Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury

Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.     

Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements

Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast.     

Diffuse T1 reduction in gray matter of sickle cell disease patients: evidence of selective vulnerability to damage?

The objective of our study was to test the hypothesis that subtle brain abnormality can be present in pediatric sickle cell disease (SCD) patients normal by conventional MR imaging (cMRI). We examined 50 SCD patients to identify those patients who were normal by cMRI. Quantitative MR imaging (qMRI) was then used to map spin-lattice relaxation time (T1) in a single slice in brain tissue of all 50 patients and in 52 healthy age-similar controls. We also used a radiofrequency (RF) pulse to saturate blood spins flowing into the T1 map slice, to characterize the effect of blood flow on brain T1. Abnormalities were noted by cMRI in 42% (21/50) of patients, with lacunae in 32%, and encephalo malacia in 20%. Brain T1 in patients normal by cMRI was significantly lower than controls, in caudate, thalamus, and cortex (p < or =0.007), and regression showed that gray matter T1 abnormality was present in caudate and cortex by age 4 (p < or =0.002). In patients abnormal by cMRI, T1 reductions in gray matter were larger and more significant. White matter T1 was not significantly increased except in patients abnormal by cMRI. RF saturation in a slab below the T1 map produced no significant change in T1, compared to RF saturation in a slab above the T1 map, suggesting that inflow of untipped spins in blood does not cause an artifactual shortening of T1. Gray matter T1 abnormality was present in patients normal by cMRI, while white matter T1 abnormality was present only in patients also abnormal by cMRI. These findings suggest that gray matter is selectively vulnerable to damage in pediatric SCD patients and that white matter damage occurs later in the disease process. Our inability to find an effect from saturation of inflowing blood implies that rapid perfusion cannot account for T1 reduction in gray matter.     

Changes of relaxation times T1 and T2 in rat tissues after biopsy and fixation

NMR spectroscopical measurements of relaxation times were conducted on muscle, intestine, fatty tissue and cerebral cortex and white matter of the rat at various time intervals following removal of the tissue. It appeared that most tissues can be stored at 4 degrees C up to 24 hours without noticeable effects on NMR relaxation parameters. Exceptions are the T2 of muscle and the T1 and T2 of intestine, which tended to change in the first hour after biopsy. Relaxation parameters change considerably after fixation of the tissues. Therefore the effects of fixation have to be taken into account when carrying out NMR measurements on fixed tissues.     

T1 and proton density at 7 T in patients with multiple sclerosis: an initial study

Magnetic resonance imaging of cortical lesions due to multiple sclerosis (MS) has been hampered by the lesions' small size and low contrast to adjacent, normal-appearing tissue. Knowing cortical lesion T1 and proton density (PD) would be highly beneficial for the process of developing and optimizing dedicated magnetic resonance (MR) sequences through computer modeling of MR tissue responses. Eight patients and seven healthy control subjects were scanned at 7 T using a series of inversion recovery turbo field echo scans with varying inversion times. Regions of interest were drawn in white matter, gray matter, cortical lesions, white matter lesions and cerebrospinal fluid. White matter and gray matter T1s were significantly higher in MS patients than in controls. Cortical and white matter lesion T1 and PD are also presented for the first time. The advantages of ultrahigh field MR imaging will be important for future investigations in MS research and sequence optimization for the detection of cortical lesions.     

Proton spin relaxation studies of fatty tissue and cerebral white matter

Proton spin longitudinal (T1) and transverse (T2) relaxation and proton density studies were carried out on human fatty tissue and bovine white matter, both in the native state and after immersion in D2O. It is concluded that nuclear magnetic resonance signals from fatty tissue result mainly from methyl and methylene protons of hydrocarbons. No contribution from lipid protons could be detected for white matter, although it contains a high percentage of lipids. Imaging experiments, resulting in T1, T2, and proton density maps, support the results obtained with spectroscopic relaxation studies.     

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.     

Age-related changes in the pediatric brain: proton T1 in healthy children and in children with sickle cell disease

The goal of this study was to characterize the expected range of variation in T1 (spin-lattice relaxation time) of brain tissue in vivo, as a function of age, and to use these maturational norms to study children with sickle cell disease (SCD). A well-validated method (TurboPAIR) was used to measure T1 in 10 tissues in a study group of 200 healthy subjects (ages 4.5 to 79.3; 101 male and 99 female), in a transverse slice at the level of the basal ganglia. Brain T1 was significantly related to age in every tissue characterized (p < 0.001), including the splenium (p < 0.01). Quantitative MRI suggests that brain T1 continues to change throughout the lifespan of healthy subjects free of neurologic complaints. Age-related changes follow a different schedule in each tissue, and age is a stronger determinant of T1 in gray matter than in white matter. Analysis of 141 patients with SCD shows that patients have lower T1 than normal, in both the caudate and the cortex (p < 0.001).     

Fast and precise T1 imaging using a TOMROP sequence

Proton spin-lattice (T1) relaxation time images were computed from a data set of 32 gradient-echo images acquired with a fast TOMROP (T One by Multiple Read Out Pulses) sequence using a standard whole-body MR imager operating at 64 MHz. The data acquisition and analysis method which permits accurate pixel-by-pixel estimation of T1 relaxation times is described. As an example, the T1 parameter image of a human brain is shown demonstrating an excellent image quality. For white and gray brain matter, the measured longitudinal relaxation processes are adequately described by a single-component least-squares fit, while more than one proton component has to be considered for fatty tissue. A quantitative analysis yielded T1 values of 547 +/- 36 msec and 944 +/- 73 msec for white and gray matter, respectively.     

MR assessment of the brain maturation during the perinatal period: quantitative T2 MR study in premature newborns

The purpose of our study is to trace in vivo and during the perinatal period, the brain maturation process with exhaustive measures of the T2 relaxation time values. We also compared regional myelination progress with variations of the relaxation time values and of brain signal. T2 relaxation times were measured in 7 healthy premature newborns at the post-conceptional age of 37 weeks, using a Carr-Purcell-Meiboom-Gill sequence (echo time 60 to 150 ms), on a 2.35 Tesla Spectro-Imaging MR system. A total of 62 measures were defined for each subject within the brain stem, the basal ganglia and the hemispheric gray and white matter. The mean and standard deviation of the T2 values were calculated for each location. Regional T2 values changes and brain signal variations were studied. In comparison to the adult ones, the T2 relaxation time values of both gray and white matter were highly prolonged and a reversed ratio between gray and white matter was found. The maturational phenomena might be regionally correlated with a T2 value shortening. Significant T2 variations in the brainstem (p < 0.02), the mesencephalon (p < 0.05), the thalami (p < 0.01), the lentiform nuclei (p < 0.01) and the caudate nuclei (p < 0.02) were observed at an earlier time than they were visible on T2-weighted images. In the cerebral hemispheres, T2 values increased from the occipital white matter to parietal, temporal and frontal white matter (p < 0.05) and in the frontal and occipital areas from periventricular to subcortical white matter (p < 0.01). Maturational progress was earlier and better displayed with T2 measurements and T2 mapping. During the perinatal period, the measurements and analysis of T2 values revealed brain regional differences not discernible with T2-weighted images. It might be a more sensitive indicator for assessment of brain maturation.     

Assessment of the metabolic profile in Type 2 diabetes mellitus and hypothyroidism through proton MR spectroscopy

The metabolic changes in the brain of patients affected with Type 2 diabetes mellitus (DM) alone, both Type 2 DM and hypothyroidism and hypothyroidism only were investigated using proton magnetic resonance spectroscopy ((1)H MRS). Single-voxel spectroscopy was carried out in right and left frontal lobe white matter, left parietal white matter and left occipital gray matter. Choline (Cho)/creatine (Cr) value was found to be increased in the left occipital gray matter of the subjects affected with Type 2 DM and both Type 2 DM and hypothyroidism as compared to controls. No significant change in the Cho/Cr value in the occipital gray matter was observed in hypothyroid subjects as compared to controls. However, they showed an increased level of Cho/Cr in the frontal white matter. High Cho is associated with altered membrane phospholipid metabolism. The high Cho in frontal white matter in hypothyroids and occipital gray matter in diabetic patients suggests that, though both the diseases are endocrine disorders, they differ from each other in terms of regional brain metabolite changes.     

Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation

Cortical lesions have recently been a focus of multiple sclerosis (MS) MR research. In this study, we present a white matter signal attenuating sequence optimized for cortical lesion detection at 7 T. The feasibility of white matter attenuation (WHAT) for cortical lesion detection was determined by scanning eight patients (four relapsing/remitting MS, four secondary progressive MS) at 7 T. WHAT showed excellent gray matter-white matter contrast, and cortical lesions were hyperintense to the surrounding cortical gray matter, The sequence was then optimized for cortical lesion detection by determining the set of sequence parameters that produced the best gray matter-cortical lesion contrast in a 10-min scan. Despite the B1 inhomogeneities common at ultra-high field strengths, WHAT with an adiabatic inversion pulse showed good cortical lesion detection and would be a valuable component of clinical MS imaging protocols.     

Detecting functional magnetic resonance imaging activation in white matter: Interhemispheric transfer across the corpus callosum

Background  

It is generally believed that activation in functional magnetic resonance imaging (fMRI) is restricted to gray matter. Despite this, a number of studies have reported white matter activation, particularly when the corpus callosum is targeted using interhemispheric transfer tasks. These findings suggest that fMRI signals may not be neatly confined to gray matter tissue. In the current experiment, 4 T fMRI was employed to evaluate whether it is possible to detect white matter activation. We used an interhemispheric transfer task modelled after neurological studies of callosal disconnection. It was hypothesized that white matter activation could be detected using fMRI.     

Brain metabolite alterations demonstrated by proton magnetic resonance spectroscopy in diabetic patients with retinopathy

Due to the homology between retinal and cerebral microvasculatures, retinopathy is a putative indicator of cerebrovascular dysfunction. This study aimed to detect metabolite changes of brain tissue in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) using proton magnetic resonance spectroscopy (¹H-MRS). Twenty-nine T2DM patients with DR (DR group), thirty T2DM patients without DR (DM group) and thirty normal controls (NC group) were involved in this study. Single-voxel ¹H-MRS (TR: 2000 ms, TE: 30 ms) was performed at 3.0 T MRI/MRS imager in cerebral left frontal white matter, left lenticular nucleus, and left optic radiation. Our data showed that NAA/Cr ratios of the DR group were significantly lower than those of the DM group in the frontal white matter and optic radiation. In the lenticular nucleus, MI/Cr ratios were significantly higher in the DM group than those in the NC group, while MI/Cr ratios were significantly lower in the DR group than those in the DM group. In the frontal white matter, NAA/Cho ratios were found to be decreased in the DR group as compared to the NC group. Additionally, our finding indicated that NAA/Cr ratios were negatively associated with DR severity in both the frontal white matter and optic radiation. A decrease in NAA indicated neuronal loss and the likely explanation for a decrease in MI was glial loss. In conclusion, we inferred that cerebral neurons and glia cells were damaged in patients with DR. Our data support that DR is associated with brain tissue damage.     

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.     

Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging.

The apparent diffusion coefficient (ADC) of tissue provides an indication of the size, shape, and orientation of the water spaces in tissue. Thus, pathologic differences between lesions in multiple sclerosis (MS) patients with different clinical courses may be reflected by changes in ADC measurements in lesions and white matter. Twelve healthy subjects and 35 MS patients with a relapsing-remitting (n = 10), benign (n = 8), secondary progressive (n = 8) and primary progressive (n = 9) clinical course were studied. T2-weighted and post-gadolinium T1-weighted images were obtained using a 1.5 T Signa Echospeed magnetic resonance imaging (MRI) system. Diffusion-weighted imaging was implemented using a pulsed gradient spin echo (PGSE) sequence with diffusion gradients applied in turn along three orthogonal directions in order to obtain the average apparent diffusion coefficient (ADCav). Navigator echo correction and cardiac gating were used to reduce motion artifact. ADC maps were derived using a two point calculation based on the Stejskal-Tanner formula. Diffusion anisotropy was estimated using the van Gelderen formula to calculate an anisotropy index. MS lesions had a higher ADC and reduced anisotropy compared with normal appearing white matter. Highest ADC values were found in gadolinium enhancing lesions and non-enhancing hypointense lesions on T1-weighted imaging. MS white matter had a slightly higher ADC and lower anisotropy than white matter of healthy subjects. Lesion and white matter ADC values did not differ between patients with different clinical courses of MS. There was no correlation between lesion ADC and disability. Diffusion-weighted imaging with measurement of ADC using the PGSE method provides quantitative information on acute edematous MS lesions and chronic lesions associated with demyelination and axonal loss but does not distinguish between clinical subtypes of MS.     

More than meets the eye: significant regional heterogeneity in human cortical T1

Segmented k-space acquisition of data was used to decrease the acquisition time and to increase the imaging resolution of the precise and accurate inversion recovery (PAIR) method of measuring T(1). We validated the new TurboPAIR method by measuring T(1) in 158 regions of interest in 12 volunteers, using both PAIR and TurboPAIR. We found a 3% difference between methods, which could be corrected by linear regression. After validation, the TurboPAIR method was used to test a hypothesis that there is significant regional heterogeneity in cortical T(1). We measured cortical gray matter T(1) in 11 right-handed volunteers, in 48 regions of interest scattered over frontal and parietal cortex, and in 46 ROIs along the central sulcus (CS). We found that T(1) in the CS is less than T(1) elsewhere in the cortex (p<0.001), and that there is considerable hemispheric asymmetry in T(1) in gray matter, but not in white matter. In central gray structures (caudate, thalamus, nucleus pulvinarus), and in the posterior CS (sensory cortex), right hemisphere T(1) was significantly greater than left hemisphere T(1) (p< or =0.004). In cortical gray matter of the frontal lobe and anterior CS (motor cortex), left hemisphere T(1) was significantly greater than right hemisphere T(1) (p< or =0.003). These findings demonstrate that there is considerable regional heterogeneity in human cortical T(1) that is unexplained by differences in tissue iron content, but may be evidence of an inherent anatomic asymmetry of the brain.     

Measurement of relative cerebral blood volume using BOLD contrast and mild hypoxic hypoxia

Relative cerebral blood volume (CBV) was estimated using a mild hypoxic challenge in humans, combined with BOLD contrast gradient-echo imaging at 3 T. Subjects breathed 16% inspired oxygen, eliciting mild arterial desaturation. The fractional BOLD signal change induced by mild hypoxia is expected to be proportional to CBV under conditions in which there are negligible changes in cerebral perfusion. By comparing the regional BOLD signal changes arising with the transition between normoxia and mild hypoxia, we calculated CBV ratios of 1.5±0.2 (mean±S.D.) for cortical gray matter to white matter and 1.0±0.3 for cortical gray matter to deep gray matter.     

White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

ABSTRACT: BACKGROUND: There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. RESULTS: Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. CONCLUSIONS: Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T.     

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.