Relaxo-volumetric multispectral quantitative magnetic resonance imaging of the brain over the human lifespan: global and regional aging patterns

The objective of this study was to determine the T1, T2 and secular-T2 relaxo-volumetric brain aging patterns using multispectral quantitative magnetic resonance imaging, both globally and regionally, and covering an age range approaching the full human lifespan. Fifty-one subjects (28 males, 23 females; age range: 0.5–87 years) were studied consisting of 18 healthy volunteers and 33 patients. Patients were selected after carefully reviewing their radiology reports to have either normal-by-MRI findings (25 patient subjects) or small focal pathology less than 6 mm in size (eight patient subjects). All subjects were MR imaged at 1.5 T with the mixed turbo spin echo pulse sequence. The soft tissues inside the cranial vault, termed intracranial matter (ICM), were segmented using a dual-clustering segmentation algorithm. ICM segments were further divided into six subsegments: bilateral anterior cerebral, posterior cerebral and cerebellar subsegments. T1, T2 and secular-T2 relaxation time histograms of all segments were generated and modeled with Gaussian functions. For each segment, the volumes of white matter, gray matter and cerebrospinal fluid were calculated from the T1 histograms. The age-related tendencies of three quantitative MRI parameters (T1, T2 and secular-T2) and the fractional tissue volumes showed four distinct periods of life, specifically a maturation period (0–2 years), a development period (2–20 years), an adulthood period (20–60 years) and a senescence period (60 years and older). For all ages, the anterior cerebral subsegment exhibited consistently longer gray matter T1s and shorter white matter T1s than the posterior cerebral and cerebellar subsegments. Volumetric age-related changes of the cerebellar subsegment were more gradual than in the cerebral subsegments. This study shows that relaxometric and volumetric age-related changes are synchronized and define the same four periods of brain evolution both globally and regionally.     

Cervical spondylosis: Evaluation of microstructural changes in spinal cord white matter and gray matter by diffusional kurtosis imaging

Introduction

We investigated microstructural changes in the spinal cord, separately for white matter and gray matter, in patients with cervical spondylosis by using diffusional kurtosis imaging (DKI).

Methods

We studied 13 consecutive patients with cervical myelopathy (15 affected sides and 11 unaffected sides). After conventional magnetic resonance (MR) imaging, DKI data were acquired by using a 3 T MR imaging scanner. Values for fractional anisotropy (FA), apparent diffusion coefficient (ADC), and mean diffusional kurtosis (MK) were calculated and compared between unaffected and affected spinal cords, separately for white matter and gray matter.

Results

Tract-specific analysis of white matter in the lateral funiculus showed no statistical differences between the affected and unaffected sides. In gray matter, only MK was significantly lower in the affected spinal cords than in unaffected spinal cords (0.60 ± 0.18 vs. 0.73 ± 0.13, P = 0.0005, Wilcoxon’s signed rank test).

Conclusions

MK values in the spinal cord may reflect microstructural changes and gray matter damage and can potentially provide more information beyond that obtained with conventional diffusion metrics.     

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.     

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.     

In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Understanding the GABA concentration, in vivo, is important to understand normal brain function. Using MEGA point-resolved spectroscopy sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex was measured using a voxel identified from a functional magnetic resonance imaging scan. The GABA level in a 20×20×20-mm³ voxel consisting of 37%±7% gray matter, 52%±12% white matter and 11%±8% cerebrospinal fluid in the sensorimotor region was measured to be 1.43±0.48 mM. In addition, using linear regression analysis, GABA concentrations within gray and white matter were calculated to be 2.87±0.61 and 0.33±0.11 mM, respectively.     

Whole-body T2* mapping at 1.5 T

This study investigated the feasibility of an MRI protocol providing whole-body T2* maps at 1.5 T. Seven healthy volunteers (mean age=30.1+/-3.7, three women and four men) and two patients (both male, 53 and 46 years old) affected by transfusion-dependent anemias participated in the study. Coronally oriented images of five subsequent body levels were acquired using a fat-suppressed multiecho 2D gradient-echo sequence (12 echo times ranging from 4.8 to 76.3 ms were selected) and afterwards composed. Parametrical T2* maps of the whole body were reconstructed on a pixel-by-pixel basis. For both, healthy volunteers and patients, representative T2* values were computed from extended regions of interest (ROIs). Good-quality whole-body T2* maps were computed in all volunteers and patients. In healthy volunteers, T2* values were assessed in the cerebral white (58.5+/-4.2 ms) and gray (81.4+/-5.5 ms) matter, liver (34.3+/-7.0 ms), spleen (63.5+/-3.3 ms), kidneys (65.4+/-10.3 ms) and skeletal muscles (~30 ms). The liver presented faster relaxation rates in males as compared to females. One patient (serum ferritin concentration=927 microg/dl) showed shortened T2* values in liver (3.6+/-5.5 ms), spleen (3.1+/-4.8 ms), kidneys (11.1+/-7.1 ms) and muscles (25.1+/-3.4 ms). The second patient (serum ferritin concentration=346 microg/dl) presented reduced T2* values in liver (3.9+/-7.3 ms), spleen (20.1+/-9.8 ms) and kidneys (24.6+/-7.7 ms). The presented technique may find clinical application in the assessment of the iron burden in the entire body, and in monitoring of chelation therapies in patients treated with frequent blood transfusions.     

Modeling brain tissue volumes over the lifespan: quantitative analysis of postmortem weights and in vivo MR images

Normative measurements of brain gray matter and white matter tissue volumes across the lifespan have not yet been established. The purpose of this article was to use mathematical modeling and analytical functions to demonstrate the growth trajectory of gray matter and white matter from age 0 to age 90. For each gender, brain weight functions were generated by utilizing existing autopsy data from 4400 subjects. Brain gray matter, white matter and lateral ventricular volumes were measured from 39 MR volumes of normal individuals. These were converted to weight by multiplying the tissue volumes by the specific gravity of that tissue. White matter volumes were described by a saturating exponential function, and the gray matter volume function was calculated by subtracting the white matter weight function from the brain weight function. For each gender, equations were generated for white matter and gray matter volumes as a function of age over the lifespan.     

Development of new population-averaged standard templates for spatial normalization and segmentation of MR images for postnatal piglet brains

Propose

To design a set of brain templates for postnatal piglet brains based on high-resolution T1-weighted imaging for voxel-based morphometric analysis.

Materials and methods

Using a 3.0 T magnetic resonance (MR) scanner, a population-based whole brain template was developed by averaging forty T1 images in the brains of postnatal piglets at 38 days of age. The templates for gray and white matter, and cerebrospinal fluid were designed based on the corresponding probability maps by adapting individual data sets using statistical parametric mapping. Anatomical labeling maps were generated from labeling propagation derived from the established Pig Brain Atlas. Differences in the coordinates from four significant structural landmarks in the template, plus an additional 12 normalized images and anatomical labeling maps were measured to validate the accuracy of the registration of the template.

Results

A whole brain template, a set of tissue-specific probability and anatomical labeling maps were developed. The location deviation of the four significant structural landmarks, including the anterior and posterior regions in the corpus callosum, and the left and right caudate nucleus, was found to be < 0.25 cm, validating the sensitivity and resolution of the template.

Conclusion

A whole brain template map and a set of tissue-specific probability and anatomical labeling maps were developed to analyze the morphometric imaging of the postnatal piglet brain, an animal model of the human infant.     

Effect of a gadodiamide contrast agent on the reliability of brain tissue T1 measurements

To determine whether brain spin-lattice relaxation time (T1) can routinely be measured after contrast-agent injection, we measured T1 by a precise and accurate inversion-recovery (PAIR) method in five brain tumor patients, before and again after contrast-agent injection. The T1 in at least 20 regions of interest (ROIs) was measured in each patient, avoiding areas of contrast enhancement visible by conventional MR imaging. Contrast-agent injection reduced T1 in 51 regions of interest in white matter by less than 1% (not significant), and in 50 regions of interest in gray matter by less than 2% (p = 0.001). Pixel-by-pixel plots demonstrate that T1 is reduced substantially in extra-parenchymal tissues, but not in brain tissues. Therefore, T1 mapping with the precise and accurate inversion-recovery method can routinely be done after contrast injection. Our results suggest that the precise and accurate inversion-recovery method is not sensitive to the T1 of blood in the presence of an intact blood-brain barrier, although a substantial T1 reduction does occur in the absence of a blood-brain barrier.     

Deconvolution with simple extrapolation for improved cerebral blood flow measurement in dynamic susceptibility contrast magnetic resonance imaging during acute ischemic stroke

Magnetic resonance (MR) perfusion imaging is a clinical technique for measuring brain blood flow parameters during stroke and other ischemic events. Ischemia in brain tissue can be difficult to accurately measure or visualize when using MR-derived cerebral blood flow (CBF) maps. The deconvolution techniques used to estimate flow can introduce a mean transit time-dependent bias following application of noise stabilization techniques. The underestimation of the CBF values, greatest in normal tissues, causes a decrease in the image contrast observed in CBF maps between normally perfused and ischemic tissues; resulting in ischemic areas becoming less conspicuous. Through application of the proposed simple extrapolation technique, CBF biases are reduced when missing high-frequency signal components in the MR data removed during deconvolution noise stabilization are restored. The extrapolation approach was compared with other methods and showed a statistically significant increase in image contrast in CBF maps between normal and ischemic tissues for white matter (P<.05) and performed better than most other methods for gray matter. Receiver operator characteristic curve analysis demonstrated that extrapolated CBF maps better-detected penumbral regions. Extrapolated CBF maps provided more accurate CBF estimates in simulations, suggesting that the approach may provide a better prediction of outcome in the absence of treatment.     

Aging effects on cerebral asymmetry: a voxel-based morphometry and diffusion tensor imaging study

The hemispheres of the human brain are functionally and structurally asymmetric. The purpose of this study was to evaluate the effects of aging on gray and white matter asymmetry. Two hundred twenty-six right-handed normal volunteers aged 21–71 years were included in this study. The effects of aging on gray matter volume asymmetry and white matter fractional anisotropy asymmetry were evaluated with use of voxel-based morphometry and voxel-based analysis of fractional anisotropy maps derived from diffusion tensor imaging (DTI), respectively. The voxel-based morphometry showed no significant correlation between age and gray matter volume asymmetry. The voxel-based analysis of DTI also showed no significant correlation between age and white matter fractional anisotropy asymmetry. Our results showed no significant effects of aging on either gray matter volume asymmetry or white matter fractional anisotropy asymmetry.     

Brain T1 in young children with sickle cell disease: evidence of early abnormalities in brain development

Measurement of tissue spin lattice relaxation time (T(1)) has been used to characterize brain development in healthy children. Here we report the first study of brain T(1) in young children with sickle cell disease (SCD). The T(1) in 10 tissue samples was measured by established techniques; 46 SCD patients under the age of 4 years were compared to 267 controls, including 55 well children under the age of 4 years. A model was developed to predict the relationship between age and brain T(1) in controls, then we compared patient T(1) to healthy normal T(1). Most white matter and gray matter tissues in infant patients (<2 years old), had T(1) values significantly higher than normal. For example, 15.0% of patient caudate T(1) values were above the upper bound of the 95% confidence interval for controls, but only 2.5% of normal values are expected to be this high (p = 0.0003). Among infant patients, brain T(1) was significantly higher than normal in every tissue (p < 0.01) except cortical gray matter. However, patient T(1) values declined rapidly to values lower than normal by about age 4. Our findings imply that patients follow an abnormal developmental trajectory beginning early in infancy.     

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.     

Utility of a diffusion-weighted arterial spin labeling (DW-ASL) technique for evaluating the progression of brain white matter lesions

PurposeTo investigate the utility of diffusion-weighted arterial spin labeling (DW-ASL) for detecting the progression of brain white matter lesions.Materials and methodsA total of 492 regions of interest (ROIs) in 41 patients were prospectively analyzed. DW-ASL was performed using the diffusion gradient prepulse of five b-values (0, 25, 60, 102, and 189) before the ASL readout. We calculated the water exchange rate (K_w) with post-processing using the ASL signal information for each b-value. The cerebral blood flow (CBF) was also calculated using b0 images. Using the signal information in FLAIR (fluid-attenuated inversion recovery) images, we classified the severity of white matter lesions into three grades: non-lesion, moderate, and severe. In addition, the normal K_w level was measured from DW-ASL data of 60 ROIs in five control subjects. The degree of variance of the K_w values (K_w-var) was calculated by squaring the value of the difference between each K_w value and the normal K_w level. All patient's ROIs were divided into non-progressive and progressive white matter lesions by comparing the present FLAIR images with those obtained 2 years before this acquisition.ResultsCompared to the non-progressive group, the progressive group had significantly lower CBF, significantly higher severity grades in FLAIR, and significantly greater K_w-var values. In a receiver operator characteristic curve analysis, a high area under the curve (AUC) of 0.89 was obtained with the use of K_w-var. In contrast, the AUCs of 0.59 for CBF and 0.72 for severity grades in FLAIR were obtained.ConclusionsThe DW-ASL technique can be useful to detect the progression of brain white matter lesions. This technique will become a clinical tool for patients with various degrees of white matter lesions.     

Multicontext wavelet-based thresholding segmentation of brain tissues in magnetic resonance images

A novel segmentation method based on wavelet transform is presented for gray matter, white matter and cerebrospinal fluid in thin-sliced single-channel brain magnetic resonance (MR) scans. On the basis of the local image model, multicontext wavelet-based thresholding segmentation (MCWT) is proposed to classify 2D MR data into tissues automatically. In MCWT, the wavelet multiscale transform of local image gray histogram is done, and the gray threshold is gradually revealed from large-scale to small-scale coefficients. Image segmentation is independently performed in each local image to calculate the degree of membership of a pixel to each tissue class. Finally, a strategy is adopted to integrate the intersected outcomes from different local images. The result of the experiment indicates that MCWT outperforms other traditional segmentation methods in classifying brain MR images.     

Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

Introduction

Diffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS.

Methods

We generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM.

Results

ADC differed (P < 0.05) between plaques and PWM and between plaques and NAWM. FA differed (P < 0.05) between plaques and NAWM. RMSD differed (P < 0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.

Conclusion

RMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.     

Principal eigenvector field segmentation for reproducible diffusion tensor tractography of white matter structures

The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways (OP), (7) superior longitudinal fasciculus (SLF), (8) arcuate fasciculus (AF), (9) fornix (FX), (10) cingulum (CG), (11) anterior thalamic radiation (ATR), (12) superior thalamic radiation (STR), (13) posterior thalamic radiation (PTR), (14) corticospinal/corticopontine tract (CST/CPT), (15) medial lemniscus (ML), (16) superior cerebellar peduncle (SCP), (17) middle cerebellar peduncle (MCP) and (18) inferior cerebellar peduncle (ICP). Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) and the principal eigenvector field have been used to create the SFM consisting of a collection of linear voxel structures which are grouped together by color-coding them into seven natural classes to provide PEVFS signature segments which greatly facilitate the selection of regions of interest (ROIs) for fiber tractography using just a single mouse click, as compared with a manual drawing of ROIs in the classical approach. All the 18 fiber bundles have been successfully reconstructed, in all the subjects, using the single ROIs provided by the SFM approach, with their reproducibility characterized by the fact that the ROI selection is user independent. The essentially automatic PEVFS method is robust, efficient and compares favorably with the classical ROI methods for diffusion tensor tractography (DTT).     

Perfusion in rat brain at 7 T with arterial spin labeling using FAIR-TrueFISP and QUIPSS

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the imaging slice. Studies in six rats at 7 T showed good perfusion contrast with minimal geometric distortion. The measured blood flow values of 152.5±6.3 ml/100 g per minute in gray matter and 72.3±14.0 ml/100 g per minute in white matter are in good agreement with previously reported values based on autoradiography, considered to be the gold standard.     

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.     

Evaluation of discrete orthogonal versus polar Stockwell Transform for local multi-resolution texture analysis using brain MRI of multiple sclerosis patients

The Stockwell Transform has the potential to perform multi-resolution texture analysis in magnetic resonance imaging (MRI). However, it is computationally intensive and memory demanding. The polar Stockwell Transform (PST) is rotation-invariant and relatively memory efficient, but still computationally demanding. The new Discrete Orthogonal Stockwell Transform (DOST) appears to have addressed both the computation and storage challenges; however, its utility in localized texture analysis remains unclear. Our goal was to investigate the theory and texture analysis ability of the DOST versus PST using both synthetic and MR images, and explore the relative importance of the associated texture features using a simple classification example based on clinical brain MRI of six multiple sclerosis patients. MRI texture analysis focused on FLAIR images, and the classification used a machine learning algorithm, random forest, that differentiated regions of interest (ROIs) into 2 classes: white matter lesions, and the contralateral normal-appearing white matter (control). Our results showed that the PST features had a greater ability in detecting subtle changes in image structure than the DOST and polar-index DOST (PDOST). Quantitatively, based on 187 lesion and 187 control ROIs, both the PST and the rotation-invariant radial PST performed better in the classification than the DOST and PDOST, where the latter were no better than guessing (p = 0.65 and 0.98). Further analysis using a hierarchical random forest showed that combining MRI signal intensity with the PST or DOST predictions increased the classification performance, with the accuracy, sensitivity, and specificity all improved to >85% in the tests. Collectively, the DOST is less competitive than the PST in localized image texture analysis. The PST features may help with texture-based lesion classification in MS based on clinical brain MRI scans following further verification.