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 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).     

Biexponential analysis of diffusion-related signal decay in normal human cortical and deep gray matter

Diffusion imaging with high-b factors, high spatial resolution and cerebrospinal fluid signal suppression was performed in order to characterize the biexponential nature of the diffusion-related signal decay with b-factor in normal cortical gray and deep gray matter (GM). Integration of inversion pulses with a line scan diffusion imaging sequence resulted in 91% cerebrospinal fluid signal suppression, permitting accurate measurement of the fast diffusion coefficient in cortical GM (1.142+/-0.106 microm2/ms) and revealing a marked similarity with that found in frontal white matter (WM) (1.155+/-0.046 microm2/ms). The reversal of contrast between GM and WM at low vs high b-factors is shown to be due to a significantly faster slow diffusion coefficient in cortical GM (0.338+/-0.027 microm2/ms) than in frontal WM (0.125+/-0.014 microm2/ms). The same characteristic diffusion differences between GM and WM are observed in other brain tissue structures. The relative component size showed nonsignificant differences among all tissues investigated. Cellular architecture in GM and WM are fundamentally different and may explain the two- to threefold higher slow diffusion coefficient in GM.     

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.     

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).     

T1 measurements incorporating flip angle calibration and correction in vivo

In this work, we propose a variable FA method that combines in vivo flip angle (FA) calibration and correction with a short TR variable FA approach for a fast and accurate T(1) mapping. The precision T(1)s measured across a uniform milk phantom is estimated to be 2.65% using the conventional (slow) inversion recovery (IR) method and 28.5% for the variable FA method without FA correction, and 2.2% when FA correction is included. These results demonstrate that the sensitivity of the variable FA method to RF nonuniformities can be dramatically reduced when these nonuniformities are directly measured and corrected. The acquisition time for this approach decreases to 10 min from 85 min for the conventional IR method. In addition, we report that the averaged T(1)s measured from five normal subjects are 900 +/- 3 ms, 1337 +/- 8 ms and 2180 +/- 25 ms in white matter (WM), gray matter (GM) and cerebral spinal fluid (CSF) using the variable flip angle method with FA correction at 3 T, respectively. These results are consistent with previously reported values obtained with much longer acquisition times. The method reduces the total scan time for whole brain T(1) mapping, including FA measurement and calibration, to approximately 6 min. The novelty of this method lies in the in vivo calibration and the correction of the FAs, thereby allowing a rapid and accurate T(1) mapping at high field for many applications.     

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.     

In vivo determination of multiexponential T2 relaxation in the brain of patients with multiple sclerosis

In vivo measurement of T2 relaxation times in multiple sclerosis (MS) lesions by magnetic resonance imaging (MRI) is potentially useful for the evaluation of the disease activity. Seven patients with definite MS were investigated over a period of three years (19 examinations), using a whole-body MRI scanner operating at 0.15 T with a specially designed high-power radio-frequency head coil. A modified CPMG sequence with a 180 degree pulse interval of TE = 6 msec and 128 echoes was used for the T2 relaxation measurement of the areas of increased signal (AIS) and white matter (WM). A biexponential T2 analysis of each pixel of the spin-echo images was computed. The T2 relaxation processes were found to be a monoexponential function in WM. The T2 relaxation times of apparently normal white matter in MS patients was significantly longer than in control subjects. The T2 relaxation curves of the AIS were found in most cases to fit a biexponential function characterized by a short and a long T2. T2 long relaxation times of AIS were spread out over a wide range (150-560 msec). The study of T2 long histograms shows that some AIS can be divided into two or three parts depending on the T2 long values. Each of these parts may correspond to a pathological process such as edema, demyelination and gliosis. Evolution of T2 relaxation times over a period of time cannot as yet be correlated with modifications in the clinical state.     

MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis

Detection of glutathione (GSH) is technically challenging at clinical field strengths of 1.5 or 3 T due to its low concentration in the human brain coupled with the fact that conventional single-echo acquisitions, typically used for magnetic resonance (MR) spectroscopy acquisitions, cannot be used to resolve GSH given its overlap with other resonances. In this study, an MR spectral editing scheme was used to generate an unobstructed detection of GSH at 7 T. This technique was used to obtain normative white (WM) and gray matter (GM) GSH concentrations over a two-dimensional region. Results indicated that GSH was significantly higher (P<.001) in GM relative to WM in normal subjects. This finding is consistent with previous radionuclide experiments and histochemical staining and validates this 7 T MR spectroscopy technique. To our knowledge, this is the first study to report normative differences in WM and GM glutathione concentrations in the human brain. Glutathione is a biomarker for oxidative status and this non-invasive in vivo measurement of GSH was used to explore its sensitivity to oxidative state in multiple sclerosis (MS) patients. There was a significant reduction (P<.001) of GSH between the GM in MS patients and normal controls. No statistically significant GSH differences were found between the WM in controls and MS patients. Reduced GSH was also observed in a MS WM lesion. This preliminary investigation demonstrates the potential of this marker to probe oxidative state in MS.     

Voxelwise analysis of diffusion MRI of cervical spinal cord using tract-based spatial statistics

Robust voxelwise analysis using tract-based spatial statistics (TBSS) together with permutation statistical method is standardly used in analyzing diffusion tensor imaging (DTI) of brain. A similar analytical method could be useful when studying DTI of cervical spinal cord.Based on anatomical data of sixty-four healthy volunteers, white (WM) and gray matter (GM) masks were created and subsequently registered into DTI space. Using TBSS, two skeleton types were created (single line and dilated for WM as well as GM). From anatomical data, percentage rates of overlap were calculated for all skeletons in relation to WM and GM masks.Voxelwise analysis of fractional anisotropy values depending on age and sex was conducted. Correlation of fraction anisotropy values with age of subjects was also evaluated. The two WM skeleton types showed a high overlap rate with WM masks (~94%); GM skeletons showed lower rates (56% and 42%, respectively, for single line and dilated). WM and GM areas where fraction anisotropy values differ between sexes were identified (p < .05). Furthermore, using voxelwise analysis such WM voxels were identified where fraction anisotropy values differ depending on age (p < .05) and in these voxels linear dependence of fraction anisotropy and age (r = −0.57, p < .001) was confirmed by regression analysis. This dependence was not proven when using WM anatomical masks (r = −0.21, p = .10).The analytical approach presented shown to be useful for group analysis of DTI data for cervical spinal cord.     

A feasibility study of in vivo T1rho imaging of the intervertebral disc

PURPOSE: Recent studies have proposed that magnetic resonance (MR) T1rho relaxation time is associated with loss of macromolecules. The depletion of macromolecules in the matrix of the intervertebral disc may be an initiating factor in degenerative disc disease. The purpose of this study was to test the feasibility of quantifying T1rho relaxation time in phantoms and intervertebral discs of healthy volunteers using in vivo MR imaging at 3 T. MATERIALS AND METHODS: A multislice T1rho spiral sequence was used to quantify T1rho relaxation time in phantoms with different agarose concentrations and in the intervertebral discs of 11 healthy volunteers (mean age=31.3 years; age range=23-60 years; gender: 5 females, 6 males). RESULTS: The phantom studies demonstrated the feasibility of using spiral imaging at 3 T. The in vivo results indicate that the median T1rho value of the nucleus (116.6+/-21.4 ms) is significantly greater (P<0.05) than that of the annulus (84.1+/-11.7 ms). The correlations between the age of the volunteers and T1rho relaxation time in the nucleus (r2=-0.82; P=0.0001) and the annulus (r2=-0.37; P=0.04) were significant. A trend of decreasing T1rho values from L3-4 to L4-5 to L5-S1 was evident. CONCLUSION: The results of this study suggest that in vivo T1rho quantification is feasible and may potentially be a clinical tool in identifying early degenerative changes in the intervertebral disc.     

In vivo diffusion tensor imaging of thoracic and cervical rat spinal cord at 7 T

In vivo diffusion tensor imaging (DTI) of rat cervical and thoracic spinal cord was performed using a three-element phased array coil at 7 T. The magnetic field was shimmed over the spinal cord in real time using an in-house developed automatic algorithm. Echo planar imaging (EPI)-based diffusion-weighted images (DWIs) were acquired with 21 gradient encoding directions. The DWIs were tensor encoded, and diffusion tensor metrics, fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity (λ₀) and transverse diffusivity (λ) were determined for both white matter (WM) and gray matter (GM). The results on six normal rats indicated no significant differences in the diffusion tensor metrics between thoracic and cervical regions. However, the DTI-derived metrics in cervical spinal cord from our study are somewhat different from the published results in rats. The possible reasons for these differences are suggested.     

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.     

In vivo evaluation of the reproducibility of T1 and T2 measured in the brain of patients with multiple sclerosis.

The precision (reproducibility) of relaxation times derived from magnetic resonance images of patients with multiple sclerosis (MS) were investigated. Measurements of 10 MS patients were performed at 1.5 T on two occasions within 1 wk. T1 and T2 was measured using a partial saturation inversion recovery sequence (6 points) and a Carr-Purcell-Meiboom-Gill phase alternating-phase shift multiple spin-echo sequence with 32 echoes. Regions of interest (ROI) were placed both in apparently normal white matter and plaques. The precision (+/- 1.96 SD) and the confidence intervals for T1 and T2 for white matter and plaques were calculated. The precision of T1 for white matter and plaques was respectively +/- 94 msec and +/- 208 msec. The precision of T2 for white matter and plaques was respectively +/- 18 msec and +/- 26 msec. For all measurements the coefficient of variation was about 9%. Judging from our own study and others as well, a precision better than 10% for T1 and T2 would seem unrealistic at present.     

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.     

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.     

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.