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OBJECTIVES: Intensified repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast clinical responses in treatment resistant depression (TRD). In these kinds of patients, subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) seems to be consistently disturbed. So far, no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available. METHODS: Twenty unipolar TRD patients, all at least stage III treatment resistant, were recruited in a randomized sham-controlled crossover high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans were collected at baseline and at the end of treatment. RESULTS: HF-rTMS responders showed significantly stronger resting-state functional connectivity (rsFC) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex. After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC). No effects on sgACC rsFC were observed in non-responders. CONCLUSIONS: Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.

Objectives: Recently, T1-weighted DCE-MRI was proposed as an alternative to T2*-weighted DSC-MRI for the quantification of perfusion and permeability in brain tumors. The aim of the present feasibility study was to explore the clinical potential of the technique in different tumor types using a case-based review of initial results. Patients and methods: The method for data analysis was adapted from cerebral perfusion CT and applied in this study to a small group of patients with grade IV glioma and other brain tumors. The possible use of the proposed methodology was also explored for characterizing, following-up and planning the therapy of brain tumors. Results: Parametric maps clearly differentiated tumor from the surrounding brain tissue, and also distinguished areas within the tumor presenting with different characteristics, thereby allowing identification of significant target areas for biopsy and/or treatment. Differences in cerebral blood flow (CBF) and lower extraction fractions (E) were observed in various tumors. Progression from a grade II to grade IV glioma over the course of a year was characterized by an increase in CBF and a decrease in E. Conclusion: DCE-MRI-based quantitative perfusion and permeability may be helpful for tumor-grade characterization, biopsy guidance, radiotherapy planning, radiotherapy monitoring and clinical follow-up, thereby improving the non-invasive characterization of brain tumors. (C) 2011 Elsevier Masson SAS. All rights reserved.

The Akaike information criterion and the associated Akaike weights (AW) rank pharmacokinetic models on the basis of goodness-of-fit and number of parameters. The usefulness of this information for improving the haemodynamic parameter estimates from DCE-MRI was investigated through two examples. In each of these, the estimates from the two-compartment exchange model (2CXM) were combined on the basis of the AW with those of a simplified model (either the uptake model or the extended Tofts model). Data were simulated using the 2CXM for a range of experimental and tissue conditions. Two multimodel approaches exploiting the AW were investigated: the ‘bestmodel’ approach which selects the parameter estimates from the model with highest AW and the ‘weighted model’ approach in which AW-weighted averages of the estimates from the competing models are calculated. Although these approaches were shown to be beneficial in some cases, they were found to frequently lead to unexpected increases in the bias and/or uncertainty of the resulting parameter estimates. Within the limited scope of this simulation study, the use of the Akaike criterion showed no systematic benefit over a fitting strategy involving only the more complex model.

The impact of bilingualism on the microstructure of the white matter pathways related to language processing is assessed in elementary school children by magnetic resonance diffusion tensor imaging (MR-DTI). Forty children, 8-11 years old, subdivided into 3 different groups (15 simultaneous bilinguals, 15 sequential bilinguals and 10 monolinguals), were scanned. The hypothesis was that the starting age and the manner of second language acquisition would affect the characteristics of language circuitry. In each subject the mean fractional anisotropy (FA) was obtained for four major white matter pathways: 1 -- the left arcuate fasciculus/superior longitudinal fasciculus (lAF/lSLF) that connects Broca's area in the opercular and triangular regions of the left inferior frontal gyrus to the posterior language zone, 2 -- the left inferior occipitofrontal fasciculus (lIFOF), connecting anterior regions in the frontal lobe with posterior regions in the temporal occipital lobes, 3 -- the bundle arising from the anterior part of the corpus callosum projecting to the orbital lobe (AC-OL) and 4 - the fibers emerging from the anterior midbody (AMB) of the corpus callosum that associate with the premotor and supplementary motor cortices (AMB-PMC). The three groups did not show significant differences in mean FA over the lAF/lSLF or AMB-PMC tracts. In simultaneous bilingual subjects the lIFOF tracts had higher mean FA value compared to monolinguals and also sequential bilinguals, whereas the comparison for the AC-OL fibers yielded a significantly lower mean FA value in simultaneous bilingual subjects compared to monolinguals. In both cases the FA value for sequential bilinguals was intermediate to that of the other two groups. To our knowledge, this study provides the first evidence of bilingualism related adaptation of white matter microstructure in the human brain.

Transcranial magnetic stimulation (TMS) is currently used as a non-invasive treatment for depression. In most clinical trials, the left dorsolateral prefrontal cortex (DLPFC) has been selected as the target site for TMS treatment and this region is commonly determined by a "standard procedure", using a fixed position with respect to the motor cortex. In this study, to evaluate the relevance of using individual anatomical data during coil positioning, we used a more individualized localization method, based on three-dimensional magnetic resonance imaging of the head (3D-MRI). We wanted to examine the intra-individual variability of the localization of the stimulation area using a method taking into account individual brain anatomy by 3D-MRI, by comparing this method to the "standard procedure". As expected, even in a gender-controlled sample, our results demonstrate that the difference between the anatomical localization and the standard procedure of a well-defined part of the prefrontal cortex varies within subjects. Therefore, our results confirm the need for a TMS-coil positioning method which incorporates individual anatomical information.

Model-free measurement of perfusion from bolus-tracking data requires a discretization of the tracer kinetic model. In this study a classification is provided of existing approaches to discretization, and the accuracy of these methods is compared. Two methods are included which are delay invariant (circulant and time shift) and three methods which are not (volterra, singular and hybrid). Simulations of magnetic resonance imaging (MRI) in the brain are performed for two tissue types (plug flow and compartment) with variable delay and dispersion times, temporal resolution and signal to noise. Simulations were compared to measurements in a patient data set. Both delay-invariant methods are equally accurate, but the circulant method is sensitive to data truncation. Overall volterra produces highest estimates of perfusion, followed by hybrid, singular and delay-invariant methods. Volterra is most accurate except in plug-flow without delay or dispersion, which represents an unrealistic tissue type. Differences between methods vanish when delay or dispersion times increase above the temporal resolution. It is concluded that when negative delays cannot be avoided or when an accurate estimate of left-right perfusion ratios is required, the time shift is the method of choice. When delays are certain to be positive and absolute accuracy is the objective, the volterra method is to be preferred.

Quantification of haemodynamic parameters with a deconvolution analysis of bolus-tracking data is an ill-posed problem which requires regularization. In a previous study, simulated data without structural errors were used to validate two methods for a pixel-by-pixel analysis: standard-form Tikhonov regularization with either the L-curve criterion (LCC) or generalized cross validation (GCV) for selecting the regularization parameter. However, problems of image artefacts were reported when the methods were applied to patient data. The aim of this study was to investigate the nature of these problems in more detail and evaluate strategies of optimization for routine application in the clinic. In addition we investigated to which extent the calculation time of the algorithm can be minimized. In order to ensure that the conclusions are relevant for a larger range of clinical applications, we relied on patient data for evaluation of the algorithms. Simulated data were used to validate the conclusions in a more quantitative manner. We conclude that the reported problems with image quality can be removed by appropriate optimization of either LCC or GCV. In all examples this could be achieved with LCC without significant perturbation of the values in pixels where the regularization parameter was originally selected accurately. GCV could not be optimized for the renal data, and in the CT data only at the cost of image resolution. Using the implementations given, calculation times were sufficiently short for routine application in the clinic.

Although numerous people grow up speaking more than one language, the impact of bilingualism on brain developing neuroanatomy is still poorly understood. This study aimed to determine whether the changes in the mean fractional-anisotropy (MFA) of language pathways are different between bilingual and monolingual children. Simultaneous-bilinguals, sequential-bilinguals and monolingual, male and female 10-13 years old children participated in this longitudinal study over a period of two years. We used diffusion tensor tractography to obtain mean fractional-anisotropy values of four language related pathways and one control bundle: 1-left-inferior-occipitofrontal fasciculus/lIFOF, 2-left-arcuate fasciculus/lAF/lSLF, 3-bundle arising from the anterior part of corpus-callosum and projecting to orbital lobe/AC-OL, 4-fibres emerging from anterior-midbody of corpus-callosum (CC) to motor cortices/AMB-PMC, 5- right-inferior-occipitofrontal fasciculus rIFOF as the control pathway unrelated to language. These values and their rate of change were compared between 3 groups. FA-values did not change significantly over two years for lAF/lSLF and AC-OL. Sequential-bilinguals had the highest degree of change in the MFA value of lIFOF, and AMB-PMC did not present significant group differences. The comparison of MFA of lIFOF yielded a significantly higher FA-value in simultaneous bilinguals compared to monolinguals. These findings acknowledge the existing difference of the development of the semantic processing specific pathway between children with different semantic processing procedure. These also support the hypothesis that age of second language acquisition affects the maturation and myelination of some language specific white-matter pathways.

Background and Purpose. To evaluate the added value of MRI with respect to peripheral quantitative computed tomography (pQCT) and dual energy X-ray absorptiometry (DXA) for predicting femoral strength.Material and Methods. Bone mineral density (BMD) of eighteen femur specimens was assessed with pQCT, DXA, and MRI (using ultrashort echo times (UTE) and the MicroView software). Subsequently biomechanical testing was performed to assess failure load. Simple and multiple linear regression were used with failure load as the dependent variable.Results. Simple linear regression allowed a prediction of failure load with either pQCT, DXA, or MRI in anr2range of 0.41–0.48. Multiple linear regression with pQCT, DXA, and MRI yielded the best prediction (r2=0.68).Conclusions. The accuracy of MRI, using UTE and MicroView software, to predict femoral strength compares well with that of pQCT or DXA. Furthermore, the inclusion of MRI in a multiple-regression model yields the best prediction.

Diffusion-weighted magnetic resonance imaging is a recognised tool in early detection of infarction of the human brain. If diffusion weighted-images with different values of b matrix are acquired during one individual investigation, it is possible to calculate diffusion coefficient maps that are elements of the diffusion tensor: they represent the apparent diffusion coefficient of protons of water molecules in each pixel in the corresponding sample. The relationship between signal intensity in the diffusion-weighted images, diffusion tensor and b matrix is derived from the Bloch equations. Our goal is to establish the error made in the calculation of the elements of the diffusion tensor when imaging gradients are ignored in the calculation of the b matrix elements. The numerical calculation of the b matrices show that a systematic error of up to 7% is introduced in the derived diffusion tensor elements when neglecting imaging gradients.

MR diffusion-weighted imaging (DWI) uses the signal loss associated with the random thermal motion of water molecules in the presence of magnetic field gradients to derive a number of parameters that reflect the translational mobility of the water molecules in tissues. In highly organized but asymmetric structures, this mobility may be affected by the obstacles present and this in a direction-dependent way. Important examples of this are white brain matter and the stem of certain plants, both containing fibrous components where diffusion of water molecules across fibers is much more restricted than along the fibers. Diffusion that exhibits such directional dependence is said to be anisotropic, and diffusion tensor magnetic resonance imaging allows localized characterization of this behavior. Interpretation of the information obtained in terms of the underlying tissue structure is often hampered by the complexity of factors that can produce the observed behavior. A phantom that exhibits well-defined anisotropic diffusion and yields sufficient signal can help the experimental testing of the relevant methods and models. In this paper, we have used a phantom consisting of asparagus stems as a test object for assessing the value of the acquisition and postprocessing techniques commonly used in the clinic for this kind of investigation. Because of its strongly fibrous and cylindrically symmetric morphology, exhibiting a well-defined sub-classification of cells on the basis of size and shape, asparagus allows a relatively simple interpretation of the results obtained in the diffusion experiments. Our experiments show that the known structural information about the main cell types encountered correlates well with the behavior patterns of the diffusion parameters.

Background In their daily communication, bilinguals switch between two languages, a process that involves the selection of a target language and minimization of interference from a nontarget language. Previous studies have uncovered the neural structure in bilinguals and the activation patterns associated with performing verbal conflict tasks. One question that remains, however is whether this extra verbal switching affects brain function during nonverbal conflict tasks. Methods In this study, we have used fMRI to investigate the impact of bilingualism in children performing two nonverbal tasks involving stimulus–stimulus and stimulus–response conflicts. Three groups of 8–11-year-old children – bilinguals from birth (2L1), second language learners (L2L), and a control group of monolinguals (1L1) – were scanned while performing a color Simon and a numerical Stroop task. Reaction times and accuracy were logged. Results Compared to monolingual controls, bilingual children showed higher behavioral congruency effect of these tasks, which is matched by the recruitment of brain regions that are generally used in general cognitive control, language processing or to solve language conflict situations in bilinguals (caudate nucleus, posterior cingulate gyrus, STG, precuneus). Further, the activation of these areas was found to be higher in 2L1 compared to L2L. Conclusion The coupling of longer reaction times to the recruitment of extra language-related brain areas supports the hypothesis that when dealing with language conflicts the specialization of bilinguals hampers the way they can process with nonverbal conflicts, at least at early stages in life.

OBJECTIVE: Bone density is distributed in a complex network of interconnecting trabecular plates and rods that are interspersed with bone marrow. A computational model to assess the dependence of the relaxation rate on the geometry of bone can consider the distribution of bone material in the form of two components: cylinders and open walls (walls with gaps). We investigate whether the experimentally known dependence of the transverse relaxation rate on the trabecular bone structure can be usefully interpreted in terms of these two components. MATERIALS AND METHODS: We established a computer model based on an elementary computational cell. The model includes a variable number of open walls and infinitely long cylinders as well as multiple geometric parameters. The transverse relaxation rate is computed as a function of these parameters. Within the model, increasing the trabecular spacing with a fixed trabecular radius is equivalent to thinning the trabeculae while maintaining constant spacing. RESULTS: Increasing the number of cylinder and wall gap elements beyond their nearest neighbors does not change the transverse relaxation rate. Although the absolute contribution to the relaxation due to open walls is on average more important than that due to cylinders, the latter drops off rapidly. The change on transverse relaxation rate is larger for changing cylinder geometry than for changing wall geometry, as it can be seen from the effect on the relaxation rate when trabecular spacing is varied, compared to varying the size of wall gaps. CONCLUSION: Our results provide strong evidence that trabecular thinning, which is associated with increasing age, decreases the relaxation rates. The effect of thinning plates and rods on the transverse relaxation can be understood in terms of simple cylinders and open walls. A reduction in the relaxation rate can be seen as an indication of thinning cylinders, corresponding to reduced bone stability and ultimately, osteoporosis.

Brain imaging studies have consistently shown subgenual Anterior Cingulate Cortical (sgACC) involvement in emotion processing. catechol-O-methyltransferase (COMT) Val(158) and Met(158) polymorphisms may influence such emotional brain processes in specific ways. Given that resting-state fMRI (rsfMRI) may increase our understanding on brain functioning, we integrated genetic and rsfMRI data and focused on sgACC functional connections. No studies have yet investigated the influence of the COMT Val(158)Met polymorphism (rs4680) on sgACC resting-state functional connectivity (rsFC) in healthy individuals. A homogeneous group of 61 Caucasian right-handed healthy female university students, all within the same age range, underwent rsfMRI. Compared to Met(158) homozygotes, Val(158) allele carriers displayed significantly stronger rsFC between the sgACC and the left parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus (IFG), and the nucleus accumbens (NAc). On the other hand, compared to Val(158) homozygotes, we found in Met(158) allele carriers stronger sgACC rsFC with the medial frontal gyrus (MFG), more in particular the anterior parts of the medial orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our sgACC rsFC results point to possible distinct differences in emotional and cognitive processes between Val(158) and Met(158) allele carriers. However, the exact nature of these directions remains to be determined.

Effect of amino acid administration on uremic muscle metabolism: A 31 P-spectroscopy study. The effect of a six-month peritoneal amino acid administration on muscle metabolism at rest and during exercise was examined in 12 patients (4 control and 8 amino acid treated) on continuous ambulatory peritoneal dialysis. 31 P-magnetic resonance spectroscopy was used to measure several high-energy phosphates (PCr, Pi) in resting muscle and during exercise and recovery. At rest, no significant changes were detected between the non-treated (control) and the amino acid treated (experimental) group. Before the administration of amino acids, the exercise-induced fall in [PCr], the increase in [ADP] and [Pi] and the pH were not significantly different in the control and experimental group. The initial rate of PCr recovery and the calculated maximal rate of ATP-synthesis (Q max ) for the control subjects was not significantly different at the onset and the end of the study. In the treated group, however, the fall in [PCr] and increase in [ADP] after exercise were significantly lower after than before treatment, while [Pi] and pH were identical. The initial rate of PCr recovery and Q max were also significantly improved. These changes indicate an improved oxidative phosphorylation under the treatment and suggest that the impaired oxidative metabolism of the dialysis patients could be the result of their bad nutritional state.

The study compared the results of three centrally reordered phase-encoded turboFLASH sequences for diffusion-weighted imaging (DWI). The sequences were conventional turboFLASH, turboFLASH with subtraction of T1-related effects, and turboFLASH with correction for T1-related effects during the imaging period only. The relative merits were studied with respect to image quality and accuracy by computer simulation and by experimental validation on phantoms and on in vivo rat brain. A T1-related underestimation of the diffusion coefficient ranging from -30% (T1 approximately 200 ms) to -5% (T1 approximately 1 s) was found to exist for the conventional sequence. Image artifacts, caused by longitudinal relaxation during the imaging period, are reflected in calculated diffusion maps. When the correction sequence is used, the artifacts and the systematic errors are reduced but longitudinal relaxation during the delay between preparation and imaging periods remains large enough to induce significant errors (-15% for T1 approximately 200 ms to -3% for T1 approximately 1 s). The subtraction sequence eliminates the influence of T1 effects on the calibrations, but leads to identical artifacts for all diffusion-weighted images.

Background: The left and right amygdalae are key regions distinctly involved in emotion-regulation processes. Individual differences, such as personality features, may affect the implicated neurocircuits. The lateralized amygdala affective processing linked with the temperament dimension Harm Avoidance (HA) remains poorly understood. Resting state functional connectivity imaging (rsFC) may provide more insight into these neuronal processes. Methods: In 56 drug-naive healthy female subjects, we have examined the relationship between the personality dimension HA on lateralized amygdala rsFC. Results: Across all subjects, left and right amygdalae were connected with distinct regions mainly within the ipsilateral hemisphere. Females scoring higher on HA displayed stronger left amygdala rsFC with ventromedial prefrontal cortical (vmPFC) regions involved in affective disturbances. In high HA scorers, we also observed stronger right amygdala rsFC with the dorsomedial prefrontal cortex (dmPFC), which is implicated in negative affect regulation. Conclusions: In healthy females, left and right amygdalae seem implicated in distinct mPFC brain networks related to HA and may represent a vulnerability marker for sensitivity to stress and anxiety (disorders).

The traditional approach to flow effects in MRI is based on the gradient moment expansion. Recently, we have presented an alternative description by using linear response theory: the distortions of the velocity waveform induced by the gradient waveforms were analyzed in the frequency domain on the basis of the transfer function. In the present paper, we perform an analysis of flow encoding and quantification in the time domain, on the basis of the impulse response. The analysis shows that flow encoding should be interpreted as a weighted averaging process. Instantaneous flow encoding is determined by the centroid of the impulse response, but care should be taken regarding the physical meaning of the instant of encoding. The relationship of this approach to the frequency domain and gradient moment expansion approaches is clarified. By way of example, some interesting applications are investigated: asymmetrical phase encoding gradients to minimize misregistration and oscillating read-out gradients for flow quantification. A variety of new applications are expected to derive from the combination of both the time and frequency domains.

The daily use of two languages may lead to conflict-specific brain adaptations in bilinguals. To evaluate the non-verbal conflict processing in bilingual children we compared simultaneous and sequential bilingual to monolingual 8-11 year old children in an fMRI study using a colour-Simon(stimulus-response) and a numerical Stroop (stimulus-stimulus conflict) paradigm. This provides a direct comparison of the performance on two kinds of conflict tasks.

Our purpose was the comparison of T1-weighted spin-echo (SE) and three-dimensional (3D) Turbo-fast low-angle shot (FLASH) (3DTFL) in detection of 14 pituitary microadenomas following intravenous gadolinium (Gd). 3DTFL represents an important improvement in the diagnosis of pituitary microadenomas. In two cases, the site of the tomour was correctly identified only by Gd-enhanced Turbo-FLASH. Nevertheless, in two other cases, the Gd-enhanced 3DTFL gave false negative (FN) results while the T1-weighted SE images enabled correct localisation. Replacement of T1-weighted SE by 3DTFL cannot therefore be advocated and use of both contrast-enhanced sequences of-fers the highest detection capability for microadenomas.

In the past, the anisotropic diffusion of water molecules in white matter in the brain has been correlated to the basic symmetry of the myelin fibers: water diffuses more readily along the fiber direction than perpendicular to it. As a consequence, diffusion sensitized magnetic resonance imaging can be expected to be useful for studying the fiber orientation. In this work, we present a method for exploiting this type of information to map the fiber orientations in the image plane. It makes use of three diffusion-weighted images with sensitizing gradients along x, y and u, an axis at 45° with respect to x and y. The orientation information contained in these images is summarized in a single image representing the angle between the fiber direction and a fixed axis, making use of a cyclic color scale. The method is evaluated using computer simulations for a variety of diffusion weighting strengths and signal-to-noise ratios, tested on a phantom and illustrated on an in vivo example. An extension to the determination of the fiber orientation in three dimensions is also described.

The two-compartment Tofts model (2CTM) has had widespread use in research and clinical practice. It assumes there is no broadening associated with the bolus transit through the capillary bed of the tissue under study. This assumption is often violated, with consequences that are hard to predict intuitively. The two-compartment exchange model is a generalization of 2CTM obtained by dropping the zero-broadening hypothesis, making it suitable for estimating the impact of violating this assumption. Using data simulated on the basis of the two-compartment exchange model, the correspondence between the hemodynamic parameters serving as input for the two-compartment exchange model and the parameters resulting from fitting the data with the 2CTM was investigated. The influence of tissue type and experimental setup was studied. Generally, a large tissue and setup dependent bias of the 2CTM fitting results with respect to the two-compartment exchange model input was observed. Extreme caution is needed when interpreting 2CTM data.

Repetitive transcranial magnetic stimulation (rTMS) studies investigating brain imaging correlates of emotion modulation in healthy volunteers can improve our understanding of the 'affective' impact of this application. In this fMRI study, we focused on lateralized amygdala functioning when processing salient emotional visual stimuli after one high-frequency (HF)-rTMS session. In a 'uniform sample' of 20 right-handed, non-depressed, healthy female subjects we examined whether one HF-rTMS session applied to the left (n=10) or right (n=10) dorsolateral prefrontal cortex (DLPFC) would influence amygdala responses to positively and negatively valenced baby faces. Subjects were given no other instructions than to focus on the emotion the visual stimuli elicited during scanning. One HF-rTMS session did not result in a conscious mood change. Whereas one left-sided HF-rTMS session did not affect amygdala processing of the positive or negative stimuli, after a single right-sided HF-rTMS session we found a significant right amygdala activity attenuation during the processing of negatively valenced baby faces. This finding provides additional evidence supporting the role of the right anterior hemisphere in the processing of negative emotional information, and increases our understanding of HF-rTMS treatment effects in mental disorders.

Objective Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion. Methods In this sham-controlled, single-blind crossover study using fMRI, we examined in 20 right-handed healthy females whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. Results While positive information was being processed, we observed after one active HF-rTMS session enhanced neuronal activity in the left superior frontal cortex and right inferior parietal cortex. After sham HF-rTMS, we found significant decreases in neuronal activity in the left superior frontal cortex, the left inferior prefrontal cortex, as well as in the right posterior cingulate gyrus. When negative information was processed, one active stimulation attenuated neuronal activity in the right insula only. Conclusions Our findings suggest that during the processing of positive information one active session enhanced the ability to empathize with the depicted emotional stimuli, while during the processing of negative information it resulted in decreased psychophysiological reactions. Significance These results provide new information on the working mechanism of left-sided HF-rTMS.

Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion.We carried out a sham-controlled single-blind crossover study using fMRI, we examined in 20 right-handed healthy female volunteers whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex (DLPFC) could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. A single HF-rTMS session selectively influenced the processing of positively and negatively valenced baby faces. In essence, our results indicate that the effects of one left-sided HF-rTMS sessions results in improved processing of positive emotions and reduced negative emotional processing in never depressed female subjects.

The psychobiological personality model of Cloninger distinguishes four heritable temperament traits (harm avoidance (HA), novelty seeking (NS), reward dependence (RD) and persistence (P)) and three character traits (self-directedness (SD), cooperativeness (CO) and self-transcendence (ST)) which develop during lifetime. Prior research already showed that individual differences in temperament are reflected in structural variances in specific brain areas. In this study, we used voxel-based morphometry (VBM) to correlate the different temperament and character traits with local gray and white matter volumes (GMV and WMV) in young healthy female volunteers. We found correlations between the temperament traits and GMV and WMV in the frontal, temporal and limbic regions involved in controlling and generating the corresponding behavior as proposed in Cloninger's theory: anxious for HA, impulsive for NS, reward-directed for RD and goal-directed for P. The character traits correlated with GMV and WMV in the frontal, temporal and limbic regions involved in the corresponding cognitive tasks: self-reflection for SD, mentalizing and empathizing with others for CO and religious belief for ST. This study shows that individual variations in brain morphology can be related to the temperament and character dimensions, and lends support to the hypothesis of a neurobiological basis of personality traits.

Object Spinal cord stimulation (SCS) is a well-known treatment option for intractable neuropathic pain after spinal surgery, but its pathophysiological mechanisms are poorly stated. The goal of this study is to analyse the feasibility of using brain MRI, functional MRI (fMRI) and Magnetic Resonance Spectroscopy (MRS) as tools to analyse these mechanisms in patients with externalised neurostimulators during trial period. Methods The authors conducted in an in vitro and in vivo study analysing safety issues when performing brain MRI, fMRI and MRS investigations in human subjects with externalised SCS. Temperature measurements in vitro were performed simulating SCS during MRI sequences using head transmit-receive coils in 1.5 and 3T MRI systems. 40 Patients with externalised SCS were included in the in vivo study. 20 patients underwent brain MRI, fMRI and another 20 patients underwent brain MRI and MRS. Results A maximal temperature increase of 0.2°C was measured and neither electrode displacements nor hardware failures were observed. None of the patients undergoing the MRS sequences at the 1.5 or 3T MRI scanners described any discomfort or unusual sensations. Conclusion We can conclude that brain MRI, fMRI and MRS studies performed in patients with externalised SCS can be safely executed.

OBJECTIVE: The present study aimed to assess the accuracy of peripheral quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) in assessing the cortical cross-sectional area (CCSA) at the level of the tibia. METHODS: Nine human whole-leg specimens were scanned with pQCT and MRI (T1-weighted and ultrashort echo-time [UTE] images) at 2 diaphyseal levels, 1 distal and the other 1 proximal. Subsequently, the bones were cut, and the CCSA was measured using digitized planimetry on the transverse sections. The correlation between CCSAs assessed via pQCT and MRI (T1 and UTE images) and assessed via planimetry, taken as a criterion standard, was evaluated using the Spearman rank correlation method. RESULTS: The mean (SD) CCSA with pQCT was 237.3 (54.3) mm2; T1-MRI, 228.8 (63.2) mm2; UTE-MRI, 178.5 (54.8) mm2; and planimetry, 250.17 (59.3) mm2. The CCSA measured with pQCT and T1-MRI was highly correlated with the planimetric CCSA (rho = 0.868 and rho = 0.880, respectively, P

Purpose: To prospectively evaluate whether dose reduction and the application of a prebolus technique can effectively alleviate signal saturation effects in T1 dynamic contrast enhanced (T1-DCE) magnetic resonance imaging (MRI) data in breast tumors and lead to increased diagnostic efficacy of the regional tumor blood flow (TBF) values obtained with deconvolution of T1-DCE MRI data. Materials and Methods: After obtaining informed consent, 23 women (32–80 years) with histologically proven breast tumors underwent MR mammography that included a whole-breast T1 DCE sequence. In the slice where the tumor enhanced maximally, a prebolus protocol was applied. One mL of Gd-DTPA solution at 2 mL/s was injected at the beginning of a dynamic axial single slice inversion-prepared turbo field echo acquisition. At the 400th dynamic, a high dose of either 20 mL (15 patients) or 10 mL (8 patients) of contrast agent was injected at 2 mL/s and a further 400 dynamics were acquired. From the aortic prebolus curve an arterial input function (AIF) was reconstructed by time-shifting and adding the prebolus data. The relative enhancement time course from the tumor region of interest was deconvolved with the reconstructed AIF to generate the impulse response function, the maximum of which yielded the TBF. The institutional ethical committee approved the study. Results: Reducing the contrast dose by a factor of 2 led to an increase in diagnostic contrast for the TBF values of malignant and benign tumors by a factor of slightly more than 2. Addition of the prebolus technique improved this further by 45%. receiver operating characteristic analysis showed a significant increase of diagnostic yield related to the combined use of a prebolus and minimal dose. Conclusion: Using a prebolus approach provides an estimate of the unsaturated AIF, while reduction of the high-dose bolus minimizes possible saturation effects in the tumor time course. J. Magn. Reson. Imaging 2010;31:556–561. ©2010 Wiley-Liss, Inc.

Current evidence concerning the neurocircuitry underlying the interplay between attention and emotion is mainly correlational. We used high-frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) to experimentally manipulate activity within the right or left dorsolateral prefrontal cortex (DLPFC) of healthy women and examined changes in attentional processing of emotional information using an emotional modification of the exogenous cueing task during event-related fMRI. Right prefrontal HF-rTMS resulted in impaired disengagement from angry faces, associated with decreased activation within the right DLPFC, dorsal anterior cingulate cortex (dACC) and left superior parietal gyrus, combined with increased activity within the right amygdala. Left prefrontal HF-rTMS resulted in diminished attentional engagement by angry faces and was associated with increased activity within the right DLPFC, dACC, right superior parietal gyrus and left orbitofrontal cortex. The present observations are in line with reports of a functionally interactive network of cortical-limbic pathways that play a central role in emotion regulation.

Background Research regarding the neurocircuitry in mood disorders suggests an important role for affective information processing of the subgenual part of the anterior cingulate cortex (Cg25: Brodmann area 25). Objective In this study, we focused on Cg25 neuronal responses in depressed females using a paradigm in which emotions are elicited without explicit cognitive control, relying on the salient nature of the mood inducing stimuli eliciting approach-related emotions (like happiness) or withdrawal-related emotions (like disgust). Methods Twelve treatment-resistant melancholic depressed women and 12 healthy female control subjects were asked to passively view blocks of emotionally valenced baby faces while undergoing functional magnetic resonance imaging (fMRI). Results Compared to the healthy females, the depressed patients displayed significantly higher bilateral Cg25 neuronal activities in both emotional conditions. In melancholically depressed women, we found significantly less left-sided than right-sided Cg25 neuronal activity during the withdrawal-related emotions, while right-sided Cg25 activity was comparable for both emotional responses. Conclusions Our results indicate that in depressed women the left Cg25 modulates intense visceral emotional responses to aversive visual stimuli. This could help explain why the left Cg25 provides a valid target region for antidepressant treatment strategies in unipolar melancholic depression.

The behavior of contrast enhancement between a microadenoma and the normal pituitary gland after gadolinium injection was evaluated in 12 operatively confirmed cases using a repetitive sequence of four coronal T1-weighted spin echo series (T1 SE) (continuous acquisition, TR = 400 ms), followed by conventional coronal T1 SE (TR = 600 ms) and a three-dimensional fast low-angle shot sequence. The first and second acquisitions were useful with respect to delayed scans only in 3 cases (25%). Nevertheless, in these cases confident diagnosis could also be made on pre-contrast studies, which diminishes the real advantage of this finding. For a 1.5 T MRI unit we advocate starting with coronal T1 SE 30 s after a rapid injection of gadolinium.

Introduction: After the introduction of the gate-control theory in 1965, the neurosurgeons were convinced they could control neuropathic back pain by placing a spinal cord stimulator (SCS) at the spinothalamic tract. Today, it is clear that the brain is playing a key role in the therapeutic effects of SCS and can make the difference between responders and non-responders to the therapy. This fMRI study focusses on the differences in brain activity related to SCS between responders and non- responders. Subjects and methods: All selected patients suffered from pain in the lower back and left leg for at least three years. Seven patients were responders and four non-responders. The fMRI-experiment was performed 1 week after implantation of a spinal cord trial stimulator (Medtronic, USA). The stimulation parameters were optimized for each patient. Patients were not allowed to use pain medication or SCS on the day of the fMRI-experiment. During the fMRI measurement, 30s blocks with and without stimulation were alternated while the patient had to rate his/her pain continuously on a VAS-score in order to focus attention on the pain. All scans were done on a 1.5T Philips MRI-scanner with an EPI (TR/TE=3000/35ms; 30 slices; thickness/gap=3/1mm;dynamic time=3s) sequence. Due to our small number of patients we only performed a fixed-effects analysis using SPM5. Results: The results are summarized in figures 1-4. Thresholding corresponding to p(uncorrected)In the responders group we found reactions in regions involved in sensory (S1/S2), affective (ACC) and cognitive (frontal) processing of pain and the thalamus. In the non-responders group, a different and much more complex pattern of brain activity was found with no reaction at the thalamus and a different pattern of cingulate activity (fig.5). Discussion/Conclusion: Where the gate-control theory states that pain can be controlled by switching a relay at the spine by SCS, our results suggest that the therapeutic effects result froman inhibition of thalamic activity. The thalamus act as a gate to cerebral pain processing and has connections to all other pain processing regions like the ACC which act as a regulator for pain related behavior (1). These results are in line with a PET study (2) on a more general group of chronic pain patients. References: (1) Saadé NE. (2008); Progress in Neurobiology; 86:22-47 (2) Nagamachi S. (2006); Anals of Nuclear Medicine; 20:303-310

Research regarding the lateralization of processing emotional visual stimuli suggests various roles for affective information-processing by the amygdalae. However, individual differences seem to influence outcome results. In this study we re-investigate this question, paying special attention to the salient nature of the mood inducing stimuli. We presented blocks of happy looking baby faces and sad looking baby faces (disfigured by severe dermatological conditions), as well as blurred isoluminescent neutral pictures to a 'homogeneous' group of 40 healthy female subjects during fMRI. We used the temperament dimension harm avoidance (HA), extracted from the Temperament and Character Inventory (TCI), to evaluate the impact of this personality feature on 'emotional' amygdala responses. HA is related to behavioral inhibition and it implies a genetically determined bias towards being cautious, apprehensive and overly pessimistic. Because emotional valence and arousal may be controlled by different neural systems, the positively and negatively valenced baby faces were selected to be equal in arousal levels. Viewing blocks of negatively valenced baby faces evoked bilateral amygdala activity, whereas viewing positively valenced ones resulted in left amygdala activity only. Globally, we found no evidence of lateralized amygdala specialization. When taking into account individual differences in HA, only in female subjects who score high on this dimension did we find predominantly left amygdala activation when viewing blocks of negatively valenced baby faces. HA did not influence amygdala activity when processing positively valenced images. Our results might indicate that personality features, such as HA, could be of importance in 'emotional' fMRI paradigms examining amygdala lateralization patterns.

Introduction: Perfusion estimates based on T1 weighted dynamic contrastenhanced (DCE) MRI have been shown to be promising for non-invasive breast tumor characterisation and assessment of anti-angiogenic treatment [1]. The exam is usually performed in the context of a comprehensive MR protocol that also comprises standard morphologic imaging as well as low temporal resolution bolus tracking, both at high spatial resolution. The protocol routinely uses a dedicated breast coil, characterised by a non-uniform spatial response [2]. Quantitative analysis of the DCE data requires translation of the acquired signals to contrast agent concentrations, typically on the basis of a signal-concentration calibration curve and scanning of a reference fluid of known concentration with the patient [3]. The aim of this study was to determine the influence of the presence of the breast coil on this procedure on a 3T system. Materials and Methods: The measurements were performed on a Philips 3T Achieva MR system. The T1-weighted turbo field echo (TFE) sequence was acquired with the same parameters as those selected for breast perfusion studies (TR/TE:4.9msec/2.4msec, non- selective 180° prepulse, inversion time 196ms, 128x90 matrix, FOV43 cm, slice thickness 6mm, temporal resolution of 0.3s). MR images of multiple 20mm-diameter syringes filled with different concentrations of contrast agent (0-4 mmole/l Gd-DTPA solution in saline) were obtained with the quadrature head coil and the corresponding signal vs concentration curve was fitted to provide a calibration curve. In order to mimic the in vivo concentration determinations and assess the effect of rf inhomogeneity, 4 syringes were placed inside the 7 channel breast coil (Figure 1) and imaged for each of four cyclical permutations of these syringes, with either the breast coil or the built-in body coil (breast coil present but not used). The syringe of highest concentration was subsequently used as reference for the concentration determinations. The root mean square (rms) procentual deviation between measurement and known concentration was used as a figure of merit. Results: The resulting concentrations (Figure 2) depend strongly on the position of the syringes inside the breast coil. In spite of the lower SNR obtained, detecting the signals with the body coil instead of the breast coil leads to a significant improvement of the results, with mean rms percentages dropping from 27% to 10%. References: [1] Makkat et al. [2008] Radiology, accepted [2] Makkat et al [2007] J Magn Reson Imaging;25(6):1159-67. [3] Makkat et al. [2008] Proc ISMRM;16;3563

Introduction: Transcranial magnetic stimulation (TMS) is a method to noninvasively disrupt brain activity and which can be combined with fMRI to study brain activity and connectivity. The feasibility of this combination of techniques has been shown earlier [1] and problems due to the interference of electromagnetic fields, have been explored [2]. This study focuses on the timing of the TMS stimulation pulse during the fMRI measurements. Methods: Measurements were performed on a Philips Achieva 3T MR scanner on a spherical phantom (diameter = 18cm) filled with distilled water doped with sodium acetate and lithium lactate. TMS pulses were applied using an MR-compatible butterfly TMS coil (20cm x 10cm) and a Rapid stimulator, both from The Magstim Company. The coil was connected to the stimulator outside the RF-shielded room with an 8m cable running through one of the waveguides. No RF filter was used. Timing of the TMS pulses was controlled with microsecond accuracy using a USB-6251 data acquisition device from National Instruments. Due to the limited space inside the standard RF volume head coil, an elliptical two element flexible surface coil (14cm x 17cm) was used instead to accommodate the TMS coil. The surface coils were positioned to the left and right side of the phantom mimicking the clinical situation. The TMS coil was placed horizontally in two different positions: inferior and posterior to the phantom (Figure 1). For both positions of the TMS coil, images were acquired of single slices parallel to the coil at 2cm and 4cm distance using a single shot EPI sequence (TR=1000ms, TE=35ms, 64x64 matrix, 3.6x3.6x5 resolution). For each acquisition of the slice, the time between the RF excitation pulse and a single TMS pulse with maximum stimulator output was increased with 1ms steps. Results: Figure 2 shows the signal intensities in the measured slices as a function of the delay between a single TMS pulse and the RF excitation pulse of the EPI sequence. Conclusions: When the TMS pulse is applied less than 65ms before or less than 50ms after the RF excitation pulse of the EPI sequence, signal loss occurs in sections at both distances. This results in a period of about 115ms during which no TMS pulses should be applied. For the posterior positioning of the TMS coil, a stronger signal loss is noted. References: [1] Bohning, D.E., 1998, Investigative Radiology, 33:336-340 [2] Bestmann, S., 2003, J. Magn. Reson. Imaging, 17:309-316.

Purpose/Introduction: An accurate assessment of the Tumor Blood Flow (TBF) can become crucial for breast cancer management. Earlier studies have demonstrated the feasibility of quantifying perfusion parameters in human breast tumors using a deconvolution analysis of DCE-MRI. However, the TBF values were on average higher than the literature PET values. Earlier in myocardium, it has been shown that a prebolus method will allow the use of high concentrations of contrast agent for tissue analysis, in combination with a lower concentration bolus to maintain the linearity of AIF signal intensity. The aim of the present study was to evaluate the use of the prebolus technique in a small cohort of breast tumors. Subjects and Methods: In vivo perfusion measurements were performed in 23 women with breast tumors on a 1.5 T scanner. The routine MR mammography protocol was applied first. At the slice where tumor enhances maximally, the prebolus protocol was applied 10 minutes later. 1ml of Gd- DTPA solution at 2ml/s was injected at the beginning of a dynamic axial single slice inversion-prepared (IR prepared) TFE acquisition (800 dynamics with a temporal resolution of 0.3s). At the 400th dynamic, a high dose of either 10ml (8 patients, 5 malignant and 3 benign) or 20ml (15 patients, 11 malignant and 4 benign) of contrast agent was injected at 2ml/s and a further 400 dynamics were acquired. ROIs were placed manually over the aorta and the region within the breast lesion with highest enhancement. From the prebolus curve, AIFs were reconstructed by time-shifting and adding the prebolus response curve until the relevant high dose equivalent was reached. The RE time course from the tumor ROI was then deconvolved to generate the parametric maps. Results: Whether the TBF calculation was performed with or without prebolus AIF estimation, the median TBF was higher in malignant tumors compared to the benign ones (p

One of the limitations of a multimodality PET/MR scanner is the lack of an attenuation map to correct the PET image for attenuation. Some methods have been developed for deriving the attenuation map from a magnetic resonance image. However, the very low signal intensity of cortical bone in images acquired with conventional MR sequences makes it difficult to distinguish this tissue type from air, while they have strongly different attenuation coefficients.

no abstract available

Introduction: MR derived Tumor Blood Flow (TBF) has the potential to become a noninvasive angiogenic marker that could also be explored in the context of anti-angiogenic therapies for which in vivo biomarkers are currently lacking [1]. Thus, an accurate assessment of TBF can become crucial in deciding the best management for breast cancer patients. We have recently shown the feasibility of quantifying perfusion parameters in human breast tumors using a deconvolution analysis of second bolus Dynamic Contrast Enhanced MR (DCE MR) data [2,3]. In these studies, after locating the lesion on low temporal resolution first bolus post contrast subtracted images, a second bolus injection of the same dose was administered during a single slice high temporal resolution dynamic inversion-prepared turbo field echo sequence. However, the mean TBF values reported in these studies were higher than the results from PET studies [4]. We believe that the methodology described in these reports establishes only a baseline for further improvements in either acquisition or post processing schemes. Factors presumed to affect the TBF estimation are given in Figure 1. In this work, we explore three different key aspects of acquisition/ post processing strategies to improve the accuracy of TBF assessment namely contrast bolus dose, Flip Angle (FA) and tracer concentration C(t) estimation. Materials & Methods: The slice where the tumor enhanced maximally was identified on the subtracted low temporal resolution whole breast first bolus dynamic data on a 1.5 T scanner (Philips Intera). High temporal resolution (360 ms) DCE MR data were acquired during the passage of a second bolus at that slice position using an inversion-prepared turbo field echo sequence (TR/TE/TI 4.9ms/2.4ms/196ms 128x67 matrix reconstructed at 256x204, FOV 230x183 mm2, slice thickness 6 mm, 600 images). The three key aspects in the acquisition/ post processing strategies that were evaluated were (1) Effect of contrast dose reduction on signal saturation and Signal to Noise Ratio (SNR) [5]. (2) Effect of varying FAs in the context of inflow effects and signal saturation [6]. (3) R1 calibration either with a two point method (two FA, 5° & 50°; local calibration) or with a phantom of known concentration (global calibration). Image post-processing was performed on a personal computer using software written inhouse in IDL [7]. Results: The main results of the optimization studies are: (1) At low FA (12°) there is virtually no first-pass peak in the AIF at higher doses, but, as the dose is reduced, a clear peak appears with signs of saturation even at the lowest second bolus dose (5ml). However inflow fluctuations are minimal. At high FA (50°) on the other hand, in spite of the presence of a first pass peak in the AIF at all concentrations, severe inflow fluctuations obscure the intensity curve.(2) Reduction of the contrast dose from the 20 ml standard injection greatly impairs the SNR in the tumor tissue using both FAs. (3) The two point calibration method yields inaccurate R1 estimation due to adding up of errors in multiple steps of R1 quantification. Global calibration in combination with using the body coil reduces the already compromised SNR and also suffers from B1 inhomogeneity due to the simultaneous presence of the breast coil. Relative enhancement (RE) can be accepted as an alternative if local concentrations stay low. Conclusion: In breast tumors, with the existing second bolus method, simultaneous accomplishment of an unsaturated AIF curve and a tissue curve with adequate SNR are diverging demands. To achieve an accurate TBF quantification within these constraints, use can be made of a prebolus technique [8] in a low FA sequence with RE as the tracer concentration estimate (Figure 1). In the prebolus technique, a low dose prebolus provides data that permit reconstruction of an accurate AIF, while a subsequent high dose bolus allows acceptable tumor SNR (Figure 2). Our preliminary results in a small cohort of breast tumors suggest that TBF values comparable to PET based literature values can be obtained by this approach (data not shown). References [1] Pollitt et al. [2005] Oncol Rep.;13(5):931-6. [2] Makkat al [2007] J Magn Reson Imaging;25(6):1159-67. [3] Makkat et al [2007] ISMRM 15:280. [4] Vaupel et al [2000] Int J Oncol 17 869-79 [5] Makkat et al. [2006] ESMRMB 23 783 [6] Sourbron et al [2005] ESMRMB 22 518 [7] Sourbron et al. [2007] Phys Med Biol ;52:429-447. [8] Kostler et al. [2004] Magn Reson Med.;52:296-299

In the therapy of depression, repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has been introduced. A crucial problem in rTMS-studies remains the exact localization of the coil with respect to the DLPFC. In most studies, the coil position is determined by identifying the subject's motor cortex and moving the coil 5 cm more rostrally from this point. This standard coil positioning method is based on the Talairach atlas and does not take in account individual anatomy. In our study we introduced an individualized method based on a 3D MRI of the head, the "3D-MRI system". The coil position was derived as the projection of the DLPFC on the skin, defined on a 3D Surface rendering of the brain relative to the nose and the right ear. To evaluate the importance of introducing individual anatomical information during coil positioning, we compared both localization techniques on 36 female volunteers. We found a mean shift between both positions of 27?14 mm.The individual positions found with the 3D-MRI system, show a variation of 18?8mm with respect to the mean coil position. Our results show the need for an rTMS-coil positioning method which incorporates anatomical information. The combination with MRI-imaging techniques can be an option. Introduction: Several studies have shown the therapeutic value of repetitive transcranial magnetic stimulation (rTMS) in depression and other psychiatric disorders (2). Although the best stimulation region for rTMS-treatment is still an issue of debate, most neuroimaging findings suggest the left dorsolateral prefrontal cortex (DLPFC) as target site (1). Crucial in rTMS-treatment is the accurate positioning of the rTMS-coil over the stimulation area. Standard methods for coil positioning are derived from the Talairach atlas (3) and do not take in account any individual anatomical information. The aim of our study was to show the importance of incorporating individual anatomical information when determining the coil position by comparing a standard method, the "5-cm rule", with an rTMS-MRI combined method, the "3D-MRI system". Materials and methods: We included 36 healthy female subjects (mean age 25?6 years) in the study. Exclusion criteria conformed the current guidelines for rTMS and MRI research. The local medical ethics committee approved of the study and all subjects gave informed consent. The standard method for coil positioning is the "5-cm rule": the DLPFC is defined as 5 cm rostral to the motor cortex (Fig 1.A). In this case the motor cortex is identified by stimulating the brain with an rTMS-stimulator (Magstim Company, Wales, UK) by looking for the maximum response recorded with EMG over the right musculus abductor pollicis brevis. To introduce individual anatomical information, all subjects underwent a T1-weighted MRI (3D-TFE, voxel size 1x1x1 mm) of the brain using a 1.5T Intera Figure 1 - (A) Schematic representation of the 5-cm rule: the DLPFC is defined 5 cm rostrally as the motor cortex (MC).(B) Schematic representation of the 3D-MRI method: the DLPFC is defined by the distances from right ear to top (|R-T|), from nose to top (|N-T|) and from top to DLPFC (|T-D|). An example is shown in (D). (C) Comparison of both methods: the distance and angle between both positions are calculated as defined in the figure. (Philips, Best, the Netherlands) MR scanner. All post processing was done on a ViewForum (Philips, Best, the Netherlands) console. We located the DLPFC visually on the 3D surface rendering of the brain based on the known gyral morphology. The corresponding coil position was found by making the projection on the skin. On a 3D-reconstruction of the head we marked 4 reference points: right ear, left ear, vertex and nose. A fifth reference point, top, is found as the crossing between two axes: one from right ear to left ear through the coil position and one from nose to vertex. For an accurate determination of the coil position on a patient's head, we measured the distance from nose to top, from right ear to top and from top to the coil position (Fig 1.B and 1.D). To compare both positioning methods, the subjects were wearing a tight fitting bathing cap on which we drew two reference axes, one from right ear tot left ear and one from nose to atlas. We measured the coordinates of both positions relative to the vertex, the crossing of both reference axes. We calculated the distance between both positions and the angle between the axis passing both positions and an axis perpendicular to the reference axis from nose to atlas (Fig 1.C). We compared the positions found with the standard method to the respective positions found with the 3D-MRI system and we compared the individual positions to the mean position found with the 3D-MRI technique. Results: Comparison between the 5-cm rule and the 3D-MRI system, shows a mean shift between both positions of 27?14 mm and an angle of -11?66° (Fig 2). In most subjects, the standard method positioned the DLPFC too rostrally. To measure the dispersal of the individual positions, we compared these individual positions with the mean position of the DLPFC as determined with the 3D-MRI system. We found a mean shift of 18?8 mm and a mean angle of 15?101°. These results demonstrate that the exact position of the DLPFC is highly individual. Discussion: A previous comparison of the standard method to a neuronavigational method showed that the current positioning method used in rTMS-studies easily fail to target the DLPFC (5). Our study confirms this result. Where Uwe focused more on whether his method positioned the DLPFC more dorsally or rostrally in comparison to the standard method, we focused on the dispersal of the individual positions. This individual heterogeneity can be a reason for the heterogeneous outcome of rTMS-treatment effect studies. If we would like to improve the efficacy of this promising technique, we should use coil positioning techniques witch take the individual anatomy in account. Making the combination with imaging techniques like MRI can be a solution. Conclusions: To improve the coil positioning in rTMS-therapy, new methods like the 10-20 EEG-system (4) and the neuronavigational system (6) are introduced. In the 10-20 EEG-system, the positioning of the DLPFC is relative to the electrode positions used in EEG-recordings. This method has still the drawback that it is determined from the Talairach brain and does not really account for anatomical differences between individuals. In the neuronavigational system, recordings of the head with a 3D-camera are coregisterd to MRI-images. This method is accurate and does take in account individual anatomy but it is very complex to perform. In our 3D-MRI system we made a combination of common software tools used on an MRI-site and tools used in psychiatry. The new positioning method is as easy to perform as the standard method but takes individual anatomy in account.

Introduction: Studies have shown a different activation pattern in the limbic and prefrontal regions between normal subjects and depressed patients who are looking at positively or negatively valenced pictures [1]. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has been introduced as a therapeutic tool for depression. Although a reduction of depressive symptoms in patients after rTMS-treatment has been reported [2], the interaction effects with the brain still remain unclear. We have investigated the effect of one rTMS-session on brain activation with fMRI with a passive viewing protocol. Methods: 19 non-depressed female subjects (25±5 years) who conformed the current guidelines for rTMS and MRI research where included. 10 underwent an active rTMS-session (10Hz; 40 trains of 3.9s; intertrain interval=26.1s) while 9 underwent a sham session. Just before and 1h after the rTMS-session, we performed an fMRI experiment consisting of 20s duration blocks of pictures of happy, pitiful and scrambled baby faces as positive, negative and neutral blocks respectively. All volunteers were asked to empathize with the facial emotions as much as possible. We measured 127 EPI images (TR/TE=3000/35ms; 18 slices; matrix size=64x64) with a 1.5T Philips MRI scanner. Results: In SPM5, we calculated for each individual and each fMRI-session the percentage signal change maps for the contrasts "positive versus neutral" and "negative versus neutral". On these maps we performed an ANOVA analysis "before versus after x active versus sham". For the first contrast, interactions (rTMS-treatment effects) were found at the temporal gyrus (BA21/22) bilateral, the right cingulate gyrus (BA24/31), the left frontal gyrus (BA10/11) and the right frontal gyrus (BA6/9/10). For the second contrast, interactions were found at the left temporal gyrus (hippocampus) the cingulate gyrus (BA24/32) bilateral and the left frontal gyrus (BA9). The interaction clusters were identified on an F-statistic image with p(unc)10 pixels. Conclusions: By measuring the second fMRI 1 hour after the rTMS-session, we looked at the impact of one rTMS-session on mood processing. Although studies observed no subjective mood changes in healthy volunteers [3], we found interactions at the cingulate and frontal gyri. Metabolic changes and changes in brain activity in these regions are shown to correlate with an antidepressant treatment response [4,5]. References: [1] Lee B.T.(2007): Progress in Neuro-Psychopharmacology & Biological Psychiatry;31:1487-1492 [2] Schutter DJ.(2008): Psychological medicine;30:1-11 [3] Baeken C.(2008): Clinical Neurophysiology;119:568-575 [4] Yu C.H.(2007): American Journal of Psychiatry;164:599-607 [5] Luborzewski A.(2007): Journal of Psychiatric Research;41:606-615

The usefulness of different magnetic resonance (MR) imaging sequences (coronal and sagittal spin-echo [SE] and three-dimensional fast low-angle shot [3D FLASH]) in the detection of pituitary microadenomas before and after gadolinium injection was prospectively evaluated in 28 patients with surgical confirmation. When evaluated separately, the most useful sequences in the detection of these microadenomas were coronal pregadolinium T1-weighted SE, coronal pregadolinium 3D FLASH, coronal postgadolinium T1-weighted SE, and coronal postgadolinium 3D FLASH. The combination of pre- and postgadolinium T1-weighted sequences with pre-and postgadolinium 3D FLASH sequences produced the highest number of true-positive findings (90%) and the lowest number of false-positive findings (5%). When a 1.5-T imaging unit with a high signal-to-noise ratio allowing useful three-dimensional acquisition is used, the authors advocate a coronal T1-weighted SE sequence, followed (if necessary) by a coronal 3D FLASH sequence, both without injection of gadolinium, in the diagnosis of pituitary microadenomas. When no confident diagnosis is reached, the same sequences should be performed after the injection of gadolinium. The sagittal pre- and postgadolinium T1-weighted SE and long-TR SE sequences are useful only in specific cases.

Purpose To test the feasibility of using a second-bolus injection, added to a routine breast MRI examination, to measure regional perfusion and permeability in human breast tumors. Materials and Methods In 30 patients with breast tumors, first a routine whole-breast T1-DCE sequence was applied, and the slice where the lesion enhanced maximally was located. At that slice position, T1-weighted MR images were acquired at 0.3-second resolution using a second-bolus dynamic inversion recovery (IR)-prepared turbo field echo (TFE) sequence. A pixel-by-pixel model-independent deconvolution of the relative signal enhancement was performed to estimate the tumor blood flow (TBF), tumor volume of distribution (TVD), mean transit time (MTT), extraction flow product (EF), and extraction fraction (E). In addition to this pilot study, a first appraisal of its sensitivity to tissue type was made on the basis of a small patient cohort. Results In the malignant tumors, the parametric maps clearly delineated tumors from the breast tissue and enabled visualization of the heterogeneity. The deconvolution analysis provided objective parametric maps of tumor perfusion with a mean TBF (84 ± 48 mL/100 mL/minute) in malignant tumors in the high range of literature values. Conclusion In terms of these perfusion values, our method appears promising to quantitatively characterize tumor pathophysiology. However, the number of patients was limited, and the separation between malignant and benign groups was not clear-cut. Additional parameters generated through compartment modeling may improve the tumor differentiation. J. Magn. Reson. Imaging 2007;25:1159–1167. © 2007 Wiley-Liss, Inc.

Purpose/Introduction: Renal MRI has the potential to provide anatomical and functional information [1-3]. The aim of this study was to determine the age dependence of T1-DCE MRI based renal blood flow heterogeneity in normal kidneys and to compare it with the results obtained in some examples of renal pathology. Subjects and Methods: Imaging was performed in 15 subjects without known renal disease and in three pathological cases. Average normal patient age was 50 years (SD 18). The pathological cases included an acute renal failure (ARF) at week 0 and 3, an end stage glomerulonephritis (GN) and a significant left renal artery stenosis (RAS) with mild right RAS. All experiments were approved by the local ethical board. Single slice IR-prepared Flash (TR 4.4 ms/ TE 2.2 ms/ TI 180 ms/ FA 50°/ matrix 128*256/ dynamics 400, temporal resolution 0.3 s/slice) was performed during the injection of 10 ml Gd-DTPA. Perfusion post-processing was performed offline using software written in-house in IDL. Signals were converted to tracer concentrations and deconvolved with an aorta AIF with a optimized deconvolution procedure [4]. Parametric maps of renal blood flow (RBF) were calculated. The parameter renal blood flow heterogeneity H(RBF) was introduced in analogy with the approach in histopathology as the standard deviation of the cortex RBF divided by RBF and calculated in each patient. The age dependence of H(RBF) in the normal group was studied. Results: Figure 1 presents a plot of H(RBF) versus age in the normal group. The data did not allow a significant correlation between these two parameters to be established (Pearson r = 0.3 , p = 0.1). The values of H(RBF) in the pathological cases (as well as the average results in the normal group for comparison) are presented in the figure 2. The bar graph indicates an increased H(RBF) in the glomerulonephritis case and a slightly lowered value in the acute phase of renal failure. No difference with normal values was found for the acute renal failure after recovery and in the patient with RAS. Discussion/Conclusion: While at first glance there does seem to be a tendency for H(RBF) to increase with age, this tendency cannot be established statistically on the basis of the present data. It would, however, be consistent with literature on aging [5] and with findings on heterogeneity of cortical circulation based on semi-quantitative measurements in CT [6]. The sensitivity of the technique to demonstrate altered blood flow heterogeneity in the cases of some significant pathology was shown in the pathological examples. The observed reduction in the case of ARF could be explained by the need to access somnolent glomeruli in kidney failure. At present, there is no obvious explanation for the increase in case of GN. More data are needed to confirm these preliminary findings. References: [1] Hermoye L. (2004) MRM 51: 1017-1025 [4] Sourbron S. (2004) PMB 49: 3307-3324 [2] Schoenberg S. (2003) MRM 49: 288-298 [5] Ueda K. (1974) NRIZ 11:147-156 [3] Dujardin M. (2005) MRM 54: 841-9 [6] Kojima S. (2000) AJH 13:346-352

Purpose: Dynamic Contrast Enhanced MRI is a promising non-invasive method for imaging renal perfusion and function [1-5]. The feasibility of voxel-by-voxel perfusion mapping based on deconvolved T1-DCE renal data has already been shown by our group [5]. This study compares the values of perfusion with this method between three different age groups. Methods: Measurements were performed in the supine position at 1.5 T on 15 humans without known or suspected renal disease. The three different age groups were: 20 to 35 years (group A, 5 patients), 50 to 60 years (group B, 6 patients) and above 70 years (group C, 4 patients). Average age was 28 years (SD 7) , 53 years (SD 3) and 72 years (SD 1) respectively in group A, B and C. All experiments were approved by the local ethical board. The first pass of 10 ml Gd-DTPA, injected by power injector at 2cc/s, was acquired using single slice axial IR-prepared Flash (FA 50 °, TI 172 ms, TR 4.4 ms, TE 2.2 ms, slice thickness of 4 mm, matrix size of 128*256, temporal resolution 0.3s/slice ). Postprocessing was performed offline on a personal computer using software written in-house in IDL for Linux (Research Systems, Boulder, CO). Signals were calibrated by using a test tube containing 2mM Gadolinium in saline solution placed in the FOV during the measurement. Signals were converted to tracer concentratios and an arterial input function (AIF) was selected manually in the aorta. The tissue time courses were deconvolved using standard-form Tikhonov regularization and the L-curve criterion for selection of the regularisation parameter [6]. A simple inflow correction was applied. Parametric maps of renal blood flow (RBF), renal blood volume (RBV) and mean transit time (MTT) were calculated as the maximum of the impulse response function (IRF) , the time integral of the IRF and the ratio RBV/ RBF. Only the vascular part of the data (manual cut of at the start of the plateau following the vascular peak in the tracer time courses) was used for calculation in order to estimate RBV.Whole cortical measures of RBF, RBV and MTT were calculated of whole left and right cortex ROIs, drawn on the RBF images. Results: Parametric images with sufficient contrast to noise were obtained in all patients. Figure 1 illustrates a typical result for the quantitative parametric maps of RBF in a patient from each age group. The average results of RBF, RBV and MTT for the different age groups are given in figure 2. Average RBF was 2.1 ml/min/ml with SD 0.5 ml/min/ml (group A), 1.3 ml/min/ml with SD 0.5 ml/min/ml (group B) and 1.5 ml/min/ml with SD 0.7 ml/min/ml (group C). Average RBV and MTT were 0.3 ml/ml SD 0.1 ml/ml and 9s SD 3s (A), 0.3 ml/ml SD 0.2 ml/ml and 11s SD 2 s (B) and 0.3 ml/ml SD 0.06 ml/ml and 13 s SD 4s (C). Based on non parametric statistics (Mann-Whitney), the difference in RBF of age group A and B (p=0.004) and A and C (p=0.03) is significant, while RBF of group B and C (p=0.7) is not significantly different. When we compare RBV, we found no difference between group A and B (p=0.7), group A and C (p=0.6) and B and C (p=1), respectively. For MTT, the results indicate a significant difference between group A and B (p=0.02) and A and C (p=0.004),respectively and no significant difference between group B and C (p=0.8). Conclusion: RBF values are lower than those found in the literature [2,3,8]. This is presumably due to dispersion and/or remaining inflow effects on the AIF estimate: flow related enhancement causes an overestimation of the arterial input function and therefore an underestimation of the perfusion values [9]. The results in these preliminary data suggest a significant difference between RBF and MTT in young patients compared to patients of >50 years, which seems in agreement with physiological considerations since especially in the age group of over 50, more sclerotic glomeruli are found in the healthy population [10]. Although preliminary and highly speculative, study of such physiological mechanisms of pathology with this patient friendly technique seems interesting. References: [1] Hermoye L. et al (2004) MRM 51: 1017- 1025 [2] Schoenberg S. et al (2003) MRM 49:288-298 [3] Aumann S. et al (2003), MRM 49: 276- 287 [4] Pedersen M. et al (2004) Proc. ISMRM 11:879 [5] Dujardin M. et al (2005) MRM 54(4):841-9 [6] Sourbron S. et al (2004) PMB 49:3307-3324 [8] Hierholzer K (1999) Physiologie des Menschen:737-776 [9] Ivancevic M. et al (2003) Proc. ISMRM 11:149 [10]Kaplan C. et al (1975) Am J. Pathol 80(2): 227-34

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