Magnetic resonance imaging of alternating electric currents.

Electric Current Density Imaging (CDI) is a new modality of magnetic resonance imaging that enables electric current distribution imaging in conductive samples containing water. So far, two CDI techniques have been in use: DC-CDI operating at zero frequency and RF-CDI operating at the RF Larmor frequency. In this paper we present a new CDI technique, which extends the CDI frequency range to alternating electric currents (AC-CDI). First, a theoretical model for the electric current response to the alternating voltage is presented. Later, this model is used for the frequency analysis of the AC-CDI sequence. Additionally, the effect of off-resonance spins and imperfect refocusing RF pulses on the stability of the AC-CDI sequence and the echo formation is studied. The new theory is verified by experiments on a model system and compared to the other two methods: DC-CDI and RF-CDI. Finally, an application of the AC-CDI sequence to biological systems is demonstrated by an experiment on a wood twig in which an increase of approximately 30% was obtained at AC as compared to DC electric current.

Specific absorption rate study for radiofrequency current density imaging using a two-dimensional finite element model.

Radiofrequency current density imaging is an MR technique that images tissue conductivity contrast. Compared to conventional MRI, RF-CDI uses two additional sources of RF power to be absorbed and that must be evaluated in terms of proper parameter optimization to prevent excessive tissue heating and effects on the nervous system. In view of possible future clinical use of RF-CDI, a simple 2D finite element model of a rat brain was built to simulate current density distribution and distribution of absorbed RF power, i.e., SAR and related tissue heating. Current density in the rat brain was also evaluated qualitatively and quantitatively in an in vivo RF-CDI experiment. The results demonstrate that a numerical model can predict SAR and tissue temperature changes. The study also shows that substantial sensitivity and resolution of RF-CDI can be achieved using imaging parameters that produce SAR and temperature changes within allowed limits.

Subchronic liver injuries caused by microcystins.

The subchronic effects of cyanobacterial lyophilizate (CL) containing microcystins on liver were investigated in female New Zealand rabbits. Sterilised CL containing microcystins was injected i.p. Liver toxicity was assessed by histological examination of liver samples. Non-invasive magnetic resonance imaging (MRI) of liver was also performed in order to assess changes in the homogeneity of liver tissue. Subchronical intoxication with microcystins caused morphological changes of liver tissue that were also detected by use of MRI. Histological analysis showed that changes seen on MRI represent liver injury characterised with fatty infiltration and periportal fibrosis. This demonstrates that subchronic exposure to microcystins can lead to liver degeneration, which can easily be detected in vivo by use of MRI.

Assessment of kainate toxicity using contrast enhanced magnetic resonance imaging.

The purpose of this study was to test the capability of contrast enhanced magnetic resonance imaging (MRI) in assessing lesion formation in rat brain after systemic (i.v.) administration of kainate. MRI was performed with T1-weighted spin echo sequence before and after the administration of kainate and contrast media. Contrast media used were based on paramagnetic gadolinium (III) ion: Gd-DTPA (gadoliniumdiethylenetriaminepentaacetic acid) and prototype agents for blood-pool enhancement. Gadomer-17 and polylysine-Gd-DTPA. Enhancement of lesion rims and other brain tissue abnormalities due to kainate with Gd-DTPA, Gadomer-17 and polylysine-Gd-DTPA were observed mainly in the region of hippocampus and in the areas not protected by the blood-brain-barrier (BBB).

Radiofrequency current density imaging of kainate-evoked depolarization.

The purpose of this study was to examine whether radiofrequency current density imaging (RF-CDI) can quantitatively monitor depolarizations evoked by excitatory amino acids in a rat's brain. To evoke depolarization, a glutamate receptor agonist, kainate, was administered into the right lateral ventricle. First, electroencephalographic activity was recorded in a basal condition and after the application of kainate. Complex behavioral patterns were observed. Second, impedance measurements were performed to assess the change in conductivity of the brain due to kainate at the Larmor frequency of the imager. Calculated changes were about 17%. Third, a set of current density images was obtained with RF-CDI before and after the administration of kainate. Kainate-induced excitatory changes were observed on current density images as brighter regions, mainly in the hippocampal area compared with the same area in the basal condition.

Contrast-enhanced MR imaging of two superparamagnetic RES-contrast agents: functional assessment of experimental radiation-induced liver injury.

The purpose of this study was to compare liver contrast-enhancing characteristics of two superparamagnetic reticuloendothelial system (RES)-directed agents with different particle sizes, polycrystalline iron oxide nanocompounds (PION) and carboxydextran-coated maghemite (DDM128N/389, later referred to as DDM128), in an experimental model of focal radiation-induced hepatitis. PION, for the small particle size (31 nm), and DDM128, for the large particle size (59 nm), RES-directed agents were compared for liver enhancement after radiation-induced liver injury. A single x-irradiation exposure varying from 10 to 60 Gy was delivered to one side of the liver. T2-weighted spinecho magnetic resonance imaging was performed 3 days after x-irradiation at 30 minutes post-contrast. Using the RES-directed PION, the normal, non-irradiated portion of the liver decreased in signal intensity with a maximum negative enhancement of -66%, while the irradiated portion of the liver decreased in signal intensity by -24% (60 Gy). The signal intensity decline of irradiated liver tissue using PION was dose dependent, but was found at all radiation dose levels (10-60 Gy). The difference in signal intensity between irradiated (-63%) and non-irradiated (-82%) portions was also statistically different using DDM128 at 60 Gy. However, lower irradiation doses (10 and 30 Gy) failed to produce a statistically significantly different enhancement in the irradiated and non-irradiated portion of the liver. Sensitivity of liver enhancement with RES-directed agents is size dependent. The smaller particle (PION) is more sensitive for detection of radiation-induced hepatitis than the larger particle (DDM128). The relative insensitivity of DDM128 enhancement for diffuse liver injury will be clinically advantageous for detecting focal lesions in the presence of diffuse hepatic injury.

Magnetic resonance current density imaging of chemical processes and reactions.

Electric current density imaging was used to image conductivity changes that occur as a chemical process or reaction progresses. Feasibility was assessed in two models representing the dissolving of an ionic solid and the formation of an insoluble precipitate. In both models, temporal and spatial changes in ionic concentrations were obtained on current density images. As expected, the images showed significant signal enhancement along the ionization/dissociation sites.

The importance of electric field distribution for effective in vivo electroporation of tissues.

Cells exposed to short and intense electric pulses become permeable to a number of various ionic molecules. This phenomenon was termed electroporation or electropermeabilization and is widely used for in vitro drug delivery into the cells and gene transfection. Tissues can also be permeabilized. These new approaches based on electroporation are used for cancer treatment, i.e., electrochemotherapy, and in vivo gene transfection. In vivo electroporation is thus gaining even wider interest. However, electrode geometry and distribution were not yet adequately addressed. Most of the electrodes used so far were determined empirically. In our study we 1) designed two electrode sets that produce notably different distribution of electric field in tumor, 2) qualitatively evaluated current density distribution for both electrode sets by means of magnetic resonance current density imaging, 3) used three-dimensional finite element model to calculate values of electric field for both electrode sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in mouse tumor model between the two electrode sets. The results of our study clearly demonstrate that numerical model is reliable and can be very useful in the additional search for electrodes that would make electrochemotherapy and in vivo electroporation in general more efficient. Our study also shows that better coverage of tumors with sufficiently high electric field is necessary for improved effectiveness of electrochemotherapy.

Contrast enhanced Gd-DTPA magnetic resonance imaging in the evaluation of rheumatoid arthritis during a clinical trial with DMARDs. A prospective two-year follow-up study on hand joints in 31 patients.

OBJECTIVE: The aim of this prospective 24-month follow-up study was to compare clinical features with radiological and magnetic resonance imaging (MRI) findings in evaluating synovial proliferation in the hand joints of 31 patients with rheumatoid arthritis (RA). A single joint was used for the follow-up of each patient. METHODS: Thirty-one small hand joints were examined by conventional radiography and MRI before and after 24 months of treatment. MRI assessment of disease progression (volume and/or signal intensity of the synovial proliferation on T1 weighted precontrast, T1 weighted postcontrast and T2 weighted images) was compared with a clinical assessment of the chosen joints, and with a plain x-ray film evaluation (Larsen's score). RESULTS: Of 26 joints which clinically improved (14 markedly and 14 slightly) during the study, on MRI 16 showed improvement, 8 showed no change, and 2 showed deterioration. Four clinically unchanged joints appeared improved on MRI. One joint deteriorated clinically and on MRI. Overall, there was a 58% congruence between clinical and MRI findings. On x-ray 23 joints showed no change; nine of these were also unchanged on MRI, while 13 showed improvement and one deterioration. Only in 2 out of 8 joints showing deterioration on x-ray were the MRI findings in accordance. In the remaining six joints MRI showed improvement. The congruence between x-ray and MRI was therefore 36%. CONCLUSION: The long-term follow-up of rheumatoid synovial proliferation of the small joints in the hand using contrast enhanced MRI is feasible and may provide additional information regarding disease activity. Important advantages over conventional radiography methods are its ability to demonstrate qualitative differences of synovial proliferation within bone erosions, and demonstrate not only deterioration, but also the improvement of inflammatory disease.

Electric current density imaging of mice tumors.

The use of electric current density imaging (CDI) to map spatial distribution of electric currents through tumors is presented. Specifically, a method previously tested on phantoms was implemented in vivo and in vitro for mapping electric current pulses of the same order of magnitude (j approximately 2500 A/m2) as in electrochemotherapy through T50/80 mammary carcinomas, B-16 melanomas and SA-1 sarcomas. A technically simplified method of electric current density imaging is discussed as well. Three geometries of electrodes (flat-flat, point-point, point-flat) indicate altered electric current distribution for the same tumor. This indicates that the method can be used for monitoring the effects of electrochemotherapy as a function of electrode geometry.

Comparison of albumin-(Gd-DTPA)30 and Gd-DTPA-24-cascade-polymer for measurements of normal and abnormal microvascular permeability.

The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). TI-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)30 or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)30 demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.

A MRI spatial mapping technique for microvascular permeability and tissue blood volume based on macromolecular contrast agent distribution.

A rapid and automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast enhanced MR imaging was developed and tested in disease models of cancer, inflammation, and myocardial reperfusion injury. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion injury clearly depicted zones of increased permeability (up to approximately 500 microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS maps, the rank ordering of studied permeability abnormalities was reperfusion injury > inflammation > tumors. A rapid, automated mapping technique derived from dynamic contrast-enhanced MRI data can be used to facilitate the identification and characterization of pathophysiologic abnormalities, specifically relative increases in blood volume and/or microvascular permeability.

Electric current density imaging of bone by MRI.

Current density imaging (CDI) has been shown to be a feasible method to map spatial distribution of electric currents through bone structures and for studying osteoporosis and bone fracture models. For the osteoporosis model, bone sample was moistened in a solution of a sodium salt of ethylendiamintetraacetic acid (EDTA) which causes chemical reaction with hydroxyapatite Ca2+ ions and lowers the mineralisation degree of the solid bone. This enables clear visualisation of conventional magnetic resonance imaging and CDI. Sensitivity of conventional magnetic resonance and CD images of bone was improved by immersing the bone samples into physiological saline containing contrast agent Gd-DTPA prior to imaging. To stimulate effects of bone fracture on electric current conductivity through bone, a transverse cut was made through the bone, and the resulting gap was filled with an insulator. Electric current density images under these conditions have shown that regions of strong conductivity can be distinguished from regions of no conductivity at the site where the insulator restricts electric current. Real bone fracture was imaged as well. To demonstrate influence of electrolyte concentration on electric current spatial distribution, the bone samples were imaged after being immersed in various saline concentrations. The same contrast in current density images was produced with the combinations of higher electrolyte concentrations and lower voltages. Our observations demonstrate the feasibility of the method in mapping current density in bone structures, which could have implications in understanding and monitoring the effects of the electrical stimulation.

Mapping abnormal synovial vascular permeability in temporomandibular joint arthritis in the rabbit using MRI.

An automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast-enhanced MRI was applied to a model of inflammatory disease represented by antigen-induced arthritis of the temporomandibular joint in the rabbit. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium designed for blood pool enhancement. Maps of PS and BV in a disease model of induced arthritis clearly depicted zones of increased permeability (up to approximately 200 microliters/cc/h-compared to 25 microliters/cc/h in normal tissues).

Prognostic value of contrast enhanced Gd-DTPA MRI for development of bone erosive changes in rheumatoid arthritis.

Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Gd-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA. The results of the study confirm that in joints in which inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone-destructive changes can be expected.

Metal implant localizers: frontiers and diagnostic feasibility.

The paper describes and analyses a method for locating metal implants based on the interaction of a conductive object with a weak alternating magnetic field. Theoretical values for the boundary of detectability and the boundary of localability are introduced to show some technical characteristics, the diagnostic feasibility and limitations of the method. Clinical experiences are described in order to compare the theoretical expectations with practical results. Several advantages of the proposed diagnostic method in terms of inexpensive instrumentation, ease of operation and sensitivity are discussed.