The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics, and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals: the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%), and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%), and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%), and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P=0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%); motor delay with non-ambulance (64%); and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P=0.003), non-ambulance (P=0.035), ongoing enteral feeds (P<0.001), and cortical visual impairment (P=0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs; provide insights into their neurological basis; and, vitally, enable meaningful genetic counselling for affected individuals and their families.

Mimics of Pediatric Small Vessel Primary Angiitis of the Central Nervous System.

OBJECTIVE: Small vessel primary angiitis of the central nervous system is a rare and often severe disease characterized by central nervous system-restricted inflammatory vasculitis on histopathology. Diagnosis requires brain biopsy for confirmation and is suggested prior to starting immunotherapy when feasible. However, emerging evidence suggests that other neuroinflammatory conditions may have a clinical and radiographic phenotype that mimics small vessel primary angiitis, at times with overlapping pathologic features as well. Such diagnoses, including myelin oligodendrocyte glycoprotein antibody-associated disease and central nervous system-restricted hemophagocytic lymphohistiocytosis, can be non-invasively diagnosed with serum antibody or genetic testing that would prompt different monitoring and treatment paradigms. To determine the ultimate diagnosis of patients who were suspected prior to biopsy to have small vessel primary angiitis, we reviewed the clinical, radiographic, and pathological features of a cohort of patients at a single center undergoing brain biopsy for non-oncologic indications. METHODS: Clinical data were retrospectively extracted from the medical record. Pathology and neuroimaging review was conducted. RESULTS: We identified 21 patients over a 19-year time-period, of whom 14 (66.7%) were ultimately diagnosed with entities other than small vessel primary angiitis that would have obviated the need for brain biopsy. Diagnoses included anti-myelin oligodendrocyte glycoprotein antibody associated disease (n = 9), central nervous system-restricted hemophagocytic lymphohistiocytosis (n = 3), anti-GABAA receptor encephalitis (n = 1), and Aicardi-Goutières syndrome (n = 1). INTERPRETATION: This study highlights the importance of pursuing now readily available non-invasive testing for mimicking diagnoses before performing a brain biopsy for suspected small vessel primary angiitis of the central nervous system. ANN NEUROL 2023;93:109-119.

Pediatric nasal chondromesenchymal hamartomas: a case series.

PURPOSE: Nasal chondromesenchymal hamartomas (NCMH) are rare, predominantly benign tumors of the sinonasal tract. The distinction from higher grade malignancy may be challenging based on imaging features alone. To increase the awareness of this entity among radiologists, we present a multi-institutional case series of pediatric NCMH patients showing the varied imaging presentation. METHODS: Descriptive assessment of imaging appearances of the lesions on computed tomography (CT) and magnetic resonance imaging (MRI) was performed. In addition, we reviewed demographic information, clinical data, results of genetic testing, management, and follow-up data. RESULTS: Our case series consisted of 10 patients, with a median age of 0.5 months. Intraorbital and intracranial extensions were both observed in two cases. Common CT findings included bony remodeling, calcifications, and bony erosions. MRI showed heterogeneous expansile lesion with predominantly hyperintense T2 signal and heterogenous post-contrast enhancement in the majority of cases. Most lesions exhibited increased diffusivity on diffusion weighted imaging and showed signal drop-out on susceptibility weighted images in the areas of calcifications. Genetic testing was conducted in 4 patients, revealing the presence of DICER1 pathogenic variant in three cases. Surgery was performed in all cases, with one recurrence in two cases and two recurrences in one case on follow-up. CONCLUSION: NCMHs are predominantly benign tumors of the sinonasal tract, typically associated with DICER1 pathogenic variants and most commonly affecting pediatric population. They may mimic aggressive behavior on imaging; therefore, awareness of this pathology is important. MRI and CT have complementary roles in the diagnosis of this entity.

Artificial Intelligence Algorithm Improves Radiologist Performance in Skeletal Age Assessment: A Prospective Multicenter Randomized Controlled Trial.

Background Previous studies suggest that use of artificial intelligence (AI) algorithms as diagnostic aids may improve the quality of skeletal age assessment, though these studies lack evidence from clinical practice. Purpose To compare the accuracy and interpretation time of skeletal age assessment on hand radiograph examinations with and without the use of an AI algorithm as a diagnostic aid. Materials and Methods In this prospective randomized controlled trial, the accuracy of skeletal age assessment on hand radiograph examinations was performed with (n = 792) and without (n = 739) the AI algorithm as a diagnostic aid. For examinations with the AI algorithm, the radiologist was shown the AI interpretation as part of their routine clinical work and was permitted to accept or modify it. Hand radiographs were interpreted by 93 radiologists from six centers. The primary efficacy outcome was the mean absolute difference between the skeletal age dictated into the radiologists' signed report and the average interpretation of a panel of four radiologists not using a diagnostic aid. The secondary outcome was the interpretation time. A linear mixed-effects regression model with random center- and radiologist-level effects was used to compare the two experimental groups. Results Overall mean absolute difference was lower when radiologists used the AI algorithm compared with when they did not (5.36 months vs 5.95 months; P = .04). The proportions at which the absolute difference exceeded 12 months (9.3% vs 13.0%, P = .02) and 24 months (0.5% vs 1.8%, P = .02) were lower with the AI algorithm than without it. Median radiologist interpretation time was lower with the AI algorithm than without it (102 seconds vs 142 seconds, P = .001). Conclusion Use of an artificial intelligence algorithm improved skeletal age assessment accuracy and reduced interpretation times for radiologists, although differences were observed between centers. Clinical trial registration no. NCT03530098 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Rubin in this issue.

Exome sequencing identifies novel missense and deletion variants in RTN4IP1 associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis.

Inherited optic neuropathies (IONs) are neurodegenerative disorders characterized by optic atrophy with or without extraocular manifestations. Optic atrophy-10 (OPA10) is an autosomal recessive ION recently reported to be caused by mutations in RTN4IP1, which encodes reticulon 4 interacting protein 1 (RTN4IP1), a mitochondrial ubiquinol oxydo-reductase. Here we report novel compound heterozygous mutations in RTN4IP1 in a male proband with developmental delay, epilepsy, optic atrophy, ataxia, and choreoathetosis. Workup was notable for transiently elevated lactate and lactate-to-pyruvate ratio, brain magnetic resonance imaging with optic atrophy and T2 signal abnormalities, and a nondiagnostic initial genetic workup, including chromosomal microarray and mitochondrial panel testing. Exome sequencing identified a paternally inherited missense variant (c.263T>G, p.Val88Gly) predicted to be deleterious and a maternally inherited deletion encompassing RTN4IP1. To our knowledge, this is the first report of a non-single nucleotide pathogenic variant associated with OPA10. This case highlights the expanding phenotypic spectrum of OPA10, the association between "syndromic" cases and severe RTN4IP1 mutations, and the importance of nonbiased genetic testing, such as ES, to analyze multiple genes and variants types, in patients suspected of having genetic disease.

Visual outcomes following everolimus targeted therapy for neurofibromatosis type 1-associated optic pathway gliomas in children.

Data for visual acuity (VA) after treatment of neurofibromatosis type 1-associated optic pathway gliomas (NF1-OPGs) are limited. We retrospectively collected VA, converted to logMAR, before and after targeted therapy with everolimus for NF1-OPG, and compared to radiologic outcomes (14/18 with NF1-OPG, 25 eyes [three without quantifiable vision]). Upon completion of treatment, VA was stable in 19 eyes, improved in four eyes, and worsened in two eyes; visual and radiologic outcomes were discordant. In summary, the majority of children with NF1-OPG exhibited stabilization of their VA after everolimus treatment. A larger, prospective study will help delineate visual outcomes after targeted therapy.

A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma.

BACKGROUND: To evaluate efficacy, pharmacokinetics (PK) and pharmacodynamics of single-agent everolimus in pediatric patients with radiographically progressive low-grade glioma (LGG). METHODS: Everolimus was administered at 5 mg/m2 once daily as a tablet or liquid for a planned 48-week duration or until unacceptable toxicity or disease progression. Patients with neurofibromatosis type 1 were excluded. PK and pharmacodynamic endpoints were assessed in consenting patients. RESULTS: Twenty-three eligible patients (median age 9.2 years) were enrolled. All patients received prior chemotherapy (median number of prior regimens two) and/or radiotherapy (two patients). By week 48, two patients had a partial response, 10 stable disease, and 11 clinical or radiographic progression; two discontinued study prior to 1 year (toxicity: 1, physician determination: 1). With a median follow up of 1.8 years (range 0.2-6.7 years), the 2-, 3-, and 5-year progression-free survivals (PFS) were 39 ± 11%, 26 ± 11%, and 26 ± 11%, respectively; two patients died of disease. The 2-, 3-, and 5-year overall survival (OS) were all 93 ± 6%. Grade 1 and 2 toxicities predominated; two definitively related grade 3 toxicities (mucositis and neutropenia) occurred. Grade 4 elevation of liver enzymes was possibly related in one patient. Predose blood levels showed substantial variability between patients with 45.5% below and 18.2% above the target range of 5-15 ng/mL. Pharmacodynamic analysis demonstrated significant inhibition in phospho-S6, 4E-BP1, and modulation of c-Myc expression. CONCLUSION: Daily oral everolimus provides a well-tolerated, alternative treatment for multiple recurrent, radiographically progressive pediatric LGG. Based on these results, everolimus is being investigated further for this patient population.

Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia.

Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.2 ± 5.47 years) received comprehensive neurological and neuropsychological evaluations, electroencephalogram (EEG) and magnetic resonance imaging (MRI). MRI data from nine healthy controls (mean age = 30.22 ± 3.52 years) were used for comparison measures. Galactosemia subjects experienced impaired memory, language processing, visual-motor skills, and increased anxiety. Neurological examinations revealed tremor and dysarthria in six subjects. In addition, there was ataxia in three subjects and six subjects had abnormal gait. Mean full scale IQ was 80.4 ± 17.3. EEG evaluations revealed right-sided abnormalities in five subjects and bilateral abnormalities in one subject. Compared to age- and gender-matched controls, subjects with galactosemia had reduced volume in left cerebellum white matter, bilateral putamen, and left superior temporal sulcus. Galactosemia patients also had lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls. Furthermore, there were significant correlations between neuropsychological test results and the T1 volume and diffusivity scalars. Our findings help to identify anatomic correlates to motor control, learning and memory, and language in subjects with galactosemia. The results from this preliminary assessment may provide insights into the pathophysiology of this inborn error of metabolism.

Motion-robust diffusion compartment imaging using simultaneous multi-slice acquisition.

PURPOSE: To achieve motion-robust diffusion compartment imaging (DCI) in near continuously moving subjects based on simultaneous multi-slice, diffusion-weighted brain MRI. METHODS: Simultaneous multi-slice (SMS) acquisition enables fast and dense sampling of k- and q-space. We propose to achieve motion-robust DCI via slice-level motion correction by exploiting the rigid coupling between simultaneously acquired slices. This coupling provides 3D coverage of the anatomy that substantially constraints the slice-to-volume alignment problem. This is incorporated into an explicit model of motion dynamics that handles continuous and large subject motion in robust DCI reconstruction. RESULTS: We applied the proposed technique, called Motion Tracking based on Simultanous Multislice Registration (MT-SMR) to multi b-value SMS diffusion-weighted brain MRI of healthy volunteers and motion-corrupted scans of 20 pediatric subjects. Quantitative and qualitative evaluation based on fractional anisotropy in unidirectional fiber regions, and DCI in crossing-fiber regions show robust reconstruction in the presence of motion. CONCLUSION: The proposed approach has the potential to extend routine use of SMS DCI in very challenging populations, such as young children, newborns, and non-cooperative patients.

Brain MRI abnormalities in patients with infantile spasms and Down syndrome.

INTRODUCTION: Infantile spasms (IS) are the most frequent epilepsy syndrome in children with Down syndrome (DS). In DS, cellular (synaptic/dendritic changes) and molecular mechanisms are believed to contribute to epileptogenesis, rather than gross structural anomalies. Neuroimaging is a standard part of the evaluation of newly diagnosed infantile epilepsy including IS and, in this age group, often requires sedation. It is unclear if neuroimaging provides additional clinically useful etiologic information in IS associated with DS. METHODS: We conducted a retrospective chart review and detailed neuroimaging review in 36 patients (24 males) with IS and DS, cared for at Boston Children's Hospital. RESULTS: Incidental imaging abnormalities were common (42%), but potentially relevant etiologic abnormalities were rare (16%). Structural congenital or acquired abnormalities were associated with ongoing antiepileptic drug (AED) use (p = 0.02), as well as refractory epilepsy (p = 0.04). However, neuroimaging did not alter the treatment plan for any of these patients. CONCLUSIONS: Clinicians must carefully weigh the benefits and risks of neuroimaging in infants with DS and IS, as neuroimaging did not lead to any changes in clinical management in our patients but may offer information regarding prognosis.

Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological Comorbidity in Tuberous Sclerosis Complex.

INTRODUCTION: Neurological manifestations in Tuberous Sclerosis Complex (TSC) are highly variable. Diffusion tensor imaging (DTI) may reflect the neurological disease burden. We analyzed the association of autism spectrum disorder (ASD), intellectual disability (ID) and epilepsy with callosal DTI metrics in subjects with and without TSC. METHODS: 186 children underwent 3T MRI DTI: 51 with TSC (19 with concurrent ASD), 46 with non-syndromic ASD and 89 healthy controls (HC). Subgroups were based on presence of TSC, ASD, ID, and epilepsy. Density-weighted DTI metrics obtained from tractography of the corpus callosum were fitted using a 2-parameter growth model. We estimated distributions using bootstrapping and calculated half-life and asymptote of the fitted curves. RESULTS: TSC was associated with a lower callosal fractional anisotropy (FA) than ASD, and ASD with a lower FA than HC. ID, epilepsy and ASD diagnosis were each associated with lower FA values, demonstrating additive effects. In TSC, the largest change in FA was related to a comorbid diagnosis of ASD. Mean diffusivity (MD) showed an inverse relationship to FA. Some subgroups were too small for reliable data fitting. CONCLUSIONS: Using a cross-disorder approach, this study demonstrates cumulative abnormality of callosal white matter diffusion with increasing neurological comorbidity.

De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.

KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate-binding loop motif and motor-like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.

White matter spongiosis with vigabatrin therapy for infantile spasms.

The histopathology, "white matter spongiosis," defined by electron microscopy (EM) as "intramyelinic edema," has been associated with vigabatrin therapy in various animal models, but its role or significance in clinical studies is unknown. We conducted a neuropathological examination on a 27-month-old boy with bilateral polymicrogyria and epilepsy after sudden unexpected death in epilepsy (SUDEP). The patient was initiated on vigabatrin at 4 months of age, which controlled infantile spasms, and was continued as maintenance therapy. Autopsy showed a combination of developmental and acquired lesions: (1) bilateral gyral malformations of the frontal, parietal, temporal, and insular cortex; (2) agenesis of the olfactory tracts and bulbs; (3) hippocampal abnormalities: dentate gyrus bilamination and granule cell dispersion; and (4) areas of microscopic bilateral, symmetric white matter spongiosis in the brainstem central tegmental tract, amiculum and hilum of the inferior olive, medial longitudinal fasciculus, paragigantocellularis lateralis, optic nerves and chiasm, and hypothalamus. The white matter spongiosis was identical to the histopathologic lesions (which by EM exhibited intramyelinic edema) that were demonstrated in animal models on vigabatrin therapy, indicating that vigabatrin toxicity is not restricted to animal models.

Active delineation of Meyer's loop using oriented priors through MAGNEtic tractography (MAGNET).

Streamline tractography algorithms infer connectivity from diffusion MRI (dMRI) by following diffusion directions which are similarly aligned between neighboring voxels. However, not all white matter (WM) fascicles are organized in this manner. For example, Meyer's loop is a highly curved portion of the optic radiation (OR) that exhibits a narrow turn, kissing and crossing pathways, and changes in fascicle dispersion. From a neurosurgical perspective, damage to Meyer's loop carries a potential risk of inducing vision deficits to the patient, especially during temporal lobe resection surgery. To prevent such impairment, achieving an accurate delineation of Meyer's loop with tractography is thus of utmost importance. However, current algorithms tend to under-estimate the full extent of Meyer's loop, mainly attributed to the aforementioned rule for connectivity which requires a direction to be chosen across a field of orientations. In this article, it was demonstrated that MAGNEtic Tractography (MAGNET) can benefit Meyer's loop delineation by incorporating anatomical knowledge of the expected fiber orientation to overcome local ambiguities. A new ROI-mechanism was proposed which supplies additional information to streamline reconstruction algorithms by the means of oriented priors. Their results showed that MAGNET can accurately generate Meyer's loop in all of our 15 child subjects (8 males; mean age 10.2 years ± 3.1). It effectively improved streamline coverage when compared with deterministic tractography, and significantly reduced the distance between the anterior-most portion of Meyer's loop and the temporal pole by 16.7 mm on average, a crucial landmark used for preoperative planning of temporal lobe surgery. Hum Brain Mapp 38:509-527, 2017. © 2016 Wiley Periodicals, Inc.

Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND).

PURPOSE: To develop a statistical model for the tridimensional diffusion MRI signal at each voxel that describes the signal arising from each tissue compartment in each voxel. THEORY AND METHODS: In prior work, a statistical model of the apparent diffusion coefficient was shown to well-characterize the diffusivity and heterogeneity of the mono-directional diffusion MRI signal. However, this model was unable to characterize the three-dimensional anisotropic diffusion observed in the brain. We introduce a new model that extends the statistical distribution representation to be fully tridimensional, in which apparent diffusion coefficients are extended to be diffusion tensors. The set of compartments present at a voxel is modeled by a finite sum of unimodal continuous distributions of diffusion tensors. Each distribution provides measures of each compartment microstructural diffusivity and heterogeneity. RESULTS: The ability to estimate the tridimensional diffusivity and heterogeneity of multiple fascicles and of free diffusion is demonstrated. CONCLUSION: Our novel tissue model allows for the characterization of the intra-voxel orientational heterogeneity, a prerequisite for accurate tractography while also characterizing the overall tridimensional diffusivity and heterogeneity of each tissue compartment. The model parameters can be estimated from short duration acquisitions. The diffusivity and heterogeneity microstructural parameters may provide novel indicator of the presence of disease or injury. Magn Reson Med 76:963-977, 2016. © 2015 Wiley Periodicals, Inc.

Evaluation of motion and its effect on brain magnetic resonance image quality in children.

BACKGROUND: Motion artifacts pose significant problems for the acquisition of MR images in pediatric populations. OBJECTIVE: To evaluate temporal motion metrics in MRI scanners and their effect on image quality in pediatric populations in neuroimaging studies. MATERIALS AND METHODS: We report results from a large pediatric brain imaging study that shows the effect of motion on MRI quality. We measured motion metrics in 82 pediatric patients, mean age 13.4 years, in a T1-weighted brain MRI scan. As a result of technical difficulties, 5 scans were not included in the subsequent analyses. A radiologist graded the images using a 4-point scale ranging from clinically non-diagnostic because of motion artifacts to no motion artifacts. We used these grades to correlate motion parameters such as maximum motion, mean displacement from a reference point, and motion-free time with image quality. RESULTS: Our results show that both motion-free time (as a ratio of total scan time) and average displacement from a position at a fixed time (when the center of k-space was acquired) were highly correlated with image quality, whereas maximum displacement was not as good a predictor. Among the 77 patients whose motion was measured successfully, 17 had average displacements of greater than 0.5 mm, and 11 of those (14.3%) resulted in non-diagnostic images. Similarly, 14 patients (18.2%) had less than 90% motion-free time, which also resulted in non-diagnostic images. CONCLUSION: We report results from a large pediatric study to show how children and young adults move in the MRI scanner and the effect that this motion has on image quality. The results will help the motion-correction community in better understanding motion patterns in pediatric populations and how these patterns affect MR image quality.

Risk of seizures in children with tectal gliomas.

The objective of this study was to determine the prevalence of seizures in children with tectal gliomas and to determine if there are common clinical, electroencephalography (EEG), or radiologic findings that predict risk of seizures in these patients. We conducted a retrospective review of all patients with tectal gliomas over a 22-year period at a single institution. Data extraction included sex, age at presentation of tectal glioma and age of presentation with seizures, magnetic resonance imaging (MRI) findings, seizure frequency and semiology, and EEG findings. We identified 79 patients, 66 of whom had adequate imaging and clinical data for further analysis. Eight patients (12.1%) had a history of seizures. Three patients had a clear symptomatic cause of seizures. Three patients were diagnosed with a tectal glioma as an incidental finding after a first seizure. One patient had a history of febrile convulsions. One patient had a generalized seizure 5 years after presenting with macrocephaly. Although the risk of seizure in children with known tectal glioma was relatively high, we did not identify specific clinical, radiologic, EEG, or MRI features that are predictive of increased risk. Thus, in children with tectal gliomas who have seizures, alternative causes for the seizures must be sought.

Normative biometrics for fetal ocular growth using volumetric MRI reconstruction.

OBJECTIVE: To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. METHOD: The 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created using super-resolution volume reconstructions from MRI slice acquisitions. These 3D images were semi-automatically segmented to measure fetal orbit volume, binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD). RESULTS: All biometry correlated with GA (Volume, Pearson's correlation coefficient (CC) = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC = 0.8429), and growth curves were plotted against linear and quadratic growth models. Regression analysis showed quadratic models to best fit BOD, IOD, and OD and a linear model to best fit volume. CONCLUSION: Orbital volume had the greatest correlation with GA, although BOD and OD also showed strong correlation. The normative data found in this study may be helpful for the detection of congenital fetal anomalies with more consistent measurements than are currently available. © 2015 John Wiley & Sons, Ltd.