Computerized detection and analysis of cancer chemotherapy-induced emesis in a small animal model, musk shrew

Abstract

Vomiting is a common side effect of cancer chemotherapy and many drug treatments and diseases. In animal studies, the measurement of vomiting usually requires direct observation, which is time consuming and often lacks temporal precision. Musk shrews have been used to study the neurobiology of emesis and have a rapid emetic episode (~1 s for a sequence of retching and expulsion). The aims of the current study were to develop a method to automatically detect and characterize emetic episodes induced by the cancer chemotherapy agent cisplatin. The body contour in each video frame was tracked and normalized to a parameterized shape basis. The tracked shape was projected to a feature space that maximizes the shape variations in the consecutive frames during retching. The resulting one dimensional projection was sufficient to detect most emetic episodes in the acute (peak at 2 h) and delayed (peak at 54 h) phases after cisplatin treatment. Emetic episodes were relatively invariant in the number of retches (~6.2), duration (~1.2 s), inter-retch interval (~198 ms), and amplitude during the 72 h after cisplatin treatment. This approach should open a new vista into emesis research to permit tracking and analysis of emesis in small animal models and facilitate the development of new antiemetic therapies. These results also yield a better understanding of the brain's central pattern generator for emesis and indicate that the retching response in the musk shrew (at ~5.4 Hz) is the fastest ever recorded in a free-moving animal.

Plasma pharmacokinetics and tissue and brain distribution of cisplatin in musk shrews

“…The musk shrew appears to be an advantageous small animal model to examine the mechanisms involved in cisplatin-induced emesis and exhibits both the acute and delayed emetic phases that are observed in humans [15,14,12]. Musk shrews demonstrate acute and delayed emesis after intraperitoneal injection of 20 to 30 mg/kg cisplatin [14,12].…”

“…Musk shrews appear to be a good model to study the biology of cisplatin-induced emesis during acute and delayed phases [12–15]; however, we currently lack critical information on the pharmacokinetics of platinum in musk shrews. Because no studies to date have examined the concentrations of platinum in shrews treated with cisplatin we examined in Study 1 the platinum plasma pharmacokinetics and tissue distribution in lungs, kidneys, fore- and midbrain, hindbrain and spinal cord between 5 min and 72 h after ip administration of cisplatin.…”

Measuring the nausea-to-emesis continuum in non-human animals: refocusing on gastrointestinal vagal signaling

“…Chemotherapeutic agents have been used extensively to define the biology of nausea and vomiting, but they exert combined actions on vagal signaling and directly on the brain (Andrews et al 1990a; Percie du Sert et al 2009b). Oddly, cytotoxic chemotherapy agents, such as cisplatin, produce an acute phase of emesis (up to 24 h) and a delayed phase (the next several days) of emesis in humans (e.g., Hesketh et al 2003) and animal models (Sam et al 2001; Sam et al 2003; Huang et al 2011). Although the role of an intact vagus seems supported in the acute phase of cisplatin-induced emesis (Hawthorn et al 1988; Sam et al 2003), the impact of the vagal ablation on the delayed reponse is generally not supported in few studies that have attempted this testing (Percie du Sert et al 2009b).…”

Wildlife@Home: Combining Crowd Sourcing and Volunteer Computing to Analyze Avian Nesting Video

“…Tracking and detecting behavior of fruit flies (Drosophilia) [11], [12], [13] has been done in similar settings. Detection of particular actions or events has also been studied, such as vomiting of musk shrews [14], [15] using non-rigid body contour matching and various actions of a grasshopper [16] using spectral clustering [17].…”