Patient-specific air puff-induced loading using machine learning

Introduction: The air puff test is a contactless tonometry test used to measure the intraocular pressure and the cornea’s biomechanical properties. Limitations that most challenge the accuracy of the estimation of the corneal material and the intraocular pressure are the strong intercorrelation between the intraocular pressure and the corneal parameters, either the material properties that can change from one person to another because of age or the geometry parameters like central corneal thickness. This influence produces inaccuracies in the corneal deformation parameters while extracting the IOP parametric equation, which can be reduced through the consideration of the patient-specific air puff pressure distribution taking into account the changes in corneal parameters. This air puff pressure loading distribution can be determined precisely from the fluid-structure interaction (FSI) coupling between the air puff and the eye model. However, the computational fluid dynamics simulation of the air puff in the coupling algorithm is a time-consuming model that is impractical to use in clinical practice and large parametric studies. Methods: By using a supervised machine learning algorithm, we predict the time-dependent air puff pressure distribution for different corneal parameters via a parametric study of the corneal deformations and the gradient boosting algorithm. Results: The results confirmed that the algorithm gives the time-dependent air puff pressure distribution with an MAE of 0.0258, an RMSE of 0.0673, and an execution time of 93 s, which is then applied to the finite element model of the eye generating the corresponding corneal deformations taking into account the FSI influence. Using corneal deformations, the response parameters can be extracted and used to produce more accurate algorithms of the intraocular pressure and corneal material stress-strain index (SSI). Discussion: Estimating the distribution of air pressure on the cornea is essential to increase the accuracy of intraocular pressure (IOP) measurements, which serve as valuable indicator of corneal disease. We find that the air puff pressure loading is largely influenced by complex changes in corneal parameters unique to each patient case. With our innovative algorithm, we can preserve the same accuracy developed by the CFD-based FSI model, while reducing the computational time from approximately 101000 s (28 h) to 720 s (12 min), which is about 99.2% reduction in time. This huge improvement in computational cost will lead to significant improvement in the parametric equations for IOP and the Stress-Strain Index (SSI)

Long-Distance Three-Color Neuronal Tracing in Fixed Tissue Using NeuroVue Dyes

Dissecting development of neuronal connections is critical for understanding neuronal function in both normal and diseased states. Charting the development of the multitude of connections is a monumental task, since a given neuron typically receives hundreds of convergent inputs from other neurons and provides divergent outputs for hundreds of other neurons. Although progress is being made utilizing various mutants and/or genetic constructs expressing fluorescent proteins like GFP, substantial work remains before a database documenting the development and final location of the neuronal pathways in an adult animal is completed. The vast majority of developing neurons cannot be specifically labeled with antibodies and making specific GFP-expressing constructs to tag each of them is an overwhelming task. Fortunately, fluorescent lipophilic dyes have emerged as very useful tools to systematically compare changes in neuronal networks between wild-type and mutant mice. These dyes diffuse laterally along nerve cell membranes in fixed preparations, allowing tracing of the position of a given neuron within the neuronal network in murine mutants fixed at various stages of development. Until recently, however, most evaluations have been limited to one, or at most, two color analyses. We have previously reported three color neuronal profiling using the novel lipophilic dyes NeuroVue (NV) Green, Red and Maroon (Fritzsch et al., Brain. Res. Bull. 66:249–258, 2005). Unfortunately such three color experiments have been limited by the fact that NV Green and its brighter successor, NV Emerald, both exhibit substantially decreased signal intensities when times greater than 48 hours at 37°C are required to achieve neuronal profile filling (unpublished observations). Here we describe a standardized test system developed to allow comparison of candidate dyes and its use to evaluate a series of 488 nm-excited green-emitting lipophilic dyes. The best of these, NV Jade, has spectral properties well matched to NV Red and NV Maroon, better solubility in DMF than DiO or DiA, improved thermostability compared with NV Emerald, and the ability to fill neuronal profiles at rates of 1 mm per day for periods of at least 5 days. Use of NV Jade in combination with NV Red and NV Maroon substantially improves the efficiency of connectional analysis in complex mutants and transgenic models where limited numbers of specimens are available

Development and organization of polarity-specific segregation of primary vestibular afferent fibers in mice

A striking feature of vestibular hair cells is the polarized arrangement of their stereocilia as the basis for their directional sensitivity. In mammals, each of the vestibular end organs is characterized by a distinct distribution of these polarized cells. We utilized the technique of post-fixation transganglionic neuronal tracing with fluorescent lipid soluble dyes in embryonic and postnatal mice to investigate whether these polarity characteristics correlate with the pattern of connections between the endorgans and their central targets; the vestibular nuclei and cerebellum. We found that the cerebellar and brainstem projections develop independently from each other and have a non-overlapping distribution of neurons and afferents from E11.5 on. In addition, we show that the vestibular fibers projecting to the cerebellum originate preferentially from the lateral half of the utricular macula and the medial half of the saccular macula. In contrast, the brainstem vestibular afferents originate primarily from the medial half of the utricular macula and the lateral half of the saccular macula. This indicates that the line of hair cell polarity reversal within the striola region segregates almost mutually exclusive central projections. A possible interpretation of this feature is that this macular organization provides an inhibitory side-loop through the cerebellum to produce synergistic tuning effects in the vestibular nuclei. The canal cristae project to the brainstem vestibular nuclei and cerebellum, but the projection to the vestibulocerebellum originates preferentially from the superior half of each of the cristae. The reason for this pattern is not clear, but it may compensate for unequal activation of crista hair cells or may be an evolutionary atavism reflecting a different polarity organization in ancestral vertebrate ears

Which feature influences on-eye power change of soft toric contact lenses: Design or corneal shape?

PurposeThis study investigates how both the peripheral zone design and corneal shape affect the behaviour of soft contact lenses on-eye.MethodsIn this study, soft contact lenses of varying nominal cylindrical powers and peripheral zone designs-a single-prism gravity-based stabilised lens (G1P), two-prism blink-based stabilised lens (B2P) and four-prism blink-based stabilised lens (B4P)-were generated as finite element models. The on-eye simulation results were analysed to identify the impact of each peripheral zone design (Each with different volume ratios) on the effective power change (EPC) when worn by a subject. Topographies of three eyes of varying average simulated anterior corneal curvature (flat, average & steep) were used in this study.ResultsThe volume of the lens's peripheral zone as a ratio of the total lens volume (Vp) recorded very weak correlations with the effective power change (EPC) among the three investigated designs when they were fitted to the flat eye (R = -0.19, -0.15 & -0.22 respectively), moderate correlations with the average eye (R = 0.42, 0.43 & 0.43 respectively) and strong correlations with the steep eye (R = 0.91, 0.9 & 0.9 respectively). No significant differences were noticed among the three investigated designs and none of the cylindrical lenses designed with axis 90° recorded EPC values outside the acceptance criteria range (ACR) of ±0.25 D. No significant differences in EPC were recorded among the three designs G1P, B2P and B4P (p>0.6) when they were designed with three axes at 90°, 45° and 0°. Moving the toric lens axis away from 90° dragged the EPC to the negative side and most of the investigated lenses with axes at 45° and 0° recorded EPCs outside the ±0.25D range.ConclusionsIn all cases, the shape of the cornea had a more dominant effect on EPC when compared to the peripheral zone design. Corneal shape influences the soft toric contact lens's on-eye power change more than the lens design

Tomographic renal cortical scintigraphy: Correlation with intravenous urography, computed tomography, ultrasonography, angiography, and nuclear magnetic resonance imaging

This study evaluates single-photon renal tomoscintigraphy (SPECT) in the evaluation of renal masses and correlates this modality, where indicated, with computed tomography (CT), ultrasonography (US), angiography (ANGIO) and nuclear magnetic resonance imaging (NMR). Eight patients with renal cortical lesions detected on intravenous urography (IVP) were evaluated by SPECT and planar nuclear imaging using Tc-99m glucoheptonate (GH). Three of these patients were felt particularly likely to have renal tumors and were additionally evaluated with US, CT, ANGIO and NMR. The five patients with nodules on IVP that were not particularly suggestive of malignancy had functioning, benign, renal tissue accounting for their IVP lesions. Four of five were found by planar-GH nuclear imaging, five/five by SPECT-GH. In addition, SPECT-GH allowed better “confidence” in the normal renal tissue diagnosis in three/five cases. Of the three renal lesions that were highly suggestive of malignancy, two were hypernephromas and one was hypertrophied functioning cortical tissue. All three were correctly identified prospectively on SPECT-GH; however, one hypernephroma was missed on planar-GH. NMR, CT, and ANGIO detected only one of two hypernephromas prospectively (US detected both); all four modalities incorrectly diagnosed the hypertrophied tissue suggestive of malignancy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46822/1/259_2004_Article_BF00279072.pd

Hair follicle bulge cultures yield class III β-tubulin-positive melanoglial cells

Class III β-tubulin (TUBB3)-positive cells from the hair follicle bulge are thought to be neuronal cells derived from a local neural crest stem cell. However, TUBB3 has recently been shown to be expressed in the melanocytic lineage. To evaluate the neural-crest-associated immunophenotype of TUBB3-positive cells from hair follicle bulge explants, we dissected hair follicle bulges out from mouse whisker pads and cultured for 1 month and assessed outgrowing cells by means of immunocytochemistry using the biomarkers TUBB3, nestin, NGFR, SOX9, TYRP1 and laminin. Large amounts of TUBB3-positive cells could be cultured that co-expressed nestin, NGFR, SOX9 and, to a lesser degree, TYRP1, matching a melanoglial phenotype. In addition, a small population of TUBB3-negative but laminin-positive cells was found, which presumably are of glial origin. It can be concluded that cells of melanoglial origin can easily be obtained from hair follicle bulge explants. These cells may be of use in experimental animal or human disease and wound healing models. Notably, the TUBB3-positive cells are of melanoglial rather than neuronal origin

Hoxb1 Controls Anteroposterior Identity of Vestibular Projection Neurons

The vestibular nuclear complex (VNC) consists of a collection of sensory relay nuclei that integrates and relays information essential for coordination of eye movements, balance, and posture. Spanning the majority of the hindbrain alar plate, the rhombomere (r) origin and projection pattern of the VNC have been characterized in descriptive works using neuroanatomical tracing. However, neither the molecular identity nor developmental regulation of individual nucleus of the VNC has been determined. To begin to address this issue, we found that Hoxb1 is required for the anterior-posterior (AP) identity of precursors that contribute to the lateral vestibular nucleus (LVN). Using a gene-targeted Hoxb1-GFP reporter in the mouse, we show that the LVN precursors originate exclusively from r4 and project to the spinal cord in the stereotypic pattern of the lateral vestibulospinal tract that provides input into spinal motoneurons driving extensor muscles of the limb. The r4-derived LVN precursors express the transcription factors Phox2a and Lbx1, and the glutamatergic marker Vglut2, which together defines them as dB2 neurons. Loss of Hoxb1 function does not alter the glutamatergic phenotype of dB2 neurons, but alters their stereotyped spinal cord projection. Moreover, at the expense of Phox2a, the glutamatergic determinants Lmx1b and Tlx3 were ectopically expressed by dB2 neurons. Our study suggests that the Hox genes determine the AP identity and diversity of vestibular precursors, including their output target, by coordinating the expression of neurotransmitter determinant and target selection properties along the AP axis

Visuomotor Cerebellum in Human and Nonhuman Primates

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula–nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed

Structure and flexibility in cortical representations of odour space

The cortex organizes sensory information to enable discrimination and generalization1-4. As systematic representations of chemical odour space have not yet been described in the olfactory cortex, it remains unclear how odour relationships are encoded to place chemically distinct but similar odours, such as lemon and orange, into perceptual categories, such as citrus5-7. Here, by combining chemoinformatics and multiphoton imaging in the mouse, we show that both the piriform cortex and its sensory inputs from the olfactory bulb represent chemical odour relationships through correlated patterns of activity. However, cortical odour codes differ from those in the bulb: cortex more strongly clusters together representations for related odours, selectively rewrites pairwise odour relationships, and better matches odour perception. The bulb-to-cortex transformation depends on the associative network originating within the piriform cortex, and can be reshaped by passive odour experience. Thus, cortex actively builds a structured representation of chemical odour space that highlights odour relationships; this representation is similar across individuals but remains plastic, suggesting a means through which the olfactory system can assign related odour cues to common and yet personalized percepts