Electronic Theses and Dissertations

Identifier

1325

Date

2015

Date of Award

4-2-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Engineering

Committee Chair

Eugene Eckstein

Committee Member

Erno Lindner

Committee Member

Amy Curry

Abstract

Retinoblastoma is an early childhood cancer presenting in about 1 of 20,000 new births, with about 200 to 300 new cases reported in the US every year. This aggressive retinal cancer is associated with loss-of-function mutations of the RB1 gene. With survival rates above 95%, preserving vision and improving quality of life for survivors is a major focus of current research. The present study investigated the validity of visual cortex activation estimates obtained from retinotopic projection of ocular lesion maps (tumor and retinal detachment) as predictors of the visual cortex response to photic stimulation measured with functional MRI. The study was based on anatomical MRI, functional neuroimaging, and clinical data acquired from 106 patients enrolled in a prospective retinoblastoma protocol at St. Jude Children's Research Hospital. Lesion contours were manually mapped and represented on a retinal polar coordinate system. Accuracy of lesion mapping was verified by comparing the mapped lesion contours with fundoscopic imaging. The numerical representation of lesion contours was processed with a conformal transformation to approximate the corresponding retinotopic cortical maps. Mapping was successful for 152 tumors in 67 patients and 91 affected eyes. Retinal and cortical lesion maps were processed to predict lesion burden densities, lesion effects on visual outcomes, and cortical activation at group level in populations defined in terms of age at diagnosis, type of mutation (somatic or germline), or laterality of disease (unilateral or bilateral). These estimates failed to predict the corresponding fMRI group activation maps. Spatial point analysis of retinal tumor centroids revealed the existence of age-dependent spatial patterns of occurrence affecting temporal and nasal hemiretinas. Distinct patterns of lesion density and visual outcome reduction also were age-dependent. Age-at-diagnosis distributions in the St. Jude cohort substantially differed from distributions described in previous publications. The statistical analysis of these distributions yielded a robust model accurately fitting datasets acquired in the last 70 years, constituting an alternative to currently accepted models supporting key cancer research concepts like the two-hit hypothesis of carcinogenesis.

Comments

Data is provided by the student.

Library Comment

dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.

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