Measurement of relative cerebral blood volume using BOLD contrast and mild hypoxic hypoxia

Relative cerebral blood volume (CBV) was estimated using a mild hypoxic challenge in humans, combined with BOLD contrast gradient-echo imaging at 3 T. Subjects breathed 16% inspired oxygen, eliciting mild arterial desaturation. The fractional BOLD signal change induced by mild hypoxia is expected to be proportional to CBV under conditions in which there are negligible changes in cerebral perfusion. By comparing the regional BOLD signal changes arising with the transition between normoxia and mild hypoxia, we calculated CBV ratios of 1.5±0.2 (mean±S.D.) for cortical gray matter to white matter and 1.0±0.3 for cortical gray matter to deep gray matter.     

Functional connectivity in the rat brain: a complex network approach

Functional connectivity analyses of fMRI data can provide a wealth of information on the brain functional organization and have been widely applied to the study of the human brain. More recently, these methods have been extended to preclinical species, thus providing a powerful translational tool. Here, we review methods and findings of functional connectivity studies in the rat. More specifically, we focus on correlation analysis of pharmacological MRI (phMRI) responses, an approach that has enabled mapping the patterns of connectivity underlying major neurotransmitter systems in vivo. We also review the use of novel statistical approaches based on a network representation of the functional connectivity and their application to the study of the rat brain functional architecture.     

Characterisation of magnetic resonance imaging (MRI) contrast agents using NMR relaxometry

ABSTRACT

This contribution describes the use of Fast Field-cycling relaxometry (FFC-NMR) for the characterisation of Gd(III)- and Mn(II)-based contrast agents for MRI. Through a series of selected examples, we analyse the role of different structural and dynamic parameters on ¹H relaxivity and on the shape of the ¹H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. The amplitude and shape of the profiles is affected by the number of water molecules coordinated to the metal ion, the water exchange rate, the rotational correlation time of the complex and the relaxation of the electron spin. As a result, ¹H NMRD profiles represent a powerful tool for the understanding of the properties of MRI contrast agent candidates at the molecular level.     

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high resolution fast low angle shot (FLASH) technique (matrix size 128²). The FLASH technique was applied additionally with a 64² matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64² matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and postior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 128² compared to FLASH 64² and EPI 64², whereas the activated areas proved to be smaller in FLASH 128² functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 128². Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.     

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.     

Tissue similarity maps (TSMs): A new means of mapping vascular behavior and calculating relative blood volume in perfusion weighted imaging

This study introduces a new processing means that uses the original signal (rather than contrast agent concentration) from dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) to calculate a relative cerebral blood volume map and a tissue similarity map (TSM). Ten healthy volunteers and eight multiple sclerosis (MS) patients were studied using high resolution PWI. The TSM is found by choosing a reference region in one slice and comparing its signal in a mean squared error sense to the signal from every pixel in all images throughout the brain. The TSMs provide a means to determine which tissues have similar flow characteristics with high contrast and signal-to-noise ratios. The effective blood volume measured from this approach is nearly identical to that from conventional relative cerebral blood volume (rCBV) maps but with better signal-to-noise. Of interest is the fact that choosing one MS lesion as the reference tissue appears to be enough to find nearly all lesions throughout the brain. That is, these lesions all behave the same from a vascular point of view. The TSM results are robust within and across slices properly nulling the same type of tissue throughout the brain for a given reference region. TSM derived rCBV agrees well with the conventional derived rCBV using contrast agent concentration. TSM may provide a new means to study similarities between blood flow patterns in tissue in the brain and in better diagnosing vascular differences between tissues and lesions.     

A serial functional connectivity MRI study in healthy individuals assessing the variability of connectivity measures: reduced interhemispheric connectivity in the motor network during continuous performance

To date, little data is available on the reproducibility of functional connectivity MRI (fcMRI) studies. Here, we tested the variability and reproducibility of both the functional connectivity itself and different statistical methods to analyze this phenomenon. In the main part of our study, we repeatedly examined two healthy subjects in 10 sessions over 6 months with fcMRI. Cortical areas involved in motor function were examined under two different cognitive states: during continuous performance (CP) of a flexion/extension task of the fingers of the right hand and while subjects were at rest. Connectivity to left primary motor cortex (lSM1) was calculated by correlation analysis. The resulting correlation coefficients were transformed to z-scores of the standard normal distribution. For each subject, multisession statistical analyses were carried out with the z-score maps of the resting state (RS) and the CP experiments. First, voxel based t tests between the two groups of fcMRI experiments were performed. Second, ROI analyses were carried out for contralateral right SM1 and for supplementary motor area (SMA). For both ROI, mean and maximum z-score were calculated for each experiment. Also, the fraction of significantly (P<.05) correlated voxels (FCV) in each ROI was calculated. To evaluate the differences between the RS and the CP condition, paired t tests were performed for the mean and maximum z-scores, and Wilcoxon signed ranks tests for matched pairs were carried out for the FCV. All statistical methods and connectivity measures under investigation yielded a distinct loss in left–right SM1 connectivity under the CP condition. For SMA, interindividual differences were apparent. We therefore repeated the fcMRI experiments and the ROI analyses in a group of seven healthy subjects (including the two subjects of the main study). In this substudy, we were able to verify the reduction of left–right SM1 connectivity during unilateral performance. Still, the direction of SMA to lSM1 connectivity change during the CP condition remained undefined as four subjects showed a connectivity increase and three showed a decrease. In summary, we were able to demonstrate a distinct reduction in left–right SM1 synchrony in the CP condition compared to the RS both in the longitudinal and in the multisubject study. This effect was reproducible with all statistical methods and all measures of connectivity under investigation. We conclude that despite intra- and interindividual variability, serial and cross-sectional assessment of functional connectivity reveals stable and reliable results.     

Fast evaluation of time domain fields in sub-wavelength source/observer distributions using accelerated Cartesian expansions (ACE)

Time domain integral equation solvers for transient scattering from electrically large objects have benefitted significantly from acceleration techniques like the plane wave time domain (PWTD) algorithm; these techniques reduce the asymptotic CPU and memory cost. However, PWTD breaks down when used in the analysis of structures that have subwavelength features or features whose length scales are orders of magnitude smaller than the smallest wavelength in the incident pulse. Instances of these occurring in electromagnetics range from antenna topologies, to feed structures, etc. In this regime, it is the geometric constraints that dictate the computational complexity, as opposed to the wavelength of interest. In this work, we present an approach for efficient analysis of such sub-wavelength source/observer distributions in time domain. The methodology that we seek to exploit is the recently developed algorithm based on Cartesian expansions for accelerating the computation of potentials of the form R^ν. In this paper, we present an efficient methodology for computing these polynomials for two different scenarios; where the size of the domain spans the distance travelled by light in (i) one time step and (ii) multiple time steps. These algorithms are cast within the framework of both uniform and non-uniform distributions. Results that demonstrate the efficiency and convergence of the proposed algorithm are presented.     

Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate

Cediranib (RECENTIN, AZD2171) is a highly potent inhibitor of the tyrosine kinase activity associated with all three vascular endothelial growth factor (VEGF) receptors and is currently in Phase II/III clinical trials. Preclinically, cediranib inhibits VEGF signaling and angiogenesis in vivo and impedes solid tumor growth significantly. Clinically, changes observed using dynamic contrast-enhanced MRI (DCE-MRI) with gadopentate suggest that acute cediranib treatment compromises tumor hemodynamics. In this study, a DCE-MRI baseline scan using gadopentate was performed in nude rats bearing Lovo (human colorectal carcinoma) or C6 (rat glioma) tumors. Cediranib (3 mg/kg per day) or vehicle was then dosed orally (2, 26 and 50 h after the baseline scan; 12 rats per group) and a second scan acquired 2 h after the final dosing event. Mean values for K(trans) (Tofts and Kermode-derived) [Magn Reson Med 17 (1991) 357-67] and the initial area under the gadolinium concentration curve over the first 60 s (iAUC) were reduced significantly following cediranib treatment: K(trans) by 33% (P<.05) in both tumor models and iAUC by 23% (P>.05) and 33% (P>.005) in Lovo and C6, respectively. This is the first preclinical investigation to examine the effect of cediranib treatment on tumors by DCE-MRI with gadopentate.