NMR shutter-speed elucidates apparent population inversion of 1 H2 O signals due to active transmembrane water cycling.

PURPOSE: The desire to quantitatively discriminate the extra- and intracellular tissue 1 H2 O MR signals has gone hand-in-hand with the continual, historic increase in MRI instrument magnetic field strength [B0 ]. However, recent studies have indicated extremely valuable, novel metabolic information can be readily accessible at ultra-low B0 . The two signals can be distinguished, and the homeostatic activity of the cell membrane sodium/potassium pump (Na+ ,K+ ,ATPase) detected. The mechanism allowing 1 H2 O MRI to do this is the newly discovered active transmembrane water cycling (AWC) phenomenon, which we found using paramagnetic extracellular contrast agents at clinical B0 values. AWC is important because Na+ ,K+ ,ATPase can be considered biology's most vital enzyme, and its in vivo steady-state activity has not before been measurable, let alone amenable to mapping with high spatial resolution. Recent reports indicate AWC correlates with neuronal firing rate, with malignant tumor metastatic potential, and inversely with cellular reducing equivalent fraction. We wish to systematize the ways AWC can be precisely measured. METHODS: We present a theoretical longitudinal relaxation analysis of considerable scope: it spans the low- and high-field situations. RESULTS: We show the NMR shutter-speed organizing principle is pivotal in understanding how trans-membrane steady-state water exchange kinetics are manifest throughout the range. Our findings illuminate an aspect, apparent population inversion, which is crucial in understanding ultra-low field results. CONCLUSIONS: Without an appreciation of apparent population inversion, significant misinterpretations of future data are likely. These could have unfortunate diagnostic consequences.

Neurophysiological effects of multiple mood episodes in bipolar disorder.

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

Magnetic resonance imaging study of eye congenital birth defects in mouse model.

PURPOSE: Embryonic eyelid closure is a well-documented morphogenetic episode in mammalian eye development. Detection of eyelid closure defect in humans is a major challenge because eyelid closure and reopen occur entirely in utero. As a consequence, congenital eye defects that are associated with failure of embryonic eyelid closure remain unknown. To fill the gap, we developed a mouse model of defective eyelid closure. This preliminary work demonstrates that the magnetic resonance imaging (MRI) approach can be used for the detection of extraocular muscle abnormalities in the mouse model. METHODS: Mice with either normal (Map3k1+/- ) or defective (Map3k1-/- ) embryonic eyelid closure were used in this study. Images of the extraocular muscles were obtained with a 9.4 T high resolution microimaging MRI system. The extraocular muscles were identified, segmented, and measured in each imaging slice using an in-house program. RESULTS: In agreement with histological findings, the imaging data show that mice with defective embryonic eyelid closure develop less extraocular muscle than normal mice. In addition, the size of the eyeballs was noticeably reduced in mice with defective embryonic eyelid closure. CONCLUSIONS: We demonstrated that MRI can potentially be used for the study of extraocular muscle in the mouse model of the eye open-at-birth defect, despite the lack of specificity of muscle group provided by the current imaging resolution.

fMRI brain activation changes following treatment of a first bipolar manic episode.

OBJECTIVES: We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers. METHODS: Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response. RESULTS: ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors. CONCLUSIONS: These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.

Imaging of brain tumors with paramagnetic vesicles targeted to phosphatidylserine.

PURPOSE: To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. MATERIALS AND METHODS: Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. RESULTS: The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)(-1) relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). CONCLUSION: These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS.

Adaptive speech enhancement using directional microphone in a 4-T MRI scanner.

OBJECTIVE: To evaluate the effectiveness of the proposed adaptive speech enhancement (ASE) system for the magnetic resonance imaging (MRI) environment to reduce the loud scanning noise without disrupting the communication between patients and MRI operators. MATERIALS AND METHODS: The developed system employed the idea of differential directional microphones for measuring and distinguishing the speech signals and MRI acoustic noises simultaneously. Two-stage adaptive filters with normalized least mean square algorithms were adopted. Two common MRI scanning sequences, echo planar imaging (EPI) and gradient echo multi-slice (GEMS), were tested using a 4T MRI scanner. RESULTS: A total of 1.4 and 3.3 dB speech enhancements quantified by the cepstral distance assessment were achieved for the speech signal contaminated with the EPI and GEMS noises, respectively. The speech signal was noticeably recovered, and a clear speech waveform was observed after treated with the ASE system. Furthermore, a non-adaptive post-processing approach [i.e. simply using spectral subtraction (SS) technique] was also adopted to process the abovementioned results. Additional reductions were achieved for the non-coherent MRI acoustic noises. CONCLUSION: The results showed that combining the proposed ASE system along with the SS approach has a great potential for treating MRI acoustic noise to guarantee an effective communication from patient to MRI operators.

Myelin water mapping by spatially regularized longitudinal relaxographic imaging at high magnetic fields.

PURPOSE: Magnetic resonance T1 -weighted images are routinely used for human brain segmentation, brain parcellation, and clinical diagnosis of demyelinating diseases. Myelin is thought to influence the longitudinal relaxation commonly described by a mono-exponential recovery, although reports of bi-exponential longitudinal relaxation have been published. The purpose of this work was to investigate if a myelin water T1 contribution could be separated in geometrically sampled Look-Locker trains of low flip angle gradient echoes. METHODS: T1 relaxograms from normal human brain were computed by a spatially regularized inverse Laplace transform after estimating the apparent inversion efficiency. RESULTS: With sufficiently long inversion-time sampling (ca. 5 × T1 of cerebrospinal fluid), the T1 relaxogram revealed a short-T1 peak (106-225 ms). The apparent fraction of this water component increased in human brain white matter from 8.3% at 3 T, to 11.3% at 4 T and 15.0% at 7 T. The T2 * of the short-T1 peak at 3 T was shorter, 27.9 ± 13.0 ms, than that of the long-T1 peak, 51.3 ± 5.6 ms. CONCLUSION: The short-T1 fraction is interpreted as the water resident in myelin. Its detection is facilitated by longer T1 of axoplasmic water at higher magnetic field.

Neurochemical effects of quetiapine in patients with bipolar mania: a proton magnetic resonance spectroscopy study.

Although the neurophysiology underlying pharmacotherapy for bipolar disorder remains poorly understood, recent studies suggest that therapeutic mechanisms may be reflected in changes in concentrations of N-acetylaspartate (NAA), a putative measure of neuronal integrity and metabolism. In this study, we used magnetic resonance spectroscopy (MRS) to examine prefrontal NAA in patients receiving quetiapine for bipolar mania. On the basis of previous findings, we hypothesized that remission would be associated with increased NAA concentrations in the prefrontal cortex. Thirty-one manic bipolar patients and 13 healthy subjects were recruited to participate in this prospective study. All subjects participated in MRS at baseline and after 8 weeks of treatment. Bipolar subjects received open-label quetiapine monotherapy (mean dose [SD], 584 [191] mg). Fourteen patients remitted (Young Mania Rating Scale ≤ 12) ("remitters"), 11 patients did not ("nonremitters"), and 6 patients were lost to follow-up. Bipolar and healthy subjects did not significantly differ in baseline NAA or degree of change during the 8 weeks. Remitters showed greater mean baseline NAA concentrations in the right ventrolateral prefrontal cortex compared with nonremitters (P < 0.05). In the anterior cingulate, remitters showed near significantly decreased baseline NAA concentrations at baseline (P < 0.06), and significant differences in NAA change during the 8 weeks of treatment (P < 0.03). Manic patients who remitted with quetiapine treatment in the course of this study exhibited distinct patterns of baseline prefrontal NAA concentration, coupled with decreased NAA in the anterior cingulate with treatment; the latter possibly reflecting disparate effects of quetiapine on neuronal metabolism. These data support suggestions that therapeutic effects of quetiapine involve metabolic effects on specific prefrontal regions.

1H NMR analysis of choline metabolites in fine-needle-aspirate biopsies of breast cancer.

OBJECT: The relative amounts of choline (Cho), phosphocholine (PC), and glycerophosphocholine (GPC) may be sensitive indicators of breast cancer and the degree of malignancy. Here we implement some simple modifications to a previously developed (1)H NMR analysis of fine-needle-aspirate (FNA) biopsies designed to yield sufficient spectral resolution of Cho, PC, and GPC for usable relative quantitation of these metabolites. MATERIALS AND METHODS: FNA biopsies of eighteen breast lesions were examined using our modified procedure for direct (1)H NMR at 400 MHz. Resonances of choline metabolites and potential interferences were fit using the computer program NUTS. RESULTS: Quantitation of PC, GPC, and Cho relative to each other and to (phospho)creatine was obtained for eleven confirmed cases of infiltrating ductal carcinoma. Reliable results could not be obtained for the remaining cases primarily due to interference from lidocaine anesthetic. CONCLUSION: Some simple modifications of a previously developed (1)H NMR analysis of FNAs yielded sufficient spectral resolution of Cho, PC, and GPC to permit usable relative quantitation at 400 MHz. In 9 of the 11 quantified cases the sum of GPC and Cho exceeded 42 % of the total choline-metabolite peak area.

Revolving hexameric ATPases as asymmetric motors to translocate double-stranded DNA genome along one strand.

DsDNA translocation through nanoscale pores is generally accomplished by ATPase biomotors. The discovery of the revolving dsDNA translocation mechanism, as opposed to rotation, in bacteriophage phi29 elucidated how ATPase motors move dsDNA. Revolution-driven, hexameric dsDNA motors have been reported in herpesvirus, bacterial FtsK, Streptomyces TraB, and T7 phage. This review explores the common relationship between their structure and mechanisms. Commonalities include moving along the 5'→3' strand, inchworm sequential action leading to an asymmetrical structure, channel chirality, channel size, and 3-step channel gating for controlling motion direction. The revolving mechanism and contact with one of the dsDNA strands addresses the historic controversy of dsDNA packaging using nicked, gapped, hybrid, or chemically modified DNA. These controversies surrounding dsDNA packaging activity using modified materials can be answered by whether the modification was introduced into the 3'→5' or 5'→3' strand. Perspectives concerning solutions to the controversy of motor structure and stoichiometry are also discussed.

Electric Fields Regulate In Vitro Surface Phosphatidylserine Exposure of Cancer Cells via a Calcium-Dependent Pathway.

Cancer is the second leading cause of death worldwide after heart disease. The current treatment options to fight cancer are limited, and there is a critical need for better treatment strategies. During the last several decades, several electric field (EF)-based approaches for anti-cancer therapies have been introduced, such as electroporation and tumor-treating fields; still, they are far from optimal due to their invasive nature, limited efficacy and significant side effects. In this study, we developed a non-contact EF stimulation system to investigate the in vitro effects of a novel EF modality on cancer biomarkers in normal (human astrocytes, human pancreatic ductal epithelial -HDPE-cells) and cancer cell lines (glioblastoma U87-GBM, human pancreatic cancer cfPac-1, and MiaPaCa-2). Our results demonstrate that this EF modality can successfully modulate an important cancer cell biomarker-cell surface phosphatidylserine (PS). Our results further suggest that moderate, but not low, amplitude EF induces p38 mitogen-activated protein kinase (MAPK), actin polymerization, and cell cycle arrest in cancer cell lines. Based on our results, we propose a mechanism for EF-mediated PS exposure in cancer cells, where the magnitude of induced EF on the cell surface can differentially regulate intracellular calcium (Ca2+) levels, thereby modulating surface PS exposure.

4-T 7Li 3D MR spectroscopy imaging in the brains of bipolar disorder subjects.

This work demonstrates the first whole brain "high spatial resolution" (7)Li MR spectroscopy imaging in bipolar disorder subjects. The in vivo quantification is validated by a phantom containing 5 mM lithium salt using the identical radiofrequency sequence and imaging protocol. This study is the first demonstration of the (7)Li distribution in the brain of bipolar disorder patients on lithium therapy using a 3D MR spectroscopy imaging approach. The results show that brain lithium level is strongly correlated with serum lithium concentration. The brain-to-serum lithium ratios for the average brain and the local maximum were 0.39 ± 0.08 (r = 0.93) and 0.92 ± 0.16 (r = 0.90), respectively. The lithium distribution is found to be nonuniform throughout the brain for all patients, which is somewhat unexpected and highly intriguing. This uneven distribution is more evident in subjects at a higher therapeutic serum lithium level. This finding may suggest that lithium targets specific brain tissues and/or certain enzymatic and macromolecular sites that are associated with therapeutic effect. Further investigations of bipolar disorder patients on lithium therapy using 3D (7)Li MR spectroscopy imaging are warranted.

Polymer beacons for luminescence and magnetic resonance imaging of DNA delivery.

The delivery of nucleic acids with polycations offers tremendous potential for developing highly specific treatments for various therapeutic targets. Although materials have been developed and studied for polynucleotide transfer, the biological mechanisms and fate of the synthetic vehicle has remained elusive due to the limitations with current labeling technologies. Here, we have developed polymer beacons that allow the delivery of nucleic acids to be visualized at different biological scales. The polycations have been designed to contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and lanthanide (Ln) chelates [either luminescent europium (Eu(3+)) or paramagnetic gadolinium (Gd(3+))]. The chelated Lns allow the visualization of the delivery vehicle both on the nm/microm scale via microscopy and on the sub-mm scale via MRI. We demonstrate that these delivery beacons effectively bind and compact plasmid (p)DNA into nanoparticles and protect nucleic acids from nuclease damage. These delivery beacons efficiently deliver pDNA into cultured cells and do not exhibit toxicity. Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers reveal effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures show bright image contrast, allowing visualization of effective intracellular delivery on the tissue-scale. Because of their versatility, these delivery beacons posses remarkable potential for tracking and understanding nucleic acid transfer in vitro, and have promise as in vivo theranostic agents.

Phosphatidylserine: The Unique Dual-Role Biomarker for Cancer Imaging and Therapy.

Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane. In many cancer cells, PS externalizes to the outer cell membrane, a process regulated by calcium-dependent flippases and scramblases. Saposin C coupled with dioleoylphosphatidylserine (SapC-DOPS) nanovesicle (BXQ-350) and bavituximab, (Tarvacin, human-mouse chimeric monoclonal antibodies) are cell surface PS-targeting drugs being tested in clinical trial for treating a variety of cancers. Additionally, a number of other PS-selective agents have been used to trigger cytotoxicity in tumor-associated endothelial cells or cancer cells in pre-clinical studies. Recent studies have demonstrated that upregulation of surface PS exposure by chemodrugs, radiation, and external electric fields can be used as a novel approach to sensitize cancer cells to PS-targeting anticancer drugs. The objectives of this review are to provide an overview of a unique dual-role of PS as a biomarker/target for cancer imaging and therapy, and to discuss PS-based anticancer strategies that are currently under active development.

In situ active control of noise in a 4 T MRI scanner.

PURPOSE: To evaluate the effectiveness of the proposed active noise control (ANC) system for the reduction of the acoustic noise emission generated by a 4 T MRI scanner during operation and to assess the feasibility of developing an ANC device that can be deployed in situ. MATERIALS AND METHODS: Three typical scanning sequences, EPI (echo planar imaging), GEMS (gradient echo multislice), and MDEFT (modified driven equilibrium Fourier transform), were used for evaluating the performance of the ANC system, which was composed of a magnetic compatible headset and a multiple reference feedforward filtered-x least mean square controller. RESULTS: The greatest reduction, about 55 dB, was achieved at the harmonic at a frequency of 1.3 kHz in the GEMS case. Approximately 21 dB and 30 dBA overall reduction was achieved for GEMS noise across the entire audible frequency range. For the MDEFT sequence, the control system achieved 14 dB and 14 dBA overall reduction in the audible frequency range, while 13 dB and 14 dBA reduction was obtained for the EPI case. CONCLUSION: The result is highly encouraging because it shows great potential for treating magnetic resonance imaging noise with an ANC application during real-time scanning.

1H MR Spectroscopy of Fine-Needle Aspiration Biopsy Specimens for the Discrimination of Breast Cancer.

Purpose: To determine whether MR spectroscopic assessment of fine-needle aspiration (FNA) biopsy specimens from suspicious breast lesions could be used to improve the diagnostic utility of FNA biopsies for the characterization of breast lesions. Materials and Methods: In this prospective study, a previously reported technique using high-spatial-resolution proton MR spectroscopy was modified and used to examine the utility of FNA biopsies in the evaluation of suspicious breast lesions. Tissue samples from 115 lesions (from 102 women; average age, 54 years) were excised by using FNA and core biopsies and were collected between September 7, 2012, and April 11, 2014. Histologic results from core biopsy specimens determined the lesions to be benign (n = 55), invasive ductal carcinoma (n = 51), invasive lobular carcinoma (n = 5), or ductal carcinoma in situ (n = 4). Measures of phosphocholine (PC), glycerophosphocholine, and choline relative to each other and to total creatine (tCr) were obtained from usable spectra. Planned comparisons among lesion groups were carried out using t test contrasts, and differences of each contrast level from zero were judged significant when the two-tailed P value was less than .05. Results: Of the 115 samples, 69 (60%) yielded no usable MR spectra. Analysis of the 46 with usable spectra found that only the difference in PC/tCr between benign and cancer lesions was statistically significant (P = .028). Conclusion: Given that 60% of FNA biopsy specimens yielded no usable spectra and that results were largely inconclusive when derived from usable spectra, the combined MR and FNA technique, as modified and implemented in this study, is of little value for detection and diagnosis of breast cancer.Keywords: Breast, MR-Spectroscopy, Neoplasms-Primary© RSNA, 2020.

A beta-cyclodextrin "click cluster" decorated with seven paramagnetic chelates containing two water exchange sites.

The development of novel macromolecular contrast agents that offer enhanced relaxivity profiles at high magnetic fields have the potential to greatly improve the diagnosis, understanding, and treatment of disease. To this end, we have designed a monodiperse paramagnetic beta-cyclodextrin click cluster decorated with seven paramagnetic arms. A novel alkyne-functionalized diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and coupled to a per-azido-beta-cyclodextrin core (7) to yield the precursor macromolecule (8). After removal of the protecting groups and titrating with Gd (3+), the final paramagnetic click cluster, Gd10, was obtained. Luminescence measurements were carried out in H 2O and D 2O on an analogous structure, Eu10, and indicated that at each lanthanide has an average of 1.8 water exchange sites, which is important for enhancing relaxivity and MRI resolution. This discrete paramagnetic click cluster yields a high relaxivity profile (43.4 mM (-1) s (-1) per molecule and 6.2 mM (-1) s (-1) per Gd (3+) at 9.4 T) and enhanced contrast on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM (-1) s (-1) at 9.4 T). Moreover, the useful inclusion properties exhibited by beta-cyclodextrin also make this an excellent host scaffold to functionalize via noncovalent assembly with receptor specific targeting moieties for biomolecular imaging.

Simulation study on active noise control for a 4-T MRI scanner.

The purpose of this work is to study computationally the possibility of the application of a hybrid active noise control technique for magnetic resonance imaging (MRI) acoustic noise reduction. A hybrid control system combined with both feedforward and feedback loops embedded is proposed for potential application on active MRI noise reduction. A set of computational simulation studies were performed. Sets of MRI acoustic noise emissions measured at the patient's left ear location were recorded and used in the simulation study. By comparing three different control systems, namely, the feedback, the feedforward and the hybrid control, our results revealed that the hybrid control system is the most effective. The hybrid control system achieved approximately a 20-dB reduction at the principal frequency component. We concluded that the proposed hybrid active control scheme could have a potential application for MRI scanner noise reduction.

4T split TEM volume head and knee coils for improved sensitivity and patient accessibility.

Split RF coils offer improved patient access by eliminating the need for the coil to be slid over the region of interest. For unshielded birdcage coils, the presence of end ring currents necessitates a direct electrical connection between two halves of the coil. For high-field (>3T) shielded birdcage coils, both the shield and the coil must be split and reliably connected electrically. This problem can be circumvented by the use of split TEM volume coils. Since the elements of a TEM coil are coupled inductively, no direct electrical connection between the halves is necessary. In this work we demonstrate that the effects of splitting the shield for head and knee TEMs can be compensated for, and performance retained. For the knee, the improved access allowed the coil diameter to be reduced, enhancing the sensitivity by 15-20%.