Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI), we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.
Understanding the dynamic nature of tumor hypoxia is vital for cancer therapy. The presence of oxygen within a tumor during radiation therapy increases the likelihood of local control. We used a novel interstitial diffuse optical probe to make real-time measurements of blood volume fraction and hemoglobin oxygen saturation within a tumor at a high temporal resolution. This device was initially characterized and benchmarked using a customized vessel designed to control hemoglobin oxygen saturation and blood volume in a solution of blood with different concentrations of an oxygen scavenger, tetrakis (hydroxymethyl) phosphonium chloride. The optical device was found to consistently monitor the changes in oxygen saturation and these changes correlated to the concentration of the oxygen scavenger added. In near-simultaneous measurements of blood volume and oxygen saturation in tumor-bearing mice, the changes in blood volume fraction and oxygen saturation measured with the interstitial diffuse optical probe were benchmarked against photoacoustic imaging system to track and compare temporal dynamics of oxygen saturation and blood volume in a patient-derived xenograft model of hypopharyngeal carcinoma. Positive correlations between our device and photoacoustic imaging in measuring blood volume and oxygen saturation were observed.
Purpose: It is now commonplace to handle treatments of hyperthyroidism using iodine‐131 as an outpatient procedure due to lower costs and less stringent federal regulations. The Nuclear Regulatory Commission has currently updated release guidelines for these procedures, but there is still a large uncertainty in the dose to the public. Current guidelines to minimize dose to the public require patients to remain isolated after treatment. The purpose of this study was to use a low‐cost common device, such as a cell phone, to estimate exposure emitted from a patient to the general public. Methods: Measurements were performed using an Apple iPhone 3GS and a Cs‐137 irradiator. The charge‐coupled device (CCD) camera on the phone was irradiated to exposure rates ranging from 0.1 mR/hr to 100 mR/hr and 30‐sec videos were taken during irradiation with the camera lens covered by electrical tape. Interactions were detected as white pixels on a black background in each video. Both single threshold (ST) and colony counting (CC) methods were performed using MATLAB®. Calibration curves were determined by comparing the total pixel intensity output from each method to the known exposure rate. Results: The calibration curve showed a linear relationship above 5 mR/hr for both analysis techniques. The number of events counted per unit exposure rate within the linear region was 19.5 ± 0.7 events/mR and 8.9 ± 0.4 events/mR for the ST and CC methods respectively. Conclusion: Two algorithms were developed and show a linear relationship between photons detected by a CCD camera and low exposure rates, in the range of 5 mR/hr to 100‐mR/hr. Future work aims to refine this model by investigating the dose‐rate and energy dependencies of the camera response. This algorithm allows for quantitative monitoring of exposure from patients treated with iodine‐131 using a simple device outside of the hospital.
The AN400 Van de Graaff accelerator at the Minnesota State University, Mankato, Applied Nuclear Science Lab has demonstrated utility as an accessible and versatile platform for student research. Despite the limits of low energy, the research team successfully developed projects with applications to the wider radioisotope production community. A target system has been developed for producing and extracting 13 N by the 12 C(d,n) 13 N reaction below 400keV. The system is both reusable and robust, with future applications to higher energy machines producing this important radioisotope for physiological imaging studies with Positron Emission Tomography. Up to 36(±1) % of the 13 N was extracted from the graphite matrix when 35 A current was externally applied to the graphite target while simultaneously flushing the target chamber with CO 2 gas.
Purpose: Oscillatory dynamics in acute hypoxia have been observed, but poorly understood. They have mostly been attributed to vascular perturbations, but no link has yet been made to metabolic causes. We set out to determine the fundamental frequencies and test for coherence in tumor oxygen dynamics and spatial properties. Methods: Severe combined immunodeficient (SCID) mice were inoculated onto bilateral flanks with human derived head and neck carcinoma (UW‐SCC22) cell line xenografts. Oxygen dynamics were monitored in the tumor every minute for an hour using three modalities: blood oxygen level dependent ‐ magnetic resonance imaging (BOLD‐MRI), hemoglobin oxygen saturation photoacoustic, and locally manufactured optical probes for spectral fitting. A statistical test was used to separate fluctuating from non‐fluctuating voxels and pixels in BOLD‐MRI and photoacoustic data respectively. The power spectrum density (PSD) and the autocorrelation functions were calculated for the time series of each voxel, pixel and region, of the BOLD‐MRI, photoacoustic or fiber optic data respectively. Results: Using all three techniques, intermittent oxygen dynamics with both coherent and incoherent signatures was observed in the tumors. Upon averaging the PSDs of fluctuating voxels and pixels, it was found that these oscillations occurred with periods of minutes to tens of minutes from all three approaches. Observations from the BOLD‐MRI and photoacoustic data showed that clusters of voxels oscillated in a synchronized manner. Conclusion: We were able to use three different modalities to show that fluctuation in tumor oxygen is both coherent and incoherent, with periods of minutes to tens of minutes. These periods are very similar to those from the well‐established metabolic, non‐linear biomechanical phenomenon called the glycolytic oscillator. This may provide an additional explanation to the cause of cyclic hypoxia. Such dynamics could have profound implications in hypofractionated radiotherapy regiments and could help guide treatment and make it more patient specific. The authors would like to thank the University of Wisconsin Carbone Cancer Center (UWCCC) for the funds to complete this project. This work is also supported in part by NIH/NCI P30 CA014520‐ UW Comprehensive Cancer Center Support”.
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