Robotic Outcome Assessment in a Non-Human Primate Model of Middle Cerebral Artery Stroke

Stroke is a prevalent disorder with immense socioeconomic impact. A variety of chronic neurological deficits result from stroke. In particular, sensorimotor deficits are a significant barrier to achieving post-stroke independence. Unfortunately, the majority of pre-clinical studies that show improved outcomes in animal stroke models have failed in clinical trials. Pre-clinical studies using non-human primate (NHP) stroke models prior to initiating human trials are a potential step to improving translation from animal studies to clinical trials. Robotic assessment tools represent a quantitative, reliable, and reproducible means to assess reaching behaviour following stroke in both humans and NHPs. We investigated the use of robotic technology to assess sensorimotor impairments in NHPs following middle cerebral artery occlusion (MCAO). Two cynomolgus macaques underwent transient MCAO for 90 minutes. Approximately 1.5 years following the procedure these NHPs and two non-stroke control monkeys were trained in a reaching task with both arms in the KINARM exoskeleton. This robot permits elbow and shoulder movements in the horizontal plane. The task required NHPs to make reaching movements from a centrally positioned start target to 1 of 8 peripheral targets uniformly distributed around the first target. We analyzed four movement parameters: reaction time, movement time (MT), initial direction error (IDE), and number of speed maxima to characterize sensorimotor deficiencies. We hypothesized reduced performance in these attributes during a neurobehavioural task with the paretic limb of NHPs following MCAO compared to controls. Reaching movements in the non-affected limbs of control and experimental NHPs showed bell-shaped velocity profiles. In contrast, the reaching movements with the affected limbs were highly variable. We found distinctive patterns in MT, IDE, and number of speed peaks between control and experimental monkeys and between limbs of NHPs with MCAO. NHPs with MCAO demonstrated more speed peaks, longer MTs, and greater IDE in their paretic limb compared to controls. These initial results qualitatively match human stroke subjects’ performance, suggesting that robotic neurobehavioural assessment in NHPs with stroke is feasible and could have translational relevance in subsequent human studies. Further studies will be necessary to replicate and expand on these preliminary findings.

Analysis of Non-Stationary Flows Using Eulerian and Lagrangian Frameworks

Recent developments have made researchers to reconsider Lagrangian measurement techniques as an alternative to their Eulerian counterpart when investigating non-stationary flows. This thesis advances the state-of-the-art of Lagrangian measurement techniques by pursuing three different objectives: (i) developing new Lagrangian measurement techniques for difficult-to-measure, in situ flow environments; (ii) developing new post-processing strategies designed for unstructured Lagrangian data, as well as providing guidelines towards their use; and (iii) presenting the advantages that the Lagrangian framework has over their Eulerian counterpart in various non-stationary flow problems. Towards the first objective, a large-scale particle tracking velocimetry apparatus is designed for atmospheric surface layer measurements. Towards the second objective, two techniques, one for identifying Lagrangian Coherent Structures (LCS) and the other for characterizing entrainment directly from unstructured Lagrangian data, are developed. Finally, towards the third objective, the advantages of Lagrangian-based measurements are showcased in two unsteady flow problems: the atmospheric surface layer, and entrainment in a non-stationary turbulent flow. Through developing new experimental and post-processing strategies for Lagrangian data, and through showcasing the advantages of Lagrangian data in various non-stationary flows, the thesis works to help investigators to more easily adopt Lagrangian-based measurement techniques.