MTT and Blood-Brain Barrier Disruption within Asymptomatic Vascular WM Lesions.

BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P < .046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.

Evaluation of cell transplant-mediated attenuation of diffuse injury in experimental autoimmune encephalomyelitis using onVDMP CEST MRI.

The development and translation of cell therapies have been hindered by an inability to predict and evaluate their efficacy after transplantation. Using an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS), we studied attenuation of the diffuse injury characteristic of EAE and MS by transplanted glial-restricted precursor cells (GRPs). We assessed the potential of on-resonance variable delay multiple pulse (onVDMP) chemical exchange saturation transfer (CEST) MRI to visualize this attenuation. Allogeneic GRPs transplanted in the motor cortex or lateral ventricles attenuated paralysis in EAE mice and attenuated differences compared to naïve mice in onVDMP CEST signal 5 days after transplantation near the transplantation site. Histological analysis revealed that transplanted GRPs co-localized with attenuated astrogliosis. Hence, diffuse injury-sensitive onVDMP CEST MRI may complement conventional MRI to locate and monitor tissue regions responsive to GRP therapy.

Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and ß-amyloid as an indicator of cognitive performance at high age.

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.

Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment.

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aß) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aß-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aß-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aß-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aß-plaques.

Quantitative Susceptibility Mapping Suggests Altered Brain Iron in Premanifest Huntington Disease.

BACKGROUND AND PURPOSE: In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression. MATERIALS AND METHODS: Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures. RESULTS: Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores. CONCLUSIONS: The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease.

Diffusion tensor imaging of the optic nerve in multiple sclerosis: association with retinal damage and visual disability.

BACKGROUND AND PURPOSE: There is a well-known relationship between MS and damage to the optic nerve, but advanced, quantitative MR imaging methods have not been applied to large cohorts. Our objective was to determine whether a short imaging protocol (< 10 minutes), implemented with standard hardware, could detect abnormal water diffusion in the optic nerves of patients with MS. MATERIALS AND METHODS: We examined water diffusion in human optic nerves via DTI in the largest MS cohort reported to date (104 individuals, including 38 optic nerves previously affected by optic neuritis). We also assessed whether such abnormalities are associated with loss of visual acuity (both high and low contrast) and damage to the retinal nerve fiber layer (assessed via optical coherence tomography). RESULTS: The most abnormal diffusion was found in the optic nerves of patients with SPMS, especially in optic nerves previously affected by optic neuritis (19% drop in FA). DTI abnormalities correlated with both retinal nerve fiber layer thinning (correlation coefficient, 0.41) and loss of visual acuity, particularly at high contrast and in nerves previously affected by optic neuritis (correlation coefficient, 0.54). However, diffusion abnormalities were overall less pronounced than retinal nerve fiber layer thinning. CONCLUSIONS: DTI is sensitive to optic nerve damage in patients with MS, but a short imaging sequence added to standard clinical protocols may not be the most reliable indicator of optic nerve damage.

ROBUST MAXIMUM LIKELIHOOD ESTIMATION IN Q-SPACE MRI.

Q-space imaging is an emerging diffusion weighted MR imaging technique to estimate molecular diffusion probability density functions (PDF's) without the need to assume a Gaussian distribution. We present a robust M-estimator, Q-space Estimation by Maximizing Rician Likelihood (QEMRL), for diffusion PDF's based on maximum likelihood. PDF's are modeled by constrained Gaussian mixtures. In QEMRL, robust likelihood measures mitigate the impacts of imaging artifacts. In simulation and in vivo human spinal cord, the method improves reliability of estimated PDF's and increases tissue contrast. QEMRL enables more detailed exploration of the PDF properties than prior approaches and may allow acquisitions at higher spatial resolution.

Diffusion tensor imaging in children with periventricular leukomalacia: variability of injuries to white matter tracts.

BACKGROUND AND PURPOSE: Conventional MR imaging shows evidence of brain injury and/or maldevelopment in 70%-90% of children with cerebral palsy (CP), though its capability to identify specific white matter tract injury is limited. The great variability of white matter lesions in CP already demonstrated by postmortem studies is thought to be one of the reasons why response to treatment is so variable. Our hypothesis is that diffusion tensor imaging (DTI) is a suitable technique to provide in vivo characterization of specific white matter tract lesions in children with CP associated with periventricular leukomalacia (PVL). MATERIALS AND METHODS: In this study, 24 children with CP associated with PVL and 35 healthy controls were evaluated with DTI. Criteria for identification of 26 white matter tracts on the basis of 2D DTI color-coded maps were established, and a qualitative scoring system, based on visual inspection of the tracts in comparison with age-matched controls, was used to grade the severity of abnormalities. An ordinal grading system (0=normal, 1=abnormal, 2=severely abnormal or absent) was used to score each white matter tract. RESULTS: There was marked variability in white matter injury pattern in patients with PVL, with the most frequent injury to the retrolenticular part of the internal capsule, posterior thalamic radiation, superior corona radiata, and commissural fibers. CONCLUSION: DTI is a suitable technique for in vivo assessment of specific white matter lesions in patients with PVL and, thus, a potentially valuable diagnostic tool. The tract-specific evaluation revealed a family of tracts that are highly susceptible in PVL, important information that can potentially be used to tailor treatment options in the future.

Neural substrates of word generation during stroke recovery: the influence of cortical hypoperfusion.

Several studies have demonstrated reorganization of cognitive and motor function caused by stroke. This study examined the influence of hypoperfused brain regions, in addition to the area of the infarct itself, on reorganization of the cognitive processes underlying word generation in stroke patients. In addition, we also sought to determine the influence of hypoperfusion on the blood oxygen level dependent/(BOLD) effect. Subjects with left and right subacute or chronic subcortical strokes, along with normal controls, were imaged while performing a verbal fluency task (word generation). The study population included six normal subject and six stroke patients with subcortical infarcts and cortical hypoperfusion in the middle cerebral artery territory who had recovered or improved markedly in word fluency. While normal subjects displayed a left-lateralized fronto-temporo-parietal and bilateral cingulo-striatal-thalamic-cerebellar network, the activation pattern of stroke patients was determined both by the hypoperfused regions and infarcted areas of the brain. Specifically, patients showed diminished BOLD effect in the cortical regions that were hypoperfused, even though their infarcts were subcortical, and showed increased BOLD effect in the homologous regions of the normal hemisphere. This finding raises the possibility that cortical hypoperfusion in the absence of infarct can cause shift of language functions to the opposite, intact hemisphere. However, reduced BOLD effect in the task relative to rest was found in hypoperfused regions in two patients, raising the possibility that regional function persisted, even though vascular reactivity was impaired. Results illustrate the complexities of functional imaging studies of recovery in patients with vascular lesions.

Quantitative characterization of the corticospinal tract at 3T.

BACKGROUND AND PURPOSE: White matter tract-specific imaging will probably become a major component of clinical neuroradiology. Fiber tracking with diffusion tensor imaging (DTI) is widely used, but variability is substantial. This article reports the ranges of MR imaging appearance and right-left asymmetry of healthy corticospinal tracts (CST) reconstructed with DTI. METHODS: For 20 healthy volunteers, whole-brain DTI data were coregistered with maps of absolute T1 and T2 relaxation times and magnetization transfer ratio (MTR), all acquired at 3T. For each individual, the 2 reconstructed CSTs and their asymmetry were analyzed with respect to the number of fibers reconstructed; tract volume; and individual MR imaging parameters restricted to the tracts. Interscan variability was estimated by repeat imaging of 8 individuals. RESULTS: Reconstructed fiber number and tract volume are highly variable, rendering them insensitive to abnormalities in disease. Individual tract-restricted MR imaging parameters are more constrained, and their population averages and normal ranges are reported. The average population asymmetry is generally zero; therefore, normal ranges for an index of asymmetry are reported. By way of example, CST-restricted MR imaging parameters and their asymmetries are shown to be abnormal in an individual with multiple sclerosis who had a lesion affecting the CST. CONCLUSIONS: The results constitute a normative dataset for the following imaging parameters of the CST: T1, T2, MTR, fractional anisotropy, mean diffusivity, transverse diffusivity, and the 3 diffusion tensor eigenvalues. These data can be used to identify, characterize, and establish the significance of changes in diseases that affect the CST.

Magnetization transfer MRI demonstrates spinal cord abnormalities in adrenomyeloneuropathy.

BACKGROUND: In adrenomyeloneuropathy (AMN) conventional MRI detects only spinal cord atrophy in the late stages. OBJECTIVE: To apply a magnetization transfer-weighted (MTw) imaging to patients with AMN and AMN-like syndrome in order to visualize and quantitatively assess the pathology of white matter tracts in the cervical spinal cord. METHODS: MTw studies were conducted in nine men with AMN, eight symptomatic heterozygous women, and 10 age- and sex-matched controls and compared to the Expanded Disability Status Scale (EDSS) and quantitative tests of vibratory sense and postural sway. MTw data sets were obtained at the level of C1 to C3 using a three-dimensional gradient echo acquisition technique, these images were then standardized between subjects by using the in-slice CSF signal as a normalization reference, allowing a quantitative assessment of the MTw signal. RESULTS: In contrast to conventional MRI, MTw images showed signal hyperintensities in the lateral and dorsal columns of all patients. The MT signal quantified in the dorsal column showed significant differences between patients with AMN, X-linked adrenoleukodystrophy heterozygotes, and controls. MT hyperintensity in the dorsal column correlated with EDSS, vibratory sense, and postural sway. CONCLUSION: Magnetization transfer-weighted imaging is a sensitive modality for the visual and quantitative assessment of spinal cord pathology in adrenomyeloneuropathy, and is a potential tool for evaluation of new therapies.

SENSE-DTI at 3 T.

While holding vast potential, diffusion tensor imaging (DTI) with single-excitation protocols still faces serious challenges. Limited spatial resolution, susceptibility to magnetic field inhomogeneity, and low signal-to-noise ratio (SNR) may be considered the most prominent limitations. It is demonstrated that all of these shortcomings can be effectively mitigated by the transition to parallel imaging technology and high magnetic field strength. Using the sensitivity encoding (SENSE) technique at 3 T, brain DTI was performed in nine healthy volunteers. Despite enhanced field inhomogeneity, parallel acquisition permitted both controlling geometric distortions and enhancing spatial resolution up to 0.8 mm in-plane. Heightened SNR requirements were met in part by high base sensitivity at 3 T. A further significant increase in SNR efficiency was accomplished by SENSE acquisition, exploiting enhanced encoding speed for echo time reduction. Based on the resulting image data, high-resolution tensor mapping is demonstrated.

Comparison of the dependence of blood R2 and R2* on oxygen saturation at 1.5 and 4.7 Tesla.

Gradient-echo (GRE) blood oxygen level-dependent (BOLD) effects have both intra- and extravascular contributions. To better understand the intravascular contribution in quantitative terms, the spin-echo (SE) and GRE transverse relaxation rates, R(2) and R(2)(*), of isolated blood were measured as a function of oxygenation in a perfusion system. Over the normal oxygenation saturation range of blood between veins, capillaries, and arteries, the difference between these rates, R'(2) = R(2)(*) - R(2), ranged from 1.5 to 2.1 Hz at 1.5 T and from 26 to 36 Hz at 4.7 T. The blood data were used to calculate the expected intravascular BOLD effects for physiological oxygenation changes that are typical during visual activation. This modeling showed that intravascular DeltaR(2)(*) is caused mainly by R(2) relaxation changes, namely 85% and 78% at 1.5T and 4.7T, respectively. The simulations also show that at longer TEs (>70 ms), the intravascular contribution to the percentual BOLD change is smaller at high field than at low field, especially for GRE experiments. At shorter TE values, the opposite is the case. For pure parenchyma, the intravascular BOLD signal changes originate predominantly from venules for all TEs at low field and for short TEs at high field. At longer TEs at high field, the capillary contribution dominates. The possible influence of partial volume contributions with large vessels was also simulated, showing large (two- to threefold) increases in the total intravascular BOLD effect for both GRE and SE.

Diffusion tensor imaging of periventricular leukomalacia shows affected sensory cortex white matter pathways.

The authors used diffusion-tensor imaging to examine central white matter pathways in two children with spastic quadriplegic cerebral palsy. Corticospinal tracts projecting from cortex to brainstem resembled controls. In contrast, posterior regions of the corpus callosum, internal capsule, and corona radiata were markedly reduced, primarily in white matter fibers connected to sensory cortex. These findings suggest that the motor impairment in periventricular leukomalacia may, in part, reflect disruption of sensory connections outside classic pyramidal motor pathways.

Independent component analysis of fMRI data in the complex domain.

In BOLD fMRI a series of MR images is acquired and examined for task-related amplitude changes. These functional changes are small, so it is important to maximize detection efficiency. Virtually all fMRI processing strategies utilize magnitude information and ignore the phase, resulting in an unnecessary loss of efficiency. As the optimum way to model the phase information is not clear, a flexible modeling technique is useful. To analyze complex data sets, independent component analysis (ICA), a data-driven approach, is proposed. In ICA, the data are modeled as spatially independent components multiplied by their respective time-courses. There are thus three possible approaches: 1) the time-courses can be complex-valued, 2) the images can be complex-valued, or 3) both the time-courses and the images can be complex-valued. These analytic approaches are applied to data from a visual stimulation paradigm, and results from three complex analysis models are presented and compared with magnitude-only results. Using the criterion of the number of contiguous activated voxels at a given threshold, an average of 12-23% more voxels are detected by complex-valued ICA estimation at a threshold of /Z/ > 2.5. Additionally, preliminary results from the complex models reveal a phase modulation similar to the magnitude time-course in some voxels, and oppositely modulated in other voxels.

Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem.

Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to investigate regional metabolite levels and ratios in the normal adult human posterior fossa. Six normal volunteers (36 +/- 3 years, five male, one female) were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280 msec). The entire cerebellum was covered using three oblique-axial slice locations, which also included the pons, mid-brain, insular cortex, and parieto-occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were estimated using the phantom replacement technique. Regional variations of the concentrations were assessed using ANOVA (P < 0.05). High-resolution MRSI data was obtained in all subjects and brain regions examined. Metabolite concentrations (mM) (mean +/- SD) were as follows: cerebellar vermis: 2.3 +/- 0.4, 8.8 +/- 1.7 and 7.6 +/- 1.0 for Cho, Cr, and NAA respectively; cerebellar hemisphere: 2.2 +/- 0.6, 8.9 +/- 2.1, 7.5 +/- 0.8; pons 2.2 +/- 0.5, 4.3 +/- 1.1, 8.3 +/- 0.9; insular cortex, 1.8 +/- 0.5, 7.8 +/- 2, 8.0 +/- 1.1, parieto-occipital gray matter, 1.3 +/- 0.3, 5.7 +/- 1.1, 7.2 +/- 0.9, and occipital white matter, 1.4 +/- 0.3, 5.3 +/- 1.3, 7.5 +/- 0.8. Consistent with previous reports, significantly higher levels of Cr were found in the cerebellum compared to parieto-occipital gray and occipital white matter, and pons (P < 0.0001). NAA was essentially uniformly distributed within the regions chosen for analysis, with the highest level in the pons (P < 0.04). Cho was significantly higher in the cerebellum and pons than parieto-occipital gray and occipital white matter (P < 0.002) and was also higher in the pons than in the insular cortex (P < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and significant regional differences in metabolite concentrations were found.

MR imaging of the human brain at 1.5 T: regional variations in transverse relaxation rates in the cerebral cortex.

BACKGROUND AND PURPOSE: Heterogeneity in cortical signal intensity on T2-weighted MR images has been recently documented. Using a whole-brain, multiecho MR imaging technique, we sought to determine the T2 relaxation times of nine predefined regions in the cerebral cortex and one region in the deep gray matter. METHODS: Ten adult volunteers (nine men and one woman; age range, 18-40 y; average age, 30.8 y) underwent whole-brain imaging with an oblique coronal multiecho 3D Carr-Purcell-Meiboom-Gill MR sequence at 1000/25, 50, 75, 100, 125, and 150 (TR/TE). T2 measurements were obtained, with variably sized regions of interest, from the primary auditory cortex, primary visual cortex, caudate nucleus, superior frontal gyrus, inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, insula cortex, cingulate gyrus, and hippocampus. Repeated-measures analysis of variance was used to assess the existence of differences in T2 measurements among the anatomic locations. RESULTS: On the basis of T2 measurements, the gray matter structures examined could be divided into four statistically different groups. In ascending order of T2 measurements, the first group consisted of the primary auditory cortex and primary visual cortex; the second group, the caudate nucleus, superior frontal gyrus, inferior temporal gyrus, middle temporal gyrus, and superior temporal gyrus; the third group, the insula cortex; and the fourth group, the cingulate gyrus and hippocampus. CONCLUSION: Significant variation in T2 values among the cortical gray matter of the human brain exists.

Diffusion tensor imaging and axonal tracking in the human brainstem.

Diffusion tensor MRI was used to demonstrate in vivo anatomical mapping of brainstem axonal connections. It was possible to identify the corticospinal tract (CST), medial lemniscus, and the superior, medial, and inferior cerebellar peduncles. In addition, the cerebral peduncle could be subparcellated into component tracts, namely, the frontopontine tract, the CST, and the temporo-/parieto-/occipitopontine tract. Anatomical landmarks and tracking thresholds were established for each fiber and, using these standards, reproducibility of automated tracking as assessed by intra- and interrater reliability was found to be high (kappa > 0.82). Reconstructed fibers corresponded well to existing anatomical knowledge, validating the tracking. Information on the location of individual tracts was coregistered with quantitative MRI maps to automatically measure MRI parameters on a tract-by-tract basis. The results reveal that each tract has a unique spatial signature in terms of water relaxation and diffusion anisotropy.

Measurement of tissue oxygen extraction ratios from venous blood T(2): increased precision and validation of principle.

It has recently been shown that parenchymal oxygen extraction ratios (OERs) can be quantified using the absolute T(2) of venous blood draining from this tissue (Oja et al., J Cereb Blood Flow Metab 1999;19:1289-1295). Here, a modified Carr-Purcell-Meiboom-Gill (CPMG) multiecho experiment was used to increase the efficiency and precision of this approach and to test the applicability of the two-compartment exchange model for spin-echo BOLD effects in pure venous blood. Relaxation measurements on bovine blood as a function of CPMG interecho spacing, oxygen saturation, and hematocrit provided the baseline relaxation and susceptibility shift parameters necessary to directly relate OER to T(2) of venous blood in vivo. Using an interecho spacing of 25 ms, the results on visual activation studies in eight volunteers showed T(2)(CPMG) values increasing from 128 +/- 9 ms to 174 +/- 18 ms upon activation, corresponding to local OER values of 0.38 +/- 0.04 and 0.18 +/- 0.05 during baseline activity and visual stimulation, respectively. These OER values are in good agreement with literature data on venous oxygenation and numbers determined previously using a single-echo approach, while the measured T(2)s are about 20-40 ms longer.