The effect of one left-sided dorsolateral prefrontal sham-controlled HF-rTMS session on approach and withdrawal related emotional neuronal processes.

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.

Error estimation for perfusion parameters obtained using the two-compartment exchange model in dynamic contrast-enhanced MRI: a simulation study.

In theory, the application of the two-compartment exchange model (2CXM) to data from a dynamic contrast-enhanced (DCE) MRI exam allows the estimation of the plasma flow, plasma volume, extraction flow and extravascular-extracellular volume. The aim of this paper was to explore whether simulations based on the 2CXM could provide useful information on the trustworthiness of the results. The deviations from the input values of the haemodynamic quantities were estimated for a 'reference tissue' with a clear bi-phasic response and four 'limit tissues' with more challenging 2CXM fitting properties. The impact of the instrumental factors sampling step (T(s)), acquisition window (T(acq)) and contrast-to-noise ratio (CNR) was investigated. Each factor was varied separately, while keeping the other ones at a value above concern. Measurement guidelines to ensure that all deviations fell within a predefined range (±20%) could not be derived, but simulations for fixed T(s) and T(acq) were found to provide a practical tool for studying the error behaviour to be expected from a given experimental set-up and for comparing measurement protocols. At the level of an individual DCE exam, a bootstrap version of the simulation approach was shown to lead to a useful estimate of the errors on the fitted parameters.

Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females.

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.

Reduced left subgenual anterior cingulate cortical activity during withdrawal-related emotions in melancholic depressed female patients.

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.

Deconvolution of bolus-tracking data: a comparison of discretization methods.

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 perfusion and permeability in breast tumors with a deconvolution-based analysis of second-bolus T1-DCE data.

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.

Pixel-by-pixel deconvolution of bolus-tracking data: optimization and implementation.

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.

Quantification of renal perfusion and function on a voxel-by-voxel basis: a feasibility study.

The feasibility of a voxel-by-voxel deconvolution analysis of T(1)-weighted DCE data in the human kidney and its potential for obtaining quantification of perfusion and filtration was investigated. Measurements were performed on 14 normal humans and 1 transplant at 1.5 T using a Turboflash sequence. Signal time-courses were converted to tracer concentrations and deconvolved with an aorta AIF. Parametric maps of relative renal blood flow (rRBF), relative renal volume of distribution (rRVD), relative mean transit time (rMTT), and whole cortex extraction fraction (E) were obtained from the impulse response functions. For the normals average cortical rRBF, rRVD, rMTT, and E were 1.6 mL/min/mL (SD 0.8), 0.4 mL/mL (SD 0.1), 17s (SD 7), and 22.6% (SD 6.1), respectively. A gradual voxelwise rRBF increase is found from the center of two infarction zones toward the edges. Voxel IRFs showed more detail on the nefron substructure than ROI IRFs. In conclusion, quantitative voxelwise perfusion mapping based on deconvolved T(1)-DCE renal data is feasible, but absolute quantification requires inflow correction. rRBF maps and quantitative values are sufficiently sensitive to detect perfusion abnormality in pathologic areas, but further research is necessary to separate perfusion from extraction and to characterize the different compartments of the nephron on the (sub)voxel level.

Choice of the regularization parameter for perfusion quantification with MRI.

Truncated singular value decomposition (TSVD) is an effective method for the deconvolution of dynamic contrast enhanced (DCE) MRI. Two robust methods for the selection of the truncation threshold on a pixel-by-pixel basis--generalized cross validation (GCV) and the L-curve criterion (LCC)--were optimized and compared to paradigms in the literature. GCV and LCC were found to perform optimally when applied with a smooth version of TSVD, known as standard form Tikhonov regularization (SFTR). The methods lead to improvements in the estimate of the residue function and of its maximum, and converge properly with SNR. The oscillations typically observed in the solution vanish entirely, and perfusion is more accurately estimated at small mean transit times. This results in improved image contrast and increased sensitivity to perfusion abnormalities, at the cost of 1-2 min in calculation time and hyperintense clusters in the image. Preliminary experience with clinical data suggests that the latter problem can be resolved using spatial continuity and/or hybrid thresholding methods. In the simulations GCV and LCC are equivalent in terms of performance, but GCV thresholding is faster.

Severe adverse reactions with contrast agents for magnetic resonance: clinical experience in 30,000 MR examinations.

We report on the frequency, manifestations and reactions to gadolinium contrast media in patients who underwent MR imaging at our institution between 1988 and 1998. During a 10-year period 30,000 patients received an intravenous injection of 0.1 mmol/kg gadoterate meglumine or gadopentetate dimeglumine for an MRI examination. When a reaction occurred a written report was made (the events were categorized into mild, moderate, and severe). In the period of 10 years we obtained three reports of moderate or severe reactions to the administration of gadolinium. This paper discusses the safety issues of intravenous contrast media in MR imaging, focusing on two gadolinium complexes, gadoterate meglumine, gadopentetate dimeglumine.

b matrix errors in echo planar diffusion tensor imaging.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a recognized tool for early detection of infarction of the human brain. DW-MRI uses the signal loss associated with the random thermal motion of water molecules in the presence of magnetic field gradients to derive parameters that reflect the translational mobility of the water molecules in tissues. If diffusion-weighted images with different values of b matrix are acquired during one individual investigation, it is possible to calculate apparent diffusion coefficient maps that are the elements of the diffusion tensor. The diffusion tensor elements represent the apparent diffusion coefficient of protons of water molecules in each pixel in the corresponding sample. The relation 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 magnitude of the error made in the calculation of the elements of the diffusion tensor when the imaging gradients are ignored.

Echo planar magnetic resonance imaging of anisotropic diffusion in asparagus stems.

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.

Diffusion-weighted MR imaging of intracerebral masses: comparison with conventional MR imaging and histologic findings.

BACKGROUND AND PURPOSE: The purposes of this study were to find the role of diffusion-weighted MR imaging in characterizing intracerebral masses and to find a correlation, if any, between the different parameters of diffusion-weighted imaging and histologic analysis of tumors. The usefulness of diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps in tumor delineation was evaluated. Contrast with white matter and ADC values for tumor components with available histology were also evaluated. METHODS: Twenty patients with clinical and routine MR imaging/CT evidence of intracerebral neoplasm were examined with routine MR imaging and echo-planar diffusion-weighted imaging. The routine MR imaging included at least the axial T2-weighted fast spin-echo and axial T1-weighted spin-echo sequences before and after contrast enhancement. The diffusion-weighted imaging included an echo-planar spin-echo sequence with three b values (0, 300, and 1200 s/mm(2)), sensitizing gradient in the z direction, and calculated ADC maps. The visual comparison of routine MR images with diffusion-weighted images for tumor delineation was performed as was the statistical analysis of quantitative diffusion-weighted imaging parameters with histologic evaluation. RESULTS: For tumors, the diffusion-weighted images and ADC maps of gliomas were less useful than the T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo images in definition of tumor boundaries. Additionally, in six cases of gliomas, neither T2-weighted spin-echo nor diffusion-weighted images were able to show a boundary between tumor and edema, which was present on contrast-enhanced T1-weighted and/or perfusion echo-planar images. The ADC values of solid gliomas, metastases, and meningioma were in the same range. In two cases of lymphomas, there was a good contrast with white matter, with strongly reduced ADC values. For infection, the highest contrast on diffusion-weighted images and lowest ADC values were observed in association with inflammatory granuloma and abscess. CONCLUSION: Contrary to the findings of previous studies, we found no clear advantage of diffusion-weighted echo-planar imaging in the evaluation of tumor extension. The contrast between gliomas, metastases, meningioma, and white matter was generally lower on diffusion-weighted images and ADC maps compared with conventional MR imaging. Unlike gliomas, the two cases of lymphomas showed hyperintense signal on diffusion-weighted images whereas the case of cerebral abscess showed the highest contrast on diffusion-weighted images with very low ADC values. Further study is required to find out whether this may be useful in the differentiation of gliomas and metastasis from lymphoma and abscess.

Diffusion and perfusion MRI: basic physics.

Diffusion and perfusion MR imaging are now being used increasingly in neuro-vascular clinical applications. While diffusion weighted magnetic resonance imaging exploits the translational mobility of water molecules to obtain information on the microscopic behaviour of the tissues (presence of macromolecules, presence and permeability of membranes, equilibrium intracellular-extracellular water, ellipsis), perfusion weighted imaging makes use of endogenous and exogenous tracers for monitoring their hemodynamic status. The combination of both techniques is extremely promising for the early detection and assessment of stroke, for tumor characterisation and for the evaluation of neurodegenerative diseases. This article provides a brief review of the basic physics principles underlying the methodologies followed.

Quantitative ultrasound of the calcaneus: an in vivo comparison with dual-energy X-ray absorptiometry and magnetic resonance imaging.

The current study was performed in a clinical setting and aimed to evaluate the relationship between quantitative ultrasound (QUS) of the calcaneus with bone mineral density (BMD) assessed with dual-energy X-ray absorptiometry (DXA) and with variables derived from magnetic resonance imaging (MRI). Thirty-two postmenopausal women (mean age 61 years) were studied at the level of the nondominant calcaneus. QUS was performed using a DTU-one device including parametric imaging and yielded speed of sound (SOS) and broadband ultrasound attenuation (BUA) data. DXA was performed at a matched region of interest (ROI) in the calcaneus, using a Hologic QDR 4500 device. MRI, also performed at a matched ROI, yielded, using a Siemens Magnetom Vision device, the inverse of the transverse relaxation time (1/T(2)(*)) and the phase standard deviation (PSD). The strongest relationship between QUS and the other variables involved BUA and BMD (r &equals: 0.677, p < 0.001); 1/T(2)(*) showed a trend to correlation with SOS (r = 0.359, p = 0. 044) and with BMD (r = 0.364, p = 0.040), while the relationship between 1/T(2)(*) and BUA, PSD and BUA, PSD and SOS, PSD and BMD remained far from significance. Regression analysis of QUS, DXA, and MRI variables against age showed a trend to significant decline only for 1/T(2)(*) (r = -0.409, p = 0.020). In conclusion, this study shows that BUA of the calcaneus has the best correlation with BMD, and that, at least in a clinical setting, the ability of QUS to give information about bone structure is limited.

MR phase imaging to quantify bone volume fraction: computer simulations and in vivo measurements.

Magnetic resonance phase images can be used to assess trabecular bone by measuring the standard deviation of the phases in a region of interest. The standard deviation of regional phase measurements reflects the degree of magnetic field inhomogeneity caused by susceptibility differences between bone and marrow. A 3D computer model of trabecular bone was developed and then used to explore the influence of bone volume fraction and imaging parameters such as pixel size and slice width on the standard deviation of regional phase measurements. The results from these tests show that with appropriate selection of these parameters, phase spread strongly reflects variations in trabecular bone density (a correlation of R(2) = 0.98 with bone volume fraction between 0 and 10%). The technique was then applied in vivo on the radius of 25 patients who already had a bone density scan with peripheral quantitative tomography and a correlation between phase standard deviation and trabecular bone density was found (R(2) = 0.46).

Benign liver lesions: differentiation by magnetic resonance.

Optimal hepatic imaging involves both detection and characterization of focal lesions. Detection involves both determination of the presence of lesions and of their segmental extent of liver involvement. In the evaluation of hypervascular lesions, magnetic resonance imaging (MRI) has a greater impact on patient management than ultrasound (US) and computed tomography (CT). Most benign tumors are incidental findings and do not produce clinical symptoms. They must be accurately diagnosed without using aggressive procedures. Knowledge of their imaging features is essential to avoid unnecessary work-up and to minimize patient anxiety. In this article, the MR appearance, vascular and functional behavior of the most common benign liver tumors will be discussed.

Multicentre magnetic resonance texture analysis trial using reticulated foam test objects.

Texture analysis in magnetic resonance imaging has the ability to provide useful diagnostic information with respect to the discrimination of disease states of a single tissue or the separation of different tissues. However, for widespread use it is necessary to determine how texture measurements carried out in one center relate to those carried out in another. To this end, a multicentre trial has been performed where reticulated foam test objects have been scanned in six European centers according to a fixed protocol. It has been concluded that texture measurements are not transportable between centers. Principal component models calculated from the texture parameters collected in one center do not fit the data collected in another. Further trials are to investigate whether the reticulated foam test objects may be used to normalize tissue texture data collected in different centers.

Computer simulations for the optimization of magnetic resonance phase imaging applied in the study of trabecular bone.

A new technique for the evaluation of bone trabeculation using magnetic resonance (MR) phase images has been recently presented. This technique calculates the phase variance in a region of interest (ROI) on the phase images of a gradient echo sequence. In this study, a computer program was developed which simulates the phase distribution in gradient echo acquired phase images of a structure that mimics trabecular bone, consisting of a three-dimensional connected network of orthogonal bone struts. Several tests were performed in order to assess the influence of imaging parameters such as the echo time, the pixel size and the slice width on phase variance. The results from this work show that with selection of appropriate imaging parameters, phase variance strongly reflects variations in trabecular bone density. Representative MR experiments were performed in the distal radius to verify the simulation results.

Comparison of computer simulated and phantom measured phase variance in the study of trabecular bone.

A new method using magnetic resonance phase images for the assessment of trabecular bone structure has recently been proposed. To test this method, a mathematical model is developed which calculates the phase distribution in gradient echo acquired phase images of a structure of Pyrex glass rods immersed in a copper sulfate solution. Several experiments were performed using a phantom built in the same way as the structure used in the mathematical model. The results from the model are compared with those from the phantom tests, and the influence of resolution and bone area fraction on the phase dispersion is studied. The good correlation between theoretical and experimental results shows that phase variance increases with increasing resolution and bone density. However, the dependence of variance on bone density is less prominent for large pixel sizes.