Cerebral maturation in the early preterm period-A magnetization transfer and diffusion tensor imaging study using voxel-based analysis.

The magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) correlates of early brain development were examined in cohort of 18 very preterm neonates (27-31 gestational weeks) presenting with normal radiological findings scanned within 2weeks after birth (28-32 gestational weeks). A combination of non-linear image registration, tissue segmentation, and voxel-wise regression was used to map the age dependent changes in MTR and DTI-derived parameters in 3D across the brain based on the cross-sectional in vivo preterm data. The regression coefficient maps obtained differed between brain regions and between the different quantitative MRI indices. Significant linear increases as well as decreases in MTR and DTI-derived parameters were observed throughout the preterm brain. In particular, the lamination pattern in the cerebral wall was evident on parametric and regression coefficient maps. The frontal white matter area (subplate and intermediate zone) demonstrated a linear decrease in MTR. While the intermediate zone showed an unexpected decrease in fractional anisotropy (FA) with age, with this decrease (and the increase in mean diffusivity (MD)) driven primarily by an increase in radial diffusivity (RD) values, the subplate showed no change in FA (and an increase in MD). The latter was the result of a concomitant similar increase in axial diffusivity (AD) and RD values. Interpreting the in vivo results in terms of available histological data, we present a biophysical model that describes the relation between various microstructural changes measured by complementary quantitative methods available on clinical scanners and a range of maturational processes in brain tissue.

Quantitative MRI in the very preterm brain: assessing tissue organization and myelination using magnetization transfer, diffusion tensor and T1 imaging.

Magnetization transfer ratio (MTR), diffusion tensor imaging (DTI) parameters and T(1) relaxometry values were used to create parametric maps characterizing the tissue microstructure of the neonatal brain in infants born very premature (24-32 gestational weeks) and scanned at preterm and term equivalent age. Group-wise image registration was used to determine anatomical correspondence between individual scans and the pooled parametric data at the preterm and term ages. These parametric maps showed distinct contrasts whose interrelations varied across brain regions and between the preterm and term period. Discrete patterns of regional variation were observed for the different quantitative parameters, providing evidence that MRI is sensitive to multiple independent aspects of brain maturation. MTR values showed a marked change in the pattern of regional variation at term equivalent age compared to the preterm period such that the ordinal ranking of regions by signal contrast changed. This was unlike all other parameters where the regional ranking was preserved at the two time points. Interpreting the data in terms of myelination and structural organization, we report on the concordance with available histological data and demonstrate the value of quantitative MRI for tracking brain maturation over the neonatal period.

Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants.

BACKGROUND: Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. METHODS: Spectroscopy data were obtained from 99 very preterm infants (born ≤32 wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LCModel. Multiple regression was used to examine the association of metabolite ratios with focal noncystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. RESULTS: Within 2 wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5 min after birth. CONCLUSION: Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures.

Quantitative MRI for studying neonatal brain development.

Quantitative MRI techniques based on morphology and tissue microstructure dependent contrast provide a unique window on brain development in the neonatal period. The dramatic changes in morphology and MRI contrast that occur during this period have the potential to be used to identify normal and abnormal developmental trajectories that predict neurodevelopmental outcome in at risk populations. Here, we review these technologies focussing on two broad categories: gross morphological analysis and tissue microstructure assessment. With respect to morphology, we examine the role of image registration and atlas-based techniques, highlighting the challenges posed by the scale of the anatomical changes and the high incidence of radiologically abnormal scans in the premature infant population. With respect to microstructure, we examine the potential and remaining challenges for using quantitative MRI to dissociate processes of cell proliferation, neuronal maturation, and myelination by combining different signal contrasts. Recent progress from our group in this area is highlighted.

Deep gray matter maturation in very preterm neonates: regional variations and pathology-related age-dependent changes in magnetization transfer ratio.

PURPOSE: To elucidate the relationship between gestational age, pathologic findings, and magnetic resonance (MR) imaging measures of tissue maturation-myelination in deep gray matter areas in very preterm neonates imaged at birth. MATERIALS AND METHODS: The study was approved by the research ethics board. Written informed consent was given by the infants' parents. Forty-two preterm neonates (19 boys; median gestational age, 28.7 weeks) with normal-appearing gray matter structures at presentation underwent MR imaging within 2 weeks of birth that included T1- and T2-weighted, magnetization transfer, and T1 relaxometry sequences. Neonates were separated into the following groups: those with normal findings (n = 23), those with white matter injury (WMI) (n = 9), those with grade I germinal matrix hemorrhage (GMH) (n = 3), and those with grade II GMH and WMI (n = 7). Analysis of covariance was used to determine regional effects of age and pathologic findings on magnetization transfer ratio (MTR) and to assess the relationship between MTR and T1. RESULTS: MTR increased linearly with age (P ≤ .0265), with a similar rate of change of 0.32% per week (95% confidence interval [CI]: 0.16, 0.49) in the basal ganglia (BG) and thalami. A lower trend (0.11% per week; 95% CI: -0.05, 0.28) was seen in the pons. Higher MTRs were seen in the thalami and pons than in the BG (P < .05), indicating earlier maturation. Accordingly, higher T1 values were observed in the BG relative to the thalami (P < .0001). Higher MTRs in the BG were observed in the group of neonates with normal findings at presentation than in the group with WMI (P = .02). CONCLUSION: MTR measurements can be used to monitor early myelination in the developing brain and to help detect changes in tissue that are not shown on T1- and T2-weighted MR images.

Visual functional magnetic resonance imaging of preterm infants.

AIM: The aim of this study was to determine the feasibility of undertaking visual functional magnetic resonance imaging (fMRI) in very preterm children. METHOD: Forty-seven infants born at less than 32 weeks gestational age (25 males, 22 females; mean (SD) age at birth 28.8 wks [1.9]) were scanned using 1.5 T MRI as part of a longitudinal neuroimaging study. These infants were scanned at preterm age (within 2 wks of birth) and at term-equivalent age. Quantitative T2* data and fMRI in response to visual stimuli (flashing strobe) were acquired in this population. T2* values were compared at preterm age and at term-equivalent age using a two-tailed t-test. A general linear model was used to evaluate occipital lobe response to visual stimuli. RESULTS: T2* values were significantly higher at preterm age than at term-equivalent age in both the medial and lateral occipital lobes (preterm infants: 187.2 ms and 198.4 ms respectively; term infants: 110.9 ms and 133.2 ms respectively; p<0.002). Significant positive occipital lobe activation (q<0.01) was found in 3 out of 65 (5%) fMRIs carried out at preterm age and in 19 out of 26 (73%) scans carried out at term-equivalent age. INTERPRETATION: Visual stimuli do not elicit a reliable blood oxygen level-dependent (BOLD) response in very preterm infants during the preterm period. This suggests that BOLD fMRI may not be the appropriate modality for investigating occipital lobe function in very preterm infants.

Preterm neonatal diffusion processing using detection and replacement of outliers prior to resampling.

In diffusion weighted MRI, subject motion and brain pulsation lead both to signal drop-outs and image misalignment. Unsedated neonates, with their higher heart rate and propensity for motion are particularly prone to degraded scan quality that impairs diffusion tensor estimation. Retrospective registration and robust estimators are two methods that have previously been demonstrated to address motion and intensity outliers, respectively, in diffusion data. However, when taken together, the resampling of images to correct for misalignment can have the effect of averaging outlier voxels with uncorrupted voxels, thereby making outliers more difficult to detect. This article presents a method to remove outliers prior to resampling while taking misalignment into account so that this averaging of outliers with good data can be avoided. The proposed method is compared to other processing pipelines using simulations and data from unsedated preterm neonates. These results demonstrate advantages to the proposed method, particularly in subjects with high motion.

Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates.

BACKGROUND: T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. OBJECTIVE: To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. MATERIALS AND METHODS: Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. RESULTS: No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. CONCLUSION: High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information.

Late stimulation of the sphenopalatine-ganglion in ischemic rats: improvement in N-acetyl-aspartate levels and diffusion weighted imaging characteristics as seen by MR.

PURPOSE: To assess, by MR spectroscopy (MRS) and diffusion weighted imaging (DWI), the ability of electrical stimulation of the sphenopalatine ganglion (SPG) to augment stroke recovery in transient middle cerebral artery occluded (t-MCAO) rats, when treatment is started 18 +/- 2 h post-occlusion. MATERIALS AND METHODS: (1)H-MRS imaging ((1)H-MRSI) and DWI were used to evaluate ischemic brain tissue after SPG stimulation in rats subjected to 2 h of t-MCAO. Rats were examined by (1)H-MRSI, DWI, and behavioral tests at 16 +/- 2 h, 8 days, and 28 days post-MCAO. RESULTS: N-Acetyl-aspartate (NAA) levels of the stimulated and control rats were the same 16 +/- 2 h post-MCAO (0.52 +/- 0.03, 0.54 +/- 0.03). At 28 days post-occlusion, NAA levels were significantly higher in the treated group (0.60 +/- 0.04) compared with those of the untreated animals (0.50 +/- 0.04; P < 0.05). This effect was more pronounced for regions with low NAA values (0.16 +/- 0.03) that changed to 0.32 +/- 0.03 (P = 0.04) for the treated group and to 0.10 +/- 0.03 (P = 0.20) for the controls. DWI data showed better ischemic tissue condition for the treated rats, but the measured parameters showed only a trend of improvement. The MR results were corroborated by behavioral examinations. CONCLUSION: Our findings suggest that SPG stimulation may ameliorate MR tissue characteristics following t-MCAO even if treatment is started 18 h post-occlusion.

Spatial and temporal damage evolution after hemi-crush injury in rat spinal cord obtained by high b-value q-space diffusion magnetic resonance imaging.

Spinal cord injury (SCI) is a major cause of disability for many living persons. Therefore, several experimental models and handful of techniques were developed to study and characterize the damage evolution following SCI. In the present study, high b-value q-space diffusion-weighted imaging (DWI) was used to follow the spatial and temporal damage evolution in excised rat spinal cords following hemi-crush injury. The DWI results were correlated with behavioral testing. It was found that the damage depends, as expected, on the severity of the insult. Significant spontaneous recovery was observed, six weeks following the insult, only for the mild hemi-crush injury but not following the severe injury. The damage was found to be more severe in the area caudal to the trauma site as compared to the rostral section of the cord.

q-Space high b value diffusion MRI of hemi-crush in rat spinal cord: evidence for spontaneous regeneration.

The development of the damage following hemi-crush trauma in rat spinal cord was studied ex vivo using high b value (bmax = 1 x 10(7) s cm(-2)) q-space diffusion weighted MRI (DWI) at five days, ten days and six weeks post-trauma. Rat spinal cord trauma, produced by hemi-crush of 15s and 60s duration, was studied. The water signal decay in these diffusion experiments was found to be non mono-exponential and was analyzed using the q-space approach. The q-space MRI parameters were compared with T1 and T2 MR images, behavioral tests and histopathological osmium staining. A very good anatomical correlation was found between the q-space MRI parameters and the osmium staining. Interestingly, we found that in the 15s hemi-crush model significant recovery was observed in both the q-space MR images and the osmium staining six weeks post-trauma. However, in the 60s hemi-crush trauma model very little recovery was observed. These results paralleled those obtained from behavioral tests demonstrating that partial spontaneous recovery seems to occur in the 15s hemi-crush spinal cord model, which should be taken in consideration when using it to evaluate new therapies.

Effect of experimental parameters on high b-value q-space MR images of excised rat spinal cord.

The influence of diffusion time (delta), gradient duration (delta), and TE on the appearance of high b-value q-space diffusion MR images of excised rat spinal cord (SC) was evaluated. The water signal decays in the white (WM) and gray matter (GM) were analyzed when the diffusion was measured perpendicular ( perpendicular) and parallel to the fibers of the SC, using three different approaches: single-component q-space analysis, the biexponential model, and the bi-Gaussian fit of the displacement distribution profile. Probability and displacement contrast and anisotropy indices were calculated for the WM and GM. It was found that WM/GM contrast increases as the diffusion time is increased when diffusion is measured perpendicular to the long axis of the SC. At a diffusion time of 50 ms, when diffusion was measured parallel to the fibers of the SC, the displacement was found to be higher for GM as compared to WM. For this direction the WM/GM contrast increased when diffusion time was increased, although here the changes were much less pronounced than for the perpendicular direction. The WM/GM displacement contrast nearly disappears for a diffusion time of 150 ms, when diffusion is measured parallel to the fibers of the SC. As expected, the anisotropy indices were found to be higher in WM than in GM, and increased with the increase in diffusion time. Both delta and TE affected the extracted parameters. It was found that long delta and long TE overemphasizes the apparent slow-diffusing water component of the SC, which is also the more restricted one. It is demonstrated that the single-component q-space analysis best describes diffusion in WM when diffusion is measured perpendicular to the fibers of the SC. In other cases, a more complete description is obtained by using two-component models.