Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).     

In vivo diffusion characteristics of rat spinal cord.

Complete apparent diffusion tensor (ADTs) of spinal cord was measured in vivo in nine rats at 2.0 T. Two rotationally invariant parameters, the trace, which is a measure of the mean diffusivity, and the lattice index (LI), which reflects the degree of orientation coherence of tissue, have been estimated from the ADT. The mean white matter (WM) trace value (3.05 +/- 0.26 mm2/sec) was found to be substantially higher than the gray matter (GM) trace (2.36 +/- 0.39 mm2/sec), in contrast with the published results on fixed, excised cord. Statistically significant anisotropic diffusion was observed in both WM and GM, with greater anisotropy in the WM (LI = 0.67 +/- 0.06) than in the GM (LI = 0.51 +/- 0.05).     

Ex vivo magnetic resonance imaging of rat spinal cord at 9.4 T

The magnetic resonance (MR) properties of the rat spinal cord were characterized at the T9 level with ex vivo experiments performed at 9.4 T. The inherent endogenous contrast parameters, proton density (PD), longitudinal and transverse relaxation times T1 and T2, and magnetization transfer ratio (MTR) were measured separately for the grey matter (GM) and white matter (WM). Analysis of the measurements indicated that these tissues have statistically different proton densities with means PD(GM)=54.8+/-2.5% versus PD(WM)=45.2+/-2.4%, and different T1 values with means T1GM=2.28+/-0.23 s versus T1WM=1.97+/-0.21 s. The corresponding values for T2 were T2GM=31.8+/-4.9 ms versus T2WM=29.5+/-4.9 ms, and the difference was insignificant. The difference between MTR(GM)=31.2+/-6.1% and MTR(WM)=33.1+/-5.9% was also insignificant. These results collectively suggest that PD and T1 are the two most important parameters that determine the observed contrast on spinal cord images acquired at 9.4 T. Therefore, in MR imaging studies of spinal cord at this field strength, these parameters need to be considered not only in optimizing the protocols but also in signal enhancement strategies involving exogenous contrast agents.     

In vivo relaxation times of gray matter and white matter in spinal cord

In vivo relaxation times and relative spin densities of gray matter (GM) and white matter (WM) of rat spinal cord were measured. Inductively coupled implanted RF coil was used to improve the signal-to-noise ratio required for making these measurements. The estimated relaxation times (in milliseconds) are: T1(GM) = 1021+/-93, T2(GM) = 64+/-3.4, T1(WM) = 1089+/-126, and T2(WM) = 79+/-6.9. The estimated relative spin densities are: rho(GM) = (60+/-2.3)% and rho(WM) = (40+/-2.1)%. The T1 values of GM and white matter are not statistically different. However, the differences in T2 values and spin densities of GM and WM are statistically significant. These in vivo measurements indicate that the observed contrast between GM and WM in spinal cord MR images mainly arises from the differences in the spin density.     

Structural changes in glutamate cell swelling followed by multiparametric q-space diffusion MR of excised rat spinal cord

Diffusion in the extracellular and intracellular spaces (ECS and ICS, respectively) was evaluated in excised spinal cords, before and after cell swelling induced by glutamate, by high b-value q-space diffusion MR of specific markers and water. The signal decays of deuterated tetramethylammonium (TMA-d(12)) chloride, an exogenous marker of the ECS, and N-acetyl aspartate (NAA), an endogenous marker of the ICS, were found to be non-mono-exponential at all diffusion times. The signal decays of these markers were found to depend on the diffusion time and the cell swelling induced by the glutamate. It was found, for example, that the mean displacements of the apparent fast and slow diffusion components of TMA-d(12) are 7.21 +/- 0.11 and 1.16 +/- 0.05 microm, respectively at a diffusion time of 496 ms. After exposure of the spinal cords to 10 mM of glutamate, these values decreased to 6.62 +/- 0.13 and 1.01 +/- 0.05 microm, respectively. The mean displacement of NAA, however, showed a less pronounced opposite trend and increased after cell swelling induced by exposure to glutamate. q-Space diffusion MR of water was found to be sensitive to exposure to glutamate, and q-space diffusion MRI showed that a more pronounced decrease in the apparent diffusion coefficient and the mean displacement of water is observed in the gray matter (GM) of the spinal cord. All these changes demonstrate that diffusion MR is indeed sensitive to structural changes caused by cell swelling induced by glutamate. Multiparametric high b-value q-space diffusion MR is useful for obtaining microstructural information in neuronal tissues.     

A combined DTI and structural MRI study in medicated-naïve chronic schizophrenia

Disconnection in white matter (WM) pathway and alterations in gray matter (GM) structure have been hypothesized as pathogenesis in schizophrenia. However, the relationship between the abnormal WM integrity and the alteration of GM in anatomically connected areas remains uncertain. Moreover, the potential influence of antipsychotic medication on WM anisotropy and cortical morphology was not excluded in previous studies. In this study, a total number of 34 subjects were enrolled, including 17 medicated-naïve chronic schizophrenia patients and 17 healthy controls. Tract-based spatial statistics (TBSS) were applied to investigate the level of WM integrity. The FreeSurfer surface-based analysis was used to determine GM volume, cortical thickness and the surface area of GM regions which corresponded to abnormal WM fiber tracts. We observed that patients possessed lower fractional anisotropy (FA) values in the left inferior fronto-occipital fasciculus (IFOF) and left inferior longitudinal fasciculus (ILF), along with smaller GM volume and cortical thinning in temporal lobe than the healthy controls, which reflected the underlying WM and GM disruption that contributed to the disease. In the patient population, the lower connectivity of ILF and IFOF was positively associated with cortical thickness in left lateral orbitofrontal cortex, superior temporal gyrus and lingual gyrus in males, and positively correlated with GM volume in left lateral orbitofrontal cortex in females. On the other hand, it was negatively correlated with cortical area of middle temporal gyrus in males and temporal pole in females respectively, but not when genders were combined. These findings suggested that abnormal WM integrity and anatomical correspondence of GM alterations in schizophrenia were interdependent on gender-separated analysis in patients with schizophrenia. Moreover, combining TBSS and FreeSurfer might be a useful method to provide significant insight into interacting processes related to WM fiber tracts and GM changes in schizophrenia.     

In vivo measurements of multi-component T2 relaxation behaviour in guinea pig brain

Multi-echo Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.5 T and 4.0 T imaging systems to test their ability to measure in vivo multi-component T2 relaxation behavior in normal guinea pig brain. The known dependence of accurate T2 measurements on the signal-to-noise ratio (SNR) was explored in vivo by comparing T2 decay data obtained using three methods to increase SNR (improved RF coil design, signal averaging and increased magnetic field strength). Good agreement between T2 values of nickel-doped agarose phantoms was found between imaging and spectroscopic methods. T2 values were determined for gray matter (GM) and white matter (WM) locations from images of guinea pig brain in vivo. T2 measurements of GM were found to be monoexponential at both field strengths. The mean T2 times for GM were 71 ms at 1.5 T, and 53 ms at 4.0T. The highest average SNR was achieved using an improved RF coil at 4.0T. In this case, two peaks were extracted in WM, a "short" T2 peak at approximately 6 ms, and a "medium" T2 peak at approximately 48 ms. T2 values in GM and the major component of WM were significantly decreased at 4.0T compared to 1.5 T. The improved SNR attained with this optimized imaging protocol at 4.0T has allowed for the first time extraction of the myelin-sensitive T2 component of WM in animal brain in vivo.     

Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study

Object

Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency.

Materials and Methods

DKI was performed on 18 AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann–Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation.

Results

In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM.

Conclusion

Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.     

Graded image segmentation of brain tissue in the presence of inhomogeneous radio frequency fields

Image segmentation is used increasingly to interpret MR spectroscopic data of the brain, using image contrast to identify gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF). T(1)- or T(2)-weighted images are typically used, but poor shimming, susceptibility effects, and small variations in B(1) and receptivity cause difficulties in tissue identification. Quantitative imaging of T(1) can reduce many of these difficulties but is still subject to complications when B(1) has large variations like those observed with the surface coils often used for spectroscopy. In this study, B(1) imaging was implemented to support quantitative imaging of T(1) with either a surface coil or a volume coil. The T(1) observed by this method is a continuous function across mixtures of WM/GM and GM/CSF, and this function was measured and used to convert the images of T(1) to maps of percent GM, WM, and CSF.     

Hybrid artificial neural network segmentation of precise and accurate inversion recovery (PAIR) images from normal human brain

This paper presents a novel semi-automated segmentation and classification method based on raw signal intensities from a quantitative T1 relaxation technique with two novel approaches for the removal of partial volume effects. The segmentation used a Kohonen Self Organizing Map that eliminated inter- and intra-operator variability. A Multi-layered Backpropagation Neural Network was able to classify the test data with a predicted accuracy of 87.2% when compared to manual classification. A linear interpolation of the quantitative T1 information by region and on a pixel-by-pixel basis was used to redistribute voxels containing a partial volume of gray matter (GM) and white matter (WM) or a partial volume of GM and cerebrospinal fluid (CSF) into the principal components of GM, WM, and CSF. The method presented was validated against manual segmentation of the base images by three experienced observers. Comparing segmented outputs directly to the manual segmentation revealed a difference of less than 2% in GM and less than 6% in WM for pure tissue estimations for both the regional and pixel-by-pixel redistribution techniques. This technique produced accurate estimates of the amounts of GM and WM while providing a reliable means of redistributing partial volume effects.     

Hybrid artificial neural network segmentation of precise and accurate inversion recovery (PAIR) images from normal human brain

This paper presents a novel semi-automated segmentation and classification method based on raw signal intensities from a quantitative T1 relaxation technique with two novel approaches for the removal of partial volume effects. The segmentation used a Kohonen Self Organizing Map that eliminated inter- and intra-operator variability. A Multi-layered Backpropagation Neural Network was able to classify the test data with a predicted accuracy of 87.2% when compared to manual classification. A linear interpolation of the quantitative T1 information by region and on a pixel-by-pixel basis was used to redistribute voxels containing a partial volume of gray matter (GM) and white matter (WM) or a partial volume of GM and cerebrospinal fluid (CSF) into the principal components of GM, WM, and CSF. The method presented was validated against manual segmentation of the base images by three experienced observers. Comparing segmented outputs directly to the manual segmentation revealed a difference of less than 2% in GM and less than 6% in WM for pure tissue estimations for both the regional and pixel-by-pixel redistribution techniques. This technique produced accurate estimates of the amounts of GM and WM while providing a reliable means of redistributing partial volume effects.     

Two-exponential analysis of spin-spin proton relaxation times in MR imaging using surface coils

Proton relaxation time measurements were performed on a standard whole body MR imager operating at 1.5 T using a conventional surface coil of the manufacturer. A combined CP/CPMG multiecho, multislice sequence was used for the T1 and T2 relaxation time measurements. Two repetition times of 2000 ms (30 echoes) and 600 ms (2 echoes) with 180 degrees-pulse intervals of 2 tau = 22 ms were interleaved in this sequence. A two-exponential T2 analysis of each pixel of the spin-echo images was computed in a case of an acoustic neurinoma. The two-exponential images show a "short" component (T2S) due to white and gray matter and a "long" component (T2S) due to the cerebrospinal fluid. In the fatty tissue two components with T2S = 35 +/- 3 ms and T2L = 164 +/- 7 ms were measured. Comparing with Gd-DTPA imaging the relaxation time images show a clear differentiation of vital tumor tissue and cerebrospinal fluid.     

Quantification of cerebral blood flow in nonhuman primates using arterial spin labeling and a two-compartment model

Noninvasive absolute quantification of cerebral blood flow (CBF) with high spatial resolution is still a challenging task. Arterial spin labeling (ASL) is a promising magnetic resonance imaging (MRI) method for accurate perfusion quantification. However, modeling of ASL data is far from being standardized and has not been investigated in great detail. In this study, two-compartment modeling of monkey ASL data in three physiological conditions (baseline, sensory activated and globally elevated CBF) is reported. Absolute perfusion and arterial transit times were derived for gray matter (GM) and white matter (WM) separately. The uncertainties of the model's result were determined by Monte Carlo simulations. The fitted CBF values for GM were 133 ml/min/100 ml at baseline condition, 165 ml/min/100 ml during visual stimulation and 234 ml/min/100 ml for globally elevated CBF after intravenous injection of acetazolamide. The ratio of GM to WM CBF was 2.5 at baseline and was found to decrease to 1.6 after application of acetazolamide. The corresponding arterial transit times decreased from 742 to 607 ms in GM and from 985 to 875 ms in WM. Monte Carlo simulations showed that absolute CBF values can be determined with an error of 11-15%, while the arterial transit time values have a coefficient of variation of 25-31%. With an alternative acquisition scheme, the precision of the arterial transit times can be improved significantly. The CBF values in the occipital lobe of the monkey brain quantified with ASL are higher than previously reported in positron emission tomography studies.     

The imaging appearance of Creutzfeldt-Jakob disease caused by the E200K mutation

The E200K mutation on chromosome 20 can cause familial Creutzfeldt-Jakob disease (CJD). Patients with this mutation are clinically similar to those with sporadic CJD, but their imaging features are not well documented. We report here the quantitative and qualitative evaluation of the magnetic resonance (MR) imaging characteristics of this unique group of patients using three-dimensional spoiled gradient recalled (SPGR) echo images, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurements, MR spectroscopy and a fluid-attenuated inversion recovery (FLAIR) sequence. The SPGR and ADC data were analyzed with SPM99. ANCOVA and regression models were used for a region-of-interest (ROI) analysis of ADC and metabolic ratios. CJD patients had a decreased fraction of gray matter and an increased fraction of cerebrospinal fluid (P=.001) in the cortex and cerebellum and increased ADC values in the cortex (P<.001). Focal decreases of ADC were found in the putamen via ROI analysis (548+/-83 vs. 709+/-9 microm(2)/s, P=.02). N-acetyl aspartate (NAA) was generally reduced, with the NAA/Cho ratio lowest in the cingulate gyrus. Qualitative assessment revealed hyperintensities on FLAIR, DWI or both in the putamen (three out of four patients), caudate (three out of four patients) and thalamus. These results provide a framework for future study of patients with genetically defined familial CJD.     

Optimization of 3D MP-RAGE for neonatal brain imaging at 3.0 T

Three-dimensional (3D) magnetic resonance imaging (MRI) has shown great potential for studying the impact of prematurity and pathology on brain development. We have investigated the potential of optimized T1-weighted 3D magnetization-prepared rapid gradient-echo imaging (MP-RAGE) for obtaining contrast between white matter (WM) and gray matter (GM) in neonates at 3 T. Using numerical simulations, we predicted that the inversion time (TI) for obtaining strongest contrast at 3 T is approximately 2 s for neonates, whereas for adults, this value is approximately 1.3 s. The optimal neonatal TI value was found to be insensitive to reasonable variations of the assumed T1 relaxation times. The maximum theoretical contrast for neonates was found to be approximately one third of that for adults. Using the optimized TI values, MP-RAGE images were obtained from seven neonates and seven adults at 3 T, and the contrast-to-noise ratio (CNR) was measured for WM versus five GM regions. Compared to adults, neonates exhibited lower CNR between cortical GM and WM and showed a different pattern of regional variation in CNR. These results emphasize the importance of sequence optimization specifically for neonates and demonstrate the challenge in obtaining strong contrast in neonatal brain with T1-weighted 3D imaging.     

Biexponential apparent diffusion coefficient parametrization in adult vs newborn brain.

The decay of brain water signal with b-factor in adult and newborn brains has been measured over an extended b-factor range. Measurements of the apparent diffusion coefficient (ADC) decay curves were made at 16 b-factors from 100 to 5000 s/mm(2) along three orthogonal directions using a line scan diffusion imaging (LSDI) sequence to acquire data from 0.09 ml voxels in a mid-brain axial slice. Regions-of-interest (ROIs) in cortical gray (CG) and white matter in the internal capsule (IC) were selected for ADC decay curve analyses using a biexponential fitting model over this extended b-factor range. Measures of the fast and slow ADC component amplitudes and the traces of the fast and slow diffusion coefficients were obtained from CG and IC ROIs in both adults and newborns. The ADC decay curves from the newborn brain regions were found to have a significantly higher fraction of the fast diffusion ADC component than corresponding regions in the adult brain. The results demonstrate that post-natal brain development has a profound affect on the biexponential parameters which characterize the decay of water signal over an extended b-factor range in both gray and white matter.     

Unbiased segmentation of diffusion-weighted magnetic resonance images of the brain using iterative clustering

Segmentation of diffusion-weighted echo-planar imaging (DW-EPI) is challenging because of concerns regarding spatial resolution and distortion. Methods commonly used require manual input and often need thresholding measures to segment white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). This may introduce operator bias and misclassification error. When comparing patients with a diffuse disease process-such as multiple sclerosis (MS)--with healthy controls, although information from all images may be biased due to disease effect, this is more so if the data set employed to perform segmentation is also used as a measured outcome for the study, for example, fractional anisotropy maps. Presented in this work is an unbiased method for segmenting DW-EPI data sets using the b=0 and single-shot inversion recovery EPI into WM, GM and CSF. The method employs an iterative clustering technique to account for partial volume effects and signal variation caused by radiofrequency inhomogeneity. The technique is evaluated with both real and synthetic brain data and results compared with statistical parametric mapping (SPM02). With synthetic brain data, where a gold standard of segmentation exists, the presented method showed less misclassification compared to SPM02. The unbiased method proposed may provide a more accurate methodology of segmentation in the analysis of DWI-EPI images in conditions such as MS.     

Short echo time multislice proton magnetic resonance spectroscopic imaging in human brain: metabolite distributions and reliability.

Multislice proton magnetic resonance spectroscopic imaging (1H MRSI) at 25 ms echo time was used to measure concentrations of myo-inositol (mI), N-acetylaspartate (NAA), and creatine (Cr) and choline (Cho) in ten normal subjects between 22 and 84 years of age (mean age 44 +/- 18 years). By co-analysis with MRI based tissue segmentation results, metabolite distributions were analyzed for each tissue type and for different brain regions. Measurement reliability was evaluated using intraclass correlation coefficients (ICC). Significant differences in metabolite distributions were found for all metabolites. mI of frontal gray matter was 84% of parietal gray matter and 87% of white matter. NAA of frontal gray matter was 86% of parietal gray matter and 85% of white matter. Cho of frontal gray matter was 125% of parietal gray matter and 59% of white matter and Cho of parietal gray matter was 47% of white matter. Cr of parietal gray matter was 113% of white matter. Reliability was relatively high (ICC from.70 to.93) for all metabolites in white matter and for NAA and Cr in gray matter, though limited (ICC less than.63) for mI and Cho in gray matter. These findings indicate that voxel gray/white matter contributions, regional variations in metabolite concentrations, and reliability limitations must be considered when interpreting 1H MR spectra of the brain.     

Magnetization transfer of water T(2) relaxation components in human brain: implications for T(2)-based segmentation of spectroscopic volumes

Biexponential T(2) relaxation of the localized water signal can be used for segmentation of spectroscopic volumes. To assess the specificity of the components an iterative relaxation measurement of the localized water signal (STEAM, 12 echo times, geometric spacing from 30 ms to 2000 ms) was combined with magnetization transfer (MT) saturation (40 single lobe pulses, 12 ms duration, 1440 degrees nominal flip angle, 1 kHz offset, repeated every 30 ms). Voxels including CSF were examined in parietal cortex and periventricular parietal white matter (10 each), as well as 13 voxels in central white matter and 16 T(1)-hypointense non-enhancing multiple sclerosis lesions without CSF inclusion. Biexponential models (excluding myelin water) were fitted to the relaxation data. In periventricular VOIs the component of long T(2) (1736 +/- 168 ms) that is attributed to CSF was not affected by MT. In cortical VOIs this component had markedly shorter T(2)'s (961 +/- 239 ms) and showed both attenuation and prolongation with MT, indicating contributions from tissue. MS lesions and central WM showed a second tissue component of intermediate T(2) (160-410 ms). In white matter similar MT attenuation indicated strong exchange between the two tissue components, prohibiting segmentation. In MS lesions, however, markedly less MT of the intermediate component was found, which is consistent with decreased cellularity and exchange in a region that is large compared to diffusion motion.