Joint multi-field T1 quantification for fast field-cycling MRI.

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.

Estimation of the magnitude of quadrupole relaxation enhancement in the context of magnetic resonance imaging contrast.

Magnetic Resonance Imaging (MRI) is one of the most powerful diagnostic tools providing maps of 1H relaxation times of human bodies. 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 theoretically 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 a 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.

High-Field Detection of Biomarkers with Fast Field-Cycling MRI: The Example of Zinc Sensing.

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.

Model - free approach to quadrupole spin relaxation in solid 209Bi-aryl compounds.

Nuclear Quadrupole Resonance (NQR) experiments were performed for deuterated and non-deuterated triphenylbismuth (BiPh3) to inquire into 209Bi relaxation mechanisms. The studies are motivated by the idea of exploiting Quadrupole Relaxation Enhancement (QRE) as a novel contrast mechanism for Magnetic Resonance Imaging. From this perspective relaxation features of nuclei possessing quadrupole moment (quadrupole nuclei) are of primary importance for the contrast effect. Spin-spin relaxation rates associated with the NQR lines were described in terms of the Redfield relaxation theory assuming that the relaxation is caused by fluctuations of the electric field gradient tensor at the position of the quadrupole nucleus that are described by an exponential correlation function. The description referred to as a model-free approach is an analogy of the description used for paramagnetic contrast agents. It was demonstrated that for the deuterated compound this approach captures the essential features of 209Bi relaxation, but it should not be applied for non-deuterated compounds as dipolar interactions between neighbouring protons and the quadrupole nucleus considerably contribute to the relaxation of the last one. Thus, the relaxation scenario for species containing quadrupole nuclei is fundamentally different than for paramagnetic contrast agents and this fact has to be taken into account when predicting contrast effects based on QRE.

R1 dispersion contrast at high field with fast field-cycling MRI.

Contrast agents with a strong R1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R1 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 B0 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 R1 dispersion imaging and demonstrate the capability of generating R1 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 R1 dispersion at a field strength of 3 T.

A cryostatic, fast scanning, wideband NQR spectrometer for the VHF range.

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 77 K (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 to 116 MHz, both at room temperature and in LN. Especially for the first transition which exhibits extremely long T1 times (64 ms) the and low signal the new approach allows an acceleration factor by more than 100 when compared to classical methods.

Assessment of skin permeability to topically applied drugs by skin impedance and admittance.

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.

An electronically tuned wideband probehead for NQR spectroscopy in the VHF range.

Nuclear quadrupole resonance spectroscopy is an analytical method which allows to characterize materials which contain quadrupolar nuclei, i.e. nuclei with spin ⩾1. The measurement technology is similar to that of NMR except that no static magnetic field is necessary. In contrast to NMR, however, it is frequently necessary to scan spectra with a very large bandwidth with a span of several tens of % of the central frequency so as to localize unknown peaks. Standard NMR probeheads which are typically constructed as resonators must be tuned and matched to comparatively narrow bands and must thus be re-tuned and re-matched very frequently when scanning over a whole NQR spectrum. At low frequencies up to few MHz dedicated circuits without the need for tuning and matching have been developed, but many quadrupole nuclei have transitions in the VHF range between several tens of MHz up to several hundreds of MHz. Currently available commercial NQR probeheads employ stepper motors for setting mechanically tuneable capacitors in standard NMR resonators. These yield high quality factors (Q) and thus high SNR but are relatively large and clumsy and do not allow for fast frequency sweeps. This article presents a new concept for a NQR probehead which combines a previously published no-tune no-match wideband concept for the transmit (TX) pulse with an electronically tuneable receive (RX) part employing varactor diodes. The prototype coil provides a TX frequency range of 57MHz with a center frequency of 97.5MHz with a return loss of ⩽-15dB. During RX the resonator is tuned and matched automatically to the right frequency via control voltages which are read out from a previously generated lookup table, thus providing high SNR. The control voltages which bias the varactors settle very fast and allow for hopping to the next frequency point in the spectrum within less than 100µs. Experiments with a test sample of ZnBr2 proved the feasibility of the method.

A deterministic approach to the adapted optode placement for illumination of highly scattering tissue.

A novel approach is presented for computing optode placements that are adapted to specific geometries and tissue characteristics, e.g., in optical tomography and photodynamic cancer therapy. The method is based on optimal control techniques together with a sparsity-promoting penalty that favors pointwise solutions, yielding both locations and magnitudes of light sources. In contrast to current discrete approaches, the need for specifying an initial set of candidate configurations as well as the exponential increase in complexity with the number of optodes are avoided. This is demonstrated with computational examples from photodynamic therapy.

High-performance image reconstruction in fluorescence tomography on desktop computers and graphics hardware.

Image reconstruction in fluorescence optical tomography is a three-dimensional nonlinear ill-posed problem governed by a system of partial differential equations. In this paper we demonstrate that a combination of state of the art numerical algorithms and a careful hardware optimized implementation allows to solve this large-scale inverse problem in a few seconds on standard desktop PCs with modern graphics hardware. In particular, we present methods to solve not only the forward but also the non-linear inverse problem by massively parallel programming on graphics processors. A comparison of optimized CPU and GPU implementations shows that the reconstruction can be accelerated by factors of about 15 through the use of the graphics hardware without compromising the accuracy in the reconstructed images.

Enhancing impedance imaging through multimodal tomography.

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.

Phase synchronization of hemodynamic variables and respiration during mental challenge.

We studied the synchronization of heart rate, blood pressure and respiration in the sympathetic and parasympathetic branches of the autonomic nervous system during a cancellation test of attention and during mental arithmetic tasks. The synchronization was quantified by the index γ, which has been adopted from the analysis of weakly coupled chaotic oscillators. We analyzed in twenty healthy women the continuous signals partitioned in low (LF, 0.04-0.15 Hz) and high (HF, 0.15-0.40 Hz) frequencies to investigate whether or not respiration is a main determinant of cardiovascular synchronization. We used surrogate data analysis to distinguish between causal relationships from those that occur by chance. The LF-components of R-R interval and blood pressure showed no synchronization with respiration, whereas synchronization between blood pressure and R-R interval exceeded that occurring by chance (p < .001). Although heart rate, blood pressure and respiratory frequency increased from rest to mental challenge, no effect of mental challenge on the synchronization of the LF-components was seen. The HF-components showed significant synchronization for all variables (p < .001). During mental challenge, synchronization between respiration and R-R interval, respiration and systolic blood pressure (SBP), as well as R-R interval and SBP decreased (p < .01), whereas under resting conditions, respiration was one of the dominant mechanisms determining heart rate variability and systolic blood pressure fluctuations. We conclude that the observed decrease of synchronization during mental challenge is not only driven by the increase in respiratory frequency but that 'top down' intervention by the control system at higher levels may play an additional role.

Total variation regularization for nonlinear fluorescence tomography with an augmented Lagrangian splitting approach.

Fluorescence tomography is an imaging modality that seeks to reconstruct the distribution of fluorescent dyes inside a highly scattering sample from light measurements on the boundary. Using common inversion methods with L(2) penalties typically leads to smooth reconstructions, which degrades the obtainable resolution. The use of total variation (TV) regularization for the inverse model is investigated. To solve the inverse problem efficiently, an augmented Lagrange method is utilized that allows separating the Gauss-Newton minimization from the TV minimization. Results on noisy simulation data provide evidence that the reconstructed inclusions are much better localized and that their half-width measure decreases by at least 25% compared to ordinary L(2) reconstructions.

Nonlinear inversion schemes for fluorescence optical tomography.

Fluorescence optical tomography is a non-invasive imaging modality that employs the absorption and re-emission of light by fluorescent dyes. The aim is to reconstruct the fluorophore distribution in a body from measurements of light intensities at the boundary. Due to the diffusive nature of light propagation in tissue, fluorescence tomography is a nonlinear and severely ill-posed problem, and some sort of regularization is required for a stable solution. In this paper we investigate reconstruction methods based on Tikhonov regularization with nonlinear penalty terms, namely total-variation regularization and a levelset-type method using a nonlinear parameterization of the unknown function. Moreover, we use the full threedimensional nonlinear forward model, which arises from the governing system of partial differential equations. We discuss the numerical realization of the regularization schemes by Newtontype iterations, present some details of the discretization by finite element methods, and outline the efficient implementation of sensitivity systems via adjoint methods. As we will demonstrate in numerical tests, the proposed nonlinear methods provide better reconstructions than standard methods based on linearized forward models and linear penalty terms. We will additionally illustrate, that the careful discretization of the methods derived on the continuous level allows to obtain reliable, mesh independent reconstruction algorithms.

Adaptation and focusing of optode configurations for fluorescence optical tomography by experimental design methods.

Fluorescence tomography excites a fluorophore inside a sample by light sources on the surface. From boundary measurements of the fluorescent light, the distribution of the fluorophore is reconstructed. The optode placement determines the quality of the reconstructions in terms of, e.g., resolution and contrast-to-noise ratio. We address the adaptation of the measurement setup. The redundancy of the measurements is chosen as a quality criterion for the optodes and is computed from the Jacobian of the mathematical formulation of light propagation. The algorithm finds a subset with minimum redundancy in the measurements from a feasible pool of optodes. This allows biasing the design in order to favor reconstruction results inside a given region. Two different variations of the algorithm, based on geometric and arithmetic averaging, are compared. Both deliver similar optode configurations. The arithmetic averaging is slightly more stable, whereas the geometric averaging approach shows a better conditioning of the sensitivity matrix and mathematically corresponds more closely with entropy optimization. Adapted illumination and detector patterns are presented for an initial set of 96 optodes placed on a cylinder with focusing on different regions. Examples for the attenuation of fluorophore signals from regions outside the focus are given.

Optimum receiver array design for magnetic induction tomography.

Magnetic induction tomography (MIT) is an imaging modality that aims at mapping the distribution of the electrical conductivity inside the body. Eddy currents are induced in the body by magnetic induction and the resulting fields are measured by an array of receiver coils. In MIT, the location of the receivers affects the quality of the image reconstruction. In this paper, a fast deterministic algorithm was applied to obtain optimum receiver array designs for a given specific excitation. The design strategy is based on the iterative exclusion of receiver locations, which yield poor conductivity information, from the space spanning all possible locations until a feasible design is reached. The applicability of "regionally focused" MIT designs that increase the image resolution at a particular region was demonstrated. Currently used design geometries and the corresponding reconstructed images were compared to the images obtained by optimized designs. The eigenvalue analysis of the Hessian matrix showed that the algorithm tends to maintain identical conductivity information content sensed by the receivers. Although the method does not guarantee finding the optimum design globally, the results demonstrate the practical usability of this algorithm in MIT experimental designs.

Magnetic induction tomography: comparison of the image quality using different types of receivers.

Magnetic induction tomography is used to image the electrical properties inside a region of interest. The systems differ in the construction of the receiver channels which can be composed of coils or gradiometers. We will compare and discuss the image quality subject to two different types of receivers, different arrangements for the exciters and receivers and different signal-to-noise ratios. In order to evaluate the image quality, the point-spread function (PSF) was determined which is used for the calculation of the resolution and the correctness of the location of a perturbation. The results show that the PSF depends on (a) the location inside the object, (b) the type of receivers and (c) the configuration used, especially the location of the receiving and excitation channels. According to this, the local resolution is changed and has the maximum near the border of the object and decreases towards the centre of the object. In addition, the evaluation of the PSF shows a dislocation with respect to the underlying point-source position.

Magnetic induction tomography: evaluation of the point spread function and analysis of resolution and image distortion.

Magnetic induction tomography (MIT) is a low-resolution imaging modality used for reconstructing the changes of the passive electrical properties in a target object. For an imaging system, it is very important to give forecasts about the image quality. Both the maximum resolution and the correctness of the location of the inhomogeneities are of major interest. Furthermore, the smallest object which can be detected for a certain noise level is a criterion for the diagnostic value of an image. The properties of an MIT image are dependent on the position inside the object, the conductivity distribution and of course on the location and the number of excitation coils and receiving coils. Quantitative statements cannot be made in general but it is feasible to predict the image quality for a selected problem. For electrical impedance tomography (EIT), the theoretical limits of image quality have been studied carefully and a comprehensive analysis for MIT is necessary. Thus, a simplified analysis on resolution, dimensions and location of an inhomogeneity was carried out by means of an evaluation of the point spread function (PSF). In analogy to EIT the PSF depends strongly on the location, showing the broadest distribution in the centre of the object. Increasing the amount of regularization according to increasing measurement noise, the PSF broadens and its centre is shifted towards the borders of the object. The resolution is indirectly proportional to the width of the PSF and increases when moving from the centre towards the border of the object and decreases with increasing noise.