Published online November 13, 2006
PEDIATRICS Vol. 118 No. 6 December 2006, pp. e1812-e1821 (doi:10.1542/peds.2006-1499)
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ARTICLE

Magnetic Resonance Imaging of Neonatal Encephalopathy at 4.7 Tesla: Initial Experiences

Enrico De Vita, PhDa,b, Alan Bainbridge, PhDa, Jeanie L. Y. Cheong, FRACPc, Cornelia Hagmann, MDc, Rosarie Lombard, ANNP, MScd, Wui K. Chong, MD, FRCRe, John S. Wyatt, FRCPCHc, Ernest B. Cady, FInstP, BSca,b, Roger J. Ordidge, PhDb and Nicola J. Robertson, FRCPCH, PhDc

a Department of Medical Physics and Bio-Engineering
d Neonatal Intensive Care Unit, Elizabeth Garrett Anderson Hospital, University College London Hospitals National Health Service Foundation Trust, London, United Kingdom
b Department of Medical Physics and Bio-Engineering
c Centre for Perinatal Brain Research, Institute for Women's Health
e Radiology and Physics Unit, Institute of Child Health, University College London, London, United Kingdom


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. The goals were to develop safe 4.7-T MRI examination protocols for newborn infants and to explore the advantages of this field strength in neonatal encephalopathy.

METHODS. Nine ventilated newborn infants with moderate or severe encephalopathy were studied at 4.7 T, with ethical approval and informed parental consent. The custom-made, 4.7-T-compatible, neonatal patient management system included acoustic noise protection and physiologic monitoring. An adult head coil was used. Acquisition parameters for T2-weighted fast spin echo MRI and a variety of T1-weighted methods were adapted for MRI of neonatal brain at 4.7 T. The pulse sequences used had a radiofrequency specific absorption rate of <2 W/kg.

RESULTS. Physiologic measures were normal throughout each scan. T2-weighted fast spin echo imaging provided better anatomic resolution and gray/white matter contrast than typically obtained at 1.5 T; T1-weighted images were less impressive.

CONCLUSIONS. With appropriate safety precautions, MRI of newborn infants undergoing intensive care is as feasible at 4.7 T as it is at 1.5 T; our initial studies produced T2-weighted fast spin echo images with more detail than commonly obtained at 1.5 T. Although T1-weighted images were not adequately informative, additional pulse sequence optimization may be advantageous. A smaller neonatal head coil should also permit greater flexibility in acquisition parameters and even more anatomic resolution and tissue contrast. In neonatal encephalopathy, interpretation of the T2-weighted pathologic detail in combination with comprehensive neurodevelopmental follow-up should improve prognostic accuracy and enable more patient-specific therapeutic interventions. In addition, more precise relationships between structural changes and functional impairment may be defined.

Key Words: magnetic resonance imaging • brain • neonatal encephalopathy • high-field MRI • developmental outcomes

Abbreviations: FOV—field of view • FSE—fast spin echo • GWMC—gray/white matter contrast • IR—inversion recovery • MDEFT—modified driven-equilibrium Fourier transform • NE—neonatal encephalopathy • SAR—specific absorption rate • SNR—signal/noise ratio • TE—echo time • TI—inversion time • TR—repetition time

MRI at 1.5 T characterizes brain development and perinatal brain injury with detail surpassing that provided by cranial ultrasonography and computed tomography.1,2 MRI has a particularly important diagnostic and prognostic role for infants with neonatal encephalopathy (NE); conventional T1-weighted and T2-weighted MRI performed at 5 to 14 days of age provides the most specific means of predicting the pattern of neuromotor outcomes and is a recommended standard of clinical care.3 NE has a wide range of prenatal, intrapartum, and postpartum risk factors, and MRI is particularly useful in diagnosing cerebral developmental abnormalities, focal lesions, stroke, and metabolic disorders that may present with NE.

In the past 3 decades, there has been a dramatic increase in clinical MRI field strengths, from 15 mT to 9.4 T.4 There are many anticipated benefits of MRI at higher field strengths, such as increased signal/noise ratio (SNR) and greater sensitivity to susceptibility-related contrast mechanisms. Properly harnessed, these benefits can result in increased spatial resolution and tissue contrast or shorter examination times. However, technical and safety issue must also be considered; greater installation difficulties, increased radio-frequency power deposition, more acoustic noise, and risk of peripheral nerve stimulation from the pulsed magnetic-field gradients are associated to higher MRI field strengths. Because of increased susceptibility-induced geometric distortion and signal dropout, increased radiofrequency field inhomogeneity, and altered relaxation times, the anticipated tissue contrast improvement may not be achieved. Given the high cost and complexity of high-field MRI systems, it is important to assess their benefits and limitations for clinical practice.

MRI scanners operating at 7 T and 8 T have been used to study adult subjects for several years.5,6 However, MRI of term and preterm infants at ≥3 T is relatively recent7–11 and raises particular safety concerns, because these subjects are unable to report unpleasant sensations and may be more sensitive to magnetic fields, tissue heating, gradient switching, and acoustic noise.12 Conservative safety limits and continuous physiologic monitoring are essential.

Our objectives were to develop safe effective protocols to study newborn infants at 4.7 T and to assess whether conventional MRI at this field strength is advantageous for infants with moderate or severe NE. Our report describes safety precautions and initial experiences of pulse sequence optimization, and we present 4.7-T neonatal brain images. Proton magnetic resonance spectroscopy at 4.7 T was also performed and was reported elsewhere.13


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Subjects and Patient Handling
Nine subjects were recruited consecutively between May and December 2004, including 5 infants with either moderate or severe encephalopathy at birth and 4 infants with normal neurologic status at birth and subsequent development of abnormal neurologic signs or seizures during the neonatal period. Infants were included if there were both abnormal neurologic examination results14 and abnormal background activity or seizures on the amplitude-integrated electroencephalogram. Ethical approval was granted by our hospital ethics committee (reference no. 03/0292), and informed parental consent was obtained.

Infants were studied in a perspex pod lined with sound-absorber (Sonex; Illbruck, Minneapolis, MN), ventilated with a MRI-compatible ventilator (BabyPac B100; Pneupac, Watford, United Kingdom), and monitored with electrocardiography, pulse oximetry (8600FO; Nonin Medical, Plymouth, MN), and skin temperature measurements, in the presence of 2 neonatologists experienced in MRI. Maintenance fluids were adjusted by using remote infusion pumps.

Two infants (subjects 3 and 4 in Table 1) had undergone whole-body cooling to a rectal temperature of 33.5°C for 72 hours, as part of a clinical therapeutic trial (Whole-Body Hypothermia for the Treatment of Perinatal Asphyxial Encephalopathy; TOBY trial, www.npeu.ox.ac.uk/toby). At the time of MRI, these infants were normothermic.


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  		TABLE 1 Clinical Details of the Infants Studied

 
Clinical Measurements and Neurodevelopmental Outcomes
Clinical measurements included cord pH, base excess, Apgar scores, and amplitude-integrated electroencephalography; details of these are shown in Table 1. At 10 to 13 months of age, all 7 surviving subjects underwent a standard neurologic assessment15 and a Griffiths developmental assessment16 performed by an experienced neonatologist. Infants were classified as having normal outcome (normal neurologic assessment results and a Griffiths quotient of ≥85), mild/moderate outcome (neuromotor signs but no functional difficulties or a Griffiths quotient between 75 and 84 in ≥1 subscale), or severe outcome (functional motor or sensory deficits or a Griffiths quotient of <75 in ≥1 subscale) (Table 1).

MRI Safety
Before the study, electrocardiographic and skin temperature measurement equipment was tested for MRI-induced heating at different positions within the MRI coil used in this study. Pulsed magnetic field gradient acoustic noise was reduced by using trimmed ear plugs (attenuation: >24 dB; Earsoft; Aearo, Indianapolis, IN) and Minimuffs (attenuation: 7 dB; Natus, San Carlos, CA), in addition to the sound-absorbing pod lining, to maintain the estimated peak sound pressure level within the patient’s ear at <90 dB, as recommended by the American Academy of Pediatrics.12 The radiofrequency power specific absorption rate (SAR) was monitored and MRI sequences were adjusted to ensure that the rate was below the Medical Devices Agency (London, United Kingdom) recommendation of 2 W/kg for fetuses.17 As a consequence, fewer slices than desired were imaged in some instances.

MRI Methods
A Surrey Medical Imaging Systems MR5000 4.7-T system (supported by Philips, Noord, Netherlands) was used with the 28-cm diameter, birdcage, adult head coil supplied by the manufacturer. Coil tuning and matching were optimized by using a loading ring (inner diameter: 152 mm; outer diameter: 193 mm), filled with doped saline solution (300 mmol/L NaCl, 18 mmol/L MnCl2), positioned around the head.

MRI sequences were selected on the basis of previous imaging experience of adult brain at 4.7 T and typical neonatal protocols at lower field strengths. MRI acquisition parameters were first estimated from the known field dependences of T1 and T2 in adult brain, compared with neonatal values at 1.5 T. After the first acquisitions, the parameters were adjusted according to measured estimates of relaxation times, to improve image quality (eg, for the first patient, fast spin echo [FSE] imaging was performed with 3 different effective echo time [TE] values).

T1-weighted MRI used a conventional 8- or 10-slice single spin echo sequence with acquisition bandwidth of 25 kHz, TE of 13 milliseconds, repetition time (TR) of 800 milliseconds, 2 averages, slice thickness of 5 mm, and interslice gap of 1 mm. For the first 4 subjects, we used a field of view (FOV) of 160 mm x 160 mm, data matrix of 256 x 128, and nominal in-plane resolution of 0.63 mm x 1.25 mm, which yielded a total acquisition time of 204 seconds; subsequently, the FOV was 230 mm x 172.5 mm and data matrix was 512 x 192, which resulted in an improved in-plane resolution of 0.45 mm x 0.9 mm but increased the acquisition time to 307 seconds.

T2-weighted MRI used a 7- or 8-slice 8-echo FSE sequence, which was optimized previously at 4.7 T for adult brain,18,19 with FOV of 240 mm x 360 mm, data matrix of 512 x 768, in-plane pixel dimensions of 0.47 mm x 0.47 mm, acquisition bandwidth of 50 kHz, effective TE of 88 milliseconds (echo spacing: 22 milliseconds), TR of 3.5 seconds, slice thickness of 2.0 mm, and interslice gap of 0.7 mm; the acquisition time was 340 seconds. The following sequences were also used: (1) for 3 patients, an inversion recovery (IR)-FSE sequence with TR of 5000 milliseconds, TE of 22 milliseconds, and inversion time (TI) of 1400 milliseconds, with 8 slices covering the basal ganglia and with FOV, data matrix, slice thickness/gap, and spatial resolution as for T2-weighted FSE imaging; (2) for 2 patients, an adapted, 3-dimensional, modified driven-equilibrium Fourier transform (MDEFT) sequence20 with TR of 13 milliseconds, TE of 4 milliseconds, TI of 367 milliseconds, delay between saturation and inversion pulses of 206 milliseconds, nominal flip angle of 18.8°, acquisition bandwidth of 25 kHz, data matrix of 256 x 224 x 176, isotropic 1-mm spatial resolution, and acquisition time of 12 minutes; (3) for 5 patients (successful for only 3) for T2 relaxometry, a spin echo sequence similar to that for T1-weighted imaging, with FOV of 160 mm x 160 mm and TR of 825 milliseconds but with only 5 axial slices, a single signal average, and TE of 14, 50, 100, and 140 milliseconds. From the latter, T2 maps were calculated (pixel by pixel) by using Matlab (MathWorks, Natick, MA); the signal amplitudes (S) for the 4 TE values were fitted to the monoexponential equation S(TE) = S(0)exp(–TE/T2). T2 values were measured over regions of interest in white matter and cortical and deep gray matter (Fig 1E). Because quantitative T2 relaxometry measurements were obtained for only 3 infants, it was inappropriate to compare these results with outcomes. Therefore, we present only a representative T2 map for a single subject.


Figure 1
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  		FIGURE 1 Images for infant 2, who was studied because of suspected perinatal hypoxic-ischemic cerebral injury but had a normal outcome. A, High-resolution, axial, T2-weighted, 4.7-T FSE MRI (voxels of 0.47 mm x 0.47 mm x 2 mm) at the level of the basal ganglia. GWMC is very good. The periatrial and deep white matter veins are particularly apparent. The myelinated and unmyelinated parts of the posterior limbs of the internal capsule are clearly delineated. B, T1-weighted spin echo MRI, which provided poor contrast, compared with the excellent GWMC obtained with T2-weighted FSE MRI. However, in this image (voxels of 0.45 mm x 0.90 mm x 5 mm; positioned slightly superior to A), a cephalhematoma over the right posterior cranium (bottom left) can be observed clearly. The slightly increased overall signal intensity in the middle of the image, relative to the periphery, is a radiofrequency field inhomogeneity effect. C, High-resolution, axial, IR-FSE MRI (voxels of 0.47 mm x 0.47 mm x 2 mm), at the same level as B, showing good GWMC and cerebrospinal fluid signal suppression. Despite these attributes, the relatively low SNR does not facilitate delineation of different nuclei within the lentiform nucleus or the thalamus. However, both anterior and posterior limbs of the internal capsule are visible. D, 3-dimensional MDEFT image (voxels of 1 mm x 1 mm x 1 mm) with a slice position similar to that of B and C; the voxel volume for this protocol was one half that of the spin echo T1-weighted image (B) and approximately twice that of the IR-FSE image (C). GWMC is good, and both anterior and posterior limbs of the internal capsule are identifiable. E, Quantitative T2 map (voxels of 0.63 mm x 1.25 mm x 5 mm), at a similar position as B to D. There is good GWMC. The regions of interest used for T2 estimation are shown.

 
Image Interpretation and Quality Assessment
MRI scans were interpreted qualitatively by a pediatric neuroradiologist (W.K.C.) experienced in neonatal neurologic MRI at ≤1.5 T. Gray/white matter contrast (GWMC) was assessed on the basis of the ease of distinguishing the cortical ribbon from adjacent white matter.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Subjects
The clinical details and neurodevelopmental outcomes are detailed in Table 1.

Physiologic Monitoring Safety
No radiofrequency heating or other adverse effects were detected during MRI.

Patient Handling
Peak inspiratory and end-inspiratory ventilator pressures decreased ~10% in the magnet bore, and the ventilator was adjusted to ensure appropriate constant pressure. Physiologic indices were stable during study, and there were no MRI-related adverse events. The total examination time was 2 to 2.5 hours (including 1–1.5 hours for magnetic resonance spectroscopy).

MRI
General Findings
Representative 4.7-T MRI brain scans for 4 of the 9 infants are displayed in Figs 1 to 4. T2-weighted FSE MRI gave remarkable GWMC and excellent structural detail; the small voxel dimensions and brief echo train enabled good delineation of small structures, with minimal blurring and partial-volume effects. All representative images used 2-mm slice thickness. White matter appeared more heterogeneous than generally seen at 1.5 T. T1-weighted GWMC was not as good. Some images showed respiration artifacts.


Figure 4
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  		FIGURE 4 High-resolution, T2-weighted, FSE MRI (voxels of 0.47 mm x 0.47 mm x 2 mm) for infant 7, who had acute bilirubin encephalopathy and a severe outcome. Bilateral and symmetrical signal abnormalities of the globi pallidi (gp) are demonstrated. The adjacent parts of the caudate (c), putamina (p), and capsular white matter also appeared involved, but to a lesser degree.

 
Perinatal Hypoxic-Ischemic Injury
Images for infant 2 (normal outcome) revealed a cephalhematoma over the right posterior cranium (Fig 1). In the T2-weighted image (Fig 1A), vascular features and periventricular spaces were particularly well defined, compared with typical 1.5-T images. There was some evidence of capsular edema (slightly worse on the left), slight thalamic and basal ganglion swelling, and prominence of the deep white matter and periatrial veins. Spin echo T1-weighted MRI (Fig 1B) provided worse GWMC; with IR-FSE MRI (Fig 1C), GWMC was good, although white matter appeared relatively featureless and the thalami and basal ganglia were poorly delineated, because of lower SNR resulting from the 1400-millisecond TI (which maximizes GWMC while minimizing cerebrospinal fluid signal). Figure 1D shows a 3-dimensional MDEFT image. With the lower SNR associated with 1-mm isotropic resolution, no prominent white matter features were seen; however, GWMC was good, and the posterior limb of the internal capsule and other deep gray matter structures were well delineated. A quantitative T2 map and the regions of interest from which T2 values were measured are shown in Fig 1E. The cortical gray matter T2 was 82 ± 5 milliseconds (mean ± SD), white matter (frontal and occipital) T2 was 128 ± 4 milliseconds, basal ganglion T2 was 90 ± 2 milliseconds, and thalamic T2 was 72 ± 1 milliseconds.

T2-weighted FSE MRI scans for infant 4 (severe outcome) are shown in Fig 2. The anatomic detail was remarkable; visible structures included the septal nuclei, the claustra separating external and extreme capsules, the internal and external medullary laminae of the globi pallidi, and conspicuous hippocampal internal architecture (Fig 2, A and B). Focal abnormalities, consistent with severe, acute, term, hypoxic-ischemic injury, could be seen in the posterior putamina, ventrolateral thalami, and intervening internal capsule. T1-weighted MRI showed abnormal increased signal in the lentiform nuclei and thalami (Fig 2C); there was little GWMC, however.


Figure 2
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  		FIGURE 2 Images for infant 4, who had perinatal hypoxic-ischemic cerebral injury and a severe outcome. A and B, High-resolution T2-weighted FSE MRIs (voxels of 0.47 mm x 0.47 mm x 2 mm) from neighboring slices at the level of the basal ganglia. As in Fig 1A, there is excellent GWMC and demonstration of fine anatomic detail. In A, arrows indicate the anterior cerebral artery branch (a), the septal nuclei (b) and fornix (c), the claustrum separating the extreme and external capsules (d), the medullary lamina separating the external and internal pallidus (e), a parenchymal vessel in the thalamic region (f), and the hippocampus, with demonstrable internal architecture (g). In B, arrows indicate a vein bordering the left anterior horn (a), the left medullary lamina (b), an apparently abnormal hypointense posterior part of the left internal globus pallidus (c), lateral (d) and medial (e) geniculate bodies, the superior colliculus (f), and symmetrical edema of the periventricular hypothalamic tissues near the walls of the third ventricle (g). C, T1-weighted spin echo MRI at the level of the basal ganglia (voxels of 0.63 mm x 1.25 mm x 5 mm). Despite poor GWMC, abnormally increased lentiform nucleus (a and b) and thalamic (c) signal intensities were noted. We speculate that such T1 hyperintensity is caused by the presence of methemoglobin as a consequence of hemorrhagic transformation after ischemic injury. Radiofrequency field inhomogeneity results in slightly decreased overall signal intensity in the middle of the image, relative to the periphery.

 
Middle Cerebral Artery Infarction
T2-weighted images for infant 6 (mild/moderate outcome) demonstrated extensive left-hemispheric involvement, left-sided cortical swelling, and reduced left-sided parietal GWMC (Fig 3). Involvement of the left caudate nucleus and anterior putamen was also noted. The MRI abnormalities were typical of extensive, acute, left middle cerebral artery territory infarction. T1-weighted MRI (not shown) provided no additional useful information. MRI angiography was not performed, but the proximal segments of both middle cerebral arteries appeared normal and symmetrical, whereas the peripheral branches on the left appeared attenuated.


Figure 3
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  		FIGURE 3 High-resolution, T2-weighted, FSE MRI (voxels of 0.47 mm x 0.47 mm x 2 mm) for infant 6, who had a mild/moderate outcome, showing MRI abnormalities typical of extensive, acute, left middle cerebral artery infarction. The image shows extensive, left-hemispheric, cortical swelling, greatly reduced parietal GWMC, and peri-Sylvian cortex abnormality. Involvement of the left caudate nucleus and anterior putamen was also evident. T1-weighted MRI (not shown) was not informative in this case.

 
Acute Bilirubin Encephalopathy
Bilateral and symmetrical signal abnormalities of the globi pallidi were revealed on T2-weighted images for infant 7 (severe outcome resulting from kernicterus) (Fig 4). The adjacent parts of the caudate, putamina, and capsular white matter also appeared involved, but to a lesser degree.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Safety
Our initial experience demonstrated that, with appropriate precautions, newborn infants undergoing intensive care could be studied safely at 4.7 T.

T2-Weighted Imaging
Appropriate imaging sequence selection and acquisition parameter optimization accounting for the different brain-water relaxation times at 4.7 T produced T2-weighted images with high spatial resolution (pixels of 0.47 mm x 0.47 mm x 2.0 mm) and excellent GWMC within 6 minutes (Figs 1A, 2A, 2B, 3, and 4). Image clarity resulted not only from the small nominal in-slice pixel dimensions but also from the small slice thickness and consequent reduced partial-volume effect.

T1-Weighted Imaging
Conventional T1-weighted spin echo imaging did not provide good GWMC at 4.7 T. This was probably attributable to increased brain-water T1, compared with, for example, 1.5 T,21,22 which typically is addressed by using 3-dimensional fast low-angle shot imaging,23 its magnetization-prepared counterpart,24,25 or MDEFT sequences.20,26,27 However, pulse-sequence optimization for neonatal brain is further complicated by the fact that most of the newborn’s white matter is unmyelinated and characterized by an increased water content close to the water content of grey matter.8,28 This has ramifications for the selection of optimal pulse sequences and acquisition parameters at various field strengths. Indeed, a recent relaxation time study suggested that T2-weighted imaging might provide better neonatal brain GWMC than T1-weighted imaging, even at 3 T.8 Furthermore, the differences in signal intensity between the brain center and periphery evident in Figs 1B and 2C are attributable to radiofrequency field inhomogeneity. The latter has both signal-excitation effects (flip-angle deviation from nominal values of 10%–15% in this study; signal amplitude is proportional to the cubed sine of the flip angle in the spin echo sequence used) and detection effects (spatial variation in MRI coil sensitivity). These could complicate radiologic interpretation of the T1-weighted images, potentially leading to incorrect diagnoses. Although spatial detection effects could be measured and corrected empirically, flip-angle deviations could be reduced only by using, for example, adiabatic radiofrequency pulses or fundamentally different sequences. Because our FSE sequence combined spin echoes and stimulated echoes, radiofrequency field inhomogeneity did not produce significant effects in our T2-weighted images.18,19

Fluid-attenuated IR imaging has also been used to image neonatal brain29,30 and, because of FSE resilience to radiofrequency field inhomogeneities, we started to evaluate IR-FSE techniques for T1-dependent imaging at 4.7 T. Initial, high-resolution images showed promising GWMC and good cerebrospinal fluid suppression (Fig 1C) although, because of the chosen TI, the overall SNR was lower and the acquisition time longer than for T2-weighted FSE imaging.

We also evaluated 3-dimensional MDEFT imaging, a modified version (combining adiabatic and nonadiabatic preparation pulses) of which proved robust against radiofrequency field inhomogeneities and delivered good tissue contrast in 4.7-T adult studies.20 The adaptation of 3-dimensional MDEFT sequence parameters for neonatal brain25 yielded GWMC (Fig 1D) sufficient for diagnostic evaluation. The possibility of reprocessing the 3-dimensional data to produce images with any desired orientation presents obvious diagnostic benefits. With accurate evaluation of neonatal T1 values, additional sequence optimization should be possible, with the potential for improved resolution.

Quantitative T2 Maps
Quantitative relaxation-time maps may help eliminate radiofrequency field inhomogeneity artifacts and may provide more objective, observer-independent interpretation than qualitative image examination. For example, in a recent study of infants ~5 days of age with NE, basal ganglion T2 was prognostic for neurodevelopmental outcomes.31 Nevertheless, quantitative T1 and T2 imaging is not yet routinely available on commercial MRI systems. Our T2 maps displayed good GWMC (Fig 1E) and confirmed decreased brain-water T2 values at higher field strength.8,21 For example, at 4.7 T, infant 2 (with a suspected hypoxic-ischemic injury but normal 1-year outcome) had thalamic and white matter T2 values of 72 and 128 milliseconds, respectively, compared with 123 and 210 milliseconds at 3 T8 and 141 and 228 milliseconds at 2.35 T.32 Additional optimization of the quantitative T2 sequence may provide higher resolution and/or acquisition of more slices.

Limitations of the Study
SAR
In this study, the number of slices per acquisition was limited by the requirement of keeping the SAR <2 W/kg. Therefore, it was not possible to examine the whole brain with FSE imaging in a single scan lasting <6 minutes. Implementation of variable-flip-angle FSE techniques, such as hyperechoes33 or transition into pseudo-steady state,34 which reduce SAR greatly with minimal SNR loss, should increase the number of slices obtainable within recommended safety limits.

Radiofrequency Coil Dimensions
The (adult) head coil used for this study had an internal diameter of 28 cm, whereas the newborn head diameter is only ~12 cm. Because SNR increases with the sample/coil volume ratio and smaller coils require less radiofrequency power, there is the potential to increase significantly the image quality and the number of slices by using a smaller neonatal coil.35–37

Pulse Sequence Optimization
Although T1-weighted spin echo and T2-weighted FSE techniques were used in all studies, the other sequences, yielding T1 contrast images and T2 maps, were used less. Although IR-FSE and MDEFT image quality was acceptable and these sequences provided a useful alternative to T1-weighted spin echo imaging, acquisition parameters must be optimized. For this purpose, T1 and T2 in neonatal brain must be evaluated more comprehensively at 4.7 T. We are investigating T1-mapping methods that are resilient to flip-angle inhomogeneities and show promise for neonatal application, including a modified fast low-angle shot sequence38 and T1 by multiple readout pulses.39

Motion Sensitivity
The smaller slice thicknesses and higher in-slice resolution used for 4.7-T FSE imaging necessitate perfect head immobilization, to minimize subject movement. Some motion artifacts were seen in a few neonatal images (eg, Fig 3, top left, and Fig 4, top right). Respiratory and cardiac gating may thus be beneficial.

Image Interpretation
Ethical permission was granted only to study ventilated infants undergoing intensive care; at this stage, permission for the study of healthy, age-matched, control infants was withheld. Lack of normative data is common for any novel modality. The appearance of pathologic brain tissue at 4.7 T requires careful appraisal, and the full clinical implications of the images presented here remain uncertain. Indeed, the first high-resolution, 4.7-T, adult, FSE images caused concern initially because the Virchov-Robin spaces appeared excessively prominent even in young healthy subjects.18 Therefore, it is very important to study control infants at 4.7 T. Furthermore, for clinical reasons, it was not possible to compare the 4.7-T images with images acquired for the same subjects with similar pulse sequences at 1.5 T and thus to carry out a quantitative field-strength comparison.

We studied 5 infants because of suspected perinatal hypoxic-ischemic injury; 2 had normal outcomes, 1 mild/moderate, and 2 severe. Abnormalities were noted in the T1-weighted and T2-weighted images for the infants with severe outcomes (compare Figs 1 and 2). Conventional MRI at 1.5 T is currently the investigation method of choice but not until the end of the first week after birth, at which time a close correlation exists between the pattern of MRI abnormalities and neurodevelopmental outcomes.3,40–44 Infants with acute insults are likely to sustain basal ganglion and thalamic lesions,45 and abnormal signal intensity in the posterior limb of the internal capsule is used frequently as a predictor of adverse outcomes.43 The increased anatomic resolution and GWMC provided by 4.7-T imaging may lead to more-accurate prognoses, may improve therapeutic interventions (eg, whole-body cooling), and may define brain structure-function relationships for this high-risk population.

Two infants (infants 3 and 4) underwent whole-body cooling at 33.5°C for 72 hours, as part of a clinical trial. Brain-water T1 and T2 values would change during cerebral hypothermia, resulting transiently in altered GWMC. However, these infants were normothermic at the time of MRI. The effect of this hypothermic treatment on the MRI pattern of injury after perinatal hypoxia-ischemia is unclear, although reports suggest reduced rates of moderate/severe neurologic impairment and death.46,47 A recent NE MRI study of both whole-body and selective head cooling demonstrated fewer basal ganglion lesions in infants who had been cooled and who, at the time of random assignment, had moderate, as opposed to severe, amplitude-integrated electroencephalographic abnormalities.48 Differential cortical protection was seen in another whole-body cooling study, although electroencephalographic entry criteria were not used.49


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
With attention to potential hazards and patient handling, newborn infants undergoing intensive care can be studied at 4.7 T with excellent results; T2-weighted FSE MRI brain images showed remarkable anatomic detail and tissue contrast. On 4.7-T T1-weighted images, GWMC was worse than that at 1.5 T. Consequently, abnormalities would have to change T1 substantially to be noticed visually. From our small cohort of infants, we have not gained adequate experience to be certain whether the T1 change required for detection is significantly greater than that at 1.5 T. The MRI examination time was not reduced, compared with imaging at 1.5 T, because of sequence adjustments required to ensure that the SAR was <2 W/kg. The increased T2-weighted image detail, however, may lead to more accurate prognoses, may improve therapeutic interventions, and may enable definition of more precise structure-function relationships in NE. Neonatal brain image quality at 4.7 T could be improved with small neonatal imaging coils and further pulse sequence development and optimization. Areas of future interest at high field include the development of sequences for 3-dimensional imaging (for voxel or deformation-based morphometric analysis) and for the measurement of apparent diffusion coefficients and diffusion anisotropy. Meaningful interpretation of pathologic 4.7-T images will require the study of normal infants and detailed long-term neurodevelopmental follow-up to define relationships between subtle MRI abnormalities and specific functional impairments.


   ACKNOWLEDGMENTS
 
We thank the Special Trustees of the Middlesex Hospital for funding the Imaging Fellows and the ventilator and the Wellcome Trust for funding the 4.7-T MRI system and associated infrastructure.

We thank Dr David Thomas for providing the program to optimize MDEFT parameters and Sahan Thalayasingam for helping to modify the neonatal examination pod for 4.7 T.


   FOOTNOTES
 
Accepted Jul 18, 2006.

Address correspondence to Nicola J. Robertson, FRCPCH, PhD, Department of Paediatrics and Child Health, University College London, 5 University St, London WC1E 6JJ, United Kingdom. E-mail: n.robertson{at}ucl.ac.uk

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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