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Purpose Recent developments in hardware design enable the use of fast field‐cycling (FFC) techniques in MRI to exploit the different relaxation rates at very low field strength, achieving novel contrast. The method opens new avenues for in vivo characterizations of pathologies but at the expense of longer acquisition times. To mitigate this, we propose a model‐based reconstruction method that fully exploits the high information redundancy offered by FFC methods. Methods The proposed model‐based approach uses joint spatial information from all fields by means of a Frobenius ‐ total generalized variation regularization. The algorithm was tested on brain stroke images, both simulated and acquired from FFC patients scans using an FFC spin echo sequences. The results are compared to three non‐linear least squares fits with progressively increasing complexity. Results The proposed method shows excellent abilities to remove noise while maintaining sharp image features with large signal‐to‐noise ratio gains at low‐field images, clearly outperforming the reference approach. Especially patient data show huge improvements in visual appearance over all fields. Conclusion The proposed reconstruction technique largely improves FFC image quality, further pushing this new technology toward clinical standards.

In biomedical MITS, slight unintentional movements of the patient during measurement can contaminate the aimed images to a great extent. This study deals with measurement optimization in biomedical MITS through the detection of these unpredictable movements during measurement and the elimination of the resulting movement artefacts in the images to be reconstructed after measurement. The proposed detection and elimination (D&E) methodology requires marking the surface of the object under investigation with specific electromagnetically perturbing markers during multi-frame measurements. In addition to the active marker concept already published, a new much simpler passive marker concept is presented. Besides the biological signal caused by the object, the markers will perturb the primary magnetic field inducing their own signals. The markers' signals will be used for the detection of any unwanted object movements and the signal frames corrupted thereby. The corrupted signal frames will be then excluded from image reconstruction in order to prevent any movement artefacts from being imaged with the object. In order to assess the feasibility of the developed D&E technique, different experiments followed by image reconstruction and quantitative analysis were performed. Hereof, target movements were provoked during multifrequency, multiframe measurements in the β-dispersion frequency range on a saline phantom of physiological conductivity. The phantom was marked during measurement with either a small single-turn coil, an active marker, or a small soft-ferrite plate, a passive marker. After measurement, the erroneous phantom signals were corrected according to the suggested D&E strategy, and images of the phantom before and after correction were reconstructed. The corrected signals and images were then compared to the erroneous ones on the one hand, and to other true ones gained from reference measurements wherein no target movements were provoked on the other hand. The obtained qualitative and quantitative measurement and image reconstruction results showed that the erroneous phantom signals could be accurately corrected, and the movement artefacts could be totally eliminated, verifying the applicability of the novel D&E technique in measurement optimization in biomedical MITS and supporting the proposed aspects.

We present an extension of a Redfield approach for calculating spin-spin relaxation rates of zero-field nuclear quadrupole resonance (NQR) coherences, which was published in [Kruk et al., PCCP, 2018, 20, 23414-23426]. The oversimplification of the secular approximation made in the recent paper makes the calculation invalid for zero-field NQR and has led to partially large deviations between predicted and experimental data from 209Bi-containing molecular crystals. Furthermore, these deviations led to speculations about an additional dipole-dipole relaxation mechanism besides the main electric field gradient (EFG) fluctuations. Here, we demonstrate how a complete application of the Redfield relaxation expression eliminates the deviation from experimental data without the need for additional assumptions. In particular, we point out the important role of off-diagonal elements in the Redfield relaxation matrix within the 3/2-1/2 block appearing due to degenerate energy levels. The resulting coupling between single and double coherence spin density elements leads to a faster coherence decay than for all other transitions. The pseudo rotational model for EFG fluctuations, as proposed in the earlier publication and usually applied for isotropic liquids, is extended in a second analysis by introducing a vibrational mode to account for the case of crystalline solids.

1H spin–lattice relaxation studies of water solutions of Bismuth-ethylenediamine-tetraacetic acid (Bi- EDTA), Bismuth-ethylenediamine-tetrakis(methylenephosphonic) acid (Bi-EDTP), Bismuth-1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid (Bi-DOTA), Bismuth-1,4,7,10-tetraazacyclodo decane-1,4,7,10-tetrakis(methylenephosphonic acid) (Bi-DOTP) and Bismuth-1,4,7,10-tetraazacyclo dodecane-1,4,7-triacetic acid (Bi-DO3A) have been performed in order to compare Quadrupole Relaxation Enhancement (QRE) effects with Paramagnetic Relaxation Enhancement (PRE) from the perspective of exploiting the first one as a novel contrast mechanism for Magnetic Resonance Imag- ing (MRI). The selected compounds can be considered as 209Bi counterparts of Gd3+ complexes. The relaxation experiments havebeenperformed in a broad frequency range of5 kHz–30 MHz.Therelax- ation contribution associated with QRE has been extracted from the data and compared with PRE. Similarities and differences between the two effects have been discussed.

H-1 spin-lattice relaxation experiments have been performed for triphenylbismuth dissolved in fully deuterated glycerol and tetrahydrofuran. The experiments have been carried out in a broad frequency range, from 10kHz to 40MHz, versus temperature. The data have been analysed in terms of a relaxation model including two relaxation pathways: H-1-H-1 dipole-dipole interactions between intrinsic protons of triphenylbismuth molecule and H-1-H-2 dipole-dipole interactions between the solvent and solute molecules. As a result of the analysis, rotational correlation times of triphenylbismuth molecules in the solutions and relative translational diffusion coefficient between the solvent and solute molecules have been determined. Moreover, the role of the intramolecular H-1-H-1 relaxation contribution has been revealed, depending on the motional parameters, as a result of decomposing the overall relaxation dispersion profile into contributions associated with the H-1-H-1 and H-1-H-2 relaxation pathways. The possibility of accessing the contribution of the relaxation of the intrinsic protons is important from the perspective of exploiting Quadrupole Relaxation Enhancement effects as possible contrast mechanisms for Magnetic Resonance Imaging.

Contrast agents with a strong R-1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R-1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of +/- 100 mT around the nominal Bo field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R-1 dispersion imaging and demonstrate the capability of generating R-1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R-1 dispersion at a field strength of 3 T. (C) 2018 Elsevier Inc. All rights reserved.

Objective: Pharmacokinetic and pharmacodynamic studies of topically applied drugs are commonly performed by sampling of interstitial fluid with dermal open flow microperfusion and subsequent analysis of the samples. However, the reliability of results from the measured concentration-time profile of the penetrating drug suffers from highly variable skin permeability to topically applied drugs that is mainly caused by inter- and intra-subject variations of the stratum corneum. Thus, statistically significant results can only be achieved by performing high numbers of experiments. To reduce the expenditures needed for such high experiment numbers we aimed to assess the correlation between skin permeability and skin impedance/skin admittance. Approach: We performed an ex vivo drug penetration study with human skin, based on the hypothesis that inter-subject variations of the respective concentration-time profiles can be correlated with variations of the passive electrical properties of the skin. Therefore, skin impedance and skin admittance were related to the skin permeability to the model drug Clobetasol-17-proprionate. Main results: The measured low frequency skin impedance and the skin admittance correlated linearly with the drug concentration-time profiles from dermal sampling. Significance: Skin permeability can be assessed by measuring the passive electrical properties of the skin, which enables correction of skin permeability variations. This allows reduction of experiment numbers in future pharmacokinetic and pharmacodynamic studies with human skin ex vivo and in vivo and leads to diminished study costs.

Based on the previous identification of metastable polymorphs in crystalline triphenylbismuth by nuclear quadrupole resonance spectroscopy (NQRS), the potential formation of similar phases was studied in Tris(2-Methoxyphenyl)Bismuthine. To this end, commercial samples with known NQRS properties were molten and re-crystallized at different speeds (shock freezing in different coolants versus slow cooling inside of a heater). In all recrystallization products we have identified a new crystal phase which has not been observed after synthesis from a solution. The new crystallographic structure has been confirmed by X-ray diffraction (XRD). The newly isolated polymorph crystallizes in the monoclinic space group P2(1)/c with only one molecule in the asymmetric unit and consequently only one 5/2-7/2 transition is observed at 88.75 MHz at 310 K. In contrast, the two transitions at 89.38 and 89.29 MHz for the well-known trigonal polymorph originate from two crystallographically distinct molecules of Tris(2-methoxy-Phenyl)Bismuthine in the asymmetric unit. Additional relaxometric NQRS shows distinctly different T2 relaxation times for the new polymorph when compared to the original samples. Additional phase transitions could not be observed during temperature sweeps between 153 K and 323 K.

Magnetic Resonance Imaging (MRI) is one of the most powerful diagnostic tools providing maps of 1H relaxation times of human body. The method needs, however, a contrast mechanism to enlarge the difference in the relaxation times between healthy and pathological tissues. In this work we discuss the potential of a novel contrast mechanism for MRI, based on Quadrupole Relaxation Enhancement (QRE) and estimate the achievable value of QRE under the most favorable conditions. It has turned out that the theoreticaly possible enhancement factors are smaller than those of typical paramagnetic contrast agents but in turn the field-selectivity of QRE-based agents makes them extremely sensitive to subtle changes of the electric field gradient in the tissue. So far QRE has been observed for solids (in most cases for 14N) as a result of very slow dynamics and anisotropic spin interactions, believed to be necessary for QRE to appear. We show the first evidence that QRE can be achieved in solutions of compounds containing a high spin nucleus (209Bi) as the quadrupole element. The finding of QRE in liquid state is explained in terms of spin relaxation theory based on the stochastic Liouville equation. The results confirm the relaxation theory and motivate further exploration of the potential of QRE for MRI., The original publication can be found at: https://doi.org/10.1063/1.5082177

H-1 spin-lattice nuclear magnetic resonance relaxation experiments have been performed for triphenylbismuth dichloride (C18H15BiCl2) and phenylbismuth dichloride (C6H5BiCl2) in powder. The frequency range of 20-128 MHz has been covered. Due to H-1-Bi-209 dipole-dipole interactions, a rich set of pronounced Quadrupole Relaxation Enhancement (QRE) peaks (quadrupole peaks) has been observed. The QRE patterns for both compounds have been explained in terms of single- and double-quantum transitions of the participating nuclei. The analysis has revealed a complex, quantum-mechanical mechanism of the QRE effects. The mechanism goes far beyond the simple explanation of the existence of three quadrupole peaks for N-14 reported in literature. The analysis has been supported by nuclear quadrupole resonance results that independently provided the Bi-209 quadrupole parameters (amplitude of the quadrupole coupling constant and asymmetry parameter).

Many smart magnetic resonance imaging (MRI) probes provide response to a biomarker based on modulation of their rotational correlation time. The magnitude of such MRI signal changes is highly dependent on the magnetic field and the response decreases dramatically at high fields (>2 T). To overcome the loss of efficiency of responsive probes at high field, with fast‐field cycling magnetic resonance imaging (FFC‐MRI) we exploit field‐dependent information rather than the absolute difference in the relaxation rate measured in the absence and in the presence of the biomarker at a given imaging field. We report here the application of fast field‐cycling techniques combined with the use of a molecular probe for the detection of Zn2+ to achieve 166 % MRI signal enhancement at 3 T, whereas the same agent provides no detectable response using conventional MRI. This approach can be generalized to any biomarker provided the detection is based on variation of the rotational motion of the probe.

1H spin-lattice relaxation studies have been performed for pure [Bi(NO3)3(H2O)3]*18-crown-6 in powder and its solution in dimethyl sulfoxide (DMSO). The experiments have been carried out in the frequency range of 10 kHz–30MHz and the temperature range of 240–277 K; at 277 K the solution is already frozen. The 1Hrelaxation of pure [Bi(NO3)3(H2O)3]*18-crown-6 has been interpreted in terms of three dynamical processes. Quadrupole Relaxation Enhancement effects have been observed in the frozen DMSO solution of [Bi(NO3)3(H2O)3]*18-crown-6. The specific mechanisms of the 1H spin- lattice relaxation enhancement have been discussed distinguishing between effects caused by time independent (residual) and fluctuating 1H-209Bi dipole-dipole interactions.

We propose a simple method to calculate and predict quadrupole relaxation enhancement (QRE) features in the spin-lattice nuclear magnetic relaxation dispersion (R1-NMRD) profile of protons (1H) in solids. The only requirement is the knowledge of the nuclear quadrupole resonance (NQR) parameters of the quadrupole nuclei in a molecule. These NQR parameters – the quadrupole coupling constant Qcc and the asymmetry parameter η – can be determined by NQR spectroscopy or using quantum chemistry calculations. As there is an increasing interest in using molecules producing high field QRE features as, e.g. for contrast enhancing agents in magnetic resonance imaging, the experimental efforts of seeking for suitable compounds can be reduced by pre-selecting molecules via calculations. Also, the method can be used to extract NQR parameter, and thus structural information, from R1-NMRD profiles showing QRE features. In this article, we describe the calculation procedure and present examples of comparing the result to experimental R1-NMRD data of two different solid 209Bi-aryl compounds.

The interaction between water protons and suitable quadrupolar nuclei (QN) can lead to quadrupole relaxation enhancement (QRE) of proton spins, provided the resonance condition between both spin transitions is fulfilled. This effect could be utilized as a frequency selective mechanism in novel, responsive T1 shortening contrast agents (CAs) for magnetic resonance imaging (MRI). In particular, the proposed contrast mechanism depends on the applied external flux density—a property that can be exploited by special field-cycling MRI scanners. For the design of efficient CA molecules, exhibiting narrow and pronounced peaks in the proton T1 relaxation dispersion, the nuclear quadrupole resonance (NQR) properties, as well as the spin dynamics of the system QN−1H, have to be well understood and characterized for the compounds in question. In particular, the energy-level structure of the QN is a central determinant for the static flux densities at which the contrast enhancement appears. The energy levels depend both on the QN and the electronic environment, i.e., the chemical bonding structure in the CA molecule. In this work, the NQR properties of a family of promising organometallic compounds containing 209Bi as QN have been characterized. Important factors like temperature, chemical structure, and chemical environment have been considered by NQR spectroscopy and abinitio quantum chemistry calculations. The investigated Bi-aryl compounds turned out to fulfill several crucial requirements: NQR transition frequency range applicable to clinical 1.5- and 3T MRI systems, low temperature dependency, low toxicity, and tunability in frequency by chemical modification.

Contrast agents with a strong R

In the search for a novel MRI contrast agent which relies on T1 shortening due to quadrupolar interaction between Bi nuclei and protons, a fast scanning wideband system for zero-field nuclear quadrupole resonance (NQR) spectroscopy is required. Established NQR probeheads with motor-driven tune-match stages are usually bulky and slow, which can be prohibitive if it comes to Bi compounds with low SNR (excessive averaging) and long quadrupolar T1 times. Moreover many experiments yield better results at low temperatures such as 77K (liquid nitrogen, LN) thus requiring easy to use cryo-probeheads. In this paper we present electronically tuned wideband probeheads for bands in the frequency range 20 - 120 MHz which can be immersed in LN and which enable very fast explorative scans over the whole range. To this end we apply an interleaved subspectrum sampling strategy (ISS) which relies on the electronic tuning capability. The superiority of the new concept is demonstrated with an experimental scan of triphenylbismuth from 24-116 MHz both at room temperature and in LN. Especially for the first transition which exhibits extremely long T1 times (64ms) and low signal the new approach allows an acceleration factor by more than 100 when compared to classical methods., 22 pages, 7figures, 2 tables

Quadrupole relaxation enhancement (QRE) has been suggested as the key mechanism for a novel class of field-selective, potentially responsive magnetic resonance imaging contrast agents. In previous publications, QRE has been confirmed for solid compounds containing Bi-209 as the quadrupolar nucleus (QN). For QRE to be effective in aqueous dispersions, several conditions must be met, i.e. high transition probability of the QN at the H-1 Larmor frequency, water exchange with the bulk and comparatively slow motion of the Bi-carrying particles. In this paper, the potential influence of structural order within the compounds (crystallinity') on QRE was studied by nuclear quadrupole resonance (NQR) spectroscopy in one crystalline and two amorphous preparations of Triphenylbismuth (BiPh3). The amorphous preparations comprised (1) a shock-frozen melt and (2) a granulate of polystyrene which contained homogeneously distributed BiPh3 after common dissolution in THF and subsequent evaporation of the solvent. In contrast to the crystalline powder which exhibits strong, narrow NQR peaks the amorphous preparations did not reveal any NQR signals above the noise floor. From these findings, we conclude that the amorphous state leads to a significant spectral peak broadening and that for efficient QRE in potential contrast agents structures with a high degree of order (near crystalline) are required.

A cheap way to speed up image-reconstruction software is to use modern graphics hardware that can execute algorithms in a massively parallel manner. Here, the authors discuss Agile, an open source library designed for image reconstruction in biomedical sciences. Its modular, object-oriented, and templated design eases the integration of the library into user code.

Several noninvasive modalities including electrical impedance tomography (EIT), magnetic induction tomography (MIT), and induced-current EIT (ICEIT) have been developed for imaging the electrical conductivity distribution within a human body. Although these modalities differ in how the excitation and detection circuitry (electrodes or coils) are implemented, they share a number of common principles not only within the image reconstruction approaches but also with respect to the basic principle of generating a current density distribution inside a body and recording the resultant electric fields. In this paper, we are interested in comparing differences between these modalities and in theoretically understanding the compromises involved, despite the increased hardware cost and complexity that such a multimodal system brings along. To systematically assess the merits of combining data, we performed 3-D simulations for each modality and for the multimodal system by combining all available data. The normalized sensitivity matrices were computed for each modality based on the finite element method, and singular value decomposition was performed on the resultant matrices. We used both global and regional quality measures to evaluate and compare different modalities. This study has shown that the condition number of the sensitivity matrix obtained from the multimodal tomography with 16-electrode and 16-coil is much lower than the condition number produced in the conventional 16-channel EIT and MIT systems, and thus, produced promising results in terms of image stability. An improvement of about 20% in image resolution can be achieved considering feasible signal-to-noise ratio levels.

Magnetic induction tomography aims to reconstruct the electrical conductivity distribution of the human body using non-contact measurements. The potential of the method has been demonstrated by various simulation studies and a number of phantom experiments. These studies have all relied on models having isotropic distributions of conductivity, although the human body has a highly heterogeneous structure with partially anisotropic properties. Therefore, whether the conventional modeling approaches used so far are appropriate for clinical applications or not is still an open question. To investigate the problem, we performed a simulation study to investigate the feasibility of (1) imaging anisotropic perturbations within an isotropic medium and (2) imaging isotropic perturbations inside a partially anisotropic background. The first is the case for the imaging of anomalies that have anisotropic characteristics and the latter is the case e.g. in lung imaging where an anisotropic skeletal muscle tissue surrounds the lungs and the rib cage. An anisotropic solver based on the singular value decomposition was used to attain conductivity tensor images to be compared with the ones obtained from isotropic solvers. The results indicate the importance of anisotropic modeling in order to obtain satisfactory reconstructions, especially for the imaging of the anisotropic anomalies, and address the resolvability of the conductivity tensor components.

Studies examining the direct effects of stimuli needed to perform mental stress tasks such as instructor commands at regular intervals during the mental task are limited to date. Because of the comprehensive effects of different stimuli, we studied the effect of short instructor commands occurring at regular intervals on the behavior of the cardiovascular system during two different types of tasks. Continuous beat-to-beat heart rate and blood pressure, respiration, thoracic impedance, skin conductance, and peripheral temperature were measured in 20 healthy females during a cancellation test of attention (stimuli interval of 20 s) and during mental arithmetic tasks (stimuli interval of 120 s). The transient effects of the stimuli on measures in the time domain as well as the effects of stimulus intervals on measures in the frequency domain (using spectral analysis) were examined. Instructor commands caused increases in several cardiovascular variables and in skin conductance. SBP (systolic blood pressure) and DBP (diastolic blood pressure) showed a significant stimulus response only during the mental arithmetic tasks. An effect of instructor commands at regular intervals was seen in the spectral analysis at 0.05 Hz (cancellation test of attention) and 1/120 Hz (mental arithmetic), according to the stimulus intervals of 20 s and 120 s used in these tasks. The findings suggest that even simple instructor commands given during high mental task load had a strong impact and can considerably influence measures of cardiovascular reactivity. The effects of paced stimuli should be considered when interpreting cardiovascular responses to task conditions with constant stimulus intervals.

Continuous monitoring of lung function is of particular interest to the mechanically ventilated patients during critical care. Recent studies have shown that magnetic induction measurements with single coils provide signals which are correlated with the lung dynamics and this idea is extended here by using a 5 by 5 planar coil matrix for data acquisition in order to image the regional thoracic conductivity changes. The coil matrix can easily be mounted onto the patient bed, and thus, the problems faced in methods that use contacting sensors can readily be eliminated and the patient comfort can be improved. In the proposed technique, the data are acquired by successively exciting each coil in order to induce an eddy-current density within the dorsal tissues and measuring the corresponding response magnetic field strength by the remaining coils. The recorded set of data is then used to reconstruct the internal conductivity distribution by means of algorithms that minimize the residual norm between the estimated and measured data. To investigate the feasibility of the technique, the sensitivity maps and the point spread functions at different locations and depths were studied. To simulate a realistic scenario, a chest model was generated by segmenting the tissue boundaries from NMR images. The reconstructions of the ventilation distribution and the development of an edematous lung injury were presented. The imaging artifacts caused by either the incorrect positioning of the patient or the expansion of the chest wall due to breathing were illustrated by simulations.

Magnetic induction tomography (MIT) attempts to obtain the distribution of passive electrical properties inside the body. Eddy currents are induced in the body using an array of transmitter coils and the magnetic fields of these currents are measured by receiver coils. In clinical usage, the relative position of the coils to the body can change during data acquisition because of the expected/unexpected movements of the patient. Especially in respiration monitoring these movements will inevitably cause artefacts in the reconstructed images. In this paper, this effect was investigated for both state and frequency differential variants of MIT. It was found that a slight shift of the body in the transverse plane causes spurious perturbations on the surface. In reconstructions, this artefact on the surface propagates towards the centre in an oscillatory manner. It was observed that the movement can corrupt all the valuable information in state differential MIT, while frequency differential MIT seems more robust against movement effects. A filtering strategy is offered in order to decrease the movement artefacts in the images. To this end, monitoring of the patient's movement during data acquisition is required.

The current paper proposes a new indicator for well-balanced dehydration of patients undergoing a haemodialysis. It is based on an estimator for the extra-cellular volume and the ultrafiltration rate. The extra-cellular fluid was computed from continuous tetrapolar bio-impedance measurements taken on the lower leg in a frequency range of several kilohertz up to 500 kHz. Finite element simulations on different leg models with anisotropic conductivities calculated with Cole models were carried out in order to incorporate the significant anisotropy of human tissue into the estimation process. The indicator was tested on measurement data gathered from 25 persons during 150 haemodialysis sessions. Its performance was determined by computing ROC curves. Results of the data analysis are reported.

The regional lung ventilation depends on the amount and direction of applied gravitational force. This article presents a technique suitable for microgravity condition, providing online information about the local dynamic behavior of the lungs. Using state-differential images measured by electrical impedance tomography (EIT), for every region of interest (ROI) of the lungs a median signal was calculated. For the detection of regional differences in the lung ventilation, local impedance signals were compared with a reference signal, which was the median value over all pixels inside the lungs. We compared both the difference in magnitude and the phase shifts between the ROIs. The phase information was calculated using the Hilbert transform. The technique was tested on five spontaneously breathing subjects. The phase difference proved to be a very sensitive indicator for changes in the regional ventilation during postural changes and therefore changes of the direction of gravitational forces.

The basic purpose of electrical impedance tomography (EIT) is the reconstruction of conductivity distributions. While multifrequency measurements are of common use, the majority of reconstructed images are still conductivity distributions from one single frequency. More interesting than conductivities at each frequency are electrical tissue parameters, which describe the frequency-dependent conductivity changes of tissue. These parameters give information about physiological or electrical properties of tissues. By using this spectral information, a classification of different tissue types is possible. To get a distribution of tissue parameters, usually a posterior fitting of a tissue model to the conductivity spectra obtained with classical reconstruction algorithms at various frequencies is used. In this work, a single-step reconstruction algorithm for differential imaging was developed for the direct estimation of Cole parameters. This method is termed differential parametric reconstruction. The Cole model was used as the underlying tissue model, where only the relative changes of the two conductivity parameters sigma(0) and sigma(infinity) were reconstructed and the other two parameters of the model which are less identifiable were set to constant values. The reconstruction algorithm was tested with simulated noisy datasets and real measurement data from EIT measurements on the human thorax. These measurements were taken from healthy subjects and from patients with a serious lung injury. The new method yields a good image quality and higher robustness against noise compared to conventional reconstruction methods.

In a previous publication, it was demonstrated that the abdominal subcutaneous fat layer thickness (SFL) is strongly correlated with the abdominal electrical impedance when measured with a transversal tetrapolar electrode arrangement. This article addresses the following questions: 1) To which extent do different abdominal compartments contribute to the impedance? 2) How does the hydration state of tissues affect the data? 3) Can hydration and fat content be assessed independently? For simulating the measured data a hierarchical electrical model was built. The abdomen was subdivided into three compartments (subcutaneous fat, muscle, mesentery). The true anatomical structure of the compartment boundaries was modeled using finite-element modeling (FEM). Each compartment is described by an electrical tissue model parameterized in physiological terms. Assuming the same percent change of the fat fraction in the mesentery and the SFL the model predicts a change of 1,24 /spl Omega//mm change of the SFL compared to 1,1 /spl Omega//mm measured. 42% of the change stem from the SFL, 56% from the mesentery and 2% from changes of fat within the muscle compartment. A 1% increase of the extracellular water in the muscle is not discernible from a 1% decrease of the SFL. The measured data reflect not only the SFL but also the visceral fat. The tetrapolar electrode arrangement allows the measurement of the abdominal fat content only if the hydration remains constant.

Magnetic induction tomography (MIT) of biological tissue is used to reconstruct the changes in the complex conductivity distribution inside an object under investigation. The measurement principle is based on determining the perturbation DeltaB of a primary alternating magnetic field B0, which is coupled from an array of excitation coils to the object under investigation. The corresponding voltages DeltaV and V0 induced in a receiver coil carry the information about the passive electrical properties (i.e. conductivity, permittivity and permeability). The reconstruction of the conductivity distribution requires the solution of a 3D inverse eddy current problem. As in EIT the inverse problem is ill-posed and on this account some regularization scheme has to be applied. We developed an inverse solver based on the Gauss-Newton-one-step method for differential imaging, and we implemented and tested four different regularization schemes: the first and second approaches employ a classical smoothness criterion using the unit matrix and a differential matrix of first order as the regularization matrix. The third method is based on variance uniformization, and the fourth method is based on the truncated singular value decomposition. Reconstructions were carried out with synthetic measurement data generated with a spherical perturbation at different locations within a conducting cylinder. Data were generated on a different mesh and 1% random noise was added. The model contained 16 excitation coils and 32 receiver coils which could be combined pairwise to give 16 planar gradiometers. With 32 receiver coils all regularization methods yield fairly good 3D-images of the modelled changes of the conductivity distribution, and prove the feasibility of difference imaging with MIT. The reconstructed perturbations appear at the right location, and their size is in the expected range. With 16 planar gradiometers an additional spurious feature appears mirrored with respect to the median plane with negative sign. This demonstrates that a symmetrical arrangement with one ring of planar gradiometers cannot distinguish between a positive conductivity change at the true location and a negative conductivity change at the mirrored location.

Magnetic induction tomography (MIT) is a low-resolution imaging modality which aims at the three-dimensional (3D) reconstruction of the electrical conductivity in objects from alternating magnetic fields. In MIT systems the magnetic field perturbations to be detected are very small when compared to the excitation field (ppm range). The voltage which is induced by the excitation field in the receiver coils must be suppressed for providing sufficient dynamic range. In the past, two very efficient strategies were proposed: adjusted planar gradiometers (PGRAD) and the orientation of a receiver coil with respect to the excitation coil such that the net magnetic flow is zero (zero flow coil, ZFC). In contrast to the PGRAD no voltage is induced in the ZFC by the main field. This is advantageous because two comparatively high voltages in the two gradiometer coils can never be subtracted perfectly, thus leaving a residual voltage which is prone to drift. However, a disadvantage of the ZFC is the higher susceptibility to interferences from far RF sources. In contrast, in the gradiometer such interferences are cancelled to a high degree. We developed a new type of gradiometer (zero flow gradiometer, ZFGRAD) which combines the advantages of ZFC and PGRAD. All three systems were compared with respect to sensitivity and perturbation to signal ratio (PSR) defined as the ratio of the signal change due to a magnetic perturbation field at the carrier frequency and the signal change due to shifting a metallic sphere between two test points. The spatial sensitivity of the three systems was found to be very similar. The PSR of the ZFGRAD was more than 12 times lower than that of the ZFC. Finally, the feasibility of image reconstruction with two arrays of eight excitation coils and eight ZFGRAD, respectively, was shown with a single-step Gauss-Newton reconstructor and simulated measurement data generated for a cylindrical tank with a spherical perturbation. The resulting images show a clear, bright feature at the correct position of the sphere and are comparable to those with PGRAD arrays.

Currently only ionizing or invasive methods are used in clinical applications for the monitoring of extracellular lung water. Alternatively a method called focused conductivity spectroscopy (FCS) is suggested, which aims at reconstructing a pulmonary edema index (PEIX) by measuring the electrical conductivity of the region of interest (ROI) at several frequencies. In contrast to electrical impedance tomography (EIT) a minimum number of strategically placed electrodes is used. The goals of this study were the analysis of the sensitivity for the PEIX, an estimate of the optimal electrode configuration and the determination of the required frequencies. In order to calculate the solution of the FCS forward problem a realistic 3D model of a human torso was developed containing both lungs, the heart, the liver and the thorax musculature. The bioelectrical properties for each compartment were described with appropriate tissue models which relate the conductivity spectra to physiological parameters. The PEIX was defined as the interstitial volume fraction of the alveolar septa. Furthermore the model includes 48 electrodes subdivided into three layers. The optimal electrode configuration was selected by minimizing the number of electrodes, among certain subsets of these electrodes. The analysis shows that eight to ten electrodes and six frequencies are theoretically sufficient to obtain a coefficient of variation.

BIA is easy, non-invasive, relatively inexpensive and can be performed in almost any subject because it is portable. Part II of these ESPEN guidelines reports results for fat-free mass (FFM), body fat (BF), body cell mass (BCM), total body water (TBW), extracellular water (ECW) and intracellular water (ICW) from various studies in healthy and ill subjects. The data suggests that BIA works well in healthy subjects and in patients with stable water and electrolytes balance with a validated BIA equation that is appropriate with regard to age, sex and race. Clinical use of BIA in subjects at extremes of BMI ranges or with abnormal hydration cannot be recommended for routine assessment of patients until further validation has proven for BIA algorithm to be accurate in such conditions. Multi-frequency- and segmental-BIA may have advantages over single-frequency BIA in these conditions, but further validation is necessary. Longitudinal follow-up of body composition by BIA is possible in subjects with BMI 16-34 kg/m(2) without abnormal hydration, but must be interpreted with caution. Further validation of BIA is necessary to understand the mechanisms for the changes observed in acute illness, altered fat/lean mass ratios, extreme heights and body shape abnormalities.

The use of bioelectrical impedance analysis (BIA) is widespread both in healthy subjects and patients, but suffers from a lack of standardized method and quality control procedures. BIA allows the determination of the fat-free mass (FFM) and total body water (TBW) in subjects without significant fluid and electrolyte abnormalities, when using appropriate population, age or pathology-specific BIA equations and established procedures. Published BIA equations validated against a reference method in a sufficiently large number of subjects are presented and ranked according to the standard error of the estimate. The determination of changes in body cell mass (BCM), extra cellular (ECW) and intra cellular water (ICW) requires further research using a valid model that guarantees that ECW changes do not corrupt the ICW. The use of segmental-BIA, multifrequency BIA, or bioelectrical spectroscopy in altered hydration states also requires further research. ESPEN guidelines for the clinical use of BIA measurements are described in a paper to appear soon in Clinical Nutrition.

Magnetic induction tomography of biological tissue is used for reconstructing the conductivity distribution /spl kappa/=/spl sigma/+j/spl omega//spl epsiv/ or changes /spl Delta//spl kappa/ in a human body by measuring the perturbation /spl Delta/B of an alternating magnetic field B/sub 0/. The aim is to simulate the eddy current problem in magnetic induction tomography for biomedical applications by symmetric tetrahedral edge finite elements of second order. The method is validated by measurement data from a representative experiment, and numerical results of an edema in a human head are presented.

The detection and continuous monitoring of brain oedema is of particular interest in clinical applications because existing methods (invasive measurement of the intracranial pressure) may cause considerable distress for the patients. A new non-invasive method for continuous monitoring of an oedema promises the use of multi-frequency magnetic induction tomography (MIT). MIT is an imaging method for reconstructing the changes of the conductivity deltakappa in a target object. The sensitivity of a single MIT-channel to a spherical oedematous region was analysed with a realistic model of the human brain. The model considers the cerebrospinal fluid around the brain, the grey matter, the white matter, the ventricle system and an oedema (spherical perturbation). Sensitivity maps were generated for different sizes and positions of the oedema when using a coaxial coil system. The maps show minimum sensitivity along the coil axis, and increasing values when moving the perturbation towards the brain surface. Parallel to the coil axis, however, the sensitivity does not vary significantly. When assuming a standard deviation of 10(-7) for the relative voltage change due to the system's noise, a centrally placed oedema with a conductivity contrast of 2 with respect to the background and a radius of 20 mm can be detected at 100 kHz. At higher frequencies the sensitivity increases considerably, thus suggesting the capability of multi-frequency MIT to detect cerebral oedema.

Magnetic induction tomography of biological tissue is used to reconstruct the changes in the complex conductivity distribution by measuring the perturbation of an alternating primary magnetic field. To facilitate the sensitivity analysis and the solution of the inverse problem a fast calculation of the sensitivity matrix, i.e. the Jacobian matrix, which maps the changes of the conductivity distribution onto the changes of the voltage induced in a receiver coil, is needed. The use of finite differences to determine the entries of the sensitivity matrix does not represent a feasible solution because of the high computational costs of the basic eddy current problem. Therefore, the reciprocity theorem was exploited. The basic eddy current problem was simulated by the finite element method using symmetric tetrahedral edge elements of second order. To test the method various simulations were carried out and discussed.

The measurement of hepatic iron overload is of particular interest in cases of hereditary hemochromatosis or in patients subject to periodic blood transfusion. The measurement of plasma ferritin provides an indirect estimate but the usefulness of this method is limited by many common clinical conditions (inflammation, infection, etc). Liver biopsy provides the most quantitative direct measurement of iron content in the liver but the risk of the procedure limits its acceptability. This work studies the feasibility of a magnetic induction (MI) low-cost system to measure liver iron overload. The excitation magnetic field (B0, frequency: 28 kHz) was produced by a coil, the perturbation produced by the object (deltaB) was detected using a planar gradiometer. We measured ten patients and seven volunteers in supine and prone positions. Each subject was moved in a plane parallel to the gradiometer several times to estimate measurement repeatability. The real and imaginary parts of deltaB/B0 were measured. Plastic tanks filled with water, saline and ferric solutions were measured for calibration purposes. We used a finite element model to evaluate the experimental results. To estimate the iron content we used the ratio between the maximum values for real and imaginary parts of deltaB/B0 and the area formed by the Nyquist plot divided by the maximum imaginary part. Measurements in humans showed that the contribution of the permittivity is stronger than the contribution of the permeability produced by iron stores in the liver. Defined iron estimators show a limited correlation with expected iron content in patients (R < or = 0.56). A more precise control of geometry and position of the subjects and measurements at multiple frequencies would improve the method.

A major drawback of electrical impedance tomography is the poor quality of the conductivity images, i.e., the low spatial resolution as well as large errors in the reconstructed conductivity values. The main reason is the necessity for regularization of the ill-conditioned inverse problem which results in excessive spatial low-pass filtering. A novel regularization method (SMORR (spectral modelling regularized reconstructor)) is proposed, which is based on the inclusion of spectral a priori information in the form of appropriate tissue models (e.g. Cole models). This approach reduces the ill-posedness of the inverse problem, when multifrequency data are available. An additional advantage is the direct reconstruction of the (physiological) tissue parameters of interest instead of the conductivities. SMORR was compared with posterior fitting of a Cole model to the conductivity spectra obtained with a classical iterative reconstruction scheme at various frequencies. SMORR performed significantly better than the reference method concerning robustness against noise in the data.

Magnetic induction tomography (MIT) is a contactless method for mapping the electrical conductivity of tissue by measuring the perturbation of an alternating magnetic field with appropriate receiver coils. Reconstruction algorithms so far suggested for biomedical applications are based on weighted backprojection, hence requiring tube-shaped zones of sensitivity between excitation coils and receiving coils, the sensitivity being essentially zero outside this 'projection beam'. This condition is met for conducting perturbations in empty space and for some special configurations of insulators in saline. In biological structures, however, perturbations with low conductivity contrast are embedded into a bulk conductor. The respective sensitivity distribution was investigated and quantified theoretically and experimentally by displacing a conducting (agar, 8 S m(-1)) and an insulating sphere within a saline tank (4 S m(-1)). In contrast to the case in the empty space the sensitivity is not confined to a tube but even increases outside the 'projection beam'. The difference can be explained by the interaction of bulk currents with the perturbing object. This effect invalidates backprojection and hence the solution of the complete inverse eddy-current problem is suggested.

Electrical impedance tomography (EIT) is a non‐invasive method to monitor conductivity changes in regions of the human body. Its robust, miniaturizable instrumentation makes EIT particularly suitable for online‐monitoring without too much inconvenience for the patient. A major methodological problem is the poor quality of the conductivity images, which is due to the low spatial resolution and low sensitivity for structures far away from the object’s surface as well as large qualitative errors in the reconstructed conductivity values. This paper outlines the advantages of multi‐frequency EIT for a simple two‐dimensional model. In the first part of the paper we assume that some a priori information from MR images is at hand, providing good starting values for the reconstruction process, while in the second part it is assumed that no a priori information about regions of different material values is available.