Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models

Abstract

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying objective non-invasive criteria for predicting imminent distress and mortality in metastatic lung tumor-bearing mice. BALB/c and C57BL/6 mice were inoculated with CT26 or B16F10 cells, respectively. The mice were housed in Vium smart cages to continuously monitor and stream respiratory rate and locomotion for up to 28 days until scheduled euthanasia or humane endpoint criteria were met. Body weight and body temperature were measured during the study. On days 11, 14, 17 and 28, lungs of subsets of animals were microCT imaged in vivo to assess lung metastasis progression and then euthanized for lung microscopic evaluations. Beginning at day 21, most tumor-bearing animals developed increased respiratory rates followed by decreased locomotion 1–2 days later, compared with the baseline values. Increases in respiratory rate did not correlate to surface tumor nodule counts or lung weight. Body weight measurement did not show significant changes from days 14–28 in either tumor-bearing or control animals. We propose that increases in respiratory rate (1.3–1.5 X) can be used to provide an objective benchmark to signal the need for increased clinical observations or euthanasia. Adoption of this novel humane endpoint criterion would allow investigators time to collect tissue samples prior to spontaneous morbidity or death and significantly reduce the distress of mice in the terminal stages of these metastatic lung tumor models.

Measuring Locomotor Activity and Behavioral Aspects of Rodents Living in the Home-Cage

“…can be stored and conveyed. It allows also for physiological characteristics (i.e., peripheral body temperature) to be measured additionally (Unified Information Devices Inc., Lake Villa, United States) ( Winn et al, 2021 ). When implanted into the animals, individual animals are tracked and identified within the home-cage or any other experimental unit.…”

Digitalization of toxicology: improving preclinical to clinical translation

“…Also, digitalization is being leveraged in pathology where histologic sections of tissues on glass slides are being digitized to facilitate sharing, computational evaluations, and artificial intelligence (AI)-assisted image analysis ( Ge et al, 2022 ). Digitization of animal behavior and non-invasive monitoring of important physiological functions like respiratory rate and locomotion could represent the next level of animal study digitalization and provide a stronger link to the human clinical setting where behavior is already a usual measure of health and wearable sensors are providing more continuous measures of physiology ( Peng et al, 2019 ; Winn et al, 2021 ).…”

Activity in Group-Housed Home Cages of Mice as a Novel Preclinical Biomarker in Oncology Studies

“…Often connected to a smartphone or reader, they have been proven useful for monitoring various physiological parameters and vital signs such as body temperature, heart rate, number of steps, respiratory rate, or blood glucose. Systems are now being developed for animal studies that could significantly improve the monitoring and detection of a particular phenotype, reduce disturbance and stress-related morbidities and the likelihood of errors, and predict certain toxicities and discomfort related to disease or treatment [15][16][17][18][19][20][21].…”