Nuclear magnetic resonance micro-imaging of the human eye lens

The exact causes of presbyopia and the development of senile cataract are still unclear. In this project magnetic resonance microscopy (MRM) has been used to study the kinetics of long-range water transport, anisotropic diffusion and refractive index distribution in the human eye lens. A decline in the transpmi process, changes to the nature of anisotropic diffusion and changes to the refractive index distribution in the lens may all be related to the onset of presbyopia and cataract. The results of the long-range water transport experiments showed that as lenses age there is reduction in the rate at which water (and presumably also water soluble low molecular weight metabolites) can enter the cells of the lens nucleus via the epithelium and cortex. Since this is the mechanism by which nuclear cells can obtain nutrients and anti-oxidants to protect the crystallins from degradation, the decrease in transport rates could lead to increased damage to lenses with age, and ultimately a potential cause of presbyopia and senile cataract. Using a modified pulsed field gradient spin echo (PFGSE) sequence, diffusion tensor maps of human lenses were acquired to study the nature of anisotropic diffusion. The nature of diffusive transport as measured by this technique was found to be related to the known morphology o the human lens. A barrier to diffusion in a region surrounding the lens nuclei was observed. Changes to the permeability of this barrier with age were also found to be significant. This may be partly responsible for degeneration of lens function and contribute to presbyopia and senile cataract. A Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used to study the nature of transverse relaxation in lenses and lens homogenates. The rate of this relaxation (R2) was found to be linearly related to the refractive index. The refractive index distribution in intact human lenses was then acquired by obtaining spatial image maps of R2 using a modified CPMG imaging sequence. The results ofthese measurements show subtle but potentially important differences in refractive index distribution from those currently used in models of the lens refractive index gradient. The results also provide new insight into changes in the refractive index distribution with aging. These changes may contribute to presbyopia and help to explain the "lens paradox"

Nuclear magnetic resonance micro-imaging of the human eye lens

The exact causes of presbyopia and the development of senile cataract are still unclear. In this project magnetic resonance microscopy (MRM) has been used to study the kinetics of long-range water transport, anisotropic diffusion and refractive index distribution in the human eye lens. A decline in the transpmi process, changes to the nature of anisotropic diffusion and changes to the refractive index distribution in the lens may all be related to the onset of presbyopia and cataract. The results of the long-range water transport experiments showed that as lenses age there is reduction in the rate at which water (and presumably also water soluble low molecular weight metabolites) can enter the cells of the lens nucleus via the epithelium and cortex. Since this is the mechanism by which nuclear cells can obtain nutrients and anti-oxidants to protect the crystallins from degradation, the decrease in transport rates could lead to increased damage to lenses with age, and ultimately a potential cause of presbyopia and senile cataract. Using a modified pulsed field gradient spin echo (PFGSE) sequence, diffusion tensor maps of human lenses were acquired to study the nature of anisotropic diffusion. The nature of diffusive transport as measured by this technique was found to be related to the known morphology o the human lens. A barrier to diffusion in a region surrounding the lens nuclei was observed. Changes to the permeability of this barrier with age were also found to be significant. This may be partly responsible for degeneration of lens function and contribute to presbyopia and senile cataract. A Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used to study the nature of transverse relaxation in lenses and lens homogenates. The rate of this relaxation (R2) was found to be linearly related to the refractive index. The refractive index distribution in intact human lenses was then acquired by obtaining spatial image maps of R2 using a modified CPMG imaging sequence. The results ofthese measurements show subtle but potentially important differences in refractive index distribution from those currently used in models of the lens refractive index gradient. The results also provide new insight into changes in the refractive index distribution with aging. These changes may contribute to presbyopia and help to explain the "lens paradox"

Development and Implementation of a Corriedale Ovine Brain Atlas for Use in Atlas-Based Segmentation

<div><p>Segmentation is the process of partitioning an image into subdivisions and can be applied to medical images to isolate anatomical or pathological areas for further analysis. This process can be done manually or automated by the use of image processing computer packages. Atlas-based segmentation automates this process by the use of a pre-labelled template and a registration algorithm. We developed an ovine brain atlas that can be used as a model for neurological conditions such as Parkinson’s disease and focal epilepsy. 17 female Corriedale ovine brains were imaged in-vivo in a 1.5T (low-resolution) MRI scanner. 13 of the low-resolution images were combined using a template construction algorithm to form a low-resolution template. The template was labelled to form an atlas and tested by comparing manual with atlas-based segmentations against the remaining four low-resolution images. The comparisons were in the form of similarity metrics used in previous segmentation research. Dice Similarity Coefficients were utilised to determine the degree of overlap between eight independent, manual and atlas-based segmentations, with values ranging from 0 (no overlap) to 1 (complete overlap). For 7 of these 8 segmented areas, we achieved a Dice Similarity Coefficient of 0.5–0.8. The amygdala was difficult to segment due to its variable location and similar intensity to surrounding tissues resulting in Dice Coefficients of 0.0–0.2. We developed a low resolution ovine brain atlas with eight clinically relevant areas labelled. This brain atlas performed comparably to prior human atlases described in the literature and to intra-observer error providing an atlas that can be used to guide further research using ovine brains as a model and is hosted online for public access.</p></div

Segmentation Metrics.

<p>Segmentation Metrics.</p

Dice Similarity Coefficients of all structures in the low resolution template.

<p>Values range from 0.12 for the amygdala to 0.75 for the cerebellum. Red = Ventricles, Green = Right Motor Cortex, Dark Blue = Left Motor Cortex, Yellow = Hippocampus, Light Blue = Thalamus, Purple = Caudate Nucleus, Peach = Amygdala, Grey = Cerebellum, Brown = Intraobserver Error. Error bars show the standard deviation of the mean for all compared structures. Intraobserver Error was calculated by comparing manual segmentations of all seven labelled structures in the four test subjects. Number of test subjects (n = 4).</p

The (a) skulled template and (b) deskulling mask.

<p>Variability displayed in extracortical areas reinforces the reason why deskulling is an important step in pre-processing.</p

Deskulling Metrics.

<p>Deskulling Metrics.</p

Methods Flowchart.

<p>To create a template, an input image (template subject) undergoes a sequence of processing steps (black boxes) such as pre-processing, template construction, labelling and registration to finally output a labelled image. Red boxes represent input and output images.</p

Atlas—Template and Associated Labels.

<p>Segmented Atlas showing (1) Ventricles, (2) Motor Cortices, (3) Hippocampi, (4) Thalami, (5) Caudate (6) Amygdala and (7) Cerebellum illustrating the (a) transverse, (b) parasagittal, (d) dorsal planes and (c) 3d rendering of labels on a ventrolateral view with rostral to the left of the image.</p

Box plot displaying the average of all comparisons performed across all segmented structures.

<p>Shows the median Dice Similarity Coefficient to be 0.61 with the False Positive and False Negative values having a very large variation. This indicates a wide spread in the accuracy of segmentation with regards to various structures. The Jaccard Coefficient is as expected lower than the Dice proportionally due to single use of the intersect in its calculation leading to a more precise comparison.</p