Dependence of BOLD signal change on tactile stimulus intensity in SI of primates

Recently, we have demonstrated that the fine-digit topography (millimeter sized) previously identified in the primary somatosensory cortex (SI), using electrophysiology and intrinsic signal optical imaging, can also be mapped with submillimeter resolution using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging at high field. In the present study, we have examined the dependence of BOLD signal response on stimulus intensity in two subregions of SI, Areas 3b and 1. In a region(s)-of-interest (ROI) analysis of Area 3b, BOLD signal amplitude increased linearly with increasing amplitude of an 8-Hz vibrotactile stimulus, and BOLD signal was sustained throughout the stimulation period. In contrast, in Area 1, a significant BOLD signal response was only observed with more intense stimuli, and ROI analysis of the dependence of BOLD response showed no significant dependence on stimulus intensity. In addition, activation was not sustained throughout the period of stimulation. Differing responses of Areas 3b and 1 suggest potentially divergent roles for subregions of SI cortices in vibrotactile intensity encoding. Moreover, this study underscores the importance of imaging at small spatial scales. In this case, such high-resolution imaging allows differentiation between area-specific roles in intensity encoding and identifies anatomic targets for detailed electrophysiological studies of somatosensory neuronal populations with different coding properties. These experiments illustrate the value of nonhuman primates for characterizing the dependence of the BOLD signal response on stimulus parameters and on underlying neural response properties.     

Fine-scale functional connectivity in somatosensory cortex revealed by high-resolution fMRI

High-resolution functional magnetic resonance imaging (fMRI) at high field (9.4 T) has been used to measure functional connectivity between subregions within the primary somatosensory (SI) cortex of the squirrel monkey brain. The hand-face region within the SI cortex of the squirrel monkey has been previously well mapped with functional imaging and electrophysiological and anatomical methods, and the orderly topographic map of the hand region is characterized by a lateral to medial representation of individual digits in four subregions of areas 3a, 3b, 1 and 2. With submillimeter resolution, we are able to detect not only the separate islands of activation corresponding to vibrotactile stimulations of single digits but also, in subsequent acquisitions, the degree of correlation between voxels within the SI cortex in the resting state. The results suggest that connectivity patterns are very similar to stimulus-driven distributions of activity and that connectivity varies on the scale of millimeters within the same primary region. Connectivity strength is not a reflection of global larger-scale changes in blood flow and is not directly dependent on distance between regions. Preliminary electrophysiological recordings agree well with the fMRI data. In human studies at 7 T, high-resolution fMRI may also be used to identify the same subregions and assess responses to sensory as well as painful stimuli, and to measure connectivity dynamically before and after such stimulations.     

On the relationship between the apparent diffusion coefficient and extravascular extracellular volume fraction in human breast cancer

MRI techniques have been developed that can noninvasively probe the apparent diffusion coefficient (ADC) of water via diffusion-weighted MRI (DW-MRI). These methods have found much application in cancer where it is often found that the ADC within tumors is inversely correlated with tumor cell density, so that an increase in ADC in response to therapy can be interpreted as an imaging biomarker of positive treatment response. Dynamic contrast enhanced MRI (DCE-MRI) methods have also been developed and can noninvasively report on the extravascular extracellular volume fraction of tissues (denoted by v_e). By conventional reasoning, the ADC should therefore also be directly proportional to v_e. Here we report measurements of both ADC and v_e obtained from breast cancer patients at both 1.5 and 3.0 T. The 1.5-T data were acquired as part of normal standard of care, while the 3.0-T data were obtained from a dedicated research protocol. We found no statistically significant correlation between ADC and v_e for the 1.5- or 3.0-T patient sets on either a voxel-by-voxel or a region-of-interest (ROI) basis. These data, combined with similar results from other disease sites in the literature, may indicate that the conventional interpretation of either ADC, v_e or their relationship is not sufficient to explain experimental findings.     

Dependence of temporal diffusion spectra on microstructural properties of biological tissues

The apparent diffusion coefficient (ADC) measured using magnetic resonance imaging methods provides information on microstructural properties of biological tissues, and thus has found applications as a useful biomarker for assessing changes such as those that occur in ischemic stroke and cancer. Conventional pulsed gradient spin echo methods are in widespread use and provide information on, for example, variations in cell density. The oscillating gradient spin echo (OGSE) method has the additional ability to probe diffusion behaviors more readily at short diffusion times, and the temporal diffusion spectrum obtained by the OGSE method provides a unique tool for characterizing tissues over different length scales, including structural features of intracellular spaces. It has previously been reported that several tissue properties can affect ADC measurements significantly, and the precise biophysical mechanisms that account for ADC changes in different situations are still unclear. Those factors may vary in importance depending on the time and length scale over which measurements are made. In the present work, a comprehensive numerical simulation is used to investigate the dependence of the temporal diffusion spectra measured by OGSE methods on different microstructural properties of biological tissues, including cell size, cell membrane permeability, intracellular volume fraction, intranucleus and intracytoplasm diffusion coefficients, nuclear size and T₂ relaxation times. Some unique characteristics of the OGSE method at relatively high frequencies are revealed. The results presented in the paper offer a framework for better understanding possible causes of diffusion changes and may be useful to assist the interpretation of diffusion data from OGSE measurements.     

Earlier detection of tumor treatment response using magnetic resonance diffusion imaging with oscillating gradients

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Noninvasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to microstructural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 h following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea, when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods.     

Localized high-resolution DTI of the human midbrain using single-shot EPI,parallel imaging,and outer-volume suppression at 7 T

Localized high-resolution diffusion tensor images (DTI) from the midbrain were obtained using reduced field-of-view (rFOV) methods combined with SENSE parallel imaging and single-shot echo planar (EPI) acquisitions at 7 T. This combination aimed to diminish sensitivities of DTI to motion, susceptibility variations, and EPI artifacts at ultra-high field. Outer-volume suppression (OVS) was applied in DTI acquisitions at 2- and 1-mm² resolutions, b = 1000 s/mm², and six diffusion directions, resulting in scans of 7- and 14-min durations. Mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in various fiber tract locations at the two resolutions and compared. Geometric distortion and signal-to-noise ratio (SNR) were additionally measured and compared for reduced-FOV and full-FOV DTI scans. Up to an eight-fold data reduction was achieved using DTI-OVS with SENSE at 1 mm², and geometric distortion was halved. The localization of fiber tracts was improved, enabling targeted FA and ADC measurements. Significant differences in diffusion properties were observed between resolutions for a number of regions suggesting that FA values are impacted by partial volume effects even at a 2-mm² resolution. The combined SENSE DTI-OVS approach allows large reductions in DTI data acquisition and provides improved quality for high-resolution diffusion studies of the human brain.     

Intrinsic equations for a generalized relaxed elastic line on an oriented surface in the galilean space

In this article, we derive the intrinsic equations for a generalized relaxed elastic line on an oriented surface in the Galilean 3-dimensional space G₃. These equations will give direct and more geometric approach to questions concerning about generalized relaxed elastic lines on an oriented surface in G₃.     

Simultaneous PET–MRI in oncology: a solution looking for a problem?

With the recent development of integrated positron emission tomography–magnetic resonance imaging (PET–MRI) scanners, new possibilities for quantitative molecular imaging of cancer are realized. However, the practical advantages and potential clinical benefits of the ability to record PET and MRI data simultaneously must be balanced against the substantial costs and other requirements of such devices. In this review, we highlight several of the key areas where integrated PET–MRI measurements, obtained simultaneously, are anticipated to have a significant impact on clinical and/or research studies. These areas include the use of MR-based motion corrections and/or a priori anatomical information for improved reconstruction of PET data, improved arterial input function characterization for PET kinetic modeling, the use of dual-modality contrast agents, and patient comfort and practical convenience. For widespread acceptance, a compelling case could be made if the combination of quantitative MRI and specific PET biomarkers significantly improves our ability to assess tumor status and response to therapy, and some likely candidates are now emerging. We consider the relative advantages and disadvantages afforded by PET–MRI and summarize current opinions and evidence as to the likely value of PET–MRI in the management of cancer.     

Measurement of thermal diffusivity by magnetic resonance imaging

Nuclear magnetic resonance (NMR) may be used for monitoring temperature changes within samples based on measurements of relaxation times, the diffusion coefficient of liquids, proton resonance frequency or phase shifts. Such methods may be extended to the explicit measurement of the thermal diffusivity of materials by NMR imaging. A method based on measuring nuclear spin phase shifts or changes in the equilibrium nuclear magnetization has been developed for measuring transient thermal diffusion effects and thermal diffusivity with potential applications in NMR thermotherapy and materials science. In this method, a thermal pulse is applied to a medium, and the resultant temporal variations of the nuclear spin phase or of the magnitude of the nuclear magnetization produced by the thermal pulse are monitored at a spatial distance. The results obtained on common fluids agree well with the data from other methods.     

Effects of hypoglycemia on human brain activation measured with fMRI

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P < .05). These changes were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain.