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Title:Ex vivo proton magnetic resonance spectroscopy (1HMRS) of normal, reactive and malignant canine lymph nodes: evaluation of the choline metabolite as a marker for malignancy
Author(s):Lynch, Katherine
Advisor(s):O'Brien, Robert T.
Department / Program:Vet Clinical Medicine
Discipline:VMS-Veterinary Clinical Medcne
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):magnetic resonance spectroscopy
cancer imaging
Abstract:Advanced imaging of veterinary cancer patients has evolved in recent years and modalities once limited to human medicine have now been described for diagnostic purposes in veterinary medicine (positron emission tomography/computed tomography, single-photon emission computed tomography, whole body magnetic resonance imaging). Magnetic resonance spectroscopy (MRS) is a non-invasive and non-ionizing technique that is well described in the human medical literature and is most frequently used to evaluate the metabolic activity of tissues with questionable malignant transformation. Differentiation of neoplastic tissue from surrounding normal tissue is dependent on variations in cellular metabolism. Choline (Cho) levels have been described as diagnostic markers for malignancy for many different tumor types in vivo and ex vivo (tissue biopsies). Monitoring of pre- and post-therapy choline metabolites in tumors has also been performed to evaluate a patient’s response to cancer treatment. Positive identification of malignancy can be made when neoplastic alterations are occurring at the cellular level prior to gross anatomic changes. This improved, early detection of cancer occurrence (or recurrence) can improve patient survival and direct medical therapy. MRS techniques are largely underutilized in veterinary medicine, with current research predominantly limited to the brain (both evaluation of normal and diseased tissue). Given the clinical utility of MRS in humans, the technique may also be useful in the staging of cancer in veterinary medicine. The first phase of this thesis provides a comprehensive review of 1HMRS in human patients, and discusses current modalities utilized for diagnostic imaging of veterinary oncology patients. The second phase of the thesis aims to characterize the detectability of the choline metabolite in canine lymph nodes ex vivo, and compare choline ii levels (via choline signal-to-noise ratio or Cho SNR) among populations of normal, reactive, and malignant lymph nodes. Our hypothesis was that choline would be detectable in canine lymph nodes ex vivo, and that the Cho SNR in malignant lymph nodes would be significantly higher than in normal and reactive lymph nodes. Peripheral, abdominal, or thoracic lymph nodes were collected intra-operatively or immediately post-euthanasia from 19 canine patients. Lymph nodes were immediately flash frozen and stored at -80 degrees Celsius until the time of imaging. High field (14.1T) 1HMRS was performed on each lymph node. Choline signal-to-noise ratios (Cho SNR) were calculated and compared between the three groups. A total of 54 lymph nodes were collected (37 malignant, 8 moderately to severely reactive/lymphoid hyperplasia, 9 normal/mildly reactive). A Cho SNR>/2 was significantly associated with malignancy (P<0.001). The Cho SNR was significantly higher in the malignant population than in both the normal (p<0.001) and reactive (p=0.001) populations. There was no significant difference in the Cho SNR between the normal and reactive group (p=0.920). Overall, 1HMRS detected malignancy via elevation of the choline metabolite with a sensitivity, specificity, positive and negative predictive value of 80.4%, 94.4%, 97.4%, and 65.4% respectively. We conclude that the choline metabolite is detectable in canine lymph nodes ex vivo, and that malignant lymph nodes have a higher Cho SNR than normal and reactive nodes. Detection of malignancy via elevation of the choline metabolite may be useful in future studies involving 1HMRS in clinical patients.
Issue Date:2014-09-16
Rights Information:Copyright 2014 Katherine Lynch
Date Available in IDEALS:2014-09-16
Date Deposited:2014-08

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