Genotoxic effects of 3 T magnetic resonance imaging in cultured human lymphocytes

The clinical and preclinical use of high-field intensity (HF, 3 T and above) magnetic resonance imaging (MRI) scanners have significantly increased in the past few years. However, potential health risks are implied in the MRI and especially HF MRI environment due to high-static magnetic fields, fast gradient magnetic fields, and strong radiofrequency electromagnetic fields. In this study, the genotoxic potential of 3 T clinical MRI scans in cultured human lymphocytes in vitro was investigated by analyzing chromosome aberrations (CA), micronuclei (MN), and single-cell gel electrophoresis. Human lymphocytes were exposed to electromagnetic fields generated during MRI scanning (clinical routine brain examination protocols: three-channel head coil) for 22, 45, 67, and 89 min. We observed a significant increase in the frequency of single-strand DNA breaks following exposure to a 3 T MRI. In addition, the frequency of both CAs and MN in exposed cells increased in a time-dependent manner. The frequencies of MN in lymphocytes exposed to complex electromagnetic fields for 0, 22, 45, 67, and 89 min were 9.67, 11.67, 14.67, 18.00, and 20.33 per 1000 cells, respectively. Similarly, the frequencies of CAs in lymphocytes exposed for 0, 45, 67, and 89 min were 1.33, 2.33, 3.67, and 4.67 per 200 cells, respectively. These results suggest that exposure to 3 T MRI induces genotoxic effects in human lymphocytes.     

Exposure classification of MRI workers in epidemiological studies

We estimate that there are about 100,000 workers from different disciplines, such as radiographers, nurses, anesthetists, technicians, engineers, etc., who can be exposed to substantial electromagnetic fields (compared to normal background levels) around magnetic resonance imaging (MRI) scanners. There is a need for well‐designed epidemiological studies of MRI workers but since the exposure from MRI equipment is a very complex mixture of static magnetic fields, switched gradient magnetic fields, and radiofrequency electromagnetic fields (RF EMF), it is necessary to discuss how to assess the exposure in epidemiological studies. As an alternative to the use of job title as a proxy of exposure, we propose an exposure categorization for the different professions working with MRI equipment. Specifically, we propose defining exposure in three categories, depending on whether people are exposed to only the static field, to the static plus switched gradient fields or to the static plus switched gradient plus RF fields, as a basis for exposure assessment in epidemiological studies. Bioelectromagnetics 34:81–84, 2013. © 2012 Wiley Periodicals, Inc.     

Physical interactions of static magnetic fields with living tissues

Clinical magnetic resonance imaging (MRI) was introduced in the early 1980s and has become a widely accepted and heavily utilized medical technology. This technique requires that the patients being studied be exposed to an intense magnetic field of a strength not previously encountered on a wide scale by humans. Nonetheless, the technique has proved to be very safe and the vast majority of the scans have been performed without any evidence of injury to the patient. In this article the history of proposed interactions of magnetic fields with human tissues is briefly reviewed and the predictions of electromagnetic theory on the nature and strength of these interactions are described. The physical basis of the relative weakness of these interactions is attributed to the very low magnetic susceptibility of human tissues and the lack of any substantial amount of ferromagnetic material normally occurring in these tissues. The presence of ferromagnetic foreign bodies within patients, or in the vicinity of the scanner, represents a very great hazard that must be scrupulously avoided. As technology and experience advance, ever stronger magnetic field strengths are being brought into service to improve the capabilities of this imaging technology and the benefits to patients. It is imperative that vigilance be maintained as these higher field strengths are introduced into clinical practice to assure that the high degree of patient safety that has been associated with MRI is maintained.     

Magnetic resonance imaging for detecting lesions of multiple sclerosis: comparison with computed tomography and clinical assessment.

Eighty-two patients with known or suspected multiple sclerosis (MS) were examined by means of magnetic resonance imaging (MRI) with a 0.15-T resistive scanner. The diagnosis could be made by MRI in 34 (97%) of the 35 patients with chronic, well-documented, stable MS and by high-volume delayed x-ray computed tomography (HVD CT) in only 6 (54%) of 11 patients in this group. The stage of the disease as judged from the MRI scans correlated poorly with the clinical status of the patient and with the known duration of the disease. MRI identified 28 (88%) of the 32 patients in whom MS was subsequently diagnosed by a neurologist, whereas regular contrast or HVD CT identified only 11 (52%) of 21 such patients. MRI is the most sensitive imaging modality for MS but is of little value in assessing the severity of the disease: many of the lesions seen on MRI scans are clinically "silent", and MRI does not usually detect small lesions in the brainstem, cerebellum or spinal cord that may be clinically significant.     

Recovery characteristics of a rigid,nonmetallic microdialysis probe for use in an electromagnetic field

It is well known that metal objects perturb electromagnetic fields. Therefore, a conventional metal microdialysis probe cannot be used to determine the bioeffects of electromagnetic radiation. Using fused-silica tubing, we developed an inexpensive nonmetallic, rigid microdialysis probe for use in electromagnetic radiation research or during magnetic resonance imaging. This probe has a concentric tube design, with the membrane length adjustable to the size of the area to be dialyzed. The probes tested had regenerated-cellulose membranes that were 3 mm in length. This report describes how to make this probe. Average relative recovery rates at flow rates of 2.0, 1.0, and 0.5 μl/min were 21%, 27%, and 42%, respectively. These rates were slightly lower than the 30%, 42%, and 68% obtained with the commercially available metallic CMA10 microdialysis probe with a 3 mm membrane. This may be due to the fused-silica probe and CMA10 probe being made with different types of dialysis membranes. © 1995 Wiley-Liss, Inc.     

Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological Tissues

Since its introduction in the mid-1980s, diffusion magnetic resonance imaging (MRI), which measures the random motion of water molecules in tissues, revealing their microarchitecture, has become a pillar of modern neuroimaging. Its main clinical domain has been the diagnosis of acute brain stroke and neurogical disorders, but it is also used in the body for the detection and management of cancer lesions. It can also produce stunning maps of white matter tracks in the brain, with the potential to aid in the understanding of some psychiatric disorders. However, in order to exploit fully the potential of this method, a deeper understanding of the mechanisms that govern the diffusion of water in tissues is needed.In the mid-1980s, we showed that water diffusion in the human brain could be imaged by using magnetic resonance imaging (MRI) [1]. Since then, diffusion MRI has enjoyed a dramatic growth, with about 24,000 articles referenced in PubMed in 2014. MRI is a medical imaging technique consisting of magnetizing body atom nuclei, generally hydrogen nuclei of water molecules, using a very strong magnetic field (typically 30,000 to 60,000 times the earth’s natural magnetic field). The resulting very tiny magnetization can be manipulated in time by sending radiofrequency wave pulses at a resonant frequency. In turn, magnetized nuclei re-emit radiofrequency waves, creating a signal that is received through a coil (a kind of antenna), giving information on the nuclei magnetization properties. Magnetic field “gradient” pulses are used in addition to induce small variations of the magnetic field (and the associated radiowaves’ resonant frequency) in space, so as to spatially encode the magnetization information and create images. Magnetization varies a lot between tissues and various disease conditions, making MRI a very versatile imaging modality. However, the resolution of MRI images used for clinical practice often remains limited, typically around 1 mm (microscopic MRI is possible, but with dedicated preclinical MRI systems using ultra-high magnetic fields; see below). The concept of diffusion MRI emerged as a way to probe tissue structure at a microscopic (invisible) scale, although images are acquired at a millimetric scale: during their random, diffusion-driven displacements in the tissue, the water molecules probe the tissue structure at a microscopic scale, interacting with cell membranes, thus providing unique information on the functional architecture of tissues. Diffusion MRI has become a pillar of modern clinical imaging, used mainly to investigate neurological disorders such as acute brain ischemia, although it is now also a standard imaging method for other organs too, especially for the management of cancer patients. Indeed, diffusion MRI that does not require any tracer injection is rapidly becoming a modality of choice to detect and characterize malignant lesions. Moreover, in the brain, diffusion anisotropy in white matter can be exploited to produce stunning three-dimensional maps of brain connections, revealing faulty connections in some psychiatric disorders. More recently, diffusion MRI has been applied to monitor the dynamic changes occurring in the neural tissue structure during activation, a new approach to investigate functional neuroimaging and the mechanisms underlying neuronal activation.It is amazing that all these applications of diffusion MRI have emerged or developed while so little is known about water diffusion mechanisms in biological tissues. The relative importance of many factors governing water in tissues and their effects on the observed MRI signal are still not fully understood and are sometimes a subject of controversy.We will discuss the main applications and the outstanding issues remaining in the field in more detail below.     

EVIDENCE OF SYNCHRONIZATION OF NEURONAL ACTIVITY OF MOLLUSCAN BRAIN GANGLIA INDUCED BY ALTERNATING 50 Hz APPLIED MAGNETIC FIELD

Experimental evidence for the appearance of synchronized bioelectric activity in neurons under applied extremely low frequency (ELF) magnetic fields is shown. We have studied the synchronizing process by recording the intracellular bioelectric activity from pairs of neurons randomly chosen from the brain ganglia of the snail Helix aspersa. The recordings were made in real time under exposure to sinusoidal low frequency (50 Hz) weak (B₀=1–15 mT) magnetic fields. Synchronization was observed in 27% of the pairs tested. A linear dependence of the firing frequency f with the energy density of the applied magnetic field (i.e., f∝B₀²) was presented. The ability of low frequency sinusoidal weak magnetic fields to promote “magnetic synchronization” is exciting and opens new avenues for induced electromagnetic field bioeffects.     

Modification of pulse sequences reduces occupational exposure from MRI switched gradient fields: Preliminary results

The gradient fields in magnetic resonance imaging (MRI) will in some circumstances exceed the ICNIRP guidelines of occupational electromagnetic field exposure when personnel are near the scanner during MRI scanning. In this work we have shown that using commercially available modified sequences for noise reduction purposes, exposure will decrease by a factor of 1.5 with preserved image quality. This is a first step toward optimizing occupational exposure within the scanner room without affecting image quality. Bioelectromagnetics 31:85–87, 2010. © 2009 Wiley‐Liss, Inc.     

Mechanism for action of electromagnetic fields on cells

A biophysical model for the action of oscillating electric fields on cells, presented by us before [Biochem. Biophys. Res. Commun. 272(3) (2000) 634-640], is extended now to include oscillating magnetic fields as well, extended to include the most active biological conditions, and also to explain why pulsed electromagnetic fields can be more active biologically than continuous ones. According to the present theory, the low frequency fields are the most bioactive ones. The basic mechanism is the forced-vibration of all the free ions on the surface of a cell's plasma membrane, caused by an external oscillating field. We have shown that this coherent vibration of electric charge is able to irregularly gate electrosensitive channels on the plasma membrane and thus cause disruption of the cell's electrochemical balance and function [Biochem. Biophys. Res. Commun. 272(3) (2000) 634-640]. It seems that this simple idea can be easily extended now and looks very likely to be able to give a realistic basis for the explanation of a wide range of electromagnetic field bioeffects.     

Present and future magnetic resonance sources of exposure to static fields

This paper considers the exposure of humans to static magnetic fields due to magnetic resonance imaging (MRI) procedures. It briefly introduces the types of magnetic fields associated with MRI. It then discusses trends in the number of people exposed to MRI, the field strength of the magnets used in MRI, and the types of applications of MRI. It also considers the types of staff who are exposed to magnetic fields due to MRI, and the alternative techniques that would be used in the absence of MRI.     

Effect of the extremely weak alternating magnetic fields on the regeneration of planarians and the gravitropic response of plants

The influence of extremely weak alternating magnetic fields (EW AMF) directed colinearly to the static Earth magnetic field on the rate of regeneration of planarians and the rate of gravitropic response in the stem segments of flax has been studied. The value of bioeffects of EW AMF is determined by the parameter gamma B(AC)/f, where y is the gyromagnetic ratio of the magnetic moments induced by the orbital movements of electrons in atoms, and B(AC) and f correspond to magnetic induction and frequency of the alternating magnetic component. It was shown that the magnitude of bioeffects depends on the amplitude (at fixed 1000 Hz - frequency) and frequency (at fixed 192 nT - amplitude) of the alternating component. Maxima of bioeffects are observed at gamma B(AC)/f = 0.9; 2.75, and minor maxima gamma B(AC)/f = 4.5; 6.1. The bioeffects are absent at gamma B(AC)/f = 1.8, 3.8, 5.3, 6.7. The positions of the maxima and minima of bioeffects correspond to the theoretical prediction (at gamma = 14000 Hz/microT). Primary targets for the EW AMF of this type are the magnetic moments induced by the orbital movements of electrons in atoms.     

Magnetic Resonance Imaging Conditional Pacemakers: Rationale, Development and Future Directions

Pacemakers and other cardiac implantable electronic devices (CIEDs) have long been considered an absolute contraindication to magnetic resonance imaging (MRI), a crucial and growing imaging modality. In the last 20 years, protocols have been developed to allow MR scanning of CIED patients with a low complication rate. However, this practice has remained limited to a relatively small number of centers, and many pacemaker patients continue to be denied access to clinically indicated imaging. The introduction of MRI conditional pacemakers has provided a widely applicable and satisfactory solution to this problem. Here, the interactions of pacemakers with the MR environment, the results of MR scanning in patients with conventional CIEDs, the development and clinical experience with MRI conditional devices, and future directions are reviewed.     

Zero echo time MRI-only treatment planning for radiation therapy of brain tumors after resection

Using magnetic resonance imaging (MRI) as the sole imaging modality for patient modeling in radiation therapy (RT) is a challenging task due to the need to derive electron density information from MRI and construct a so-called pseudo-computed tomography (pCT) image. We have previously published a new method to derive pCT images from head T1-weighted (T1-w) MR images using a single-atlas propagation scheme followed by a post hoc correction of the mapped CT numbers using local intensity information. The purpose of this study was to investigate the performance of our method with head zero echo time (ZTE) MR images. To evaluate results, the mean absolute error in bins of 20 HU was calculated with respect to the true planning CT scan of the patient. We demonstrated that applying our method using ZTE MR images instead of T1-w improved the correctness of the pCT in case of bone resection surgery prior to RT (that is, an example of large anatomical difference between the atlas and the patient).     

Studies on magnetism and bioelectromagnetics for 45 years: from magnetic analog memory to human brain stimulation and imaging

Forty-five years of studies on magnetism and bioelectromagnetics, in our laboratory, are presented. This article is prepared for the d'Arsonval Award Lecture. After a short introduction of our early work on magnetic analog memory, we review and discuss the following topics: (1) Magnetic nerve stimulation and localized transcranial magnetic stimulation (TMS) of the human brain by figure-eight coils; (2) Measurements of weak magnetic fields generated from the brain by superconducting quantum interference device (SQUID) systems, called magnetoencephalography (MEG), and its application in functional brain studies; (3) New methods of magnetic resonance imaging (MRI) for the imaging of impedance of the brain, called impedance MRI, and the imaging of neuronal current activities in the brain, called current MRI; (4) Cancer therapy and other medical treatments by pulsed magnetic fields; (5) Effects of static magnetic fields and magnetic control of cell orientation and cell growth; and (6) Effects of radio frequency magnetic fields and control of iron ion release and uptake from and into ferritins, iron cage proteins. These bioelectromagnetic studies have opened new horizons in magnetism and medicine, in particular for brain research and treatment of ailments such as depression, Parkinson's, and Alzheimer's diseases.     

Biological effects of exposure to magnetic resonance imaging: an overview

The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to allow the integration of the specific literature on the bio-effects produced by magnetic resonance systems with the vast literature concerning the bio-effects produced by electromagnetic fields. This work gives an overview of the findings about the safety concerns of exposure to static magnetic fields, radio-frequency fields, and time varying magnetic field gradients, focusing primarily on the physics of the interactions between these electromagnetic fields and biological matter. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts, international safety guidelines are also cited.     

核磁共振磁场照射对子代大鼠海马突触形态的影响

研究观察了孕期磁共振磁场照射对子代大鼠海马突触超微结构的影响。SD孕鼠妊娠第12-18d给予0．35T核磁共振(magnetic resonance imaging,MRI)磁场照射。测量1、2和5月龄雌性仔鼠海马CAl区和齿状回的突触结构参数,用立体计量学方法进行定量测定。结果显示,磁场照射可引起2月龄子代大鼠海马CAl区突触间隙增宽．齿状回突触活性区长度变短、突触界面曲率和活性区面密度减小;5月龄子代大鼠CAl区突触间隙增宽,突触后致密物变薄,突触界面曲率减小,齿状回突触间隙增宽。结果提示,妊娠期接受MRI磁场照射可引起海马突触超微结构的改变。对这些结构变化与行为损害之间的关系进行了讨论。     

Human ASPM participates in spindle organisation, spindle orientation and cytokinesis

Background

For clinical applications of mesenchymal stem cells (MSCs), labeling and tracking is crucial to evaluate cell distribution and homing. Magnetic resonance imaging (MRI) has been successfully established detecting MSCs labeled with superparamagnetic particles of iron oxide (SPIO). Despite initial reports that labeling of MSCs with SPIO is safe without affecting the MSC's biology, recent studies report on influences of SPIO-labeling on metabolism and function of MSCs. Exposition of cells and tissues to high magnetic fields is the functional principle of MRI. In this study we established innovative labeling protocols for human MSCs using clinically established SPIO in combination with magnetic fields and investigated on functional effects (migration assays, quantification of colony forming units, analyses of gene and protein expression and analyses on the proliferation capacity, the viability and the differentiation potential) of magnetic fields on unlabeled and labeled human MSCs. To evaluate the imaging properties, quantification of the total iron load per cell (TIL), electron microscopy, and MRI at 3.0 T were performed.

Results

Human MSCs labeled with SPIO permanently exposed to magnetic fields arranged and grew according to the magnetic flux lines. Exposure of MSCs to magnetic fields after labeling with SPIO significantly enhanced the TIL compared to SPIO labeled MSCs without exposure to magnetic fields resulting in optimized imaging properties (detection limit: 1,000 MSCs). Concerning the TIL and the imaging properties, immediate exposition to magnetic fields after labeling was superior to exposition after 24 h. On functional level, exposition to magnetic fields inhibited the ability of colony formation of labeled MSCs and led to an enhanced expression of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in labeled MSCs under adipogenic differentiation, and to a reduced expression of alkaline phosphatase in unlabeled MSCs under osteogenic differentiation as detected by qRT-PCR. Moreover, microarray analyses revealed that exposition of labeled MSCs to magnetic fields led to an up regulation of CD93 mRNA and cadherin 7 mRNA and to a down regulation of Zinc finger FYVE domain mRNA. Exposition of unlabeled MSCs to magnetic fields led to an up regulation of CD93 mRNA, lipocalin 6 mRNA, sialic acid acetylesterase mRNA, and olfactory receptor mRNA and to a down regulation of ubiquilin 1 mRNA. No influence of the exposition to magnetic fields could be observed on the migration capacity, the viability, the proliferation rate and the chondrogenic differentiation capacity of labeled or unlabeled MSCs.

Conclusions

In our study an innovative labeling protocol for tracking MSCs by MRI using SPIO in combination with magnetic fields was established. Both, SPIO and the static magnetic field were identified as independent factors which affect the functional biology of human MSCs. Further in vivo investigations are needed to elucidate the molecular mechanisms of the interaction of magnetic fields with stem cell biology.     

A review of the current use of magnetic resonance imaging in pregnancy and safety implications for the fetus

This paper presents an overview of the application of and risks of exposure to Magnetic Resonance Imaging (MRI) in pregnancy. It reviews the risks to the fetus by considering the hazards in terms of the three main components of an MRI system. These are the static magnetic field, the time-varying magnetic gradient fields and the pulsed radio frequency fields. The hazards discussed are biological effects, miscarriage, heating effects and acoustic noise exposure. This paper also presents a survey of MRI sites within the United Kingdom to ascertain the extent of MRI usage in pregnancy. To validate the situation of MRI in pregnancy a survey was sent to 352 MR units throughout the United Kingdom. The questions were grouped to assess (a) maternal MRI diagnosis (b) fetal MRI and (c) work practices for pregnant MRI staff. The results showed that 91% of sites were imaging pregnant women in need of diagnosis in the second and third trimester. This paper highlights that MRI can add information for fetal central nervous system abnormalities identified by ultrasound screening, however within the UK direct fetal imaging was only performed in 8% of sites. This paper indicates the need for research to be undertaken for specific MRI clinical conditions. It also advises that risk assessment for pregnant staff working in MRI is performed, and that there is a clear need for further research into the effects of MRI in pregnancy as there is a need for clear authoritive advice.     

Effects of magnetic resonance imaging (MRI) on the formation of mouse dentin and bone

The effects of magnetic resonance imaging (MRI) on dentin and bone formation in mice were examined using standard autoradiographic and liquid scintillation procedures. It was observed that exposure to a standard 23.2 min clinical multislice MRI (0.15T) procedure caused a significant increase in the synthesis of the collagenous matrix of dentin in the incisors of mice. There were no significant effects on alveolar and tibial bone matrix synthesis. These results suggest that the magnetic fields associated with MRI can affect the activity of cells and/or tissues that are involved in rapid synthetic activity.     

Magnetic resonance imaging in patients with ICDs and pacemakers

Magnetic resonance (MR) imaging has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter/defibrillators (ICDs), however, is historically considered a contraindication to MR imaging. These devices are now smaller, with less magnetic material and improved electromagnetic interference protection. This review summarizes the potential hazards of the device-MR environment interaction, and presents updated information regarding in-vivo and in-vitro experiments. Recent reports on patients with implantable pacemakers and ICDs who underwent MR scan shows that under certain conditions patients with these implanted systems may benefit from this imaging modality. The data presented suggests that certain modern pacemaker and ICD systems may indeed be MR safe. This may have major clinical implications on current imaging practice.