An optimized 3T MRI scan protocol to assess iris melanoma with subsequent histopathological verification - A prospective study.

INTRODUCTION: Magnetic resonance imaging (MRI) has demonstrated high levels of tissue contrast, accuracy and reproducibility in evaluating posterior uveal melanoma. Owing to smaller size, the role of MRI in detecting and characterising iris melanoma has not yet been explored. AIMS: To develop a protocol to image iris melanoma and describe the MRI characteristics of histopathological-confirmed iris melanoma. MATERIALS AND METHODS: An optimised MRI protocol, using a 3T MRI scanner and a 32-channel head coil, was developed to image iris tumours. A prospective, single-centre, 12-month study was conducted on all patients with lesions suspicious for iris melanoma. All patients were offered an MRI scan in addition to the standardised clinical procedures. Image quality comparison was made with existing clinical investigations. Iris melanoma characteristics on MRI are described. RESULTS: A successful optimised MRI scan protocol was developed that was able to detect and characterise iris melanoma. One normal participant and five patients with subsequent histopathological-confirmed iris melanoma (n = 6) were recruited. Four patients completed the full MRI sequence. All iris melanoma were detected on at least one T1- or T2-weighted images. When compared to the vitreous, all iris melanomas demonstrated hyper-intensity on T1-weighted images and hypo-intensity on T2-weighted images. On T1-mapping, T1-values of iris melanoma demonstrated an inverse relationship with the degree of tumour pigmentation. CONCLUSIONS: This study highlights an optimised, easily reproducible MRI scan protocol to image iris melanoma. Numerous MR imaging characteristics of iris melanoma are reported for the first time and a potential non-invasive tumour biomarker is described.

Alterations in Lens Free Water Distribution Are Associated with Shape Deformation in Accommodation.

Objective: To investigate whether a redistribution of water within the crystalline lens is associated with the shape deformation that occurs during accommodation. Design: Observational, cross sectional study. Subjects: Eleven young adults without presbyopia (aged 18-39 years) and 9 middle-aged adults with presbyopia (aged 40-55 years). Methods: Magnetic resonance imaging (MRI) scans of the lens were acquired on a 3 Tesla clinical MRI scanner, without and with the presentation of a 3 Diopter accommodative stimulus. The MRIs were postprocessed using established methods to extract the geometric dimensions and spatial maps of water distribution of the lens. Main Outcome Measures: Accommodative changes in the full 3-dimensional description of lens shape, the lens total-water distribution profile, and the lens free-water distribution profile. Results: Viewing of an accommodative stimulus by young subjects elicited an elastic shape deformation of the lens consistent with accommodation that was associated with an elevated, smoother free-water distribution, primarily in the anterior region of the lens. In contrast, viewing of an accommodative stimulus by presbyopic subjects produced an atypical shape deformation of the lens that was instead associated with a lowered free-water distribution, primarily in the anterior region of the lens. No discernible changes to the lens total-water distribution were observed in response to the accommodative stimulus in either subject cohort. Conclusions: The present study suggests that protein-mediated alterations in the free-water distribution of the anterior region of the lens influence the shape deformation in accommodation, presenting pharmacological modulation of free-water distribution as an attractive novel approach for treating presbyopia. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Age-Dependent Changes in the Water Content and Optical Power of the In Vivo Mouse Lens Revealed by Multi-Parametric MRI and Optical Modeling.

Purpose: The purpose of this study was to utilize in vivo magnetic resonance imaging (MRI) and optical modeling to investigate how changes in water transport, lens curvature, and gradient refractive index (GRIN) alter the power of the mouse lens as a function of age. Methods: Lenses of male C57BL/6 wild-type mice aged between 3 weeks and 12 months (N = 4 mice per age group) were imaged using a 7T MRI scanner. Measurements of lens shape and the distribution of T2 (water-bound protein ratios) and T1 (free water content) values were extracted from MRI images. T2 values were converted into the refractive index (n) using an age-corrected calibration equation to calculate the GRIN at different ages. GRIN maps and shape parameters were inputted into an optical model to determine ageing effects on lens power and spherical aberration. Results: The mouse lens showed two growth phases. From 3 weeks to 3 months, T2 decreased, GRIN increased, and T1 decreased. This was accompanied by increased lens thickness, volume, and surface radii of curvatures. The refractive power of the lens also increased significantly, and a negative spherical aberration was developed and maintained. Between 6 and 12 months of age, all physiological, geometrical, and optical parameters remained constant, although the lens continued to grow. Conclusions: In the first 3 months, the mouse lens power increased as a result of changes in shape and in the GRIN, the latter driven by the decreased water content of the lens nucleus. Further research into the mechanisms regulating this decrease in mouse lens water could improve our understanding of how lens power changes during emmetropization in the developing human lens.

Age-Dependent Changes in Total and Free Water Content of In Vivo Human Lenses Measured by Magnetic Resonance Imaging.

Purpose: To use magnetic resonance imaging (MRI) to measure age-dependent changes in total and free water in human lenses in vivo. Methods: Sixty-four healthy adults aged 18 to 86 years were recruited, fitted with a 32-channel head receiver coil, and placed in a 3 Tesla clinical MR scanner. Scans of the crystalline lens were obtained using a volumetric interpolated breath-hold examination sequence with dual flip angles, which were corrected for field inhomogeneity post-acquisition using a B1-map obtained using a turbo-FLASH sequence. The spatial distribution and content of corrected total (ρlens) and free (T1) water along the lens optical axis were extracted using custom-written code. Results: Lens total water distribution and content did not change with age (all P > 0.05). In contrast to total water, a gradient in free water content that was highest in the periphery relative to the center was present in lenses across all ages. However, this initially parabolic free water gradient gradually developed an enhanced central plateau, as indicated by increasing profile shape parameter values (anterior: 0.067/y, P = 0.004; posterior: 0.050/y, P = 0.020) and central free water content (1.932 ms/y, P = 0.022) with age. Conclusions: MRI can obtain repeatable total and free water measurements of in vivo human lenses. The observation that the lens steady-state free, but not total, water gradient is abolished with age raises the possibility that alterations in protein-water interactions are an underlying cause of the degradation in lens optics and overall vision observed with aging.

Using the Lens Paradox to Optimize an In Vivo MRI-Based Optical Model of the Aging Human Crystalline Lens.

Purpose: To optimize our in vivo magnetic resonance imaging (MRI)-based optical model of the human crystalline lens, developed with a small group of young adults, for a larger cohort spanning a wider age range. Methods: Subjective refraction and ocular biometry were measured in 57 healthy adults ages 18 to 86 years who were then scanned using 3T clinical magnetic resonance imaging (MRI) to obtain lens gradient of refractive index (GRIN) and geometry measurements. These parameters were combined with ocular biometric measurements to construct individualized Zemax eye models from which ocular refractive errors and lens powers were determined. Models were optimized by adding an age-dependent factor to the transverse relaxation time (T2)-refractive index (n) calibration to match model-calculated refractive errors with subjective refractions. Results: In our subject cohort, subjective refraction shifted toward hyperopia by 0.029 diopter/year as the lens grew larger and developed flatter GRINs with advancing age. Without model optimization, lens powers did not reproduce this clinically observed decrease, the so-called lens paradox, instead increasing by 0.055 diopter/year. However, modifying the T2-n calibration by including an age-dependent factor reproduced the decrease in lens power associated with the lens paradox. Conclusions: After accounting for age-related changes in lens physiology in the T2-n calibration, our model was capable of accurately measuring in vivo lens power across a wide age range. This study highlights the need for a better understanding of how age-dependent changes to the GRIN impact the refractive properties of the lens. Translational Relevance: MRI is applied clinically to calculate the effect of age-related refractive index changes in the lens paradox.

Multi-parametric MRI of the physiology and optics of the in-vivo mouse lens.

The optics of the ocular lens are determined by its geometry (shape and volume) and its inherent gradient of refractive index (water to protein ratio), which are in turn maintained by unique cellular physiology known as the lens internal microcirculation system. Previously, magnetic resonance imaging (MRI) has been used on ex vivo organ cultured bovine lenses to show that pharmacological perturbations to this microcirculation system disrupt ionic and fluid homeostasis and overall lens optics. In this study, we have optimised in vivo MRI protocols for use on wild-type and transgenic mouse models so that the effects of genetically perturbing the lens microcirculation system on lens properties can be studied. In vivo MRI protocols and post-analysis methods for studying the mouse lens were optimised and used to measure the lens geometry, diffusion, T1 and T2, as well as the refractive index (n) calculated from T2, in wild-type mice and the genetically modified Cx50KI46 mouse. In this animal line, gap junctional coupling in the lens is increased by knocking in the gap junction protein Cx46 into the Cx50 locus. Relative to wild-type mice, Cx50KI46 mice showed significantly reduced lens size and radius of curvature, increased T1 and T2 values, and decreased n in the lens nucleus, which was consistent with the developmental and functional changes characterised previously in this lens model. These proof of principle experiments show that in vivo MRI can be applied to transgenic mouse models to gain mechanistic insights into the relationship between lens physiology and optics, and in the future suggest that longitudinal studies can be performed to determine how this relationship is altered by age in mouse models of cataract.

Relationship between rheological properties and transverse relaxation time (T2) of artificial and porcine vitreous humour.

Vitreous liquefactive processes play an integral role in ocular health. Knowledge of the degree of liquefaction would allow better monitoring of ocular disease progression and enable more informed therapeutic dosing for an individual patient. Presently this process cannot be monitored in a non-invasive manner. Here, we evaluated whether magnetic resonance imaging (MRI) could predict the viscoelasticity and in turn liquefactive state of artificial and biological vitreous humour. Gels comprising identical concentrations of hyaluronic acid and agar ranging from 0.125 to 2.25 mg/ml of each polymer were prepared and their T2 was measured using a turbo-spin echo sequence via 3T clinical MRI. The gels were subsequently subjected to rheological frequency and flow sweeps and trends between T2 and rheological parameters were assessed. The relationship between T2 and vitreous humour rheology was further assessed using ex vivo porcine eyes. An optimised imaging technique improved homogeneity of obtained artificial vitreous humour T2 maps. Strong correlations were observed between T2 and various rheological parameters of the gels. Translation to porcine vitreous humour demonstrated that the T2 of biological tissue was related to its viscoelastic properties. This study shows that T2 can be correlated with various rheological parameters within gels. Future investigations will assess the translatability of these findings to live models.

Development of an in vivo magnetic resonance imaging and computer modelling platform to investigate the physiological optics of the crystalline lens.

We have developed and validated in vivo magnetic resonance imaging (MRI) protocols to extract parameters (T2 and geometry) of the human lens that, combined with biometric measures of the eye and optical modelling, enable us to investigate the relative contributions made by the gradient of refractive index (GRIN) and the shape of the lens to the refractive properties of each subject tested. Seven young and healthy participants (mean age: 25.6 ± 3.6 years) underwent an ophthalmic examination, and two sessions of MRI scans using a 3 T clinical magnet. Our MRI protocols for studying lens physiological optics and geometrical measurements were repeatable and reliable, using both 1D (95% confidence interval (CI) for mean differences for exponents = [-2.1, 2.6]) and 2D analysis (anterior T2 CI for differences [-6.4, 8.1] ms; posterior T2 CI for differences [-6.4, 8.3] ms). The lens thickness measured from MRI showed good correlation with that measured with clinical 'gold standard' LenStar (mean differences = [-0.18, 0.2] mm). The predicted refractive errors from ZEMAX had reasonable agreements with participants' clinic records (mean differences = [-1.7, 1.2] D). Quantitative measurements of lens geometry and GRIN with our MRI technique showed high inter-day repeatability. Our clinical MRI technique also provides reliable measures of lens geometry that are comparable to optical biometry. Finally, our ZEMAX optical models produced accurate refractive error and lens power estimations.

Detection of the Recovery Phase of in vivo gastric slow wave recordings.

Gastric motility is coordinated by bio-electrical events known as slow waves. Abnormalities in slow waves are linked to major functional and motility disorders. In recent years, the use of high-resolution (HR) recordings have provided a unique view of spatiotemporal activation profiles of normal and dysrhythmic slow wave activity. To date, in vivo studies of gastric slow wave activity have primarily focused on the activation phase of the slow wave event. In this study, the recovery phase of slow waves was investigated through the use of HR recording techniques. The recovery phase of the slow wave event was detected through the use of the signal derivative, computed via a wavelet transform. The activation to recovery interval (ARi) metric was computed as a difference between the recovery time and activation time. The detection method was validated with synthetic slow wave signals of varying morphologies with the addition of synthetic ventilator and high frequency noise. The methods was then applied to HR experimental porcine gastric slow wave recordings. Ventilator noise more than 10% of the slow wave amplitude affected the estimation of the ARi metric. Signal to noise ratio below 3 dB affected the ARi metric, but with minor deviation in accuracy. Experimental ARi values ranged from 3.7-4.7 s from three data sets, with significant differences across them.