Volumetric quantification of brain swelling after hypobaric hypoxia exposure.

We applied a novel MR imaging technique to investigate the effect of acute mountain sickness on cerebral tissue water. Nine volunteers were exposed to hypobaric hypoxia corresponding to 4572 m altitude for 32 h. Such an exposure may cause acute mountain sickness. We imaged the brains of the volunteers before and at 32 h of hypobaric exposure with two different MRI techniques with subsequent data processing. (1) Brain volumes were calculated from 3D MRI data sets by applying a computerized brain segmentation algorithm. For this specific purpose a novel adaptive 3D segmentation program was used with an automatic correction algorithm for RF field inhomogeneity. (2) T(2) decay rates were analyzed in the white matter. The results demonstrated that a significant brain swelling of 36.2 +/- 19.6 ml (2.77 +/- 1.47%, n = 9, P < 0.001) developed after the 32-h hypobaric hypoxia exposure with a maximal observed volume increase of 5.8% (71.3 ml). These volume changes were significant only for the gray matter structures in contrast to the unremarkable changes seen in the white matter. The same study repeated 3 weeks later in 6 of 9 original subjects demonstrated that the brains recovered and returned approximately to the initially determined sea-level brain volume while hypobaric hypoxia exposure once again led to a significant new brain swelling (24.1 +/- 12.1 ml, 1.92 +/- 0.96%, n = 6, P < 0.005). On the contrary, the T(2) mapping technique did not reveal any significant effect of hypobaria on white matter. We present here a technique which is able to detect reversible brain volume changes as they may occur in patients with diffuse brain edema or increased cerebral blood volume, and which may represent a useful noninvasive tool for future evaluations of antiedematous drugs.

Protection of privacy by third-party encryption in genetic research in Iceland.

As the new human genetics continues its dramatic expansion into many laboratories and medical institutions, the concern for the protection of the personal privacy of individuals who participate increases. It seems that even the smallest of laboratories must confront the issue of how to protect the genetic and phenotypic information of participants in their research. Some have promoted the use of anonymity as a way out of this dilemma. But we are reminded by others that the future cannot be predicted, and that future benefits may be lost when the links to these benevolent volunteers are gone forever. More recently, some ethical bodies have suggested, without specific recommendations, that a reversible third-party encryption system may be a solution to this problem. However, they have not provided a route or even examples of how to proceed. We present here the Icelandic approach to this issue by developing a third-party encryption system in direct collaboration with the Data Protection Commission (DPC) of Iceland. We have incorporated the encryption system within our sample collection and storage software, which minimises inconvenience but enhances security. The strategy assures a barrier between the laboratory and the outside world that can only be crossed by the DPC.

Multi-component apparent diffusion coefficients in human brain: relationship to spin-lattice relaxation.

In vivo measurements of the human brain tissue water signal decay with b-factor over an extended b-factor range up to 6,000 s/mm(2) reveal a nonmonoexponential decay behavior for both gray and white matter. Biexponential parametrization of the decay curves from cortical gray (CG) and white matter voxels from the internal capsule (IC) of healthy adult volunteers describes the decay process and serves to differentiate between these two tissues. Inversion recovery experiments performed in conjunction with the extended b-factor signal decay measurements are used to make separate measurements of the spin-lattice relaxation times of the fast and slow apparent diffusion coefficient (ADC) components. Differences between the spin-lattice relaxation times of the fast and slow ADC components were not statistically significant in either the CG or IC voxels. It is possible that the two ADC components observed from the extended b-factor measurements arise from two distinct water compartments with different intrinsic diffusion coefficients. If so, then the relaxation results are consistent with two possibilities. Either the spin-lattice relaxation times within the compartments are similar or the rate of water exchange between compartments is "fast" enough to ensure volume averaged T(1) relaxation yet "slow" enough to allow for the observation of biexponential ADC decay curves over an extended b-factor range. Magn Reson Med 44:292-300, 2000.

Using quality measures to facilitate allele calling in high-throughput genotyping.

Currently, the main limitation in high-throughput microsatellite genotyping is the required manual editing of allele calls. Even though programs for automated allele calling have been available for several years, they have limited capability because accurate data could only be assured by manual inspection of the electropherograms for confirmation. Here we describe the development of a parametric approach to allele call quality control that eliminates much of the time required for manual editing of the data. This approach was implemented in an editing tool, Decode-GT, that works downstream of the allele calling program, TrueAllele (TA). Decode-GT reads the output data from TA, displays the underlying electropherograms for the genotypes, and sorts the allele calls into three categories: good, bad, and ambiguous. It discards the bad calls, accepts the good calls, and suggests that the user inspect the ambiguous calls, thereby reducing dependence on manual editing. For the categorization we use the following parameters: (1) the quality value for each allele call from TrueAllele; (2) the peak height of the alleles; and (3) the size of the peak shift needed to move peaks into the nearest bin. Here we report how we optimized the parameters such that the size of the ambiguous category was minimized, and both the number of miscalled genotypes in the good category and the useable genotypes in the bad category were negligible. This approach reduces the manual editing time and results in <1% miscalls.

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.

Line scan diffusion imaging: characterization in healthy subjects and stroke patients.

OBJECTIVE: Our objective was to evaluate a new scanning method, MR line scan diffusion imaging, and assess the apparent diffusion coefficient in the brains of healthy subjects and stroke patients. SUBJECTS AND METHODS: Line scan diffusion imaging without cardiac gating or head restraints was implemented on low- (0.5 T) and medium- (1.5 T) field-strength scanners with conventional hardware. Diffusion-weighted images were obtained in six healthy subjects and eight stroke patients. Unidirectional diffusion encoding was used for fast localization of stroke lesions. For further characterization, orthogonal diffusion encoding was applied, and the trace of the apparent diffusion coefficient was calculated. Single-shot diffusion-weighted echoplanar imaging served as the reference standard. For healthy subjects, imaging was repeated four times on each scanner. Mean and relative precision of the apparent diffusion coefficient trace values were calculated for each pixel. In stroke lesions and adjacent normal tissue, apparent diffusion coefficient trace values were determined. RESULTS: In the 108 scans obtained, line scan diffusion imaging proved to be robust, virtually free of artifact (independent of slice location and orientation), reproducible, and rapid for localization of a stroke. Scan time for 14 slices at 7-mm thickness was 8 min at 0.5 T and 7 min at 1.5 T. Image qualities with line scan diffusion imaging and single-shot diffusion-weighted echoplanar imaging were comparable. At 1.5 T, precision was essentially the same for line scan diffusion imaging (4.3%) and echoplanar imaging (4.7%). With line scan diffusion imaging at 0.5 T and 1.5 T, normal paraventricular apparent diffusion coefficient trace values averaged 0.71 microm2/msec, and with echoplanar imaging these values averaged 0.69 microm2/msec. In acute lesions apparent diffusion coefficient trace values were low, and in chronic lesions these values were high. CONCLUSION: Line scan diffusion imaging on low- and medium-field-strength MR scanners equipped with conventional hardware was reliable and practical for measuring brain apparent diffusion values, which can be applied to the early diagnosis, and hence timely management, of stroke.

Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis.

PURPOSE: Hypertensive encephalopathy, a complex of cerebral disorders, including headache, seizures, visual disturbances, and other neurologic manifestations, is associated with a variety of conditions in which blood pressure rises acutely. It has been ascribed to either exuberant vasospasm with ischemia/infarction or breakthrough of autoregulation with interstitial edema. Diffusion-weighted MR imaging may be used to determine whether the edema in hypertensive encephalopathy is cytotoxic or vasogenic in origin. METHODS: Diffusion-weighted imaging was performed using the double line scan diffusion imaging technique on a 1.5-T MR system. Seven patients with hypertensive encephalopathy were imaged within 1 day of the onset of their symptoms. Apparent diffusion coefficient maps as well as low and high b-factor images were acquired. The two-tailed paired Student's t-test was used to compare the apparent diffusion coefficients in edematous brain regions with those of normal white matter. RESULTS: In all cases the apparent diffusion coefficient maps of the patients with hypertensive encephalopathy showed increased signal in regions corresponding to increased T2 signal on standard T2-weighted (low b-factor) images. Quantitative apparent diffusion coefficients in regions of abnormal T2 signal were 1.36 +/- 0.14 microm2/ms, compared with 0.80 +/- 0.05 microm2/ms in normal white matter. Diffusion-weighted (high b-factor) T2-weighted images did not show abnormal signal. CONCLUSION: Diffusion-weighted MR imaging shows that the edema in hypertensive encephalopathy is of vasogenic origin and does not represent ischemia or infarction. This finding may have therapeutic implications.

Brain edema development after MRI-guided focused ultrasound treatment.

The aim of this study was to investigate a potential technique for image-guided minimally invasive neurosurgical interventions. Focused ultrasound (FUS) delivers thermal energy without an invasive probe, penetrating the dura mater, entering through the cerebrospinal fluid (CSF) space, or harming intervening brain tissue. We applied continuous on-line monitoring by MRI to demonstrate the effect of the thermal intervention on the brain tissue. For this, seven rabbits had a part of their skull removed to create access for the FUS beam into the brain through an acoustic window of 11 mm in diameter. Dura was left intact and skin was sutured. One week later, the rabbits were sonicated for 3 seconds with 21 W acoustic power, and the FUS focus was visualized with a temperature-sensitive T1-weighted MRI pulse sequence. The tissue reaction was documented over 7 days with T2-weighted images of the brain. The initial area of the central low signal intensity in the axial plane was .4+/-.3 mm2, and for the bright hyperintensity surrounding the lesion, it was 2.3+/-.6 mm2 (n = 7). In the coronal plane, the corresponding values were .4+/-.1 mm2 and 3.4+/-.9 mm2 (n = 5). The developing brain edema culminated 48 hours later and thereafter diminished during the next 5 days. Histology revealed a central necrosis in the white matter surrounded by edematous tissue with inflammatory cells. In summary, the image-guided thermal ablation technique described here produced a relatively small lesion in the white matter at the targeted location. This was accomplished without opening the dura or the need for a stereotactical device. MRI allowed on-line monitoring of the lesion setting and the deposition of thermal energy and demonstrated the tissue damage after the thermal injury.

MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia.

A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but this concept has been based primarily on indirect evidence from psychopharmacology and analogies with animal research. Diffusion tensor imaging, a new MRI technique that permits direct assessment of the large axon masses stretching from the prefrontal cortex to the striatum, was used to study white matter axon bundles. Diffusion tensor images, high-resolution structural MRI and positron emission tomography scans with 18-fluorodexoyglucose were obtained on five patients with schizophrenia and six age- and sex-matched normal controls. Significantly lower diffusion anisotropy in the white matter of the prefrontal cortex in schizophrenic patients than in normal controls was observed in statistical probability maps. Co-registered PET scans revealed significantly lower correlation coefficients between metabolic rates in the prefrontal cortex and striatum in patients than in controls. These twin findings provide convergent evidence for diminished fronto-striatal connectivity in schizophrenia.

Magnetic resonance imaging shows orientation and asymmetry of white matter fiber tracts.

Apparent diffusion tensor maps of the human brain were acquired with a magnetic resonance imaging sequence (Gudbjartsson, H., Maier, S.E., Mulkern, R.V., M6rocz, I.A., Patz, S., Jolesz, F.A., Magn. Reson. Med. 36 (1996) 509-519). It was shown that the geometric nature of the apparent diffusion tensors can quantitatively characterize the tissue structure. Display of the orientation and directional uniformity of the water diffusion in the brain demonstrated most of the known major anatomical constituents of human white matter. A comparison of corresponding anatomic regions in the white matter of both hemispheres in 24 healthy volunteers revealed that fiber tracts within the anterior limb of the internal capsule have a significantly higher (P < 0.01) measure of alignment in the right hemisphere. This method offers a unique tool for the in vivo demonstration of neural connectivity in healthy and diseased brain.

Double line scan diffusion imaging.

A new double line scan diffusion imaging sequence (DLSDI) is presented. In DLSDI, two lines from two separate slices are acquired in each shot. As its predecessor, LSDI, DLSDI is insensitive to motion artifacts and it can be used on conventional MR scanners. In addition, DLSDI is almost twice as fast as LSDI. Preliminary results from phantom and patient studies show excellent agreement between ADC trace maps obtained with DLSDI and LSDI. The technical and the theoretical aspects of DLSDI are studied, and it is shown how the conditional random walk model can be used as an analytical tool to derive the diffusion sensitivity in the DLSDI sequence.

Line scan diffusion imaging.

A novel line scan diffusion imaging sequence (LSDI) is introduced. LSDI is inherently insensitive to motion artifacts and high quality diffusion maps of the brain can be obtained rapidly without the use of head restraints or cardiac gating. Results from a stroke study and abdominal diffusion images are presented. The results indicate that it is feasible to use the LSDI technique for clinical evaluation of acute ischemic stroke. In contrast to echo-planar diffusion imaging, LSDI does not require modified gradient hardware and can be implemented on conventional scanners. Thus, LSDI should dramatically increase the general availability of robust clinical diffusion imaging.

The Rician distribution of noisy MRI data.

The image intensity in magnetic resonance magnitude images in the presence of noise is shown to be governed by a Rician distribution. Low signal intensities (SNR < 2) are therefore biased due to the noise. It is shown how the underlying noise can be estimated from the images and a simple correction scheme is provided to reduce the bias. The noise characteristics in phase images are also studied and shown to be very different from those of the magnitude images. Common to both,however, is that the noise distributions are nearly Gaussian for SNR larger than two.

Simultaneous calculation of flow and diffusion sensitivity in steady-state free precession imaging.

In this paper the authors quantitatively evaluate the combined effect of both flow and diffusion in steady-state free precession (SSFP) imaging. A partition analysis (PA) is used to derive a fourth order approximation (in E2) of the signal in an echo SSFP sequence. The authors also introduce a novel very fast simulation technique, based on a circular convolution, which accurately accounts for both flow and diffusion. A 2D SSFP-echo sequence was implemented to obtain experimental data from a phantom containing three different solutions. Excellent agreement between the theory and the experimental data was found. Then by using the simulation algorithm and experimental measurements of in vivo brain motion, the authors estimated the artifacts to be expected in SSFP diffusion imaging of the brain and found them to be comparable with those of pulsed gradient spin echo. Finally, the authors point out the equivalence between the flow sensitivity of SSFP and RF spoiling commonly used in fast imaging.

NMR diffusion simulation based on conditional random walk.

The authors introduce here a new, very fast, simulation method for free diffusion in a linear magnetic field gradient, which is an extension of the conventional Monte Carlo (MC) method or the convolution method described by Wong et al. (in 12th SMRM, New York, 1993, p.10). In earlier NMR-diffusion simulation methods, such as the finite difference method (FD), the Monte Carlo method, and the deterministic convolution method, the outcome of the calculations depends on the simulation time step. In the authors' method, however, the results are independent of the time step, although, in the convolution method the step size has to be adequate for spins to diffuse to adjacent grid points. By always selecting the largest possible time step the computation time can therefore be reduced. Finally the authors point out that in simple geometric configurations their simulation algorithm can be used to reduce computation time in the simulation of restricted diffusion.