Due to its unique sensitivity to tissue microstructure, diffusion-weighted magnetic resonance imaging (MRI) has found many applications in clinical and fundamental science. With few exceptions, a more precise correspondence between physiological or biophysical properties and the obtained diffusion parameters remain uncertain due to lack of specificity. In this work, we address this problem by comparing diffusion parameters of a recently introduced model for water diffusion in brain matter to light microscopy and quantitative electron microscopy. Specifically, we compare diffusion model predictions of neurite density in rats to optical myelin staining intensity and stereological estimation of neurite volume fraction using electron microscopy. We find that the diffusion model describes data better and that its parameters show stronger correlation with optical and electron microscopy, and thus reflect myelinated neurite density better than the more frequently used diffusion tensor imaging (DTI) and cumulant expansion methods. Furthermore, the estimated neurite orientations capture dendritic architecture more faithfully than DTI diffusion ellipsoids.

Mindfulness meditation is a set of attention-based, regulatory and self-inquiry training regimes. Although the impact of mindfulness meditation training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act on attention through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures has made it difficult to distinguish the role of these mechanisms. To resolve this question we conducted a fully randomized 6-week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active control group. We measured behavioral metacognition and whole-brain Blood Oxygenation Level Dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex (DLPFC) responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group by time interactions on negative affect-related RTs or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response-inhibition and increased recruitment of dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), and right anterior insula during negative valence processing. Collectively our findings highlight the importance of active control in MT research, and indicate unique neural mechanisms for progressive stages of mindfulness training.

Summary: In six young, healthy volunteers, a novel method to determine cerebral blood flow (CBF) using magnetic reso nance (MR) bolus tracking was compared with [,sO]H20 pos itron emission tomography (PET). The method yielded para metric CBF images with tissue contrast in good agreement withRecent results indicate that it may be possible to mea sure CBF by dynamic magnetic resonance imaging (MRI) of paramagnetic contrast agent bolus passage (0stergaard et aI., 1996a). Because of the complexity of susceptibility contrast, this technique initially only al lowed determination of relative flow rates. In a prelimi nary study in six normal volunteers, the mean gray to white flow ratio was found to be in good agreement with PET literature values for age-matched subjects (0ster gaard et aI., 1996b). In a recent animal hypercapnia study (0stergaard et aI., 1998), an approach was introduced to

Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices.

Background and Purpose-The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion-and perfusionweighted MRI (DWI and PWI, respectively). Methods-DWI and PWI were performed in 11 patients Յ6 hours after the onset of symptoms of acute ischemic stroke.Regions of interest (ROIs) were placed covering the ischemic core (ROI 1), the penumbra that progressed to infarction on the basis of follow-up scans (ROI 2), and the penumbra that recovered (ROI 3). The ratios of relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and apparent diffusion coefficient were calculated as lesion ROIs relative to the contralateral mirror ROIs. Results-The post hoc analysis showed that the penumbra progressed to infarction at the following cutoff values: rCBF Ͻ0.59 and MTT Ͼ1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. Conclusions-The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically.

The authors determined cerebral blood flow (CBF) with magnetic resonance imaging (MRI) of contrast agent bolus passage and compared the results with those obtained by O-15 labeled water (H215O) and positron emission tomography (PET). Six pigs were examined by MRI and PET under normo- and hypercapnic conditions. After dose normalization and introduction of an empirical constant phi Gd, absolute regional CBF was calculated from MRI. The spatial resolution and the signal-to-noise ratio of CBF measurements by MRI were better than by the H215O-PET protocol. Magnetic resonance imaging cerebral blood volume (CBV) estimates obtained using this normalization constant correlated well with values obtained by O-15 labeled carbonmonooxide (C15O) PET. However, PET CBV values were approximately 2.5 times larger than absolute MRI CBV values, supporting the hypothesized sensitivity of MRI to small vessels.

The study demonstrated the feasibility of fibretracking as a segmentation tool for mapping distal parts of the corticospinal motor pathways and showed that fractional anisotropy in the segmented corticospinal tract is a sensitive measure of structural changes after stroke.

Functional magnetic resonance imaging (fMRI) has become the leading modality for studying the working brain. Being based on measuring the haemodynamic changes after enhanced mass neuronal activity the spatiotemporal resolution of the method is somewhat limited. Alternative MR-based methods for detection of brain activity have been proposed and investigated and studies have reported functional imaging based on diffusion weighted (DW) MRI. The basis for such DW fMRI is believed to be the sensitivity of diffusion weighted MRI to changes in tissue micro-structure. However, it remains unclear whether signal changes observed with these methods reflect cell swelling related to neural activation, residual vascular effects, or a combination of both. Here we present evidence of a detectable activity related change in the diffusion weighted MR-signal from the cellular level in live hippocampal slices in the absence of vasculature. Slices are exposed to several substances and the effects evaluated and compared. The results are also compared to earlier DW fMRI studies in humans.