CASA: tracking the past and plotting the future

Gallagher, Meurig Thomas; Smith, D. J.; Kirkman-Brown, Jackson

doi:10.1071/rd17420

Cited by 45 publications

(36 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such systems are widely used for veterinary work and in domestic animal breeding, conservation, and toxicology (Amann and Waberski, 2014), but have not yet made the breakthrough into routine clinical usage. The reasons for this have been discussed elsewhere (Gallagher et al, 2018b).…”

Section: Introductionmentioning

confidence: 94%

“…The package will be shown to provide positions in time of tracked sperm head and flagellum, and associated measurement of the flagellar arc-wavelength, flagellar beat frequency, and power dissipation by the flagellum in addition to providing the existing CASA measures. FAST is not designed to analyse raw semen, it is specifically for precise analysis of flagellar kinematics, as that is the promising area for computer use (Gallagher et al, 2018b). Flagellar capture will always require that cells are at a dilution where their paths do not frequently cross.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid sperm capture: High-throughput flagellar waveform analysis

Gallagher

Cupples

Ooi

et al. 2019

Preprint

View full text Add to dashboard Cite

The FAST software package and all documentation can be downloaded from www.flagellarCapture.com. Summary 1 Flagella are critical across all eukaryotic life, and the human sperm 2 flagellum is crucial to natural fertility. Existing automated sperm di-3 agnostics (CASA) rely on tracking the sperm head and extrapolating 4 measures. We describe fully-automated tracking and analysis of flag-5 ellar movement for large cell numbers. The analysis is demonstrated 6 on freely-motile cells in low and high viscosity fluids, and validated on 7 published data of tethered cells undergoing pharmacological hyperac-8 tivation. Direct analysis of the flagellar beat reveals that the CASA 9 measure 'beat cross frequency', does not measure beat frequency. A 10 new measurement, track centroid speed, is validated as an accurate 11 differentiator of progressive motility. Coupled with fluid mechanics 12 codes, waveform data enables extraction of experimentally intractable 13 quantities such as energy dissipation, disturbance of the surrounding 14 medium and viscous stresses. We provide a powerful and accessible 15 research tool, enabling connection of the cell's mechanical activity to 16 its motility and effect on its environment. 17 Introduction 18About 100 million men worldwide are suggested to be subfertile (Inhorn and 19 Patrizio, 2015), but for many of them an accurate diagnostic cause remains 20 elusive. The ability of sperm to successfully migrate through the female re-21 productive tract is key to natural fertilisation, however current techniques for 22 assessing sperm motility lack diagnostic power and mechanistic insight. The 23 heterogeneity of human sperm requires tools that can acquire and analyse 24 2 (2018) and associated special issue). Such systems are widely used for vet-25 erinary work and in domestic animal breeding, conservation, and toxicology 26 (Amann and Waberski, 2014), but have not yet made the breakthrough into 27 routine clinical usage. The reasons for this have been discussed elsewhere 28 (Gallagher et al., 2018b). 29 Standard CASA systems produce a motility assessment from the track of 30 the head movement, however this does not enable causative or mechanistic 31 insight because it lacks detail on the movement of the flagellum. Knowledge 32 of this beat could provide hitherto untapped information for the estimation 33 of non-visible attributes such as the contribution of different metabolic path-34 ways, and modulation in response to the physical and biochemical environ-35 ments (Ooi et al., 2014). The capability to capture flagellar movements and 36 associated mechanistic insights has broader applicability in the life sciences 37 including the role of cilia in embryonic development (Smith et al., 2019), 38 swimming of multiflagellate microorganisms (Wan and Goldstein, 2018), the 39 use of high-speed holographic microscopy to image the flagellar waveforms 40 of malaria parasites (Wilson et al., 2013), and even the design of hybrid 41 bio-robots for biomedical applications (Xu et al., 2017).42 The use of comp...

show abstract

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Rapid sperm capture: High-throughput flagellar waveform analysis

Gallagher

Cupples

Ooi

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…However, the extensive user intervention still required for such packages as well as basic thresholding based techniques, for example by Smith et al [4] who reported on the beats of 36 swimmers, has to date largely restricted population-level computer-assisted sperm analysis (CASA) to head-based investigations [5][6][7][8] and assessments of flagellar morphology [9], with flagellar waveforms neglected. Despite such limitations, and its only partial acceptance in clinical diagnostics [10], CASA has also found extensive application in reproductive toxicology, quality assurance for semen marketing in livestock breeding, improvements in sperm technologies such as cryopreservation, and studies of basic sperm function [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Computer-assisted beat-pattern analysis and the flagellar waveforms of bovine spermatozoa

Walker

Phuyal

Ishimoto

et al. 2020

Preprint

View full text Add to dashboard Cite

Plagued by hurdles in information extraction, handling, and processing, computer-assisted sperm analysis (CASA) systems have typically neglected the complex flagellar waveforms of spermatozoa, despite their defining role in cell motility. Recent developments in imaging techniques and data processing have produced significantly-improved methods of waveform digitisation. Here, we utilise these improvements to demonstrate that near-complete flagellar capture is realisable on the scale of hundreds of cells, and, further, that meaningful statistical comparisons of flagellar waveforms may be readily performed with widely-available tools. Representing the advent of high-fidelity computer-assisted beat-pattern analysis (CABA), we show how such a statistical approach can distinguish between samples using complex flagellar beating patterns rather than crude summary statistics. Dimensionality-reduction techniques applied to entire samples also reveal qualitatively-distinct components of the beat, and a novel data-driven methodology for the generation of representative synthetic waveform data is proposed.

show abstract

“…There has long been interest in understanding the mechanics and regulation of sperm flagellar movement, in particular problems relating to: understanding the mechanical struc-ture and motor regulation [5,[12][13][14], investigating the response of the flagellar beat to its rheological environment [15][16][17], understanding the dynamics of sperm due to surrounding solid walls [18,19], and studying the effect of viscosity on sperm swimming [20]. For a detailed review surrounding the importance of the sperm flagellum see Gallagher et al [21]. Furthermore, such a method could be used to investigate phenomena associated with epithelial cilia driven flows such as: cilia waveform modulation by length [5], the effects of flow induced by cilia on embryonic development [22], studying the physical limits of flow sensing [23], and investigating the mechanical structure of the axoneme in cilia [24].…”

Section: Introductionmentioning

confidence: 99%

Efficient implementation of elastohydrodynamics via integral operators

et al. 2019

Self Cite

View full text Add to dashboard Cite

The dynamics of geometrically non-linear flexible filaments play an important role in a host of biological processes, from flagella-driven cell transport to the polymeric structure of complex fluids. Such problems have historically been computationally expensive due to numerical stiffness associated with the inextensibility constraint, as well as the often non-trivial boundary conditions on the governing high-order PDEs. Formulating the problem for the evolving shape of a filament via an integral equation in the tangent angle has recently been found to greatly alleviate this numerical stiffness. The contribution of the present manuscript is to enable the simulation of nonlocal interactions of multiple filaments in a computationally efficient manner using the method of regularized stokeslets within this framework. The proposed method is benchmarked against a nonlocal bead and link model, and recent code utilizing a local drag velocity law. Systems of multiple filaments (1) in a background fluid flow, (2) under a constant body force, and (3) undergoing active self-motility are modeled efficiently. Buckling instabilities are analyzed by examining the evolving filament curvature, as well as by coarse-graining the body frame tangent angles using a Chebyshev approximation for various choices of the relevant non-dimensional parameters. From these experiments, insight is gained into how filament-filament interactions can promote buckling, and further reveal the complex fluid dynamics resulting from arrays of these interacting fibers. By examining active moment-driven filaments, we investigate the speed of worm-and sperm-like swimmers for different governing parameters. The MATLAB R implementation is made available as an open-source library, enabling flexible extension for alternate discretizations and different surrounding flows.

show abstract

CASA: tracking the past and plotting the future

Cited by 45 publications

References 66 publications

Rapid sperm capture: High-throughput flagellar waveform analysis

Rapid sperm capture: High-throughput flagellar waveform analysis

Computer-assisted beat-pattern analysis and the flagellar waveforms of bovine spermatozoa

Efficient implementation of elastohydrodynamics via integral operators

Contact Info

Product

Resources

About