Noninvasive mapping of water diffusional exchange in the human brain using filter-exchange imaging.

We present the first in vivo application of the filter-exchange imaging protocol for diffusion MRI. The protocol allows noninvasive mapping of the rate of water exchange between microenvironments with different self-diffusivities, such as the intracellular and extracellular spaces in tissue. Since diffusional water exchange across the cell membrane is a fundamental process in human physiology and pathophysiology, clinically feasible and noninvasive imaging of the water exchange rate would offer new means to diagnose disease and monitor treatment response in conditions such as cancer and edema. The in vivo use of filter-exchange imaging was demonstrated by studying the brain of five healthy volunteers and one intracranial tumor (meningioma). Apparent exchange rates in white matter range from 0.8±0.08 s(-1) in the internal capsule, to 1.6±0.11 s(-1) for frontal white matter, indicating that low values are associated with high myelination. Solid tumor displayed values of up to 2.9±0.8 s(-1). In white matter, the apparent exchange rate values suggest intra-axonal exchange times in the order of seconds, confirming the slow exchange assumption in the analysis of diffusion MRI data. We propose that filter-exchange imaging could be used clinically to map the water exchange rate in pathologies. Filter-exchange imaging may also be valuable for evaluating novel therapies targeting the function of aquaporins.

Alzheimer's disease (AD) and executive dysfunction. A case-control study on the significance of frontal white matter changes detected by diffusion tensor imaging (DTI).

White matter (WM) changes are frequently seen on structural imaging in AD but the clinical relevance of these changes is uncertain. Frontal WM pathology is often observed upon neuropathological examination in AD. Since frontal cortical/sub-cortical pathology is known to relate to executive dysfunction, the aim was to elucidate if frontal WM changes in AD correlated with executive dysfunction. In all, 15 AD patients and 15 age-matched control cases were investigated in the study, which covered conventional magnetic resonance imaging (MRI), DTI, neuropsychiatric and neuropsychological examinations. Reduced performance on neuropsychological testing of executive function correlated significantly with an increasing degree of frontal WM changes detected by DTI in the AD group, while no such correlation was observed for the controls. Conventional semi-quantitative MRI assessment did not correlate with results on neuropsychological testing of executive function in any of the groups. The structural correlate to certain dimensions of executive dysfunction in AD patients could be related to changes in the deep frontal WM. DTI appears to be more sensitive in the detection of clinically significant WM alterations than conventional semi-quantitative MRI.

On the effects of a varied diffusion time in vivo: is the diffusion in white matter restricted?

The aim of this work was to study the diffusion-related signal attenuation curves (signal-vs.-b curves) measured perpendicular and parallel to the neuronal fibers of the corticospinal tract in vivo and to determine whether effects of restricted diffusion could be observed when varying the diffusion time (T(D)). A biexponential model and a two-compartment model including exchange according to the Kärger formalism were employed to analyze the signal-vs.-b curves. To validate the two-compartment model, restricted diffusion with exchange was simulated for uniformly sized cylinders, using different diameters and exchange times. The model was shown to retrieve the simulated parameters well, also when the short gradient pulse approximation was not met. The in vivo measurements performed perpendicular to the tracts, using b values up to 28000 s/mm(2) and T(D) values between 64 and 256 ms, did not show the effects of restricted diffusion as expected from previous ex vivo studies. The applied two-compartment model yielded an average axonal diameter of about 4 mum and an intracellular exchange time of about 300 ms, but did not fit statistically well to the data. In conclusion, this study indicates that if the diffusion is modeled as two compartments, of which one is restricted, exchange must be included in the model.

In vivo visualization of displacement-distribution-derived parameters in q-space imaging.

OBJECTIVE: This study aimed to explore the potential of in vivo q-space imaging in the differentiation between different cerebral water components. MATERIALS AND METHODS: Diffusion-weighted imaging was performed in six directions with 32 equally spaced q values and a maximum b value of 6600 s/mm(2). The shape of the signal-attenuation curve and the displacement propagator were examined and compared with a normal distribution using the kurtosis parameter. Maps displaying kurtosis, fast and slow components of the apparent diffusion coefficients, fractional anisotropy and directional diffusion were calculated. The displacement propagator was further described by the full width at half and at tenth maximum and by the probability density of zero displacement P(0). Three healthy volunteers and three patients with previously diagnosed multiple sclerosis (MS) were examined. RESULTS: Simulations indicated that the kurtosis of a signal-attenuation curve can determine if more than one water component is present and that care must be taken to select an appropriate threshold. It was possible to distinguish MS plaques in both signal and diffusional kurtosis maps, and in one patient, plaques of different degree of demyelinization showed different behavior. DISCUSSION: Our results indicate that in vivo q-space analysis is a potential tool for the assessment of different cerebral water components, and it might extend the diagnostic interpretation of data from diffusion magnetic resonance imaging.

Accuracy of q-space related parameters in MRI: simulations and phantom measurements.

The accuracy of q-space measurements was evaluated at a 3.0-T clinical magnetic resonance imaging (MRI) scanner, as compared with a 4.7-T nuclear magnetic resonance (NMR) spectrometer. Measurements were performed using a stimulated-echo pulse-sequence on n-decane as well as on polyethylene glycol (PEG) mixed with different concentrations of water, in order to obtain bi-exponential signal decay curves. The diffusion coefficients as well as the modelled diffusional kurtosis K(fit) were obtained from the signal decay curve, while the full-width at half-maximum (FWHM) and the diffusional kurtosis K were obtained from the displacement distribution. Simulations of restricted diffusion, under conditions similar to those obtainable with a clinical MRI scanner, were carried out assuming various degrees of violation of the short gradient pulse (SGP) condition and of the long diffusion time limit. The results indicated that an MRI system can not be used for quantification of structural sizes less than about 10 microm by means of FWHM since the parameter underestimates the confinements due to violation of the SGP condition. However, FWHM can still be used as an important contrast parameter. The obtained kurtosis values were lower than expected from theory and the results showed that care must be taken when interpreting a kurtosis estimate deviating from zero.

Effects of restricted diffusion in a biological phantom: a q-space diffusion MRI study of asparagus stems at a 3T clinical scanner.

INTRODUCTION: The aim of this work was to study the effects of restricted diffusion in a biological phantom consisting of green asparagus stems using q-space MRI at a clinical scanner. METHOD: Measurements of the full width at half maximum (FWHM) of the displacement distribution were performed with varied diffusion time (Td). The accuracy of the measurements was investigated with respect to the degree of violation of the short gradient pulse (SGP) condition, partial volume effects and a FWHM-based tensor model. RESULTS: The measurements showed a reasonably constant FWHM perpendicular to the capillaries in the vascular bundles and an increased FWHM parallel with the bundles when the Td was increased. A 15% decrease in FWHM perpendicular to the bundles was observed when the diffusion encoding duration was prolonged from 24 to 74 ms, owing to the violation of the SGP condition. For a population of different confinement sizes, simulations indicated that the FWHM reflects the smaller sizes rather then the mean size of the confinements. CONCLUSION: A new method allowing tensor analysis of FWHM was derived and yielded accurate results. In conclusion, we found it possible to measure the effects of restricted diffusion with q-space MRI using a clinical MRI scanner.

Denoising of complex MRI data by wavelet-domain filtering: application to high-b-value diffusion-weighted imaging.

The Rician distribution of noise in magnitude magnetic resonance (MR) images is particularly problematic in low signal-to-noise ratio (SNR) regions. The Rician noise distribution causes a nonzero minimum signal in the image, which is often referred to as the rectified noise floor. True low signal is likely to be concealed in the noise, and quantification is severely hampered in low-SNR regions. To address this problem we performed noise reduction (or denoising) by Wiener-like filtering in the wavelet domain. The filtering was applied to complex MRI data before construction of the magnitude image. The noise-reduction algorithm was applied to simulated and experimental diffusion-weighted (DW) images. Denoising considerably reduced the signal standard deviation (SD, by up to 87% in simulated images) and decreased the background noise floor (by approximately a factor of 6 in simulated and experimental images).

Mapping the intracellular fraction of water by varying the gradient pulse length in q-space diffusion MRI.

Finite gradient pulse lengths are traditionally considered a nuisance in q-space diffusion NMR and MRI, since the simple Fourier relation between the acquired signal and the displacement probability is invalidated. Increasing the value of the pulse length leads to an apparently smaller value of the estimated compartment size. We propose that q-space data at different gradient pulse lengths, but with the same effective diffusion time, can be used to identify and quantify components with free or restricted diffusion from multiexponential echo decay curves obtained on cellular systems. The method is demonstrated with experiments on excised human brain white matter and a series of model systems with well-defined free, restricted, and combined free and restricted diffusion behavior. Time-resolved diffusion MRI experiments are used to map the spatial distribution of the intracellular fraction in a yeast cell suspension during sedimentation, and observe the disappearance of this fraction after a heat treatment.

Magnetic resonance imaging artifacts caused by aneurysm clips and shunt valves: dependence on field strength (1.5 and 3 T) and imaging parameters.

PURPOSE: To evaluate artifact sizes at 3 T compared to at 1.5 T, and to evaluate the influence of scanning parameters with respect to artifact size on a 3-T magnetic resonance imaging (MRI) system. MATERIALS AND METHODS: Two aneurysm clips and five shunt valves were imaged in a water phantom at 1.5 and 3 T. At 3 T the influence of bandwidth (spin echo (SE) images) and echo time (gradient echo (GRE) images) on artifact size (area and extension in two orthogonal directions) was investigated. RESULTS: Artifact sizes increased substantially (typically 5-10 mm) at 3 T, compared to at 1.5 T, for implants entirely made of metallic materials, whereas the increase was the size less prominent (0-5 mm) for implants only partly containing metal. Artifact areas could be altered by changing the bandwidth or the echo time to about the same extent as it was affected by the increased field strength. CONCLUSION: Artifact sizes increase at 3 T, compared to at 1.5 T, depending on the type and composition of the implant, but can be substantially reduced by altering the imaging parameters. Optimization of imaging protocols to minimize artifacts is therefore important at higher field strengths.

MRI with diffusion tensor imaging post-mortem at 3.0 T in a patient with frontotemporal dementia.

The formalin-fixed brain of a patient with clinically diagnosed frontotemporal dementia (FTD) was examined post-mortem using magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) at 3.0 T. Frontotemporal atrophy as well as bilateral frontal white matter abnormalities were seen. The white matter changes were slightly more extensive on DTI than on conventional MRI. Correlation with histopathology of the corresponding regions revealed typical frontal lobe degeneration of non-Alzheimer type, with mild frontotemporal degeneration in the outer cortical layers and a moderate frontal white matter gliosis with demyelination. Post-mortem MRI/DTI with histopathologic correlation will enhance our understanding of the basis of white matter changes observed in dementia patients and may improve the in vivo MRI/DTI diagnostic assessment in FTD.