Access Type

Open Access Dissertation

Date of Award

1-1-2010

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

Gregory W. Auner

Second Advisor

Abhilash K. Pandya

Abstract

Introduction: Neuroblastoma is the most common cancer of infancy. It is one of several peripheral nervous system tumors, including ganglioneuroma, peripheral nerve sheath tumor, and pheochromocytoma. It is commonly situated on the adrenal gland. It displays similar histology to other small round blue cell tumors, including non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma. One method of judging neuroblastoma aggressiveness uses tumor histology factors, including mitosis-karyorrhexis index, Schwannian stromal development, degree of differentiation, and patient age. Tumor aggressiveness can also be judged based on the amplification of certain genes, including MYCN. Raman spectroscopy is a physics-based method which identifies the biochemical fingerprint of a sample. It has recently been applied to disease classification, specifically in adult cancers.

Methods: To identify neuroblastoma from adrenal gland, peripheral nervous system tumors, and small round blue cell tumors, and to identify tumor histology, fresh and frozen samples were collected from the operating room and tested with Raman spectroscopy. Tissues were assigned a `gold standard' diagnosis by experienced pediatric pathologists. Tumor histology was further evaluated with blinded tissues provided by the Children's Oncology Group. To test identification of gene amplification, the tet-on MYCN-3 cell line was cultured in the presence and absence of tetracycline to induce or repress MYCN gene expression. Cells were harvested and tested with Raman spectroscopy and polymerase chain reaction. All Raman spectra were preprocessed and classified with discriminant function analysis.

Results: Raman spectroscopy identified neuroblastoma from healthy adrenal gland, peripheral nervous system tumors, and small round blue cell tumors with 100% sensitivity and specificity. It identified favorable, unfavorable, and treated neuroblastoma with high accuracy. Neuroblastoma cells with and without MYCN amplification were identified with 100% sensitivity and specificity.

Conclusions: This is the first study applying Raman spectroscopy to identify pediatric tumors, and the first blinded Raman spectroscopy study performed in collaboration with the Children's Oncology Group, a national tumor bank. It provides the first in-depth examination of specific markers of aggressiveness, including tumor favorability and MYCN gene amplification. Raman spectroscopy has the potential to revolutionize the field of cancer diagnostics. It can provide a detailed, accurate diagnosis in minutes instead of days.

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