Robert Luypaert

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.

A method for myelin fiber orientation mapping using diffusion-weighted MR images

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 degrees 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.

DTI reveals structural differences in white matter tracts between bilingual and monolingual children.

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 Brocas 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.

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 T1‐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 T1‐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. Magn Reson Med, 2005.

Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity

Abstract 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.

Using 3D-MRI to localize the dorsolateral prefrontal cortex in TMS research.

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.

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.

Fat fraction of lumbar bone marrow using in vivo proton nuclear magnetic resonance spectroscopy

Localized proton spectra of the human lumbar vertebral body were recorded in vivo at 1.5 T, using the STEAM (stimulated echo acquisition mode) pulse sequence. Thirty-seven patients (18 men, 19 women) were examined, ranging in age from 21 to 68 years (mean = 40, SD = 13). The fat fraction of the bone marrow was calculated from the areas of the fat and water peaks in the spectrum. The results demonstrate that, in the course of aging, there is a systematic increase in measured fat percentage of about 7% per decade of age. No sex difference could be established on the basis of our results.

Deconvolution-based Dynamic Contrast-enhanced MR Imaging of Breast Tumors: Correlation of Tumor Blood Flow with Human Epidermal Growth Factor Receptor 2 Status and Clinicopathologic Findings—Preliminary Results

PURPOSE To prospectively determine whether breast carcinomas possess characteristic values of tumor blood flow (TBF) that correlate with pathologic and molecular prognostic markers. MATERIALS AND METHODS The institutional ethics committee approved this study. After informed consent was obtained, 57 women (age range, 31-80 years) with histologically proved breast cancer underwent routine magnetic resonance (MR) mammography, which included a whole-breast dynamic contrast material-enhanced (DCE) sequence. A second contrast material bolus was injected during dynamic single-section turbo field-echo imaging of the section where the lesion was maximally enhanced. The relative signal intensity changes were deconvolved in a pixelwise fashion to yield the TBF. Formalin-fixed paraffin-embedded tumor specimens on slides were evaluated for histologic size and grade, as well as for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) protein. In patients with a HER2 protein score of 2+ or 3+, HER2 gene status was assessed. For all prognostic parameters, the Mann-Whitney U test was used to compare median TBF in the HER2-positive group with that in the HER2-negative group. RESULTS Significantly higher TBF was observed in tumors larger than 2 cm in diameter and in PR-negative and HER2 gene-amplified tumors (P < .05). In the HER2-positive and HER2-negative groups, ER-positive PR-positive tumors had a lower median TBF than did ER-negative PR-negative tumors, and the difference was significant in the HER2-positive group (P < .05). CONCLUSION Pixelwise deconvolution analysis of DCE MR data in patients with breast cancer can provide preoperative information regarding TBF. These results also support the hypothesis that there is increased TBF in HER2-positive tumors.

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.