Effects of barrier-induced nuclear spin magnetization inhomogeneities on diffusion-attenuated MR signal.

The spatial distribution of the transverse nuclear spin magnetization, appearing in a single compartment with impermeable boundaries in a Stejskal-Tanner gradient pulse MR experiment, is analyzed in detail. At short diffusion times the presence of diffusion-restrictive barriers (membranes) reduces effective diffusivity near the membranes and leads to an inhomogeneous spin magnetization distribution (the edge-enhancement effect). In this case, the signal reveals a quasi-two-compartment behavior and can be empirically modeled remarkably well by a biexponential function. The current results provide a framework for interpreting experimental MR data on various phenomena, including water diffusion in giant axons, metabolite diffusion in the brain, and hyperpolarized gas diffusion in lung airways.     

Use of ethylene glycol to evaluate gradient performance in gradient-intensive diffusion MR sequences

Imaging a phantom of known dimensions is a widely used and simple method for calibrating MRI gradient strength. However, full-range characterization of gradient response is not achievable using this approach. Measurement of the apparent diffusion coefficient of a liquid with known diffusivity allows for calibration of gradient amplitudes across a wider dynamic range. An important caveat is that the temperature dependence of the liquid's diffusion characteristics must be known, and the temperature of the calibration phantom must be recorded. In this report, we demonstrate that the diffusion coefficient of ethylene glycol is well described by Arrhenius-type behavior across the typical range of ambient MRI magnet temperatures. Because of ethylene glycol's utility as an NMR chemical-shift thermometer, the same (1)H MR spectroscopy measurements that are used for gradient calibration also simultaneously "report" the sample temperature. The high viscosity of ethylene glycol makes it well-suited for assessing gradient performance in demanding diffusion-weighted imaging and spectroscopy sequences.     

A simplified method to measure the diffusion tensor from seven MR images

Analytical expressions of the diffusion tensor of water, D , and of scalar invariants derived from it, are given in terms of the intensities of seven diffusion-weighted images (DWIs). These formulas simplify the post-processing steps required in diffusion tensor imaging, including estimating D in each voxel (from the set of b-matrices and their corresponding DWIs), and then computing its eigenvalues, eigenvectors, and scalar invariants. In a study conducted using artifact-free DWIs with high diffusion weighting (b_max ? 900 s/mm²), maps of Trace(D ) and the Relative and Lattice Anisotropy indices calculated analytically and by multivariate linear regression showed excellent agreement in brain parenchyma of a healthy living cat. However, the quality of the analytically computed maps degraded markedly as diffusion weighting was reduced. Although diffusion tensor MRI with seven DWIs may be useful for clinical applications where rapid scanning and data processing are required, it does not provide estimates of the uncertainty of the measured imaging parameters, rendering it susceptible to noise and systematic artifacts. Therefore, care should be taken when using this technique in radiological applications.     

Effects of intracellular organelles on the apparent diffusion coefficient of water molecules in cultured human embryonic kidney cells

The apparent diffusion coefficient (ADC) of water in tissues is dependent on the size and spacing of structures in the cellular environment and has been used to characterize pathological changes in stroke and cancer. However, the factors that affect ADC values remain incompletely understood. Measurements of ADC are usually made using relatively long diffusion times; so they reflect the integrated effects of cellular structures over a broad range of spatial scales. We used temporal diffusion spectroscopy to study diffusion in packed cultured human embryonic kidney cells over a range of effective diffusion times following microtubule and actin/cytoskeleton depolymerization and disassembly of the Golgi complex. While Golgi disruption did not change ADC, depolymerization of the microtubule and the actin filament networks caused small decreases in ADC at short diffusion times only. Temporal diffusion spectroscopy provided a novel way to assess intracellular influences on the diffusion properties of tissue water. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Model‐based analysis of multishell diffusion MR data for tractography: How to get over fitting problems

In this article, we highlight an issue that arises when using multiple b‐values in a model‐based analysis of diffusion MR data for tractography. The non‐monoexponential decay, commonly observed in experimental data, is shown to induce overfitting in the distribution of fiber orientations when not considered in the model. Extra fiber orientations perpendicular to the main orientation arise to compensate for the slower apparent signal decay at higher b‐values. We propose a simple extension to the ball and stick model based on a continuous gamma distribution of diffusivities, which significantly improves the fitting and reduces the overfitting. Using in vivo experimental data, we show that this model outperforms a simpler, noise floor model, especially at the interfaces between brain tissues, suggesting that partial volume effects are a major cause of the observed non‐monoexponential decay. This model may be helpful for future data acquisition strategies that may attempt to combine multiple shells to improve estimates of fiber orientations in white matter and near the cortex. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Helium-3 diffusion MR imaging of the human lung over multiple time scales

RATIONALE AND OBJECTIVES: Diffusion magnetic resonance imaging (MRI) with hyperpolarized (3)He gas is a powerful technique for probing the characteristics of the lung microstructure. A key parameter for this technique is the diffusion time, which is the period during which the atoms are allowed to diffuse within the lung for measurement of the signal attenuation. The relationship between diffusion time and the length scales that can be explored is discussed, and representative, preliminary results are presented from ongoing studies of the human lung for diffusion times ranging from milliseconds to several seconds. MATERIALS AND METHODS: (3)He diffusion MRI of the human lung was performed on a 1.5T Siemens Sonata scanner. Using gradient echo-based and stimulated echo-based techniques for short and medium-to-long diffusion times, respectively, measurements were performed for times ranging from 2 milliseconds to 6.5 seconds in two healthy subjects, a subject with subclinical chronic obstructive pulmonary disease and a subject with bronchopulmonary dysplasia. RESULTS: In healthy subjects, the apparent diffusion coefficient decreased by about 10-fold, from approximately 0.2 to 0.02 cm(2)/second, as the diffusion time increased from approximately 1 millisecond to 1 second. Results in subjects with disease suggest that measurements made at diffusion times substantially longer than 1 millisecond may provide improved sensitivity for detecting certain pathologic changes in the lung microstructure. CONCLUSIONS: With appropriately designed pulse sequences it is possible to explore the diffusion of hyperpolarized (3)He in the human lung over more than a 1,000-fold variation of the diffusion time. Such measurements provide a new opportunity for exploring and characterizing the microstructure of the healthy and diseased lung.     

Influence of cell cycle phase on apparent diffusion coefficient in synchronized cells detected using temporal diffusion spectroscopy

The relationship between the apparent diffusion coefficient of tissue water measured by MR methods and the physiological status of cells is of particular relevance for better understanding and interpretation of diffusion‐weighted MRI. In addition, there is considerable interest in developing diffusion‐dependent imaging methods capable of providing novel information on tissue microstructure, including intracellular changes. To this end, both the conventional pulsed gradient spin–echo methods and the oscillating gradient spin–echo method, which probes diffusion over very short distance (<<cell size) and time scales, were used to measure apparent diffusion coefficient of synchronized packed HL‐60 cells at 7 T. The results show that the pulsed gradient spin–echo method with relatively long diffusion times does not detect changes in apparent diffusion coefficient when structural variations arise during cell division. On the contrary, the oscillating gradient spin–echo method can detect and quantify major changes in intracellular organization that occur during mitosis by appropriate choice of gradient frequency. Cell structural parameters, including cell size, intracellular diffusion coefficient, and surface‐to‐volume ratio were also obtained by fitting the oscillating gradient spin–echo data to simple analytical models. These oscillating gradient spin–echo features may be used in diffusion‐weighted MRI to create parametric maps that may be useful for detecting cancer or changes caused by treatment. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Construction of a temperature‐controlled diffusion phantom for quality control of diffusion measurements

Purpose

To construct a temperature‐controlled diffusion phantom with known diffusion properties and geometry in order to facilitate the comparison and optimization of diffusion sequences with the objective of increasing the precision of experimentally derived diffusion parameters.

Materials and Methods

A temperature‐stabilized diffusion phantom made up of two crossing strands of hydrophobic polyethylene fibers was constructed. Reproducibility and temperature dependence of several diffusion parameters was investigated and compared with computer simulations. Furthermore, in order to stimulate actual use, the precision of measurement of different diffusion‐encoding schemes was compared using bootstrap analysis.

Results

The measured values of the diffusion parameters are highly reproducible and feature strong temperature dependence which is reproduced in simulations, underlining the necessity of a temperature‐stabilized environment for quality control. The exemplary application presented here demonstrates that the phantom allows comparing and optimizing different diffusion sequences with regard to their measurement precision.

Conclusion

The present work demonstrates that the diffusion phantom facilitates and improves the comparison and quality control of diffusion sequences and the ensuing parameters. The results show that an accurate temperature control is a vital prerequisite for highly reproducible calibration measurements. As such, the phantom might provide a valuable calibration tool for clinical studies. J. Magn. Reson. Imaging 2009;29:692–698. © 2009 Wiley‐Liss, Inc.     

Comparison of 3 Tesla proton MR spectroscopy, MR perfusion and MR diffusion for distinguishing glioma recurrence from posttreatment effects

Purpose:

To compare 3 Tesla (3T) multi‐voxel and single‐voxel proton MR spectroscopy (MRS), dynamic susceptibility contrast perfusion MRI (DSC), and diffusion‐weighted MRI (DWI) for distinguishing recurrent glioma from postradiation injury.

Materials and Methods:

We reviewed all 3T MRS, DSC and DWI studies performed for suspicion of malignant glioma recurrence between October 2006 and December 2008. Maximum Cho/NAA and Cho/Cr peak‐area and peak‐height ratios were recorded for both multi‐voxel and single‐voxel MRS. Maximum cerebral blood volume (CBV) and minimum apparent diffusion coefficient (ADC) were normalized to white matter. Histopathology and clinical‐radiologic follow‐up served as reference standards. Receiver operating characteristic curves for each parameter were compared.

Results:

Forty lesions were classified as glioma recurrence (n = 30) or posttreatment effect (n = 10). Diagnostic performance was similar for CBV ratio (AUC = 0.917, P < 0.001), multi‐voxel Cho/Cr peak‐area (AUC = 0.913, P = 0.002), and multi‐voxel Cho/NAA peak‐height (AUC = 0.913, P = 0.002), while ADC ratio (AUC = 0.726, P = 0.035) did not appear to perform as well. Single‐voxel MRS parameters did not reliably distinguish tumor recurrence from posttreatment effects.

Conclusion:

A 3T DSC and multi‐voxel MRS Cho/Cr peak‐area and Cho/NAA peak‐height appear to outperform DWI for distinguishing glioma recurrence from posttreatment effects. Single‐voxel MRS parameters do not appear to distinguish glioma recurrence from posttreatment effects reliably, and therefore should not be used in place of multi‐voxel MRS. J. Magn. Reson. Imaging 2012;35:56‐63. © 2011 Wiley Periodicals, Inc.     

Ischemia‐induced changes of intracellular water diffusion in rat glioma cell cultures

Diffusion‐weighted MRI is commonly used in the diagnosis and evaluation of ischemic stroke because of the rapid decrease observed in the apparent diffusion coefficient (ADC) of tissue water following ischemia. Although this observation has been clinically useful for many years, the biophysical mechanisms underlying the reduction of tissue ADC are still unknown. To help elucidate these mechanisms, we have employed a novel three‐dimensional (3D) hollow‐fiber bioreactor (HFBR) perfused cell culture system that enables cells to be grown to high density and studied via MRI and MRS. By infusing contrast media into the HFBR, signals from intracellular water and extracellular water are spectroscopically resolved and can be investigated individually. Diffusion measurements carried out on C6 glioma HFBR cell cultures indicate that ischemia‐induced cellular swelling results in an increase in the ADC of intracellular water from 0.35 μm²/ms to approximately 0.5 μm²/ms (diffusion time = 25 ms). Magn Reson Med 60:258–264, 2008. © 2008 Wiley‐Liss, Inc.     

Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance

The diffusion characteristics of water in brain white matter were studied in patients with benign and secondary progressive multiple sclerosis (MS), and also in normal controls. In the MS patients, both lesions and normal-appearing white matter (NAWM) were examined to assess whether pathological differences might be evident from the diffusion behavior. A volume-selective technique was used to reduce data acquisition time and improve the reliability and precision of the measurements. This also allowed the time-dependence of apparent diffusion coefficients to be assessed. While lesions from both patient groups showed an elevated diffusion coefficient, no differences between the two groups were found. In addition, NAWM was elevated for both patient groups compared with the control group, although this was only statistically significant for patients with a benign disease course. The degree of elevation of the diffusion coefficient within the individual lesions measured was not related to the disability of the patient. Pathological differences between lesions in patients with different disease courses, if they exist, have not been detected in this study of brain water diffusion.     

On the nature of the NAA diffusion attenuated MR signal in the central nervous system.

In the brain, on a macroscopic scale, diffusion of the intraneuronal constituent N-acetyl-L-aspartate (NAA) appears to be isotropic. In contrast, on a microscopic scale, NAA diffusion is likely highly anisotropic, with displacements perpendicular to neuronal fibers being markedly hindered, and parallel displacements less so. In this report we first substantiate that local anisotropy influences NAA diffusion in vivo by observing differing diffusivities parallel and perpendicular to human corpus callosum axonal fibers. We then extend our measurements to large voxels within rat brains. As expected, the macroscopic apparent diffusion coefficient (ADC) of NAA is practically isotropic due to averaging of the numerous and diverse fiber orientations. We demonstrate that the substantially non-monoexponential diffusion-mediated MR signal decay vs. b value can be quantitatively explained by a theoretical model of NAA confined to an ensemble of differently oriented neuronal fibers. On the microscopic scale, NAA diffusion is found to be strongly anisotropic, with displacements occurring almost exclusively parallel to the local fiber axis. This parallel diffusivity, ADCparallel, is 0.36 +/- 0.01 microm2/ms, and ADCperpendicular is essentially zero. From ADCparallel the apparent viscosity of the neuron cytoplasm is estimated to be twice as large as that of a temperature-matched dilute aqueous solution.     

Intracellular water specific MR of microbead-adherent cells: HeLa cell intracellular water diffusion.

The (1)H MR signal arising from flowing extracellular media in a perfused, microbead-adherent cultured cell system can be suppressed with a slice-selective, spin-echo pulse sequence. The signal from intracellular water can, thus, be selectively monitored. Herein, this technique was combined with pulsed field gradients (PFGs) to quantify intracellular water diffusion in HeLa cells. The intracellular water MR diffusion-signal attenuation at various diffusion times was well described by a biophysical model that characterizes the incoherent displacement of intracellular water as a truncated Gaussian distribution of apparent diffusion coefficients (ADCs). At short diffusion times, the water "free" diffusion coefficient and the surface-to-volume ratio of HeLa cells were estimated and were, 2.0 +/- 0.3 microm(2)/ms and 0.48 +/- 0.1 microm(-1) (mean +/- SD), respectively. At long diffusion times, the cell radius of 10.1 +/- 0.4 microm was inferred and was consistent with that measured by optical microscopy. In summary: 1) intracellular water "free" diffusion in HeLa cells was rapid, two-thirds that of pure water; and 2) the cell radius inferred from modeling the incoherent displacement of intracellular water by a truncated Gaussian distribution of ADCs was confirmed by independent optical microscopy measures.