Seminar

Medical Physics Seminar – Monday, March 11, 2019

Intrinsic microenvironment fluorescence signals in clinically relevant wound healing models

speaker

Alexandra Schroeder (student of Dr. Kevin Eliceiri)
Research Assistant, Department of Medical Physics, UW-School of Medicine & Public Health, Madison, WI - USA

One of the primary challenges during surgery is to define, detect and remove cancerous or damaged tissue while sparing viable tissue. Fluorescence imaging offers the ability to obtain high spatial resolution information regarding wound healing using intrinsic excitation or extrinsic contrast. There is great need within the surgical suite to identify viable tissue from necrotic skin on burn victims as well as differentiate brain tumor tissue from normal brain. In particular there is significant interest in label free approaches to facilitate clinical adoption. In this talk we present two intrinsic fluorescent probes, collagen and NADH as candidates for biomedical studies of wound healing in burns and brain tumors including eventual surgical application. In both wound cases, collagen - the most abundant protein in the body - has been shown to play a key role. Collagen's non-centrosymmetric structure allows for unstained imaging using second harmonic generation (SHG) imaging on a multiphoton microscope. We have shown in glioblastoma multiforme (GBM), a malignant primary brain cancer, that collagen structure is prognostic and changes depending on GBM invasiveness. The presence of glioblastoma stem cells (GSCs) in GBM create a heterogeneous environment prone to recurrence if cells are left behind, highlighting the significance in understanding more about the changes cancer imposes on the tumor microenvironment including emerging biomarkers such as collagen structure and metabolism. Nicotinamide adenine dinucleotide (NADH) is an autofluorescent electron carrier during metabolism and has been used as a biomarker for examining variations in cancer metabolism. Through the use of fluorescence lifetime imaging microscopy (FLIM) on the same multiphoton microscope, the intrinsic fluorescence of NADH can be captured to examine the bound and free states of NADH. FLIM is measure of how long fluorescence stays in an excited state and the binding of proteins such as NADH can change the fluorescence lifetime value. Measured values of free and bound NADH in cancer can give valuable insight into metabolic processes such as glycolysis. These intrinsic biomarkers can be combined with extrinsic fluorescence labels for improved mechanistic understanding. As an example we show in burn victims, a collagen-mimetic peptide with an attached cyanine fluorophore binding to damaged collagen, can provide contrast to determine burn depth in the clinic. Leveraging both intrinsic and extrinsic fluorescence signals can offer clinicians enhanced information regarding the wound response.


Development of a framework for the quantitative assessment of treatment response in head and neck PET/MRI

speaker

Alexander Antolak (student of Ed Jackson)
Research Assistant, Department of Medical Physics, UW-School of Medicine & Public Health, Madison, WI - USA

Assessment of treatment response in head and neck cancer is crucial to ensure maximal tumor control and minimal side effects of treatment. Quantitative imaging biomarker measures using MRI and PET data have demonstrated potential for early assessment of the effects of radiation therapy on both tumor and normal tissues, and may provide a means of guiding adaptive therapy delivery. However, longitudinal assessment of quantitative imaging biomarkers requires a comprehensive quality control program to ensure that device and analysis software levels of bias and variance are characterized and mitigated to the degree possible and to establish the confidence intervals on the quantitative imaging biomarker measurements. The purpose of this work is to develop an optimized imaging protocol for PET/MRI head and neck studies and to assess and track equipment and software levels of bias and variance with physical and digital phantoms. Preliminary results are shown from a clinical trial investigating dose de-escalation strategies in a population of oropharyngeal cancer patients.


Location: 1325 HSLC (Health Sciences Learning Center), 750 Highland Ave., Madison, WI 53705 - USA

Time: 4:00pm-5:00pm