruction results in improved image quality. (c) 2006 Wiley Periodicals, Inc.

Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain

A complex set of axonal guidance mechanisms are utilized by axons to locate and innervate their targets. In the developing mouse forebrain, we previously described several midline glial populations as well as various guidance molecules that regulate the formation of the corpus callosum. Since agenesis of the corpus callosum is associated with over 50 different human congenital syndromes, we wanted to investigate whether these same mechanisms also operate during human callosal development. Here we analyze midline glial and commissural development in human fetal brains ranging from 13 to 20 weeks of gestation using both diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our combined radiological and histological studies, we demonstrate the morphological development of multiple forebrain commissures/decussations, including the corpus callosum, anterior commissure, hippocampal commissure, and the optic chiasm. Histological analyses demonstrated that all the midline glial populations previously described in mouse, as well as structures analogous to the subcallosal sling and cingulate pioneering axons, that mediate callosal axon guidance in mouse, are also present during human brain development. Finally, by Northern blot analysis, we have identified that molecules involved in mouse callosal development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1, and GAP-43, are all expressed in human fetal brain. These data suggest that similar mechanisms and molecules required for midline commissure formation operate during both mouse and human brain development. Thus, the mouse is an excellent model system for studying normal and pathological commissural formation in human brain development. (c) 2006 Wiley-Liss, Inc.

High-field magnetic resonance imaging with reduced field/tissue RF artefacts - A modeling study using hybrid MoM/FEM and FDTD technique

Due to complex field/tissue interactions, high-field magnetic resonance (MR) images suffer significant image distortions that result in compromised diagnostic quality. A new method that attempts to remove these distortions is proposed in this paper and is based on the use of transceiver-phased arrays. The proposed system uses, in the examples presented herein, a shielded four-element transceive-phased array head coil and involves performing two separate scans of the same slice with each scan using different excitations during transmission. By optimizing the amplitudes and phases for each scan, antipodal signal profiles can be obtained, and by combining both the images together, the image distortion can be reduced several fold. A combined hybrid method of moments (MoM)/finite element method (FEM) and finite-difference time-domain (FDTD) technique is proposed and used to elucidate the concept of the new method and to accurately evaluate the electromagnetic field (EMF) in a human head model. In addition, the proposed method is used in conjunction with the generalized auto-calibrating partially parallel acquisitions (GRAPPA) reconstruction technique to enable rapid imaging of the two scans. Simulation results reported herein for 11-T (470-MHz) brain imaging applications show that the new method with GRAPPA reconstruction theoretically results in improved image quality and that the proposed combined hybrid MoM/FEM and FDTD technique is. suitable for high-field magnetic resonance imaging (MRI) numerical analysis.

Heterogeneity of MUC1 expression by human breast carcinoma cell lines in vivo and in vitro

Increased expression of the epithelial mucin MUC1 has been linked to tumor aggressiveness in human breast carcinoma. Recent studies have demonstrated that overexpression of MUC1 interferes with cell-substrate and cell-cell adhesion by masking cell surface integrins and E-cadherin. Additionally, the cytoplasmic tail of MUC1 is involved in signal transduction and interactions with catenins. In the present study, we have examined the in vitro expression of MUC1 mRNA and protein in a panel of 14 human breast cancer cell lines using northern blotting, western blotting, immunocytochemistry, and flow cytometry. Considerable variability of expression was noted not only between cell lines but also within several individual lines. Many cell lines such as BT 20, KPL-1, and T47D expressed abundant MUC1 whilst others such as MDA-MB-231 and MCF-7 showed intermediate expression, and MDA-MB-435 and MDA-MB-453 expressed very low levels. Low levels of MUC1 expression were associated with decreased expression of cytokeratin and increased expression of vimentin. Additionally, 12 of the cell lines were established as xenografts in immunocompromised (SCID) mice, and MUC1 expression in both the primary tumors as well as metastases was assessed immunohistochemically. In general, in vivo expression mirrored in vitro expression, although there was reduced in vivo expression in T47D and ZR-75-1 xenografts. Although we showed no correlation between tumorigenicity or metastasis and MUC1 expression, this study will assist development of experimental models to assess the influence of MUC1 of on breast cancer progression.

Real-time imaging of human cortical activity evoked by painful esophageal stimulation

Background & Aims: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. Methods: In 16 healthy subjects (8 men; mean age, 30.2 ± 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 ± 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. Results: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (∼85 ms). Significantly later activity was seen in the anterior insula (∼103 ms) and cingulate cortex (∼106 ms; P = .0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P = .16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P = .001). No sex differences were seen for psychophysical or neurophysiological measures. Conclusions: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate - brain regions that process the affective aspects of esophageal pain - occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity. © 2005 by the American Gastroenterological Association.

Three-dimensional modeling of the human eye based on magnetic resonance imaging

PURPOSE. A methodology for noninvasively characterizing the three-dimensional (3-D) shape of the complete human eye is not currently available for research into ocular diseases that have a structural substrate, such as myopia. A novel application of a magnetic resonance imaging (MRI) acquisition and analysis technique is presented that, for the first time, allows the 3-D shape of the eye to be investigated fully. METHODS. The technique involves the acquisition of a T2-weighted MRI, which is optimized to reveal the fluid-filled chambers of the eye. Automatic segmentation and meshing algorithms generate a 3-D surface model, which can be shaded with morphologic parameters such as distance from the posterior corneal pole and deviation from sphericity. Full details of the method are illustrated with data from 14 eyes of seven individuals. The spatial accuracy of the calculated models is demonstrated by comparing the MRI-derived axial lengths with values measured in the same eyes using interferometry. RESULTS. The color-coded eye models showed substantial variation in the absolute size of the 14 eyes. Variations in the sphericity of the eyes were also evident, with some appearing approximately spherical whereas others were clearly oblate and one was slightly prolate. Nasal-temporal asymmetries were noted in some subjects. CONCLUSIONS. The MRI acquisition and analysis technique allows a novel way of examining 3-D ocular shape. The ability to stratify and analyze eye shape, ocular volume, and sphericity will further extend the understanding of which specific biometric parameters predispose emmetropic children subsequently to develop myopia. Copyright © Association for Research in Vision and Ophthalmology.

Functional localisation of human sensory-motor cortex using magnetoencephalography

The 19 channel Neuromagnetometer system in the Clinical Neurophysiology Unit at Aston University is a multi-channel system, unique in the United Kingdom. A bite bar head localisation and MRI co-registration strategy which enabled accurate and reproducible localisation of MEG data into cortical space was developed. This afforded the opportunity to study magnetic fields of the human cortex generated by stimulation of peripheral nerve, by stimulation of visceral sensory receptors and by those evoked through voluntary finger movement. Initially, a study of sensory-motor evoked data was performed in a healthy control population. The techniques developed were then applied to patients who were to undergo neurosurgical intervention for the treatment of epilepsy and I or space occupying lesions. This enabled both validation of the effective accuracy of source localisation using MEG as well as to determine the clinical value of MEG in presurgical assessment of functional localisation in human cortex. The studies in this thesis have demonstrated that MEG can repeatedly and reliably locate sources contained within a single gyrus and thus potentially differentiate between disparate gyral activation. This ability is critical in the clinical application of any functional imaging technique; which is yet to be fully validated by any other 'non-invasive' functional imaging methodology. The technique was also applied to the study of visceral sensory representation in the cortex which yielded important data about the multiple cortical representation of visceral sensory function.

Simultaneous en-face imaging of two layers in human retina by low-coherence reflectometry

We show that with a fiberized multiple Michelson-interferometer-type configuration, transverse images from several layers in the human eye can be simultaneously obtained. We demonstrate the principle by producing simultaneous 100×100 pixel en-face images of a 4 mm×4 mm region on a postmortem retina for two depth positions 250 µm apart.