Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex affects divided attention immediately after cessation of stimulation

Transcranial magnetic stimulation has evolved into a powerful neuroscientific tool allowing to interfere transiently with specific brain functions. In addition, repetitive TMS (rTMS) has long-term effects (e.g. on mood), probably mediated by neurochemical alterations. While long-term safety of rTMS with regard to cognitive functioning is well established from trials exploring its therapeutic efficacy, little is known on whether rTMS can induce changes in cognitive functioning in a time window ranging from minutes to hours, a time in which neurochemical effects correlated with stimulation have been demonstrated. This study examined effects of rTMS on three measures of executive function in healthy subjects who received one single rTMS session (40 trains of 2 s duration 20 Hz stimuli) at the left dorsolateral prefrontal cortex (DLPFC). Compared to a sham condition one week apart, divided attention performance was significantly impaired about 30-60 min after rTMS, while Stroop-interference and performance in the Wisconsin Card Sorting Test was unaffected after rTMS. Repetitive TMS of the left DLPFC, at stimulation parameters used in therapeutic studies, does not lead to a clinically relevant impairment of executive function after stimulation. However, the significant effect on divided attention suggests that cognitive effects of rTMS are not limited to the of acute stimulation, and may possibly reflect known neurochemical alterations induced by rTMS. Sensitive cognitive measures may be useful to trace those short-term effects of rTMS non-invasively in humans.

Magnetic field exposure and neurodegenerative diseases--recent epidemiological studies

OBJECTIVES: To analyse the results of recent studies not yet included in a 2003 report of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) on occupational exposure to low-frequency electromagnetic fields as potential risk factor for neurodegenerative diseases. METHODS: A literature search was conducted in the online databases of PubMed, ISI Web of Knowledge, DIMDI and COCHRANE, as well as in specialised databases and journals. Eight studies published between January 2000 and July 2005 were included in the review. RESULTS: The findings of these studies contribute to the evidence of an association between occupational magnetic field exposure and the risk of dementia. Regarding amyotrophic lateral sclerosis, the recent results confirm earlier observations of an association with electric and electronic work and welding. Its relationship with magnetic field exposure remains unsolved. There are only few findings pointing towards an association between magnetic field exposure and Parkinson's disease. CONCLUSIONS: The epidemiological evidence for an association between occupational exposure to low-frequency electromagnetic fields and the risk of dementia has increased during the last five years. The impact of potential confounders should be evaluated in further studies.

A multivariate approach for processing magnetization effects in triggered event-related functional magnetic resonance imaging time series

Triggered event-related functional magnetic resonance imaging requires sparse intervals of temporally resolved functional data acquisitions, whose initiation corresponds to the occurrence of an event, typically an epileptic spike in the electroencephalographic trace. However, conventional fMRI time series are greatly affected by non-steady-state magnetization effects, which obscure initial blood oxygen level-dependent (BOLD) signals. Here, conventional echo-planar imaging and a post-processing solution based on principal component analysis were employed to remove the dominant eigenimages of the time series, to filter out the global signal changes induced by magnetization decay and to recover BOLD signals starting with the first functional volume. This approach was compared with a physical solution using radiofrequency preparation, which nullifies magnetization effects. As an application of the method, the detectability of the initial transient BOLD response in the auditory cortex, which is elicited by the onset of acoustic scanner noise, was used to demonstrate that post-processing-based removal of magnetization effects allows to detect brain activity patterns identical with those obtained using the radiofrequency preparation. Using the auditory responses as an ideal experimental model of triggered brain activity, our results suggest that reducing the initial magnetization effects by removing a few principal components from fMRI data may be potentially useful in the analysis of triggered event-related echo-planar time series. The implications of this study are discussed with special caution to remaining technical limitations and the additional neurophysiological issues of the triggered acquisition.

COVARIATE-ADJUSTED NONPARAMETRIC ANALYSIS OF MAGNETIC RESONANCE IMAGES USING MARKOV CHAIN MONTE CARLO

Permutation tests are useful for drawing inferences from imaging data because of their flexibility and ability to capture features of the brain that are difficult to capture parametrically. However, most implementations of permutation tests ignore important confounding covariates. To employ covariate control in a nonparametric setting we have developed a Markov chain Monte Carlo (MCMC) algorithm for conditional permutation testing using propensity scores. We present the first use of this methodology for imaging data. Our MCMC algorithm is an extension of algorithms developed to approximate exact conditional probabilities in contingency tables, logit, and log-linear models. An application of our non-parametric method to remove potential bias due to the observed covariates is presented.

Leukaemia, brain tumours and exposure to extremely low frequency magnetic fields: cohort study of Swiss railway employees

AIMS: To investigate the relationship between extremely low frequency magnetic field (ELF-MF) exposure and mortality from leukaemia and brain tumour in a cohort of Swiss railway workers. METHODS: 20,141 Swiss railway employees with 464,129 person-years of follow-up between 1972 and 2002 were studied. Mortality rates for leukaemia and brain tumour of highly exposed train drivers (21 muT average annual exposure) were compared with medium and low exposed occupational groups (i.e. station masters with an average exposure of 1 muT). In addition, individual cumulative exposure was calculated from on-site measurements and modelling of past exposures. RESULTS: The hazard ratio (HR) for leukaemia mortality of train drivers was 1.43 (95% CI 0.74 to 2.77) compared with station masters. For myeloid leukaemia the HR of train drivers was 4.74 (95% CI 1.04 to 21.60) and for Hodgkin's disease 3.29 (95% CI 0.69 to 15.63). Lymphoid leukaemia, non-Hodgkin's disease and brain tumour mortality were not associated with magnetic field exposure. Concordant results were obtained from analyses based on individual cumulative exposure. CONCLUSIONS: Some evidence of an exposure-response association was found for myeloid leukaemia and Hodgkin's disease, but not for other haematopoietic and lymphatic malignancies and brain tumours.

Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer's disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

Abdominal magnetic resonance imaging in small rodents using a clinical 1.5 T MR scanner

Because of superior soft-tissue contrast compared to other imaging techniques, non-invasive abdominal magnetic resonance imaging (MRI) is ideal for monitoring organ regeneration, tissue repair, cancer stage, and treatment effects in a wide variety of experimental animal models. Currently, sophisticated MR protocols, including technically demanding procedures for motion artefact compensation, achieve an MRI resolution limit of < 100 microm under ideal conditions. However, such a high spatial resolution is not required for most experimental rodent studies. This article describes both a detailed imaging protocol for MR data acquisition in a ubiquitously and commercially available 1.5 T MR unit and 3-dimensional volumetry of organs, tissue components, or tumors. Future developments in MR technology will allow in vivo investigation of physiological and pathological processes at the cellular and even the molecular levels. Experimental MRI is crucial for non-invasive monitoring of a broad range of biological processes and will further our general understanding of physiology and disease.

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.

In vivo biochemical 7.0 Tesla magnetic resonance: preliminary results of dGEMRIC, zonal T2, and T2* mapping of articular cartilage

INTRODUCTION: Ultra-high-field whole-body systems (7.0 T) have a high potential for future human in vivo magnetic resonance imaging (MRI). In musculoskeletal MRI, biochemical imaging of articular cartilage may benefit, in particular. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping have shown potential at 3.0 T. Although dGEMRIC, allows the determination of the glycosaminoglycan content of articular cartilage, T2 mapping is a promising tool for the evaluation of water and collagen content. In addition, the evaluation of zonal variation, based on tissue anisotropy, provides an indicator of the nature of cartilage ie, hyaline or hyaline-like articular cartilage.Thus, the aim of our study was to show the feasibility of in vivo dGEMRIC, and T2 and T2* relaxation measurements, at 7.0 T MRI; and to evaluate the potential of T2 and T2* measurements in an initial patient study after matrix-associated autologous chondrocyte transplantation (MACT) in the knee. MATERIALS AND METHODS: MRI was performed on a whole-body 7.0 T MR scanner using a dedicated circular polarization knee coil. The protocol consisted of an inversion recovery sequence for dGEMRIC, a multiecho spin-echo sequence for standard T2 mapping, a gradient-echo sequence for T2* mapping and a morphologic PD SPACE sequence. Twelve healthy volunteers (mean age, 26.7 +/- 3.4 years) and 4 patients (mean age, 38.0 +/- 14.0 years) were enrolled 29.5 +/- 15.1 months after MACT. For dGEMRIC, 5 healthy volunteers (mean age, 32.4 +/- 11.2 years) were included. T1 maps were calculated using a nonlinear, 2-parameter, least squares fit analysis. Using a region-of-interest analysis, mean cartilage relaxation rate was determined as T1 (0) for precontrast measurements and T1 (Gd) for postcontrast gadopentate dimeglumine [Gd-DTPA(2-)] measurements. T2 and T2* maps were obtained using a pixelwise, monoexponential, non-negative least squares fit analysis; region-of-interest analysis was carried out for deep and superficial cartilage aspects. Statistical evaluation was performed by analyses of variance. RESULTS: Mean T1 (dGEMRIC) values for healthy volunteers showed slightly different results for femoral [T1 (0): 1259 +/- 277 ms; T1 (Gd): 683 +/- 141 ms] compared with tibial cartilage [T1 (0): 1093 +/- 281 ms; T1 (Gd): 769 +/- 150 ms]. Global mean T2 relaxation for healthy volunteers showed comparable results for femoral (T2: 56.3 +/- 15.2 ms; T2*: 19.7 +/- 6.4 ms) and patellar (T2: 54.6 +/- 13.0 ms; T2*: 19.6 +/- 5.2 ms) cartilage, but lower values for tibial cartilage (T2: 43.6 +/- 8.5 ms; T2*: 16.6 +/- 5.6 ms). All healthy cartilage sites showed a significant increase from deep to superficial cartilage (P < 0.001). Within healthy cartilage sites in MACT patients, adequate values could be found for T2 (56.6 +/- 13.2 ms) and T2* (18.6 +/- 5.3 ms), which also showed a significant stratification. Within cartilage repair tissue, global mean values showed no difference, with 55.9 +/- 4.9 ms for T2 and 16.2 +/- 6.3 ms for T2*. However, zonal assessment showed only a slight and not significant increase from deep to superficial cartilage (T2: P = 0.174; T2*: P = 0.150). CONCLUSION: In vivo T1 dGEMRIC assessment in healthy cartilage, and T2 and T2* mapping in healthy and reparative articular cartilage, seems to be possible at 7.0 T MRI. For T2 and T2*, zonal variation of articular cartilage could also be evaluated at 7.0 T. This zonal assessment of deep and superficial cartilage aspects shows promising results for the differentiation of healthy and affected articular cartilage. In future studies, optimized protocol selection, and sophisticated coil technology, together with increased signal at ultra-high-field MRI, may lead to advanced biochemical cartilage imaging.

Magnetic resonance imaging for diagnosis and assessment of cartilage defect repairs

Clinical magnetic resonance imaging (MRI) is the method of choice for the non-invasive evaluation of articular cartilage defects and the follow-up of cartilage repair procedures. The use of cartilage-sensitive sequences and a high spatial-resolution technique enables the evaluation of cartilage morphology even in the early stages of disease, as well as assessment of cartilage repair. Sequences that offer high contrast between articular cartilage and adjacent structures, such as the fat-suppressed, 3-dimensional, spoiled gradient-echo sequence and the fast spin-echo sequence, are accurate and reliable for evaluating intrachondral lesions and surface defects of articular cartilage. These sequences can also be performed together in reasonable examination times. In addition to morphology, new MRI techniques provide insight into the biochemical composition of articular cartilage and cartilage repair tissue. These techniques enable the diagnosis of early cartilage degeneration and help to monitor the effect and outcome of various surgical and non-surgical cartilage repair therapies.

COMPARISON OF NON-HEATING PALEOINTENSITY TECHNIQUES USING BASALTS FROM LEMPTÉGY VOLCANO, FRANCE AND SYNTHETIC MAGNETITE-BEARING SAMPLES

Data of the strength of Earth’s magnetic field (paleointensity) in the geological past are crucial for understanding the geodynamo. Conventional paleointensity determination methods require heating a sample to a high temperature in one or more steps. Consequently, many rocks are unsuitable for these methods due to a heating-induced experimental alteration. Alternative non-heating paleointensity methods are investigated to assess their effectiveness and reliability using both natural samples from Lemptégy Volcano, France, and synthetic samples. Paleointensity was measured from the natural and synthetic samples using the Pseudo-Thellier, ARM, REM, REMc, REM’, and Preisach methods. For the natural samples, only the Pseudo-Thellier method was able to produce a reasonable paleointensity estimate consistent with previous paleointensity data. The synthetic samples yielded more successful estimates using all the methods, with the Pseudo-Thellier and ARM methods producing the most accurate results. The Pseudo-Thellier method appears to be the best alternative to the heating-based paleointensity methods.

Postmortem multislice computed tomography and magnetic resonance imaging of odontoid fractures, atlantoaxial distractions and ascending medullary edema

Non-invasive imaging methods are increasingly entering the field of forensic medicine. Facing the intricacies of classical neck dissection techniques, postmortem imaging might provide new diagnostic possibilities which could also improve forensic reconstruction. The aim of this study was to determine the value of postmortem neck imaging in comparison to forensic autopsy regarding the evaluation of the cause of death and the analysis of biomechanical aspects of neck trauma. For this purpose, 5 deceased persons (1 female and 4 male, mean age 49.8 years, range 20-80 years) who had suffered odontoid fractures or atlantoaxial distractions with or without medullary injuries, were studied using multislice computed tomography (MSCT), magnetic resonance imaging (MRI) and subsequent forensic autopsy. Evaluation of the findings was performed by radiologists, forensic pathologists and neuropathologists. The cause of death could be established radiologically in three of the five cases. MRI data were insufficient due to metal artefacts in one case, and in another, ascending medullary edema as the cause of delayed death was only detected by histological analysis. Regarding forensic reconstruction, the imaging methods were superior to autopsy neck exploration in all cases due to the post-processing possibilities of viewing the imaging data. In living patients who suffer medullary injury, follow-up MRI should be considered to exclude ascending medullary edema.

Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts

In spite of the facts that magnetic resonance spectroscopy (MRS) is applied as clinical tool in non-specialized institutions and that semi-automatic acquisition and processing tools can be used to produce quantitative information from MRS exams without expert information, issues of spectral quality and quality assessment are neglected in the literature of MR spectroscopy. Even worse, there is no consensus among experts on concepts or detailed criteria of quality assessment for MR spectra. Furthermore, artifacts are not at all conspicuous in MRS and can easily be taken for true, interpretable features. This article aims to increase interest in issues of spectral quality and quality assessment, to start a larger debate on generally accepted criteria that spectra must fulfil to be clinically and scientifically acceptable, and to provide a sample gallery of artifacts, which can be used to raise awareness for potential pitfalls in MRS.

Magic angle spinning magnetic resonance: a novel method opening up translational research into NAFLD?

NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) are of increasing importance, both in connection with insulin resistance and with the development of liver cirrhosis. Histological samples are still the 'gold standard' for diagnosis; however, because of the risks of a liver biopsy, non-invasive methods are needed. MAS (magic angle spinning) is a special type of NMR which allows characterization of intact excised tissue without need for additional extraction steps. Because clinical MRI (magnetic resonance imaging) and MRS (magnetic resonance spectroscopy) are based on the same physical principle as NMR, translational research is feasible from excised tissue to non-invasive examinations in humans. In the present issue of Clinical Science, Cobbold and co-workers report a study in three animal strains suffering from different degrees of NAFLD showing that MAS results are able to distinguish controls, fatty infiltration and steatohepatitis in cohorts. In vivo MRS methods in humans are not obtainable at the same spectral resolution; however, know-how from MAS studies may help to identify characteristic changes in crowded regions of the magnetic resonance spectrum.

3D Ultrasound imaging--a useful non-invasive tool to detect AV fistulas in transplanted kidneys

BACKGROUND: A precise, non-invasive, non-toxic, repeatable, convenient and inexpensive follow-up of renal transplants, especially following biopsies, is in the interest of nephrologists. Formerly, the rate of biopsies leading to AV fistulas had been underestimated. Imaging procedures suited to a detailed judgement of these vascular malformations are to be assessed. METHODS: Three-dimensional (3D) reconstruction techniques of ultrasound flow-directed and non-flow-directed energy mode pictures were compared with a standard procedure, gadolinium-enhanced nuclear magnetic resonance imaging angiography (MRA) using the phase contrast technique. RESULTS: Using B-mode and conventional duplex information, AV fistulas were localized in the upper pole of the kidney transplant of the index patient. The 3D reconstruction provided information about the exact localization and orientation of the fistula in relation to other vascular structures, and the flow along the fistula. The MRA provided localization and orientation information, but less functional information. Flow-directed and non-flow-directed energy mode pictures could be reconstructed to provide 3D information about vascular malformations in transplanted kidneys. CONCLUSION: In transplanted kidneys, 3D-ultrasound angiography may be equally as effective as MRA in localizing and identifying AV malformations. Advantages of the ultrasound method are that it is cheaper, non-toxic, non-invasive, more widely availability and that it even provides more functional information. Future prospective studies will be necessary to evaluate the two techniques further.