Room: Track 1
Purpose: examine the sensitivity of wide-field optical imaging (WFOI) to monitor changes in functional connectivity after whole brain irradiation in mice. Genetic engineering techniques in mice have provided new opportunities for extending wide-field optical imaging methods linking hemodynamic measures of brain activity to direct measures of neural activity using fluorescent, genetically encoded calcium indicators (e.g. GCaMP). In this study, we utilize WFOI to capture evolving cortical calcium dynamics in excitatory cells along with hemodynamic activity in awake mice over a 4 week period following whole brain irradiation.
Methods: transgenic Thy1-GCaMP6f mice were irradiated with 11.3Gy to the whole brain using parallel opposed 10mmX10mm beams on small animal irradiation system. Mice were imaged weekly for 4 weeks using WFOI. Resting state functional connectivity (RSFC) was measured over the delta band (0.5Hz-4Hz) by correlating seed time traces in select functional brain regions. Band limited power spectral density of spontaneous, infraslow activity (0.01Hz-0.1Hz) was determined using the Fast Fourier Transform.
Results: to brain irradiation, neural RSFC patterns in somatosensory and retrosplenial cortex exhibit strong connectivity with ipsilateral and homotopic, contralateral cortex. Beginning 1 week post irradiation, RSFC in somatosensory cortex exhibited reduced spatial specificity and appreciably lower RSFC between ipsilateral sensory and motor regions. These trends continued to worsen over the 4 week monitoring period. Similarly, band-limited power of hemodynamic and neural fluctuations of infraslow activity significantly declined over time over the whole brain.
Conclusion: provides a bridge between preclinical imaging results in mouse models and human fMRI findings. Previous studies have demonstrated that WFOI is useful for mapping RSFC in healthy mice and several mouse models of disease. The results show WFOI is also sensitive to evolving patterns of functional brain network connectivity following whole brain irradiation, suggesting that WFOI could be invaluable in pre-clinical studies of cognitive dysfunction in radiotherapy.