neuroMetrix

neuroMetrix Brochure

Be it for clinical trials or research, the diversity and complementarity of neuroimaging methods makes them an ultimate tool for integrative translational research. Neuroimaging is therefore at the heart of basic and clinical efforts attempting to elucidate the complex processes in the human and animal brain.

Overview of different quantitative neurological imaging techniques.

As highlighted in the table above, the different imaging techniques highlight complementary aspects of the human brain. Such techniques yield biomarkers, which, as multiple studies demonstrate, correlate with clinical results. This is one of the reasons why advanced neuroimaging has already been incorporated in several clinical trials.

icoMetrix has bundled its extensive experience in neuroimaging ininto neuroMetrix, covering all neurological imaging and image analysis techniques. This makes icoMetrix your preferred partner, from study design to reproducible, quantitative analysis. Some examples of our previous work are highlighted below.

MR diffusion tensor imaging (DTI) to quantifying cognitive dysfunction in multiple-sclerosis patients

VBA of (top) Mann-Whitney U tests comparing L23 between the healthy subjects and the moderately impared MS patients (MS group 2) and (bottom) Spearmann correlation test between FA and the PASAT scores. Significantly relevant pixels are shown in white.

Diffusion tensor imaging (DTI) is a relatively new MR modality and has been used increasingly over the last 5 years. DTI can characterize the orientation and integrity of white matter fibers in vivo and in a non-invasive manner.

Cognitive dysfunction is an important symptom of multiple sclerosis (MS). Together with the partners in this project, icoMetrix has identified regions in the brain related to this decline and has shown significant correlation between the fractional anisotropy (FA) in these regions and the PASAT score of the subject. icoMetrix’ technology enables the objective quantification of cognitive dysfunction.

A total of 20 patients with definite MS according to the McDonald criteria and a control group of 10 healthy volunteers were included in the study. The MS group was further divided based upon the expanded disability status scale (EDSS): 10 patients with EDSS between 0 and 3 are referred to as MS group 1, the other 10 patients with EDSS between 4 and 7 are referred to as MS group 2.

All subjects underwent a DTI scan and performed a PASAT-test. DTI data sets were obtained on a 1.5 T MR scanner using a spin echo (SE) echo planar imaging (EPI) sequence. The DTI data sets were processed using icoMetrix’ proprietary voxel-based analysis pipeline:

Pre-processing

• A population specific DTI atlas is constructed using affine and high-dimensional non-rigid coregistration, especially adapted to process tensor data.
• The resulting images are smoothed with an adaptive, anisotropic smoothing kernel. This spatially dependent, anisotropic kernel is estimated from the FA maps.
• From each image, the FA-map, longitudinal (L1), transverse (L23) and mean (MD) diffusivity is calculated.

Analysis

• Analysis 1: the diffusion properties of the different subject groups are quantitatively and statistically compared
• Analysis 2: Non-parametric Spearman correlation tests are performed in each voxel to quantify the relation between the different diffusion properties and the PASAT score.

The results of our study clearly show a significant correlation between the white matter structure, EDSS and PASAT, as can be seen in the figure. It provides greater insight into the underlying pathology, by highlighting the relevant affected brain regions.

This type of Voxel-Based Analysis (VBA) is being increasingly applied to examine DTI data sets of subjects with various neurological or psychiatric disorders. Compared to the region of interest (ROI) post-processing approach, VBA is less laborious, is not observer-dependent, does not need to outline the complex three-dimensional (3D) WM architecture by 2D ROIs, and does not need an a priori hypothesis regarding the spatial location and extent of the expected pathology induced WM differences.

Wim Van Hecke, Guy Nagels, Alexander Leemans, Evert Vandervliet, Jan Sijbers, and Paul M. Parizel, Correlation of Cognitive Dysfunction and Diffusion Tensor MRI Measures in Patients With Mild and Moderate Multiple Sclerosis, Journal of Magnetic Resonance Imaging 31:1492–1498 (2010)

Functional MRI (fMRI) to assess treatment effect of exposure therapy on arachnophobia

(Top) Activation maps showing significantly more blood oxygen level–dependent (BOLD) signal to spiders than to neutral pictures at baseline, posttreatment, and in control subjects. (Bottom) Plots showing the percentage of increase in BOLD signal to spiders compared with neutral pictures.

Functional MRI (fMRI) is an important technique to evaluate the function of different brain regions of healthy subjects and subjects with various pathologies. fMRI locates and quantifies brain activity in the brain regions that are activated when the patient performs motor or cognitive tasks, or when specific stimuli are presented. Advantages such as minimal invasiveness, no radioactivity, widespread availability, and virtually unlimited study repetitions make fMRI ideally suited to the study of in vivo brain function.

In the study we present here, event-related fMRI was used to measure and compare responses to phobia-related, general threat, and neutral pictures before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and healthy control subjects. Phobic subjects showed increased amygdala activity, the key brain structure in fear processing, at baseline. This hyperactivity was significantly reduced 2 weeks after exposure therapy. Furthermore, a significant reduction of hyperactivity in anterior cingulate cortex and insula was also found post-exposure.

Liesbet Goossens, Stefan Sunaert, Ronald Peeters, Eric JL Griez, Koen RJ Schruers, Amygdala hyperfunction in phobic fear normalizes after exposure, Biol. Psychiatry. 2007;62(10):1119-25

DTI Group Study of the Spinal cord in MS patients

Boxplots are shown for the cross-sectional spinal cord area A, the fractional anisotropy, the mean diffusivity, and for the ratio of the longitudinal and transverse eigenvalues. Results of both segmentation methods are displayed for the control subjects, the MS patients with T2 spinal cord lesions (MS patient group 1), and the MS patients without T2 spinal cord lesions (MS patient group 2).

Diffusion tensor imaging (DTI) can provide complementary diagnostic information regarding the microstructural white matter (WM) organization in MS lesions and white matter regions that appear normal on conventional MR. Recent studies demonstrate the potential of quantitative DTI parameters, such as the fractional anisotropy (FA), which is a normalized measure of the degree of anisotropy, and the mean diffusivity (MD), that is, the average diffusion, for detecting WM alterations in patients with MS.

Diffusion tensor images of the spinal cord were acquired from 21 healthy subjects, 11 MS patients with spinal cord lesions, and 10 MS patients without spinal cord lesions on the T2-weighted MR images. Different diffusion measures were evaluated using both a region of interest (ROI)-based and a diffusion tensor tractography-based segmentation approach.

It was observed that the FA, the transverse diffusivity, and the ratio of the longitudinal and transverse diffusivities were significantly lower in the spinal cord of MS patients with spinal cord lesions compared with the control subjects. The FA and the ratio of longitudinal and transverse diffusivities values were significantly different between the control group and the MS patient group without T2 spinal cord lesions (P = 0.013).

We demonstrated that diffusion tensor tractography is a robust tool to analyze the spinal cord of MS patients. Our results also suggest that the spinal cord may still be affected by MS, even when lesions are not detected on a conventional MR scan.

(a) A sagittal slice of the spinal cord. The color is encoded for the diffusion direction, and the intensity is proportional with the diffusion anisotropy. (b) In the ROI-based segmentation method, ROIs are drawn on all axial slices, as demonstrated for three axial slices. In the tractography-based segmentation method, diffusion measures are derived from the tracts. (c) The tractography result of a healthy subject an MS patient with T2 spinal cord lesions and an MS patient without T2 spinal cord lesions are visualized.

Wim Van Hecke, Guy Nagels, Griet Emonds, Alexander Leemans, Jan Sijbers, Johan Van Goethem, and Paul M. Parizel, A diffusion tensor imaging group study of the spinal cord in multiple sclerosis patients with and without T2 spinal cord lesions, J Magn Reson Imaging. 2009;30(1):25-34.