Hypofractionated stereotactic body radiotherapy treatments (SBRT) have improved patient treatment outcomes. Extensive studies were performed investigating how vascular changes during treatment affect its efficacy. Unfortunately, histology is unable to perform non-invasive longitudinal assessments by directly measuring blood perfusion. Here, we present a novel preclinical theranostic μCT-guided irradiator/Fluorescence Molecular Imager, designed to perform a fast, non-invasive, and longitudinal assessment of tumor vascular response (TVR) to targeted radiotherapy. Our technique allows rapid assessment of spatiotemporal differences in indocyanine green (ICG) kinetics in tumors using principal component (PC) analysis, before and after tumor irradiation. Results show that changes were observed in the normalized first and second PC feature pixel values (p=0.0559, 0.0432 paired t-test). Moreover, we implemented a fast PC-based classification algorithm that yields spatially-resolved TVR maps. Our first-of-its-kind theranostic system, allowing automated assessment of TVR to SBRT, will be used to better understand the role of tumor perfusion in metastasis and tumor control.
Patients with B-ALL (Ph +ve) acute lymphoblastic leukemia are at high risk of relapse and mortality. We seek to establish a mechano-biological testing technique to assess biophysical properties of cell motility, potentiating the ability to distinguish between high and low risk leukemia populations and behaviors. Two experiments were performed to test the mechano-biological behavior of B-ALL using the ThorLabs modular optical tweezers and a microfluid chemotaxis chamber. The first experiment measured the relative mechanical energy carried by a cell in the optical trap, which was performed on B-ALL in control conditions and under SDF1 chemotaxis. The relative mechanical energy was found through an extension of the back-focal-plane calibration method for optical tweezers, and assumed that increased cellular activity manifests as random movements. There was no discernable difference in the relative mechanical energies between the control B-ALL, B-ALL under SDF1 chemotaxis, and B-ALL in the presence of mesenchymal stem cells. The second experiment quantified the real-time migrational force of B-ALL under SDF1 chemotaxis. This was found through prior calibration of the optical tweezers through determination of the terms κ and β. Of the viable measurements, 3 of 8 cells exhibited a significant force towards the SDF1 gradient. Further experimentation is necessary to normalize the experimental set-up conditions, and increase the number of viable measurements during cell migration.
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