Noninvasive Monitoring of Radiation-Induced Salivary Gland Vascular Injury

Abstract

Xerostomia is a common side effect of radiation therapy (RT) in patients with head and neck cancer. However, limited information is available on the temporal dynamics of parenchymal and vascular changes in salivary glands following RT. To address this gap in knowledge, we conducted experimental studies in mice employing ultrasound (US) with coregistered photoacoustic imaging (PAI) to noninvasively assess the early and late changes in salivary gland size, structure, vascularity, and oxygenation dynamics following RT. Multiparametric US-PAI of salivary glands was performed in immune-deficient and immune-competent mice before and after RT along with correlative sialometry and ex vivo histologic-immunohistochemical validation. US revealed reduction in gland volume and an early increase in vascular resistance postradiation. This was accompanied by a reduction in glandular oxygen consumption on PAI. Imaging data correlated strongly with salivary secretion and histologic evidence of acinar damage. The magnitude and kinetics of radiation response were impacted by host immune status, with immunodeficient mice showing early and more pronounced vascular injury and DNA damage response compared to immunocompetent animals. Our findings demonstrate the ability of noninvasive US-PAI to monitor dynamic changes in salivary gland hemodynamics following radiation and highlight the impact of the host immune status on salivary gland radiation injury.

Ultrasound-Guided Photoacoustic Imaging of Salivary Gland Hemodynamics in Rabbits

“…No change in parotid gland hemodynamics (HbT/%sO 2 ) was observed in control rabbits between the two imaging sessions (d0 and d8), highlighting the reliability of PAI. These results, along with our published studies in mice [16][17][18], confirm the ability of PAI to reliably measure salivary gland hemodynamics.…”

“…To date, a comparative assessment of the salivary gland radiation response between mice and rabbits has not been reported. In our previous study [18], immunocompetent mice exposed to a single high dose of radiation did not show any change in HbT or %sO 2 at 1 week post RT. In comparison, we observed an increase in HbT and %sO 2 at 1 week post RT in rabbits, which suggests that the kinetics of radiation-induced vascular injury may vary between rabbits mice.…”

“…Our studies in murine models have validated US-PAI measures of salivary gland hemodynamics with histology and demonstrated the strong correlation between a vascular response to parasympathetic stimulation or blockade and saliva secretion [16,17]. Recently, we have also examined the ability of US-PAI to monitor the early and late vascular response of murine salivary glands to radiation [18]. However, to the best of our knowledge, the safety and performance of US-PAI for evaluation of salivary gland hemodynamics in rabbits has not been evaluated.…”

“…We have recently demonstrated the potential of PAI to non-invasively monitor radiation injury in murine models [18]. Building on our previous work, in the present study, we assessed acute changes in parotid gland hemodynamics (HbT/sO 2 ) following radiation treatment in rabbits.…”