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Diffusion-weighted MR imaging in closed head injury: high correlation with initial glasgow coma scale score and score on modified Rankin scale at discharge.

PURPOSE: To determine whether diffusion-weighted magnetic resonance (MR) imaging findings and conventional MR imaging findings correlate with initial Glasgow Coma Scale score and score on modified Rankin scale at discharge. MATERIALS AND METHODS: Twenty-six patients (18 male and eight female patients; mean age, 25.2 years; age range, 4-72 years) with diffuse axonal injury were examined with diffusion-weighted MR imaging and with fluid-attenuated inversion recovery, T2-weighted fast spin-echo, and T2*-weighted gradient-echo sequences. All images were evaluated by two neuroradiologists in consensus. Tissue volume with trauma-related signal-intensity abnormality on images from each sequence, number of lesions for each sequence, number of lesions for all sequences, and number of lesions with reduced apparent diffusion coefficient were correlated with scores on Glasgow Coma Scale and modified Rankin scale. Involvement of brainstem, deep gray matter, and corpus callosum were also correlated with clinical scores. Spearman rank correlation coefficients (r) were calculated. RESULTS: The strongest correlation was between signal-intensity abnormality volume on diffusion-weighted images and modified Rankin score (r = 0.772, P <.001). The strength of this correlation did not improve when only volume of lesions with decreased apparent diffusion coefficient was considered. For lesion number, the strongest correlation was between lesion number on images acquired with all sequences and modified Rankin score (r = 0.662, P <.001). For lesion location, the strongest correlation was between lesion location in the corpus callosum and modified Rankin score (r = 0.513, P =.007). CONCLUSION: Volume of lesions on diffusion-weighted MR images provides the strongest correlation with a score of subacute on modified Rankin scale at discharge. Total lesion number also correlates well with modified Rankin score. In future, diffusion-weighted images may be useful in determining treatment strategies for acute head injury.

Adolescent↗

Clinical correlates of cerebral water diffusion in Wilson disease.

OBJECTIVE: To investigate the course of diffusion changes in Wilson disease (WD) and to evaluate their clinical and radiologic correlates. METHODS: MRI with fluid-attenuated inversion recovery (FLAIR) and diffusion weighted images (DWI) were performed in 13 symptomatic patients with WD who had typical neurologic manifestations of the disease (sWD patients) and in 5 presymptomatic patients (psWD patients). Follow-up clinical and MRI data were obtained in 12/13 patients with sWD. Ten subjects without neurologic disease and with normal cerebral MRI were used as controls. Apparent diffusion coefficient (ADC) was measured in areas where hyperintense lesions were detected on FLAIR images and in the normal-appearing white matter. RESULTS: Hyperintense lesions were detected in all symptomatic patients on FLAIR MR images but only in 11 of 13 patients with sWD on DWI. These lesions were absent in patients with psWD. The mean ADC was found increased in the putamen, pallidum, internal capsule, mesencephalon, and within the white matter in the symptomatic group in comparison to controls. This was not observed in patients with psWD, who even had a decreased ADC in the putamen. A significant correlation was found between the increase in diffusion and the modified Rankin Scale in presence of symptoms. Moreover, the variation of the clinical scale was significantly correlated with the variation of diffusion in the putamen of symptomatic patients. CONCLUSION: A decrease in diffusion in the putamen can be detected before the occurrence of neurologic manifestations in WD. In contrast, a large increase in diffusion is detected after the occurrence of symptoms within the putamen, pallidum, internal capsule, and subcortical white matter parallel to the signal changes as seen on fluid-attenuated inversion recovery and diffusion weighted images.

Adolescent↗

In vivo and in vitro bi-exponential diffusion of N-acetyl aspartate (NAA) in rat brain: a potential structural probe?

Diffusion measurements were performed on the N-acetyl aspartate (NAA) signal in in situ brains (in vivo and post-mortem) and on in vitro brain tissue at 37 degrees C using wide ranges of b-values (from 0 up to 4.5 x 10(6) s/cm2 and 35.8 x 10(6) s/cm2 for the in vivo and the in vitro cases, respectively). In vivo and in vitro NAA signals attenuation due to diffusion was measured at fixed diffusion times (tD). In the in vitro cases the effect of tD on the apparent diffusion coefficients (ADCs) of NAA was evaluated. From these experiments the following observations and conclusions were made: (1) NAA signal attenuation both in vivo and in vitro is not mono-exponential and could be fitted by bi-exponential fitting function; (2) analysis of the low b-value range only (up to 0.5 x 10(6) s/cm2) gives a mono-exponential decay (r = 0.999); (3) in both cases the obtained ADCs are sensitive to the diffusion time; (4) the ADCs of the pre- and post-mortem cases are nearly similar; (5) the ADCs obtained from the bi-exponential fitting function decrease when the diffusion time increases; and (6) both the fast and the slow diffusing components of NAA show a considerable restriction by what seems to be a non-permeable barrier from which two compartments were identified, one having a size of 6-8 microns and the other of approximately 1-2 microns in size. It seems conceivable that the two populations identified in the diffusion experiments represent primarily the NAA in the cell body (soma) and in the neurital space (axons and proximal dendrites).

Animals↗

Multi-component apparent diffusion coefficients in human brain.

The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/ mm2, a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b-factor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 x 15 x 1 mm3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 microm2/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 microm2/ms. Simple models which might explain the non-exponential behavior, such as intra- and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm2, the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 microm2/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization.

Adult↗

Reduced xenon diffusion for quantitative lung study--the role of SF(6).

The large diffusion coefficients of gases result in significant spin motion during the application of gradient pulses that typically last a few milliseconds in most NMR experiments. In restricted environments, such as the lung, this rapid gas diffusion can lead to violations of the narrow pulse approximation, a basic assumption of the standard Stejskal-Tanner NMR method of diffusion measurement. We therefore investigated the effect of a common, biologically inert buffer gas, sulfur hexafluoride (SF(6)), on (129)Xe NMR and diffusion. We found that the contribution of SF(6) to (129)Xe T(1) relaxation in a 1:1 xenon/oxygen mixture is negligible up to 2 bar of SF(6) at standard temperature. We also measured the contribution of SF(6) gas to (129)Xe T(2) relaxation, and found it to scale inversely with pressure, with this contribution approximately equal to 1 s for 1 bar SF(6) pressure and standard temperature. Finally, we found the coefficient of (129)Xe diffusion through SF(6) to be approximately 4.6 x 10(-6) m(2)s(-1) for 1 bar pressure of SF(6) and standard temperature, which is only 1.2 times smaller than the (129)Xe self diffusion coefficient for 1 bar (129)Xe pressure and standard temperature. From these measurements we conclude that SF(6) will not sufficiently reduce (129)Xe diffusion to allow accurate surface-area/volume ratio measurements in human alveoli using time-dependent gas diffusion NMR.

Diffusion↗

Burst excitation for quantitative diffusion imaging with multiple b-values.

A quantitative imaging sequence has been developed to exploit the intrinsic sensitivity of Burst NMR data to molecular diffusion. In the scan time of a single spin echo experiment, it is possible to acquire many images of the same slice, with a different T(2) and diffusion weighting. Under favorable conditions, it is possible to obtain both the diffusion coefficient and T(2) from the same experiment; or, by correcting for T(2) relaxation using a control image, more precise diffusion coefficients may be measured. The quantitative values in rat brain are in agreement with those from conventional experiments. The major gains of this method are the potentially reduced scan time, the higher number of acquired images corresponding to different diffusion weightings, the reduced sensitivity to inter-scan motion artifact and to local variations in magnetic susceptibility, and an automatic co-registration between T(2) and diffusion images. Problems with the sequence include a lower signal-to-noise ratio than is achievable with diffusion-weighted spin-echo imaging, the limitation of measuring only in-plane components of diffusion and, at present, single-slice acquisition.

Animals↗

Single breath-hold diffusion-weighted imaging of the abdomen.

PURPOSE: To generate high quality diffusion-weighted images (DWI) and corresponding isotropic ADC maps of the abdomen with full organ (kidneys) coverage in a single breath-hold. MATERIALS AND METHODS: DWI was performed in 12 healthy subjects with an asymmetric, spin-echo, single-shot EPI readout on a system with high performance gradients (40 mT/minute). The isotropic diffusion coefficient was measured from maps and SNR was determined for both diffusion-weighted and reference images in the liver, spleen, pancreas, and kidneys. In six patients, single-axis diffusion encoding along three orthogonal axes (12 NEX) was employed to assess anisotropic diffusion in kidneys. RESULTS: This technique yielded images of quality and resolution which compares favorably to that of prior work. SNR ranged from 27.0 in liver to 44.1 in kidneys for the diffusion-weighted images, and from 19.6 in liver to 39.0 in kidneys in reference images. ADCs obtained in the renal medulla, renal cortex, liver, spleen, and pancreas were (2091 +/- 55) x 10(-6), (2580 +/- 53) x 10(-6), (1697 +/- 52) x 10(-6), (1047 +/- 82) x 10(-6), and (2605 +/- 168) x 10(-6) mm(2)/second, respectively (mean +/- SE). Apparent diffusion coefficient (ADC) in the renal medulla and cortex were significantly different by paired t-test (P = 4.22 x 10(-10)). Renal medulla and cortex yielded anisotropy indices (AI) of 0.129 and 0.067, respectively. CONCLUSIONS: 1) Single-shot SE EPI DWI in the abdomen with this technique provides high quality images and maps with full organ coverage in a single breath-hold; 2) ADCs obtained in the renal medulla and cortex are significantly different; and 3) diffusion within the renal medulla is moderately anisotropic.

Abdomen↗

Diffusion tensor MRI of the human kidney.

This study characterizes the diffusion anisotropy of the human kidney using a diffusion-weighted, single-shot echo planar imaging (EPI) sequence in order to access the full apparent diffusion tensor (ADT) within one breathhold. The fractional anisotropy (FA) of the cortex and the medulla were found to be 0.22 +/- 0.12 and 0.39 +/- 0.11, respectively (N = 10), which emphasizes the need for rotationally invariant diffusion measurements for clinical applications. Additional limitations for clinical diffusion imaging on the kidney are the strong susceptibility variations within the abdomen that restrict the use of imaging techniques employing long echo trains, and the severe motion sensitivity that limits the available imaging time to one breath-hold. To overcome these problems an isotropic, diffusion-weighted, segmented EPI protocol that facilitates the acquisition of high-resolution diffusion-weighted images within a single breath-hold was implemented. Using this method, the apparent diffusion coefficient (ADC) of the cortex and medulla were found to be 2.89 +/- 0.28. 10(-9) m2/s and 2.18 +/- 0.36. 10(-9) m2/s (N = 10).

Anisotropy↗

Diffusion imaging with the MP-RAGE sequence.

Diffusion-weighted magnetic resonance (MR) images obtained with conventional spin-echo techniques are known to be sensitive to subject motion because of long image acquisition times. To reduce the acquisition time, use of a magnetization-prepared rapid gradient-echo (MP-RAGE) sequence modified for diffusion sensitivity was studied. In this sequence, a preparation phase with a 90 degrees-180 degrees-90 degrees pulse train is used to sensitize the magnetization to diffusion. Centric-ordered phase encoding, short TRs (5.2-6.5 msec), and small flip angles (5 degrees-8 degrees) are necessary to minimize saturation effects from tissues with short relaxation times. Phantom studies with various concentrations of copper sulfate (T1 ranging from 2,459 to 90 msec) were performed to validate that the diffusion-weighted signal obtained with the MP-RAGE sequence was independent of relaxation time. Diffusion-weighted images of water, isopropyl alcohol, and acetone were acquired to confirm the accuracy of measured diffusion coefficients. Brain images of healthy normal volunteers were obtained to demonstrate motion insensitivity and general image quality of the technique. The results indicate that accurate diffusion-weighted images can be obtained with a diffusion-weighted MP-RAGE sequence, with imaging times of about 1 second.

1-Propanol↗

Prediction of steady-state skin permeabilities of polar and nonpolar permeants across excised pig skin based on measurements of transient diffusion: characterization of hydration effects on the skin porous pathway.

The applicability of a two-parameter Fickian diffusion model for predicting the skin steady-state permeability based on measurements of the transient transport of permeants across the skin was tested. Using five model permeants possessing different physicochemical properties and pig skin as the model membrane, the skin permeabilities predicted by the two-parameter Fickian diffusion model were compared with the measured skin permeabilities. Results show that the transient skin permeation profiles of the hydrophobic permeants, estradiol, testosterone, and dolichol, across split-thickness pig skin can be modeled adequately by the two-parameter Fickian diffusion model (with constant parameter values), and therefore, that this model can be utilized to shorten the experimental time required to determine the skin permeabilities of these compounds. However, the skin permeabilities of the highly hydrophilic permeants, mannitol and sucrose, predicted by the two-parameter Fickian diffusion model (with constant parameter values) were significantly lower than the experimentally determined values, indicating that the dominant skin pathway of polar permeants within the excised pig skin undergoes significant structural changes during the in vitro diffusion cell studies. Although the skin permeability values determined experimentally using the traditional steady-state method normally correspond to a highly hydrated skin sample, the two-parameter Fickian diffusion model enables an estimation of the skin permeability of the skin membrane at its less-hydrated state (a condition more representative of in vivo and clinical situations). Using the two-parameter Fickian diffusion model and a recently developed skin porous-pathway theory, the effects of skin hydration on the skin porous pathway within the excised pig skin were characterized. Specifically, we found that hydration leads to induction of new pores/reduction of the tortuosity of existing pores within the excised pig skin during the 48 h diffusion cell studies conducted, while the skin average pore radii remain relatively constant (approximately 26 A) for up to 48 h.

Algorithms↗

Measurement of aroma compound self-diffusion in food models by DOSY.

Self-diffusion measurement of solutes in polymer gels has been investigated using pulsed gradient spin echo NMR spectroscopy. However, few data are available on the self-diffusion of small solutes in natural polysaccharide polymers used as thickeners in the food industry. Since aroma diffusion in food matrices could have an impact on flavor release, this is an interesting and economic challenge. Diffusion ordered spectroscopy (DOSY) resolves diffusion data for each component in complex mixtures. We used DOSY with the inverse Laplace transform approach with the maximum entropy algorithm to investigate diffusion of two aroma compounds, ethyl butanoate and linalool, in an iota-carrageenan matrix as the food model. We showed that the self-diffusion coefficient values of small molecules in a polysaccharide matrix could be easily extracted using this method. We then investigated the impact of the gelling state of iota-carrageenan matrices on the self-diffusion of ethyl butanoate.

Acyclic Monoterpenes↗

Characterization of continuously distributed cortical water diffusion rates with a stretched-exponential model.

Experience with diffusion-weighted imaging (DWI) shows that signal attenuation is consistent with a multicompartmental theory of water diffusion in the brain. The source of this so-called nonexponential behavior is a topic of debate, because the cerebral cortex contains considerable microscopic heterogeneity and is therefore difficult to model. To account for this heterogeneity and understand its implications for current models of diffusion, a stretched-exponential function was developed to describe diffusion-related signal decay as a continuous distribution of sources decaying at different rates, with no assumptions made about the number of participating sources. DWI experiments were performed using a spin-echo diffusion-weighted pulse sequence with b-values of 500-6500 s/mm(2) in six rats. Signal attenuation curves were fit to a stretched-exponential function, and 20% of the voxels were better fit to the stretched-exponential model than to a biexponential model, even though the latter model had one more adjustable parameter. Based on the calculated intravoxel heterogeneity measure, the cerebral cortex contains considerable heterogeneity in diffusion. The use of a distributed diffusion coefficient (DDC) is suggested to measure mean intravoxel diffusion rates in the presence of such heterogeneity.

Animals↗

Relative indices of water diffusion anisotropy are equivalent in live and formalin-fixed mouse brains.

Formalin fixation of tissue is a common laboratory practice. A direct comparison of diffusion tensor imaging (DTI) parameters from mouse brains before (in vivo) and after (ex vivo) formalin fixation is reported herein. Five diffusion indices were examined in a cohort of seven mice: relative anisotropy (RA), directional correlation (DC), trace (Tr(D)), trace-normalized axial diffusivity (D(axially)), and radial diffusivity (D(radially)). Seven regions of interest (ROIs), including five in white matter and two in gray matter, were selected for examination. Consistent with previous findings, a significant decrease of Tr(D) was observed for all ROIs after fixation. However, water diffusion anisotropy, as defined by the indices RA, DC, D(axially), and D(radially), remained unchanged after fixation. Thus, fixation does not appear to alter diffusion anisotropy in the mouse brain. This finding supports the utility of diffusion anisotropy analysis of fixed tissue. The combination of DTI measurements and standard histology may shed light on the microstructural determinants of diffusion anisotropy in normal and disease states.

Animals↗

Compartmentation of intracellular water in multicellular tumor spheroids: diffusion and relaxation NMR.

Diffusion and relaxation of water in C6 glioma and MLS human ovarian carcinoma spheroids were measured from 1D projections acquired using a 2D diffusion-relaxation correlation pulse sequence and processed by non-negative least-square (NNLS) analysis. Systematic underestimation of I(s) and ADC(s) were observed for I(s)/(I(s) + I(f)) < 0.001. In the presence of spheroids, two apparent diffusion coefficient (ADC) compartments were observed, where ADC(f), ADC(s), and I(f), I(s) are the respective ADCs and signal intensities of the fast and slow compartments. These compartments differed also in their T(2) relaxation (ADC(s) = 0.5-0.74 x 10(-5) cm(2)/s, T(2) = 36-45 ms; and ADC(f) = 2.2-2.8 x 10(-5) cm(2)/s, T(2) = 280-316 ms). The two ADC compartments and the slow T(2) compartment were consistent with slow exchange. The fast T(2) compartment showed a drift with diffusion weighting, suggesting that it represents water exchanging between compartments that differ in their ADC and T(2). Both ADC(s) and I(s) were markedly attenuated with increasing diffusion time (Delta) for Delta < 100 ms, and increased at longer Delta. These results are consistent with restricted diffusion and fast relaxation of intracellular water for short diffusion time (T(1)' = 46.6 ms), and with predominant extracellular contribution to ADC(s) at longer diffusion times. Magn Reson Med 46:68-77, 2001.

Animals↗

Diffusion imaging of the human brain in vivo using high-speed STEAM MRI.

This paper describes a new method for diffusion imaging of the human brain in vivo that is based on a combination of diffusion-encoding gradients with high-speed STEAM MR imaging. The single-shot sequence 90 degrees-TE/2-90 degrees-TM-(alpha-TE/2-STE)n generates n = 32-64 differently phase-encoded stimulated echoes STE yielding image acquisition times of 576 ms for a 48 x 128 data matrix. Diffusion encoding is performed during the first TE/2-interval as well as during each readout period. Phantom studies reveal a quantitative agreement of calculated diffusion coefficients with literature values. EKG triggering completely eliminates motion artifacts from diffusion-weighted single-shot STEAM images of human brain in vivo. While signal attenuation of the cerebrospinal fluid (CSF) is predominantly due to flow, that observed for gray and white matter results from diffusion. Evaluated diffusion coefficients yield (1.0 +/- 0.1) x 10(-5) cm2 s-1 for gray matter, (0.5 +/- 0.1) x 10(-5) cm2 s-1 for white matter with the diffusion encoding parallel to the main orientation of the myelin sheath of the neurofibrils, and (0.3 +/- 0.1) x 10(-5) cm2 s-1 for white matter and a perpendicular orientation. All studies were performed at 2.0 T using a conventional 10 mT m-1 gradient system.

Brain↗

The diffusion sensitivity of fast steady-state free precession imaging.

Steady-state free precession (SSFP) imaging with an added field gradient pulse is strongly sensitive to self-diffusion and other motions of water. In an earlier theoretical analysis of diffusion attenuation due to a single gradient pulse Wu and Buxton (J. Magn. Reson. 90, 243, 1990) concluded that the diffusion sensitivity would be increased with smaller flip angles. In this paper a partial partition analysis of the different echo pathways contributing to the signal is used to illustrate the contribution of stimulated echo pathways with long diffusion times as the source of the enhanced diffusion sensitivity with low flip angles. Experimental imaging studies in phantoms and the brain of a human subject demonstrate substantially greater signal attenuation with small flip angles (< 30 degrees). The theoretical equation of Wu and Buxton provides a reasonable fit to the experimental data, accounting for the flip angle and TR dependence, but the estimated diffusion coefficients are larger than expected from previous studies. The large attenuation observed in the human studies, particularly in cerebrospinal fluid, is most likely due to other tissue motions. Both the theoretical calculations and the experimental data show that for the same gradient strength the diffusion sensitivity of SSFP is much greater than the diffusion sensitivity of conventional spin-echo methods.

Brain↗

Water diffusion and acute stroke.

The occlusion of the middle cerebral artery was used as an experimental acute stroke model in 30 cats. The diffusion of water was followed by diffusion-sensitized MRI between 1 and 15 h after induction of stroke. It is demonstrated that images representing the trace of the diffusion tensor provide a much more accurate delineation of affected area than images representing the diffusion in one direction only. The reason is that the strong contrast caused by the anisotropy and orientation of myelin fibers is completely removed in the trace of the diffusion tensor. The trace images show a small contrast between white and gray matter. The diffusion coefficient of white matter is decreased in acute stroke to approximately the same extent as gray matter. It is further shown that the average lifetime of water in extra and intracellular space is shorter than 20 ms both for healthy and ischemic tissue indicating that myelin fibers are permeable to water. The anisotropy contrast did not change before or after induction of stroke, nor after sacrifice. Together, these observations are consistent with the view that the changes in water diffusion during acute stroke are directly related to cytotoxic oedema, i.e., to the change in relative volume of intra- and extracellular spaces. Changes in membrane permeability do not appear to contribute significantly to the changes in diffusion.

Acute Disease↗

Modulation of water diffusion during gonadotropin-induced ovulation: NMR microscopy of the ovarian follicle.

The preovulatory rat follicle reaches a diameter of 1 mm with no internal blood vessels. Nutrient supply to the enclosed oocyte depends solely on passive diffusion across the follicular wall and the follicular fluid. Spin-echo and stimulated-echo NMR microscopy experiments were applied here for studying modulations in water diffusion during gonadotropin-induced maturation of perfused rat ovarian follicles (32 degrees C). Two diffusion compartments were observed for the follicular wall. The intracellular water diffusion coefficient, measured at a short diffusion time (9 ms) was 0.28 x 10(-5) cm2/s. Diffusion at long diffusion times was restricted to 16 microns, the size of cells in the follicular wall, and did not change during maturation. In the follicular fluid a transient 26% decrease in the diffusion coefficient was observed 4-7 h after gonadotropin stimulation, a change that is bound to affect the metabolic balance of the oocyte before ovulation.

Animals↗