Is Low-Grade Intraventricular Hemorrhage in Very Preterm Infants an Innocent Condition? Structural and Functional Evaluation of the Brain Reveals Regional Neurodevelopmental Abnormalities.

BACKGROUND AND PURPOSE: There is increasing evidence of abnormal neurodevelopmental outcomes in very preterm infants with low-grade intraventricular hemorrhage grades I and II. Our purpose was to evaluate the effects of low-grade intraventricular hemorrhage on gray and white matter integrity. MATERIALS AND METHODS: MR imaging at around term-equivalent age was performed in 16 very preterm infants (mean gestational age, 28.8 ± 5.3 weeks) with mild intraventricular hemorrhage on brain sonography and 13 control subjects (mean gestational age, 29.6 ± 4.1 weeks) without intraventricular hemorrhage. Structural and functional evaluation of the cortex was performed using regional measurements of surface area, thickness and volume, and resting-state fMRI, respectively, and of WM microstructural integrity, applying Tract-Based Spatial Statistics to diffusion tensor imaging data. RESULTS: Compared with the control infants, the infants with low-grade intraventricular hemorrhage had decreases in the following: 1) GM surface area in Brodmann areas 19 left and 9 and 45 right, and GM volume in Brodmann areas 9 and 10 right; 2) fractional anisotropy bilaterally in major WM tracts; and 3) brain activity in the left lower lateral and in the right higher medial somatosensory cortex. CONCLUSIONS: Very premature infants with low-grade intraventricular hemorrhage at around term-equivalent age may present with regional abnormalities, appearing on imaging studies as cortical underdevelopment, functional impairment, and microstructural immaturity of major WM tracts.

White matter water diffusion changes in primary Sjögren syndrome.

BACKGROUND AND PURPOSE: Histopathologic studies have demonstrated WM damage in primary Sjögren syndrome. The purpose of this study was to evaluate WM microstructural changes by use of DTI-derived parameters in patients with primary Sjögren syndrome. MATERIALS AND METHODS: DTI was performed in 19 patients with primary Sjögren syndrome (age, 64.73 ± 9.1 years; disease duration, 11.5 ± 7.56 years) and 16 age-matched control subjects. Exclusion criteria were a history of major metabolic, neurologic, or psychiatric disorder and high risk for cardiovascular disease. Data were analyzed by use of tract-based spatial statistics, for which the WM skeleton was created, and a permutation-based inference with 5000 permutations was used with a threshold of P < .01, corrected for multiple comparisons to enable identification of abnormalities in fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. RESULTS: Tract-based spatial statistics showed decreased fractional anisotropy in multiple areas in patients with primary Sjögren syndrome compared with control subjects, located mainly in the corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus. Increased mean diffusivity and radial diffusivity and decreased axial diffusivity were observed in most of the fiber tracts of the brain in patients with primary Sjögren syndrome, compared with control subjects. CONCLUSIONS: Patients with primary Sjögren syndrome show loss of WM microstructural integrity, probably related to both Wallerian degeneration and demyelination.

Investigation of unmedicated early onset restless legs syndrome by voxel-based morphometry, T2 relaxometry, and functional MR imaging during the night-time hours.

BACKGROUND AND PURPOSE: The pathophysiology of eRLS has not yet been elucidated. The purpose of the study was to assess, in patients with eRLS, the volume, iron content, and activation of the brain during night-time episodes of SLD and PLMs. MATERIALS AND METHODS: Eleven right-handed unmedicated patients with eRLS (mean age, 55.3 ± 8.4 years; disease duration, 17.5 ± 14.05 years) and 11 matched control subjects were studied with a T1-weighted high-resolution 3D spoiled gradient-echo sequence used for VBM and a multisection spin-echo T2-weighted sequence used for T2 relaxometry. Additionally, a single-shot multisection gradient echo-planar sequence was used for fMRI. Brain activation was recorded during spontaneous SLD and PLMs. SPM software was used for analysis of the functional data. RESULTS: The patients showed no regional brain volume change, but T2 relaxometry revealed decreased T2 relaxation time in the right globus pallidus internal and the STN, indicating increased iron content. The patients were observed to activate the following areas: in the left hemisphere, the primary motor and somatosensory cortex, the thalamus, the pars opercularis, and the ventral anterior cingulum; and in the right hemisphere, the striatum, the inferior and superior parietal lobules, and the dorsolateral prefrontal cortex. Bilateral activation was observed in the cerebellum, the midbrain, and the pons. CONCLUSIONS: eRLS is associated with increased iron content of the globus pallidus internal and STN, suggesting dysfunction of the basal ganglia. Activation of the striatofrontolimbic area may represent the neurofunctional substrate mediating the repetitive compulsive movements seen in RLS.

Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI.

BACKGROUND: Preterm children may have cognitive deficits and behavioural disorders suggestive of grey matter (GM) injury. The prevalence is higher in preterm children with diffuse periventricular leukomalacia (dPVL). OBJECTIVE: Evaluate changes in the volume of 116 GM areas in preterm children with dPVL. METHODS AND MATERIALS: Eleven preterm children with dPVL, gestational age 32.8 ± 2.6 weeks, examined at corrected age 22.0 ± 18.2 months and 33 matched preterm controls with normal brain MRI were studied. Volumes of 116 individual GM areas, and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1-weighted high-resolution images after segmentation. RESULTS: Relative to controls, children with dPVL had decreased GM volume of the hippocampus, amygdala, and frontal lobes and temporal middle gyrus (P < 0.05); increased GM volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of the parietal and occipital lobes (P < 0.05) and lower WM volume/higher CSF volume (P < 0.05). WM/CSF ratios also differed (P < 0.05). CONCLUSIONS: Preterm children with dPVL have increased regional GM volume in some areas probably related with a process of brain plasticity-regeneration and reduced GM volume in areas associated with cognition and memory.

Voxel-based diffusion tensor imaging detects pyramidal tract degeneration in primary lateral sclerosis.

OBJECTIVE: Primary lateral sclerosis (PLS) is a progressive degenerative disorder affecting upper motor neurons and requires a clinical diagnosis. Diffusion tensor imaging (DTI) is a quantitative method for assessing white matter fibre integrity. The purpose of the study was to evaluate the involvement of upper motor neurons by using DTI in PLS. METHODS: A patient with PLS was compared with eight age-matched controls. Differences in fractional anisotropy (FA) index were assessed using DTI on a voxel-by-voxel basis. RESULTS: Decreased FA was observed in the proximal part of the pyramidal tract bilaterally, which indicated degeneration of the pyramidal cells. CONCLUSION: Voxel-based DTI could be used as an objective marker for detecting upper motor neuron degeneration in PLS.

Age-related grey matter changes in preterm infants: an MRI study.

Grey matter (GM) maturation has not been previously studied in healthy preterm children. The purpose of this study was to evaluate the age dependency of GM development in 116 GM areas in preterm subjects. Sixty one preterm infants (corrected age: 13.7+/-9.92 months, gestational age: 33.4+/-1.9 weeks) with normal structural appearance on MRI were included in the study. Using a T1-weighted high resolution 3D spoiled gradient echo sequence, volumes of 116 GM areas were calculated after their segmentation using the Voxel Based Morphometry Toolboxes and the Individual Brain Atlas Statistical Parametric Mapping (IBASPM) software packages. Non linear regression analysis assessed age dependency of volume data for every GM area using the monoexponential function y=A-Bexp(-x/C). All supratentorial GM areas followed the monoexponential function model reasonably well. Cerebellar structures had a poor goodness of fit. Volume increase of the individual GM areas followed an inferior to superior and a posterior to anterior pattern. The putamen, thalamus, and caudate nucleus reached 99% of the final volume earlier than most cortical GM areas. The visual cortex and the postcentral and precentral cortices matured earlier than the parietal, frontal and temporal cortices. The fronto-occipital asymmetry or torque seen in adults was observed in the preterm infants; the left occipital areas reached maturation earlier than the right, while the right prefrontal and frontal areas matured earlier than the left. To conclude, GM development progresses in a region-specific manner coinciding with functional, phylogenetical and regional white matter (WM) maturation.

T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome.

OBJECTIVE: To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI. METHODS: The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55-82 years; mean 66.5 +/- 8.9 years; disease duration 6.5 +/- 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Tau2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data. RESULTS: T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex. CONCLUSION: Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex.

MRI and 1H MRS findings in Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by a defect in cholesterol biosynthesis, associated with mental retardation and multisystem structural abnormalities. This study investigated the prevalence of congenital CNS abnormalities by MRI in a large series of patients with SLOS and the correlation of the clinical and biochemical findings with the results of MRI and 1H MRS. Eighteen patients were studied; all underwent MRI of the brain, and 16 had 1H MRS of the cerebral white matter. The ratios choline:NAA, lipid:NAA, and lipid:choline metabolite were found to be correlated with the clinical degree of disease severity, serum total sterol ratios (cholesterol/cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol) and in two cases with the effect of cholesterol therapy. Abnormal CNS findings were noted in five patients, including callosal abnormalities (n = 4), Dandy-Walker variant (n = 1), and arachnoid cyst (n = 1). Holoprosencephaly was noted in one patient with a prevalence of 6%. Choline:NAA was elevated in seven patients. There was a statistically significant positive correlation between the lipid:choline ratio and the serum cholesterol precursor, 8-dehydrocholesterol. In two patients 1H MRS demonstrated abnormally elevated lipids prior to cholesterol therapy, which improved on therapy. The use of MRI and 1H MRS is an effective way to demonstrate brain structural abnormalities in patients with SLOS and may prove to be an effective method for the assessment of the effects of cholesterol replacement therapy in the brain.

Multiparametric MR assessment of pediatric brain tumors.

MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse ( P<0.001). The relationship between rCBV and ADC was also inverse ( P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated ( P=0.51). A positive relationship was found between lipids and ADC ( P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors ( P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors.

Magnetic resonance spectroscopy and magnetic resonance imaging findings in Krabbe's disease.

Two twins with late infantile globoid cell leukodystrophy of Krabbe's disease were studied with conventional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy. Brain MRI demonstrated brain atrophy with extensive bilateral symmetric abnormal T2 signal in the posterior periventricular white matter, parietal lobes, corona radiata, centrum semiovale, and splenium of the corpus callosum. Magnetic resonance imaging-guided proton magnetic resonance spectroscopy revealed prominent peaks from choline-containing compounds, total creatine, and inositols. The N-acetylaspartate peak was markedly reduced, and the choline-to-N-acetylaspartate ratio was abnormally high; in one of the twins, lactic acid was also detected. The constellation of magnetic resonance spectroscopy findings is indicative of extensive demyelination, gliosis, and loss of axons in the involved white matter; the latter two events occur in the later stages of globoid cell leukodystrophy. In conjunction with brain MRI, these magnetic resonance spectroscopy findings may alert clinicians to the possibility of leukodystrophy in children with progressive encephalopathy.

Proton magnetic spectroscopic imaging of the child's brain: the response of tumors to treatment.

Our aim was to determine and/or predict response to treatment of brain tumors in children using proton magnetic resonance spectro-scopic imaging (MRSI). We studied 24 patients aged 10 months to 24 years, using MRI and point-resolved spectroscopy (PRESS; TR 2000 TE 65 ms) with volume preselection and phase-encoding in two dimensions on a 1.5 T imager. Multiple logistic regression was used to establish independent predictors of active tumor growth. Biologically vital cell metabolites, such as N-acetyl aspartate and choline-containing compounds (Cho), were significantly different between tumor and control tissues (P < 0.001). The eight brain tumors which responded to radiation or chemotherapy, exhibited lower Cho (P = 0.05), higher total creatine (tCr) (P = 0.02) and lower lactate and lipid (L) (P = 0.04) than 16 tumors which were not treated (except by surgery) or did not respond to treatment. The only significant independent predictor of active tumor growth was tCr (P < 0.01). We suggest that tCr is useful in assessing response of brain tumors to treatment.