Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI.

Canavan disease is a childhood leukodystrophy caused by mutations in the gene for human aspartoacylase ( ASPA), which leads to an abnormal accumulation of the substrate molecule N-acetyl-aspartate (NAA) in the brain. This study was designed to model the natural history of Canavan disease using MRI and proton magnetic resonance spectroscopy ( (1)H-MRS). NAA and various indices of brain structure (morphology, quantitative T1, fractional anisotropy, apparent diffusion coefficient) were measured in white and gray matter regions during the progression of Canavan disease. A mixed-effects statistical model was used to fit all outcome measures. Longitudinal data from 28 Canavan patients were directly compared in each brain region with reference data obtained from normal, age-matched pediatric subjects. The resultant model can be used to non-invasively monitor the natural history of Canavan disease or related leukodystrophies in future studies involving drug, gene therapy, or stem cell treatments.

Acute diffusion abnormalities in the hippocampus of children with new-onset seizures: the development of mesial temporal sclerosis.

We studied the role of early diffusion-weighted imaging DWI in the investigation of children with new-onset prolonged seizures which eventually result in unilateral hippocampal sclerosis (HS). We carried out MRI on five children aged 17 months to 7 years including conventional and diffusion-weighted sequences. We calculated apparent diffusion coefficients (ADC) for the affected and the normal opposite hippocampus. Follow-up examinations were performed, including DWI and ADC measurements in four. We studied four children within 3 days of the onset of prolonged psychomotor seizures and showed increased signal on T2-weighted images, and DWI, indicating restricted diffusion, throughout the affected hippocampus. The ADC were reduced by a mean of 14.4% in the head and by 15% in the body of the hippocampus. In one child examined 15 days after the onset of seizures, the ADC were the same on both sides. All five patients showed hippocampal atrophy on follow-up 2-18 months later. In the four patients in whom ADC were obtained on follow-up, they were increased by 19% in the head and 17% in the body. DWI may represent a useful adjunct to conventional MRI for identifying acute injury to the hippocampus which results in sclerosis.

Diffusion-weighted imaging in acute bacterial meningitis in infancy.

Bacterial meningitis is frequently fatal or leads to severe neurological impairment. Complications such as vasculitis, resulting in infarcts, should be anticipated and dealt with promptly. Our aim was to demonstrate the complications of meningitis by diffusion weighted imaging (DWI) in patients who deteriorated despite therapy. We studied 13 infants between the ages of 1 day and 32 months who presented with symptoms ranging from fever and vomiting to seizures, encephalopathy and coma due to bacterial meningitis, performing MRI, including DWI, 2-5 days after presentation. Multiple infarcts were found on DWI in 12 of the 13, most commonly in the frontal lobes (in 10). Global involvement was seen in four children, three of whom died; the fourth had a very poor outcome. In one case abnormalities on DWI were due to subdural empyemas. We diagnosed vasculitis in three of five patients studied with MRA. We think DWI an important part of an MRI study in infants with meningitis. Small cortical or deep white-matter infarcts due to septic vasculitis can lead to tissue damage not easily recognized on routine imaging and DWI can be used to confirm that extra-axial collections represent empyemas.

Functional magnetic resonance imaging of the visual system.

Functional magnetic resonance imaging (fMRI), which is a technique useful for non-invasive mapping of brain function, is well suited for studying the visual system. This review highlights current clinical applications and research studies involving patients with visual deficits. Relevant reports regarding the investigation of the brain's role in visual processing and some newer fMRI techniques are also reviewed. Functional magnetic resonance imaging has been used for presurgical mapping of visual cortex in patients with brain lesions and for studying patients with amblyopia, optic neuritis, and residual vision in homonymous hemianopia. Retinotopic borders, motion processing, and visual attention have been the topics of several fMRI studies. These reports suggest that fMRI can be useful in clinical and research studies in patients with visual deficits.

Functional magnetic resonance imaging of eye dominance at 4 tesla.

We studied eye dominance in visual cortex and lateral geniculate nucleus (LGN) using functional magnetic resonance imaging (fMRI) at a very high magnetic field (4 tesla). Eight normal volunteers were studied with fMRI at 4 tesla during alternating monocular visual stimulation. The acquisition was repeated twice in 4 subjects to confirm reproducibility. In addition, magnetic resonance signal intensities during three conditions (right eye stimulation, left eye stimulation, and control condition) were compared to determine whether the observed area was truly or relatively monocular in 2 subjects. In both the individual and group analyses, the anterior striate cortex was consistently activated by the contralateral eye more than the ipsilateral eye. Additionally, we found evidence that there were areas in the bilateral LGN which were more active during the stimulation of the contralateral eye than during the stimulation of the ipsilateral eye. The activated areas were reproducible, and the mean ratio of the overlapping area was 0.71 for the repeated scans. The additional experiment revealed that the area in the anterior visual cortex could be divided into two parts, one truly monocular and the other relatively monocular. Our finding confirmed previous fMRI results at 1.5 tesla showing that eye dominance was observed in the contralateral anterior visual cortex. However, the eye dominance in the visual cortex was found not only in the most anterior area corresponding to the monocular temporal crescent but also in the more posterior area, presumably showing the greater sensitivity of the temporal visual field (nasal retina) as compared with the nasal visual field (temporal retina) in the peripheral visual field (peripheral retina). In addition, it is suggested that the nasotemporal asymmetry of the retina and the visual fields is represented in the LGN as well as in the visual cortex.

Effects of check size on visual cortex activation studied by functional magnetic resonance imaging.

We studied functional magnetic resonance imaging (fMRI) of visual cortex during checkerboard visual stimulation with three standard check sizes to examine whether activation in the visual cortex varied among these sizes. We acquired fMRI at 1.5 T in 8 normal subjects, each receiving the best refractive correction. Each subject underwent an experiment consisting of four conditions: black and white checkerboards with three check sizes (0.25-, 0.5-, and 1.0-degree) flickering at 8 Hz, and a black screen. SPM96 was used for a group data analysis with a random effects model after each of the subject's data was motion-corrected and spatially normalized to a standard brain. The activation in the visual cortex showed the greatest signal changes with the 0.5-degree check among the three check sizes. When standard check sizes are used to stimulate visual cortex in fMRI experiments, our results suggest that 0.5-degree checks flickering at 8 Hz produce the most vigorous activation in visual cortex.

Reproducibility of visual activation during checkerboard stimulation in functional magnetic resonance imaging at 4 Tesla.

PURPOSE: To investigate the reproducibility of visual activation by checkerboard stimulation, we used functional magnetic resonance imaging (fMRI) at 4 Tesla (T). METHODS: Four subjects were studied with fMRI at 4 T during checkerboard visual stimulation. The functional images were realigned and spatially normalized to the standard brain. For each subject, statistical parametric maps were made for each study, and the reproducibility was determined based on the number of supra-threshold voxels (Z > 3.5, 4.5, and 5.5). RESULTS: The mean ratio for the number of supra-threshold (Z > 4.5) voxels was 0.75, and the mean ratio for the overlapping voxels was 0.61. Restricting the region of interest within the posterior half of the brain improved reproducibility values at the low threshold (Z > 3.5), but did not improve the values at the higher thresholds. CONCLUSIONS: Despite the fact that more than half of the supra-threshold voxels were found to be active for the repeated scans, visual activation with checkerboard stimulation seems to be less reproducible than that by flash stimulation.

Visual activation in functional magnetic resonance imaging at very high field (4 Tesla).

OBJECTIVES: Functional magnetic resonance imaging (fMRI) at very high field strengths provides functional brain mapping with the enhanced signal to noise ratio and the larger blood oxygenation level-dependent (BOLD) effect. We report activated areas in the standard space detected by fMRI at 4 Tesla (T) during simple visual stimulation. MATERIALS AND METHODS: Twelve healthy young subjects were scanned using a 4 T scanner during binocular flashing visual stimulation. Functional images were realigned to the first scan and then spatially normalized. Individual and group data analyses were performed to identify areas of visual activation. RESULTS: Activation of the bilateral primary visual cortex (V1/V2) was observed along the entire calcarine fissure in all subjects. The activated area extended to the extrastriate cortex in all subjects. Activation of the bilateral lateral geniculate nucleus (LGN) was detected in all subjects. The group data showed activation of the bilateral primary visual cortex and the bilateral lateral geniculate nucleus. CONCLUSIONS: Robust activation of the vision-related areas was successfully obtained in all subjects using a 4 T magnetic resonance scanner. These results suggest that fMRI at very high field strengths may be effective in showing visual system physiology, and that it can be a promising method to assess visual function of human subjects.

Ocular dominance in anterior visual cortex in a child demonstrated by the use of fMRI.

Negative signal changes in the visual cortex have been observed during visual stimulation when performing functional magnetic resonance imaging (fMRI) in children. This report investigated whether the ocular dominance, which has been demonstrated in the contralateral anterior visual cortex in adults, could be observed in a child by the use of fMRI. A 5-year-old child was studied using fMRI at 1.5 T during alternating monocular visual stimulation under sedation with morphine and pentobarbital. The functional images were motion corrected, and statistical parametric maps were made by contrasting the left or right eye stimulation conditions vs the right or left eye stimulation conditions, respectively, at each voxel. Areas with negative signal changes were found on the left anterior visual cortex during monocular visual stimulation of the right eye and vice versa. There was no area with negative or positive signal change on the ipsilateral visual cortex to the stimulated eye and no area with positive signal change on the contralateral visual cortex. Contralateral ocular dominance of anterior visual cortex similar to that of adults was demonstrated in this child with a negative correlation with the visual stimulus. This finding suggests that peripheral visual fields are represented in the anterior visual cortex of 5-year-old children.

Magnetic resonance imaging of the upper airway in children with Down syndrome.

As compared with control subjects, children with Down syndrome have different size and shape relationships among tissues composing the upper airway, which may predispose them to obstructive sleep apnea (OSA). We hypothesized that Down syndrome children without OSA have similar subclinical differences. We used magnetic resonance imaging to study the upper airway in 11 Down syndrome children without OSA (age, 3.2 +/- 1.4 yr) and in 14 control subjects (age, 3.3 +/- 1.1 yr). Sequential T1- and T2-weighted spin-echo axial and sagittal images were obtained. We found a smaller airway volume in subjects with Down syndrome (1.4 +/- 0.4 versus 2.3 +/- 0.8 cm(3) in controls, p < 0.005). Subjects with Down syndrome had a smaller mid- and lower face skeleton. They had a shorter mental spine-clivus distance (5.7 +/- 0.6 versus 6.2 +/- 0.4 cm, p < 0.05), hard palate length (3.2 +/- 0.4 versus 3.7 +/- 0.2 cm, p < 0.005), and mandible volume (11.5 +/- 3.7 versus 16.9 +/- 2.9 cm3, p < 0.0005). Adenoid and tonsil volume was significantly smaller in the subjects with Down syndrome. However, the tongue, soft-palate, pterygoid, and parapharyngeal fat pads were similar to those of control subjects. This study shows that Down syndrome children without OSA do not have increased adenoid or tonsillar volume; reduced upper airway size is caused by soft tissue crowding within a smaller mid- and lower face skeleton.

Quantitative apparent diffusion coefficient measurements in term neonates for early detection of hypoxic-ischemic brain injury: initial experience.

PURPOSE: To determine the utility of using quantitative apparent diffusion coefficient (ADC) values as an objective means of early detection of brain injury caused by hypoxic-ischemic encephalopathy (HIE) in term neonates. MATERIALS AND METHODS: Conventional images, diffusion-weighted images, ADC maps, and clinical charts from 13 term neonates clinically suspected of having HIE were retrospectively reviewed. Four term neonates without HIE served as control subjects. ADC values were calculated in predefined regions in patients and compared with those in control subjects. A Student t test was performed for each region to compare patients and control subjects. RESULTS: Abnormalities were more easily detected on diffusion-weighted images and ADC maps, compared with conventional images. ADC values in patients with HIE were significantly different from those of control subjects in the posterior limb of the internal capsule, corona radiata, posterior frontal white matter, and parietal white matter bilaterally. CONCLUSION: Evaluation of ADC maps can improve conspicuity of hypoxic-ischemic injury in the acute and/or subacute setting (within 12 days of insult), and calculation of ADC values can provide an objective measure of hypoxic-ischemic injury.

Reproducibility of visual activation in functional magnetic resonance imaging at very high field strength (4 Tesla).

PURPOSE: The reproducibility of functional magnetic resonance imaging (fMRI) has been studied on 1.5 Tesla (T) (high field strength) scanners. We report the reproducibility of visual activation in fMRI at 4 T (very high field strength). METHODS: Five healthy subjects were scanned twice in the same session with a 4 T scanner during binocular flashing visual stimulation. The activated areas during the first and second acquisition were compared. RESULTS: Activation of the visual cortex was observed in all subjects and activation of lateral geniculate nucleus was also detected in four subjects. The ratio of overlapping activated voxels in the first and second acquisition was 0.81 +/- 0.05. CONCLUSIONS: Reproducibility of visual activation using fMRI at 4 T was found to be acceptable, and the results from 4T scanners show a reliability similar to those at 1.5 T.

Diffusion-weighted imaging in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients.

The purpose of our study was to determine the usefulness of echo-planar diffusion-weighted imaging (EPDI) in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients. Eighteen patients ranging in age from 3 weeks to 12 years were evaluated for evidence of ischemic/infarction changes on conventional MR and EPDI. Included in the study group were five patients with sickle cell disease, four with congenital heart disease, four with hypotensive episodes with various etiologies, three with sepsis, and two with encephalitis or meningitis. Patients were examined 2 h to 6 days after the initial insult, with follow-up studies in four patients at 1 to 62 days after the initial examination. After conventional MR imaging (T1, FSE T2, and FLAIR), diffusion-weighted MR imaging was performed using high-speed, single-shot EP techniques with TR 6000, TE 144, matrix 96 x 128, FOV 23.3 x 31 and five b values of 0, 160, 360, 640, and 1,000 s/mm2. EPDI demonstrated abnormally increased signal in watershed ischemic/infarction zones in all initial cases. Apparent diffusion coefficients (ADC) were obtained in 59 lesions. When compared with radiographically normal (on EPDI) contralateral brain parenchyma, 45 demonstrated a relatively decreased ADC, while eight had normal ( +/- 10%) and six had increased ADC. In four cases, signal abnormalities on EPDI were not seen or exceeded that seen with conventional MR imaging. In the remaining cases, signal abnormalities were obvious on EPDI and more subtle on conventional MR imaging. Follow-up studies demonstrated resolution of abnormal EPDI signal with persistent abnormalities on conventional imaging in some cases, while others revealed an increase in size or number of EPDI signal abnormalities, suggesting ongoing acute ischemic/infarctive changes. EPDI is a rapid, sensitive technique for detecting watershed ischemic/infarction changes in pediatric patients with hypoperfusion episodes, at times before such changes are apparent on conventional MR images and/or are clinically apparent.

Diffusion-weighted imaging and fluid attenuated inversion recovery imaging in the evaluation of primitive neuroectodermal tumors.

The aim of our study was to determine whether fluid-attenuated inversion recovery (FLAIR) imaging and diffusion-weighted imaging (DWI) would be helpful in characterizing primitive neuroectodermal tumors (PNET) from other pediatric brain tumors. We expected that the compact cellular nature and the relatively small extracellular space of this tumor would affect the signal intensity on both pulse sequences relative to the more sparsely cellular glial tumors that have larger extracellular spaces. Eighteen pediatric patients with PNET were examined on a 1.5 T MRI with routine imaging plus FLAIR and compared with 28 patients with nonPNET. DWI was also performed in 7 PNET and 18 non-PNET. Seventyeight percent of PNET were isointense to gray matter on FLAIR while 82% of non-PNET were hyperintense and only one was isointense (3%). Diffusion was abnormally restricted in all 7 PNET examined (100%) but was restricted in non-PNET in only 1 out of 18 (6%) patients who had DWI. The differences in the histologic architecture between PNET and non-PNET are reflected in both FLAIR imaging and in DWI.

Diffusion imaging in pediatric central nervous system infections.

Our purpose was to investigate the role of diffusion imaging (DI) in central nervous system (CNS) infections in pediatric patients. It was anticipated that DI would be more sensitive than conventional MRI in the detection of the infarctive complications of infection, and possibly, in the detection of the infectious process as well. Seventeen pediatric patients, eight having meningitis,, five with herpes encephalitis, three with brain abscess or cerebritis and one with sepsis, were evaluated at 1.5-T with DI. All herpes patients had positive DI at the site of herpetic involvement, and two had the addition of watershed infarctions. DI demonstrated more lesions in three of the four cases of herpetic encephalitis. Half the meningitis cases had watershed infarction where DI was better and half had vasculitic infarctions in which DI was equal to or better than conventional MRI. Diffusion imaging was more sensitive than conventional MRI alone in detection of changes due to infections and ischemic lesions, but did not differentiate between them by DI or apparent diffusion coefficient (ADC), although anatomic distribution of lesions proved useful.

Functional magnetic resonance imaging of lateral geniculate nucleus at 1.5 tesla.

Although activation of the lateral geniculate nucleus has been detected by functional magnetic resonance imaging with magnetic field strengths higher than 2.0 Tesla, there have been no reports of functional magnetic resonance imaging of the lateral geniculate nucleus with the more widely available 1.5 Tesla scanner. The authors used functional magnetic resonance imaging techniques at 1.5 Tesla to detect lateral geniculate nucleus activation in five of seven healthy subjects. This study shows that visual activation of the lateral geniculate nucleus can be obtained with functional magnetic resonance imaging using conventional 1.5 Tesla scanners.

Contralateral monocular dominance in anterior visual cortex confirmed by functional magnetic resonance imaging.

PURPOSE: Although it is known that the damage to anterior striate cortex results in temporal peripheral visual field loss of the contralateral eye in patients with cerebral visual disturbance, the monocularity of anterior striate cortex has not been demonstrated in normal living humans. The aim of this study was to investigate whether this could be shown noninvasively using functional magnetic resonance imaging of the human visual cortex. METHODS: Eleven normal volunteers were studied with functional magnetic resonance imaging during alternating monocular visual stimulation using a 1.5 Tesla scanner. The data were motion corrected and spatially normalized to the standard brain. The monocular activation of the visual cortex was compared with the activation by the other eye. RESULTS: In the individual data analysis, contralateral eye dominance was always observed in the anterior striate cortex. In the group analysis from 11 subjects, the area with contralateral eye dominance was found in the most anterior part of primary visual cortex where the calcarine fissure merged with the parieto-occipital sulcus. CONCLUSIONS: This study shows that the contralateral eye dominance of anterior striate cortex can be detected noninvasively with functional magnetic resonance imaging during monocular visual stimulation. The finding confirms that the anterior striate cortex, where the monocular temporal crescent is represented, is primarily monocular, but the fact that greatest density of retinal ganglion cells and photoreceptors is in the nasal hemiretina must also be taken into account when interpreting these results.

Diastolic biomechanics in normal infants utilizing MRI tissue tagging.

BACKGROUND: Most of what is known about diastolic function in normal infants is derived from flow and pressure measurements. Little is known about regional diastolic strain and wall motion. METHODS AND RESULTS: Magnetic resonance tissue tagging was performed in 11 normal infants to determine regional diastolic strain and wall motion. Tracking diastolic motion of the intersection points and finite strain analysis yielded regional rotation, radial displacement, and E(1) and E(2) strains at 3 short-axis levels (significance was defined as P<0.05). E(2) "circumferential lengthening" strains were significantly greater at the lateral wall, regardless of short-axis level, whereas E(1) "radial thinning" strains were similar in all wall regions at all short-axis levels. In general, no differences were noted in strain dispersion within a wall region or in endocardial/epicardial strain at all short-axis levels. At all short-axis levels, septal radial motion was significantly less than in other wall regions. No significant differences in radial wall motion between short-axis levels were noted. Rotation was significantly greater at the apical short-axis level in all wall regions than in other short-axis levels, and it was clockwise. At the atrioventricular valve, septal and anterior walls rotated slightly clockwise, whereas the lateral and inferior walls rotated counterclockwise. CONCLUSIONS: Diastolic biomechanics in infants are not homogeneous. The lateral walls are affected most by strain, and the septal walls undergo the least radial wall motion. Apical walls undergo the most rotation. These normal data may help in the understanding of diastolic dysfunction in infants with congenital heart disease.

Reproducibility of visual activation in functional MR imaging and effects of postprocessing.

BACKGROUND AND PURPOSE: Functional MR imaging studies of the brain should be interpreted in the context of their reproducibility. We assessed the reproducibility of visual activation measured by functional MR imaging and analyzed the effect of image transformation to standard space. METHODS: Seven healthy volunteers were studied twice with echo-planner functional MR imaging at 1.5 T during visual stimulation. The studies were separated by an interval of 2 to 7 days. Functional images were analyzed after spatial normalization to the space described by Talairach and Tournoux and/or after coregistration of the images of the second study with the images of the first study. The number of active voxels for each study was determined at three thresholds. In addition, the change in the center of the mass of activation, the mean change in signal intensity, and the mean t value within the activated area were measured. These reproducibility indexes were calculated for the spatially normalized and nonnormalized data for each subject. RESULTS: Variations in visual activation were observed between the two studies in the same individual as well as across subjects. There was no evidence of an effect from image transformation on reproducibility on any of the measures. CONCLUSION: Our findings show that the reproducibility of activation in functional MR imaging may be much more variable across subjects than suggested in previous studies. The use of different types of image transformation (coregistration, spatial normalization) does not significantly affect the reproducibility of visual activation.

Functional MRI in children with congenital structural abnormalities of the occipital cortex.

Functional MRI techniques were used to map the position of visual cortex in an awake and a sedated child with congenital anomalies of the posterior hemispheres. In one subject with cortical heterotopia, an activated cortex was found distinct from the structurally abnormal area detected on conventional MRI. In a sedated patient with holoprosencephaly, activated cortical areas in the posterior-medial portions of the hemispheres were identified. This study demonstrates the utility of functional MRI in such patients, both awake and sedated.