Fetal head biometry assessed by fetal magnetic resonance imaging following in utero myelomeningocele repair.

OBJECTIVE: To examine the impact of fetal myelomeningocele (MMC) repair on fetal head biometry and cerebrospinal fluid (CSF) spaces assessed by magnetic resonance imaging (MR) studies. STUDY DESIGN: Axial measurements of intracranial structures were taken at defined anatomical landmarks. Pre- and postnatal head biometry data and CSF spaces obtained from in utero repaired MMC fetuses (n = 22) were compared to the pre- and postnatal measurements of MMC patients that underwent standard neurosurgical MMC repair after birth (n = 16) and a cohort of age-matched control patients (prenatal, n = 52; postnatal, n = 9). RESULTS: In fetuses with MMC, initial MR scans showed an almost complete absence of supratentorial and posterior fossa CSF spaces. No differences in postnatal CSF spaces were found between controls and prenatally repaired MMC newborns. In fetuses with postnatal MMC repair, CSF spaces remained significantly reduced (p < 0.0001). The mean ventricular diameter (VD) increase in the postnatal repaired MMC group was significantly higher compared to the mean percentage of VD increase in the fetal repaired MMC group (6.4 vs. 4.2 mm; p = 0.02). Pre- and postnatal brain thickness measurements were significantly reduced in both MMC populations compared to age-matched normal values (p < 0.0001). In contrast to postnatally repaired patients, in utero repair fetuses showed significant reversal of hindbrain herniation and normalization of the posterior fossa CSF spaces. CONCLUSION: Mid-gestational repair of MMC promotes normalization of extra-axial CSF spaces. Due to progressive ventriculomegaly, brain thickness remains decreased in both prenatal repaired and age-matched non-repaired MMC patients when compared to age-matched normal values. Restoration of CSF volume in the posterior fossa after in utero repair is indicative of reversal of hindbrain herniation.

Fetal posterior fossa volume: assessment with MR imaging.

PURPOSE: To retrospectively determine the relationship between posterior fossa volume (PFV) and estimated gestational age (EGA) and/or femur length (FL) during pregnancy for the purpose of developing a normal growth curve. MATERIALS AND METHODS: Advance institutional review board approval was obtained for this HIPAA-compliant study, and the need for parent informed consent was waived. A cross-sectional retrospective study was performed to measure PFV on in vivo magnetic resonance (MR) images obtained in 76 fetuses of 18-36 weeks gestation who had a morphologically normal CNS. Because this was a retrospective series, MR imaging techniques varied slightly, but all fetuses underwent imaging at contiguous 3-5-mm intervals in at least two orthogonal planes, with repetition time msec/echo time msec, 5-12/62-95; number of signals acquired, one; flip angle, 150 degrees -180 degrees; and matrix, 128-192 x 256. Posterior fossa areas were manually traced on half-Fourier rapid acquisition with relaxation enhancement in utero fetal MR images by one observer. PFVs were then calculated by manually summing areas from the contiguous sections and multiplying the total area by the section thickness. An average PFV (APFV) across orthogonal planes was calculated for each fetus, and the relationship between APFV and EGA was mathematically modeled. Coronal, transverse, and sagittal views were compared with correlations and Bland-Altman plots. Two additional observers repeated the measurements for a small subset of fetuses (n = 5). Paired t test analyses were also performed to determine significant differences between sagittal, transverse, and coronal measurements, as well as to determine preliminary intraobserver and interobserver variability of measurements in a subset of cases. RESULTS: The relationship between APFV (in cubic centimeters) and EGA (in weeks) was well described by a single exponential function [APFV = 0.689 exp(EGA/9.10)]. APFV doubling time was 6.31 weeks. Root-mean-square variation of values around the model line was 1.63 cm(3). There was no statistically significant intra- or interobserver variation (P > .16 for all fetuses) at preliminary analysis. No correlation between APFV and FL could be found. CONCLUSION: The normal fetal PFV growth curve generated in this study may have potential as a model for clinical application.

Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in children.

BACKGROUND AND PURPOSE: Methotrexate is a major cause of treatment-related acute neurotoxicity in children with hematologic malignancies. The purpose of this study was to investigate whether diffusion-weighted MR imaging (DWI) detects acute methotrexate white matter neurotoxicity in this patient population. METHODS: Six children-three female and three male-with hematologic malignancies were studied at time of onset of neurologic dysfunction during the delayed intensification or consolidation phase of therapy, when intensive intrathecal methotrexate is given. MR imaging including DWI was performed on 1.5 T MR scanners. RESULTS: DWI demonstrated abnormal restriction of motion of water in the centrum semiovale in all six patients. This finding correlated to the acute onset of hemiparesis or aphasia. Fluid-attenuated inversion recovery imaging was not positive at this time, but it was positive in all five patients in whom follow-up imaging was performed. CONCLUSION: Early detection of methotrexate white matter injury by DWI has the potential to alert the oncologist to this event and provide a technique by which treatment of neurotoxicity can be monitored.

Biotinidase deficiency: the importance of adequate follow-up for an inconclusive newborn screening result.

UNLABELLED: Biotinidase deficiency is an inherited metabolic disorder characterized by inability to recycle protein-bound biotin. It usually presents with ataxia and seizures, though atypical presentations have also been described. We report a 15-month-old boy with profound biotinidase deficiency who presented with laryngeal stridor and subsequently developed severe ataxia and lactic acidosis. Subsequently, it was discovered that the patient's newborn screening test for biotinidase activity had been inconclusive, but confirmatory testing had not been done. Brain magnetic resonance imaging showed multiple white matter non-enhancing T2 hyperintensities, which largely resolved following 6 months of biotin therapy; however, there was residual deafness and mental retardation. CONCLUSION: An argument is made for universal newborn screening in biotinidase deficiency and improved mechanisms for follow-up of positive screens, because delay in diagnosis results in irreversible morbidity, newborn screening is cost effective, and early therapy prevents the neurologic sequelae.

MRI of the fetal spine.

Magnetic resonance imaging of the fetal spine is a vital complement to fetal sonographic examination. Assessing the wide spectrum of spinal dysraphism, as well as spinal neoplasia, allows for more correct prenatal diagnoses, patient care planning, and patient counselling. Proper appraisal of the value of experimental procedures, such as fetal myelomeningocoele repair, requires a high level of diagnostic accuracy for the selection and follow-up of appropriate candidates.

Diffusion-weighted MR imaging of subdural empyemas in children.

BACKGROUND AND PURPOSE: Subdural empyema (SDE), an infection of the subdural space, occurs most often in pediatric patients as a complication of meningitis, sinusitis, or otitis media. Diffusion-weighted imaging (DWI) has been used in the past to investigate intracerebral infections. The purpose of this study was to determine the signal intensity characteristics of SDE on DWIs as well as the corresponding apparent diffusion coefficient (ADC) maps. METHODS: MR studies of 10 patients with SDEs were retrospectively reviewed. Included were routine sequences and DWI, which consisted of an axial single-shot echo-planar spin-echo sequence (TR/TE, 4000/110) with b values of 0, 500, and 1000 s/mm(2). Signal-intensity characteristics on routine MR images and DWIs were evaluated. In seven patients, ADC values of the lesions were calculated by using two b values. Follow-up imaging study was performed in seven patients. RESULTS: In nine patients, the empyema was hyperintense on DWIs. In the remaining patient, the empyema showed mixed hyperintensity and hypointensity. ADC values were lower than those of normal cortical gray matter and much lower than those of reactive subdural effusions. In all seven patients with persistent clinical signs of infection, the empyemas were hyperintense on follow-up DWIs. CONCLUSION: SDE had high signal intensity on DWIs and low signal intensity on ADC maps, with an ADC value lower than that of the normal cortical gray matter. Diffusion MR imaging can be valuable in distinguishing SDE from effusion and in the follow-up of subdural collections.

Prenatal MR findings of the middle interhemispheric variant of holoprosencephaly.

We report a case of the middle interhemispheric variant of holoprosencephaly (MIH) with noncleavage of the posterior portion of the frontal lobes and the parietal regions in a fetus at 22 weeks' gestation. To our knowledge, this is the first case of the rare MIH variant to be diagnosed in utero by use of ultrafast MR imaging and one of the few such reports to document gross and microscopic pathologic findings. Neuroimaging results correlated with those of gross and microscopic pathologic specimens obtained from the stillborn child. We conclude that ultrafast MR imaging can accurately distinguish holoprosencephaly subtypes in utero, which may affect counseling of parents.

In vivo pyruvate detected by MR spectroscopy in neonatal pyruvate dehydrogenase deficiency.

We present a unique finding of an elevated level of pyruvate at 2.37 ppm revealed by in vivo MR spectroscopy of a female neonate. Low fibroblast pyruvate dehydrogenase (PDH) complex activity subsequently confirmed a diagnosis of PDH deficiency. Abnormalities of brain development consistent with PDH deficiency were also evident on fetal and postnatal MR images. To our knowledge, this is the first report of pyruvate being shown in vivo in a child and the first report of MR spectroscopy aiding in the diagnosis of inborn error in pyruvate metabolism before confirmation by conventional enzymatic testing. This finding has potential implications for earlier diagnosis in patients with defects in mitochondrial metabolism.

High-resolution 3D T2-weighted fast spin echo: new applications in the orbit.

Recent developments have made available for ophthalmologic MR imaging a very high-resolution 3D fast spin echo T2 (3D FSE T2) sequence, which runs in a standard head coil. A modification of this technique, 3D FSEz T2, uses a zero-filled slice interpolation method during post-processing to further improve spatial resolution. We describe the technique and share our early clinical observations in patients with ocular masses. Briefly, the additional information from the 3D FSEz T2 resulted in a change in diagnosis from the conventional imaging series in 11 of (41%) 27 studies, usually through the identification of previously treated retinoblastoma lesions. The new sequence significantly increased diagnostic confidence in six (38%) of the remaining 16 cases, usually through better anatomical detail and lesion conspicuity, and did not change interpretation in 10 cases. Such an approach improves diagnostic confidence and may eliminate the need for a dedicated surface coil examination.

Fetal imaging.

Presently, MRI is an adjunct to prenatal sonography. It provides information that can aid in the diagnosis of fetal anomalies, affect prenatal counseling and management of the pregnancy, and guide prenatal intervention and delivery planning. With further advances in technology, particularly shorter scan times and better image resolution, the applications for fetal imaging are likely to increase.

Three-dimensional high-resolution magnetic resonance imaging of ocular and orbital malignancies.

BACKGROUND: Ultrathin-section 3-dimensional fast spin-echo (3-D FSE) T2-weighted imaging is a new magnetic resonance imaging (MRI) technique that we used in the evaluation of ocular and orbital malignancies. We evaluated the usefulness of this new technique compared with conventional MRI. METHODS: Imaging data from 26 consecutive patients seen in the Ocular Oncology Unit at the University of California-San Francisco were retrospectively reviewed by physicians from the ocular oncology and neuroradiology units. For all patients, 3-D FSE T2-weighted images (27 scans) were compared with results of conventional MRI and correlated with results of computed tomography (CT), A- and B-scan ultrasonography, ultrasound biomicroscopy, clinical examinations, and histopathology, when available. RESULTS: The 3-D FSE T2-weighted imaging sequence resulted in an overall improvement in accuracy of imaging findings in 17 (63%) of our 27 cases compared with the standard MRI protocol. The increased resolution led to the radiographic detection of additional lesions in 11 (41%) of 27 cases and to an increase in confidence in radiographic diagnosis in 6 (22%) of the remaining cases. The improved resolution of the 3-D FSE T2-weighted sequence resulted in a change of disease management in 3 (60%) of the 5 patients with nonretinoblastoma lesions. One hundred percent of active retinoblastoma lesions could be detected by means of 3-D FSE and conventional imaging; however, inactive lesions were not always detected using conventional imaging. CONCLUSIONS: The 3-D FSE T2-weighted sequence offers superior resolution of intraocular and orbital structures compared with conventional MRI. It is particularly useful in the evaluation of intraocular tumors and the nerve-sheath complex. This new technique contributes significantly to improved diagnosis and management in patients with ocular and orbital malignancies.

Analysis of the cerebral cortex in holoprosencephaly with attention to the sylvian fissures.

BACKGROUND AND PURPOSE: Analysis of specific features in the brain of patients with holoprosencephaly (HPE) may clarify normal and abnormal brain development and help predict outcomes for specific children. We assessed sulcal and gyral patterns of cerebral cortex in patients with HPE and developed a method of grading brain development. METHODS: Neuroimaging studies (75 MR imaging, 21 CT) of 96 patients with HPE were retrospectively reviewed, with specific attention paid to the cerebral cortex. Thickness of cortex, width of gyri, and depth of sulci were assessed subjectively and by measurement. The angle between lines drawn tangential to the sylvian fissures ("sylvian angle") was measured in each patient with HPE and in 20 control patients. RESULTS: Thickness of cortex was normal in all 96 patients. Gyral shape and width and sulcal depth were normal in 80 patients. Twelve patients, all with very severe HPE and microcephaly, had reduced sulcal depth, diffusely in eight and limited to the anteromedial cortex in four with lobar HPE. Four patients had subcortical heterotopia, located anterior to the interhemispheric fissure, associated with shallow sulci in the overlying cortex. Sylvian fissures were displaced further anteriorly and medially as HPE became more severe, until, in the most severe cases, no sylvian fissures could be identified. Sylvian angle measurements corresponded closely with severity of HPE, being largest in the most severe and smallest in the least severe cases. All patients with HPE had sylvian angles significantly larger than the mean of 15 degrees measured in the control patients. CONCLUSION: The only true malformations of cortical development were subcortical heterotopia. However, diffuse and focal abnormal sulci were observed. We propose our sylvian angle measurement of extent of frontal lobe development as an objective means of quantifying the severity of HPE.

The middle interhemispheric variant of holoprosencephaly.

BACKGROUND AND PURPOSE: The middle interhemispheric variant of holoprosencephaly (MIH) is a rare malformation in which the cerebral hemispheres fail to divide in the posterior frontal and parietal regions. We herein describe the structural abnormalities of the brain in a large group of patients with MIH, compare these features with those of classic holoprosencephaly (HPE), and propose a developmental mechanism, based on current knowledge of developmental neurogenetics, by which MIH develops. METHODS: Brain images obtained in 21 patients with MIH (MR images in 16 patients and high-quality X-ray CT scans in five patients) were retrospectively reviewed to classify cerebral abnormalities. The cerebral parenchyma, hypothalami, caudate nuclei, lentiform nuclei, thalami, and mesencephalon were examined for the degree of midline separation (cleavage) of the two hemispheres. The orbits, olfactory apparati, and presence or absence of a dorsal cyst were also assessed. RESULTS: In all patients, by definition, midportions of the cerebral hemispheres were continuous across the midline, with an intervening interhemispheric fissure. The sylvian fissures were abnormally connected across the midline over the vertex in 18 (86%) of 21 patients. Two patients had relatively normal-appearing sylvian fissures; one had unilateral absence of a sylvian fissure owing to substantial subcortical heterotopia. Heterotopic gray matter or dysplastic cerebral cortex was also seen in 18 (86%) of 21 patients. MIH differed from classic HPE as follows. 1) In all subjects, the midline third ventricle separated the hypothalamus and lentiform nuclei. 2) The caudate nuclei were separated by the cerebral ventricles in 17 (89%) of the 19 [corrected] patients in whom they could be assessed. 3) The most commonly affected basal nucleus was the thalamus (non-cleavage in seven [33%] of 21 cases, abnormal alignment in 1 [5%]). 4) Three (18%) of the 17 [corrected] patients in whom the mesencephalon could be assessed showed some degree of mesencephalic non-cleavage. 5) No patients had hypotelorism (four had hypertelorism, the remainder manifested normal intraocular distances). Dorsal cysts were present in five (25%) of the 20 patients in whom they could be assessed (dorsal cysts could not be assessed after shunt surgery), and as in classic HPE, were associated with severe thalamic non-cleavage in three of these five patients. CONCLUSION: MIH appears to cause non-cleavage of midline structures in a completely different pattern than does classic HPE. In MIH, impaired induction or expression of genetic factors appears to influence the embryonic roof plate, whereas in classic HPE, induction or expression of the embryonic floor plate seems to be affected.