Ranji, Mahsa

Metabolic dysfunction can present in conditions like cancer and neurodegeneration. Optical imaging techniques were employed to assist in the diagnosis and understanding of disease pathologies. A cryomesoscopy modality was designed and incorporated into an imaging device to investigate metabolic biomarkers. The new lens design provided higher magnifications and resolution of tissue data. The improved imaging capabilities gave detailed access to structural and biochemical changes that occur in disease progression. Cryomesoscopy was applied to study mitochondrial redox state in preclinical models of Alzheimer’s and cancer. The optical imaging tools were utilized to visualize the livers and kidneys of mutated mice and investigate their metabolic states. The results in both investigations revealed oxidized metabolic states, a marker of oxidative stress and metabolic dysfunction. The cryomesoscopy system has proven instrumental in quantifying metabolic shifts and offers new insights into disease pathologies. Optical imaging can be applied to understanding metabolic mechanisms in many diseases.

Significant efforts are being made to understand and treat cancer, though methods are costly, invasive, and detrimental to healthy surrounding tissues. Techniques in optical imaging assess cancer cells’ state in response to treatments. The purpose of this study is to employ non-ionizing radiation as a potential safer therapeutic option and use timelapse fluorescence microscopy to monitor and quantify treatments to lung cancer cells. This thesis (1) measures and visualizes effects of a combinatory repurposed drug treatment through monitoring cellular metabolic state with time-lapse fluorescence microscopy and (2) develops a non-ionizing electromagnetic radiation system as a possible therapy modality. Results obtained demonstrate the effectiveness of a combinatory drug treatment and promising capability of non-ionizing radiation treatment, determined by an increase in fluorescence intensity correlated with metabolic state. In the future, different irradiation doses and drug combinations will be used for additional cancer cell lines, such as prostate and breast cancer.