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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.

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.

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.

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.

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.

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.

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.

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.

Magnetic induction tomography (MIT) is a contactless method for mapping the electrical conductivity of tissue. MIT is based on the perturbation of an alternating magnetic field by a conducting object. The perturbation is detected by a voltage change in a receivercoil. At physiologically interesting frequencies (10 kHz-10 MHz) and conductivities (2 S m(-1)) the lower limit for the relative voltage change (signal/carrier ratio = SCR) to be resolved is 10(-7)-10(-10). A new MIT hardware has been developed consisting of a coil system with planar gradiometers and a high-resolution phase detector (PD). The gradiometer together with the PD resolves an SCR of 2.5 x 10(-5) (SNR = 20 dB at 150 kHz, acquisition speed: 100 ms). The system operates between 20 and 370 kHz with the possibility of extending the range up to 1 MHz. The feasibility of measuring conductivity spectra in the beta-dispersion range of biological tissues is experimentally demonstrated. An improvement of the resolution towards SCR = 10(-7) with an SNR ofor = 20 dB at frequencies100 kHz is possible. On-line spectroscopy of tissue conductivity with low spatial resolution appears feasible, thus enabling applications such as non-invasive monitoring of brain oedema.

Most measurement devices for bioimpedance spectroscopy are coupled to the measured object (tissue) via electrodes. At frequencies > 500 kHz, they suffer from artifacts due to stray capacitances between electrode leads as well as between the ground and object. The noninvasive measurement of the brain conductivity is hardly possible with surface electrodes. These disadvantages can be obviated by inductive coupling. The aim of this work was the development of a wideband transceiver for inductive impedance spectroscopy. In order to define its specifications, a feasibility study has been carried out with a simulation model for three different coil systems above a homogeneous conducting plate. According to simulation results, all systems render it possible to resolve conductivity changes down to 10(-3) (omega m)-1 at frequencies > 50 kHz. The transceiver electronics must then provide a resolution of > or = 1 microV and an excitation current of up to 1 A. The realized receiver matches these specifications with an S/N ratio of 22 dB at 1 microV in the frequency range of 50 kHz to 5 MHz.

We have developed a novel model for the simulation of artefacts which are produced by stray capacitance during bioimpedance spectroscopy. We focused on whole body and segmental measurements in the frequency range 5-1000 kHz. The current source was assumed to by asymmetric with respect to ground as is the case for many commercial devices. We considered the following stray pathways: 1, cable capacitance; 2, capacitance between neighbouring electrode leads; 3. capacitance between different body segments and earth; 4, capacitance between signal ground of the device and earth. According to our results the pathways 3 and 4 cause a significant spurious dispersion in the measured impedance spectra at frequencies > 500 kHz. During segmental measurements the spectra have been found to be sensitive to an interchange of the electrode cable pairs. The sensitivity was also observed in vivo and is due to asymmetry of the potential distribution along the segment with respect to earth. In contrast to previously published approaches, our model renders possible the simulation of this effect. However, it is unable to fully explain the deviations of in vivo measured impedance spectra from a single Cole circle. We postulate that the remaining deviations are due to a physiologically caused superposition of two dispersions from two different tissues.

Fluorescence diffuse optical tomography (fDOT) is an imaging modality which goes beyond well-established techniques such as 2D fluorescence imaging and fluorescence microscopy. Being a 3D tomographic modality, it seeks to overcome limitations of 2D systems as are: (i) the determination of the depth of fluorescent objects and (ii) a correction of the broadening of the fluorescence signal due to the massive scattering of photons.

Magnetic induction tomography (MIT) is a low resolution imaging modality which attempts to reconstruct the electrical conductivity distribution in the body. In MIT, eddy currents are induced within the body via transMITter coils and the magnetic field of these currents are measured by an array of receiver coils encircling the body. The multi-frequency excitation perMITs imaging of motionless organs like the brain, since the frequency dependence of the biological tissue conductivities. In this work, the feasibility of the head imaging using multi-frequency MIT was investigated using a multi-shell spherical head model. The excitaion frequency was chosen from 10 kHz to 10 MHz which covers the β-dispersion region of the biological tissues of interest and the conductivities for the head tissues were assigned based on a Cole model. Moreover, the bleeding in head was modeled and the recostructed head images were presented.

With the increasing importance of molecular imaging fluorescence based methods are continuously gaining impact. In fluorescence optical tomography excitation light is injected into the tissue where the fluorophore converts it to radiation of another wavelength. From the emitted light reaching the boundary the 3-D distribution of the fluorophore is reconstructed. This paper aims at finding the optimal spatial distribution of optodes in order to keep their number (hardware costs) low while gaining maximum information from the target object. The implemented algorithm starts with an arbitrary pool of feasible optodes. The optimal subset is searched by minimizing the mutual information between the different measurements. This goal is reached by subsequently removing those sources and detectors which add the least independent information until a stopping criterion is reached. Mutual information is estimated by calculating the inner products between the rows of the sensitivity matrix i.e. the first derivative of the forward mapping with respect to the optical parameters to be reconstructed. We assembled this matrix with a finite element implementation of the diffusion approximation of light propagation in scattering tissues. When starting with an initial pool of 96 optodes regularly spaced on a cylindrical surface and focusing on different target regions within the cylinder, the algorithm always converged towards physically reasonable optimal sets. Optimal source/detector patterns are be presented graphically and numerically.

Magnetic induction tomography (MIT) is a low resolution imaging modality and attempts to reconstruct the interior conductivity distribution of the body. In MIT, the transmitter coils induce eddy currents in the body and the response field caused by the conductivity perturbations is sensed by an array of receiver coils. All the applications that were offered for electrical impedance tomography (EIT) are also a potential application for MIT. However, unlike EIT, MIT can look better through insulating tissues, e.g. ribcage which is made of bone tissue, and since the method is contactless, it does not suffer from the poor electrode contact. In this paper, the feasibility of lung imaging was investigated using a realistic thorax model of which the tissue boundaries were segmented from MRI images. The images were reconstructed from different simulated datasets, i.e. static, temporal and spectral datasets, to cover all the potential imaging approaches that MIT can offer. It was shown that the lung imaging is a feasible application for MIT, however, still some software and hard-ware improvements are essential before a clinical usage.

Magnetic induction tomography (MIT) aims at the contact-less imaging of the electrical conductivity and related pathophysiological processes. Systems operating at frequencies below 1 MHz are desirable but suffer from poor SNR which can be dramatically impaired by mechanical vibrations. We present an algorithm which suppresses vibration noise in the imaginary part of the data and improves the SNR up to 35 dB.

Nuclear quadrupole resonance (NQR) spectroscopy is a method for the characterization of chemical compounds containing so-called quadrupolar nuclei. Similar to nuclear magnetic resonance (NMR), the sample under investigation is irradiated with strong radiofrequency (RF) pulses, which stimulate the emission of weak RF signals from the quadrupolar nuclei. The signals are then amplified and Fourier transformed so as to obtain a spectrum. In principle, narrowband NQR spectra can be measured with NMR spectrometers. However, pure NQR signals require the absence of a static magnetic field and several special applications require the characterization of a substance over a large bandwidth, e.g. 50–100% of the central frequency, which is hardly possible with standard NMR equipment. Dedicated zero-field NQR equipment is not widespread and current concepts employ resonating probes which are tuned and matched over a wide range by using mechanical capacitors driven by stepper motors. While providing the highest signal to noise ratio (SNR) such probes are slow in operation and can only be operated from dedicated NMR consoles. We developed a low-cost NQR wideband probe without tuning and matching for applications in the very high frequency (VHF) range below 300 MHz. The probe coil was realized as part of a reactive network which approximates an exponential transmission line. The input reflection coefficient of the two developed prototype probe coils is ≤ 20 dB between 90–145 MHz and 74.5–99.5 MHz, respectively. Two wideband NQR spectra of published test substances were acquired with an SNR of better than 20 dB after sufficient averaging. The measured signals and the SNR correspond very well to the theoretically expected values and demonstrate the feasibility of the method. Because there is no need for tuning and matching, our probes can be operated easily from any available NMR console.

During dialysis the ion concentrations in many body fluids change significantly. The influence of these changes on the accuracy of volume measurements with bioimpedance spectroscopy is investigated by the following procedure: Plasma ion concentrations and impedance spectra (5–500 kHz) are measured during six standard haemodialyses. Intracellular ion concentrations are estimated using a multi-compartment model. Intra-(ICV) and extracellular (ECV) volumes are calculated using a fluid distribution model (FDM) based on Hanai's mixture theory. The input variables of the FDM are intra-and extracellular resistance data that have been fitted from impedance spectra with a Cole-Cole model. Resistivity changes (RCs) due to concentration changes of Na+, K+ Cl−, HCO3 − and unspecified intracellular ions are estimated. The FDM is corrected for the Rcs. Corrected ICVs and ECVs are calculated and compared with uncorrected values. The range of relative RCs between the start and end of the dialyses is −3.2% to 1.4% in the ECV and −3.7% to 1.7% in the ICV. From the RCs, volume estimation errors of −1.0% to 1.9% (ECV) and −1.2% to 2.1% (ICV) relative to the initial values have been calculated. At the end of dialysis, the percentage of the error with respect to the volume change is 20% for the ICV. Consequently, a correction of the FDM for RCs is necessary to obtain more reliable ICV data.

Neurological aggraviations of patients with craniocerebralinjury can trace back in most cases to a swelling of the brain.The survey of these patients is carried out with intracranial pressure sensors in combination with different imaging techniques. This method causes a big distress for the patients, thus new non-invasive methods are required. One promising possibility is magnetic induction tomography, a nonivasive and contactless imaging method for reconstructing the electrcal tissue properties in the region of interest. This technique is attractive for the detection of brain oedema, because the magnetic field penetrates easily through the skull and due to the increased fluid accumulation an oedema represents a more or less localized perturbation of the conductivity within a normal brain. We carried out a feasibility study with a 3D arrangement, which comprises a human brain model, an array of 16 excitation coils and 32 receiving coils. The human brain model consists of a about 35000 tetrhedral finite elements and considers the cerebrospinal fluid around the brain, the grey matter, the white matter and a spherical oedema. The inverse problem is solved by means of a single step algorithm withfour regularization methods and the results show the possibility of the detection of pathological hydration changes with good localization.

We study the feasibility of a new noninvasive method to measure hepatic iron overload using a magnetic induction (Ml) based system. Experimental data (in vitro and in-vivo) were acquired with a custom measurement system using an excitation coil and a planar gradiometer as receiver. We estimate the response of the system using analytical expressions for the in-vitro study and the finite element method (FEM) for the in-vivo study. Seventeen in-vitro liver samples have been measured. Measurements were compared with a biochemical iron estimation procedure. A significant agreement is observed (R=0.94, P

The aim was to develop a fluid estimator for haemodialysis with the potential to indicate hypotensive disorders so that counter measures can be taken in time. The bioimpedance was measured longitufinally on the lower leg with a four-electrode arrangement at six frequencies ranging from 10 kHz to 500kHz. The estimator proposed considers the anisotropy of music tissue and is based on a cylindrical model with homogeneously distributed extra- and intra-celluar compartments. The dependence of the cell constants on the circumference was determined with anisotropic FE models in which the conductivities were simulated with Cole-Cole models. Data was gathered from 25 persons during 108 haemodialysis sessions. It was fitted to a Cole-Cole model with parameters Z 0 and Z ∞ , the lumped tissue impedance at low and high frequencies. From these parameters the extra-celluar volume fraction was estimated with the help of the cell constants from the FE simulations. Results of the data analysis and a proposal for a new predictor for a circulatory are presented.