Three-dimensional modeling of the human eye based on magnetic resonance imaging

PURPOSE. A methodology for noninvasively characterizing the three-dimensional (3-D) shape of the complete human eye is not currently available for research into ocular diseases that have a structural substrate, such as myopia. A novel application of a magnetic resonance imaging (MRI) acquisition and analysis technique is presented that, for the first time, allows the 3-D shape of the eye to be investigated fully. METHODS. The technique involves the acquisition of a T2-weighted MRI, which is optimized to reveal the fluid-filled chambers of the eye. Automatic segmentation and meshing algorithms generate a 3-D surface model, which can be shaded with morphologic parameters such as distance from the posterior corneal pole and deviation from sphericity. Full details of the method are illustrated with data from 14 eyes of seven individuals. The spatial accuracy of the calculated models is demonstrated by comparing the MRI-derived axial lengths with values measured in the same eyes using interferometry. RESULTS. The color-coded eye models showed substantial variation in the absolute size of the 14 eyes. Variations in the sphericity of the eyes were also evident, with some appearing approximately spherical whereas others were clearly oblate and one was slightly prolate. Nasal-temporal asymmetries were noted in some subjects. CONCLUSIONS. The MRI acquisition and analysis technique allows a novel way of examining 3-D ocular shape. The ability to stratify and analyze eye shape, ocular volume, and sphericity will further extend the understanding of which specific biometric parameters predispose emmetropic children subsequently to develop myopia. Copyright © Association for Research in Vision and Ophthalmology.

Three-dimensional magnetic resonance imaging of the phakic crystalline lens during accommodation

To quantify changes in crystalline lens curvature, thickness, equatorial diameter, surface area, and volume during accommodation using a novel two-dimensional magnetic resonance imaging (MRI) paradigm to generate a complete three-dimensional crystalline lens surface model.

Nuclear magnetic resonance studies of molecular interactions and structures

This thesis is concerned with the investigation, by nuclear magnetic resonance spectroscopy, of the molecular interactions occurring in mixtures of benzene and cyclohexane to which either chloroform or deutero-chloroform has been added. The effect of the added polar molecule on the liquid structure has been studied using spin-lattice relaxation time, 1H chemical shift, and nuclear Overhauser effect measurements. The main purpose of the work has been to validate a model for molecular interaction involving local ordering of benzene around chloroform. A chemical method for removing dissolved oxygen from samples has been developed to encompass a number of types of sample, including quantitative mixtures, and its supremacy over conventional deoxygenation technique is shown. A set of spectrometer conditions, the use of which produces the minimal variation in peak height in the steady state, is presented. To separate the general diluting effects of deutero-chloroform from its effects due to the production of local order a series of mixtures involving carbon tetrachloride, instead of deutero-chloroform, have been used as non-interacting references. The effect of molecular interaction is shown to be explainable using a solvation model, whilst an approach involving 1:1 complex formation is shown not to account for the observations. It is calculated that each solvation shell, based on deutero-chloroform, contains about twelve molecules of benzene or cyclohexane. The equations produced to account for the T1 variations have been adapted to account for the 1H chemical shift variations in the same system. The shift measurements are shown to substantiate the solvent cage model with a cage capacity of twelve molecules around each chloroform molecule. Nuclear Overhauser effect data have been analysed quantitatively in a manner consistent with the solvation model. The results show that discrete shells only exist when the mole fraction of deutero-chloroform is below about 0.08.

Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin

The number of new chemical entities (NCE) is increasing every day after the introduction of combinatorial chemistry and high throughput screening to the drug discovery cycle. One third of these new compounds have aqueous solubility less than 20µg/mL [1]. Therefore, a great deal of interest has been forwarded to the salt formation technique to overcome solubility limitations. This study aims to improve the drug solubility of a Biopharmaceutical Classification System class II (BCS II) model drug (Indomethacin; IND) using basic amino acids (L-arginine, L-lysine and L-histidine) as counterions. Three new salts were prepared using freeze drying method and characterised by FT-IR spectroscopy, proton nuclear magnetic resonance ((1)HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). The effect of pH on IND solubility was also investigated using pH-solubility profile. Both arginine and lysine formed novel salts with IND, while histidine failed to dissociate the free acid and in turn no salt was formed. Arginine and lysine increased IND solubility by 10,000 and 2296 fold, respectively. An increase in dissolution rate was also observed for the novel salts. Since these new salts have improved IND solubility to that similar to BCS class I drugs, IND salts could be considered for possible waivers of bioequivalence.

Proteomic analysis of a noninvasive human model of acute inflammation and its resolution:the twenty-one day gingivitis model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC-MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins.

Bend sensing by measuring the resonance splitting of long-period fiber gratings

An application of long-period fiber gratings (fabricated in standard fiber) as bend sensors is reported. A simple model, taking account of the strain and compression in the fiber cladding, is used to calculate the splitting of the cladding modes and is found to be in excellent agreement with the experimental results. Over 80 nm resonance splitting was observed under a 5.6 m-1 bend curvature giving a bend sensitivity of 14.5 nm/(m-1), the best obtained data so far. © 2001 Elsevier Science B.V.