Optic pathway glioma volume predicts retinal axon degeneration in neurofibromatosis type 1.

OBJECTIVE: To determine whether tumor size is associated with retinal nerve fiber layer (RNFL) thickness, a measure of axonal degeneration and an established biomarker of visual impairment in children with optic pathway gliomas (OPGs) secondary to neurofibromatosis type 1 (NF1). METHODS: Children with NF1-OPGs involving the optic nerve (extension into the chiasm and tracts permitted) who underwent both volumetric MRI analysis and optical coherence tomography (OCT) within 2 weeks of each other were included. Volumetric measurement of the entire anterior visual pathway (AVP; optic nerve, chiasm, and tract) was performed using high-resolution T1-weighted MRI. OCT measured the average RNFL thickness around the optic nerve. Linear regression models evaluated the relationship between RNFL thickness and AVP dimensions and volume. RESULTS: Thirty-eight participants contributed 55 study eyes. The mean age was 5.78 years. Twenty-two participants (58%) were female. RNFL thickness had a significant negative relationship to total AVP volume and total brain volume (p < 0.05, all comparisons). For every 1 mL increase in AVP volume, RNFL thickness declined by approximately 5 microns. A greater AVP volume of OPGs involving the optic nerve and chiasm, but not the tracts, was independently associated with a lower RNFL thickness (p < 0.05). All participants with an optic chiasm volume >1.3 mL demonstrated axonal damage (i.e., RNFL thickness <80 microns). CONCLUSIONS: Greater OPG and AVP volume predicts axonal degeneration, a biomarker of vision loss, in children with NF1-OPGs. MRI volumetric measures may help stratify the risk of visual loss from NF1-OPGs.

Quantitative MRI criteria for optic pathway enlargement in neurofibromatosis type 1.

OBJECTIVE: To determine quantitative size thresholds for enlargement of the optic nerve, chiasm, and tract in children with neurofibromatosis type 1 (NF1). METHODS: Children 0.5-18.6 years of age who underwent high-resolution T1-weighted MRI were eligible for inclusion. This consisted of children with NF1 with or without optic pathway gliomas (OPGs) and a control group who did not have other acquired, systemic, or genetic conditions that could alter their anterior visual pathway (AVP). Maximum and average diameter and volume of AVP structures were calculated from reconstructed MRI images. Values above the 95th percentile from the controls were considered the threshold for defining an abnormally large AVP measure. RESULTS: A total of 186 children (controls = 82; NF1noOPG = 54; NF1+OPG = 50) met inclusion criteria. NF1noOPG and NF1+OPG participants demonstrated greater maximum optic nerve diameter and volume, optic chiasm volume, and total brain volume compared to controls (p < 0.05, all comparisons). Total brain volume, rather than age, predicted optic nerve and chiasm volume in controls (p < 0.05). Applying the 95th percentile threshold to all NF1 participants, the maximum optic nerve diameter (3.9 mm) and AVP volumes resulted in few false-positive errors (specificity >80%, all comparisons). CONCLUSIONS: Quantitative reference values for AVP enlargement will enhance the development of objective diagnostic criteria for OPGs secondary to NF1.

Deep Learning Guided Partitioned Shape Model for Anterior Visual Pathway Segmentation.

Analysis of cranial nerve systems, such as the anterior visual pathway (AVP), from MRI sequences is challenging due to their thin long architecture, structural variations along the path, and low contrast with adjacent anatomic structures. Segmentation of a pathologic AVP (e.g., with low-grade gliomas) poses additional challenges. In this work, we propose a fully automated partitioned shape model segmentation mechanism for AVP steered by multiple MRI sequences and deep learning features. Employing deep learning feature representation, this framework presents a joint partitioned statistical shape model able to deal with healthy and pathological AVP. The deep learning assistance is particularly useful in the poor contrast regions, such as optic tracts and pathological areas. Our main contributions are: 1) a fast and robust shape localization method using conditional space deep learning, 2) a volumetric multiscale curvelet transform-based intensity normalization method for robust statistical model, and 3) optimally partitioned statistical shape and appearance models based on regional shape variations for greater local flexibility. Our method was evaluated on MRI sequences obtained from 165 pediatric subjects. A mean Dice similarity coefficient of 0.779 was obtained for the segmentation of the entire AVP (optic nerve only =0.791 ) using the leave-one-out validation. Results demonstrated that the proposed localized shape and sparse appearance-based learning approach significantly outperforms current state-of-the-art segmentation approaches and is as robust as the manual segmentation.

Exposure to phthalates affects calcium handling and intercellular connectivity of human stem cell-derived cardiomyocytes.

BACKGROUND: The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes. METHODS AND RESULTS: The effect of DEHP on calcium handling was examined using monolayers of gCAMP3 human embryonic stem cell-derived cardiomyocytes, which contain an endogenous calcium sensor. Cardiomyocytes were exposed to DEHP (5 - 50 µg/mL), and calcium transients were recorded using a Zeiss confocal imaging system. DEHP exposure (24 - 72 hr) had a negative chronotropic and inotropic effect on cardiomyocytes, increased the minimum threshold voltage required for external pacing, and modified connexin-43 expression. Application of Wy-14,643 (100 µM), an agonist for the peroxisome proliferator-activated receptor alpha, did not replicate DEHP's effects on calcium transient morphology or spontaneous beating rate. CONCLUSIONS: Phthalates can affect the normal physiology of human cardiomyocytes, including DEHP elicited perturbations in cardiac calcium handling and intercellular connectivity. Our findings call for additional studies to clarify the extent by which phthalate exposure can alter cardiac function, particularly in vulnerable patient populations who are at risk for high phthalate exposure.

Risk factors and types of cerebral palsy.

OBJECTIVE: To determine the risk factors and associated types of cerebral palsy in a squatter settlement of Karachi. METHODS: The pilot cross-sectional study was conducted in Karachi during 2010 and 2011. Data was collected through an interviewed questionnaire from the mothers of cerebral palsy victims children from a population of 6000. Sample sizes of 20 pre-diagnosed victims were selected through snowball sampling. SPSS 20 was used for statistical significance. RESULTS: The mean age of the 20 children was 8.7 +/- 6.4 years. Of them, 16 (80%) were males and 4 (20%) were females. Major risk factors identified were; home and assisted delivery 5 (75%), consanguinity 10 (50%), infections 8 (40%) and lack of antenatal care 6 (30%). Out of 20 cases, 15 (75%) had spastic type of cerebral palsy, which was further classified as diplegia 7 (35%), quadriplegia 6 (30%) and hemiplegia 2 (10%). Mixed and dystonic types were found in 3 (15%) and 2 (10%) children respectively. CONCLUSION: Important risk factors identified were home delivery, consanguinity and infections during pregnancy. Spastic type of cerebral palsy was the most common type in the study population.