Development of real-time cellular impedance analysis system

The cell impedance analysis technique is a label-free, non-invasive method, which simplifies sample preparation and allows applications requiring unmodified cell retrieval. However, traditional impedance measurement methods suffer from various problems (speed, bandwidth, accuracy) for extracting the cellular impedance information. This thesis proposes an improved system for extracting precise cellular impedance in real-time, with a wide bandwidth and satisfactory accuracy. The system hardware consists of five main parts: a microelectrode array (MEA), a stimulation circuit, a sensing circuit, a multi-function card and a computer. The development of system hardware is explored. Accordingly, a novel bioimpedance measurement method coined digital auto balancing bridge method, which is improved from the traditional analogue auto balancing bridge circuitry, is realized for real-time cellular impedance measurement. Two different digital bridge balancing algorithms are proposed and realized, which are based on least mean squares (LMS) algorithm and fast block LMS (FBLMS) algorithm for single- and multi-frequency measurements respectively. Details on their implementation in FPGA are discussed. The test results prove that the LMS-based algorithm is suitable for accelerating the measurement speed in single-frequency situation, whilst the FBLMS-based algorithm has advantages in stable convergence in multi-frequency applications. A novel algorithm, called the All Phase Fast Fourier Transform (APFFT), is applied for post-processing of bioimpedance measurement results. Compared with the classical FFT algorithm, the APFFT significantly reduces spectral leakage caused by truncation error. Compared to the traditional FFT and Digital Quadrature Demodulation (DQD) methods, the APFFT shows excellent performance for extracting accurate phase and amplitude in the frequency spectrum. Additionally, testing and evaluation of the realized system has been performed. The results show that our system achieved a satisfactory accuracy within a wide bandwidth, a fast measurement speed and a good repeatability. Furthermore, our system is compared with a commercial impedance analyzer (Agilent 4294A) in biological experiments. The results reveal that our system achieved a comparable accuracy to the commercial instrument in the biological experiments. Finally, conclusions are given and the future work is proposed

MODERNIZATION OF THE MOCK CIRCULATORY LOOP: ADVANCED PHYSICAL MODELING, HIGH PERFORMANCE HARDWARE, AND INCORPORATION OF ANATOMICAL MODELS

A systemic mock circulatory loop plays a pivotal role as the in vitro assessment tool for left heart medical devices. The standard design employed by many research groups dates to the early 1970\u27s, and lacks the acuity needed for the advanced device designs currently being explored. The necessity to update the architecture of this in vitro tool has become apparent as the historical design fails to deliver the performance needed to simulate conditions and events that have been clinically identified as challenges for future device designs. In order to appropriately deliver the testing solution needed, a comprehensive evaluation of the functionality demanded must be understood. The resulting system is a fully automated systemic mock circulatory loop, inclusive of anatomical geometries at critical flow sections, and accompanying software tools to execute precise investigations of cardiac device performance. Delivering this complete testing solution will be achieved through three research aims: (1) Utilization of advanced physical modeling tools to develop a high fidelity computational model of the in vitro system. This model will enable control design of the logic that will govern the in vitro actuators, allow experimental settings to be evaluated prior to execution in the mock circulatory loop, and determination of system settings that replicate clinical patient data. (2) Deployment of a fully automated mock circulatory loop that allows for runtime control of all the settings needed to appropriately construct the conditions of interest. It is essential that the system is able to change set point on the fly; simulation of cardiovascular dynamics and event sequences require this functionality. The robustness of an automated system with incorporated closed loop control logic yields a mock circulatory loop with excellent reproducibility, which is essential for effective device evaluation. (3) Incorporating anatomical geometry at the critical device interfaces; ascending aorta and left atrium. These anatomies represent complex shapes; the flows present in these sections are complex and greatly affect device performance. Increasing the fidelity of the local flow fields at these interfaces delivers a more accurate representation of the device performance in vivo

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Apport de nouvelles techniques dans l’évaluation de patients candidats à une chirurgie d’épilepsie : résonance magnétique à haut champ, spectroscopie proche infrarouge et magnétoencéphalographie

L'épilepsie constitue le désordre neurologique le plus fréquent après les maladies cérébrovasculaires. Bien que le contrôle des crises se fasse généralement au moyen d'anticonvulsivants, environ 30 % des patients y sont réfractaires. Pour ceux-ci, la chirurgie de l'épilepsie s'avère une option intéressante, surtout si l’imagerie par résonance magnétique (IRM) cérébrale révèle une lésion épileptogène bien délimitée. Malheureusement, près du quart des épilepsies partielles réfractaires sont dites « non lésionnelles ». Chez ces patients avec une IRM négative, la délimitation de la zone épileptogène doit alors reposer sur la mise en commun des données cliniques, électrophysiologiques (EEG de surface ou intracrânien) et fonctionnelles (tomographie à émission monophotonique ou de positrons). La faible résolution spatiale et/ou temporelle de ces outils de localisation se traduit par un taux de succès chirurgical décevant. Dans le cadre de cette thèse, nous avons exploré le potentiel de trois nouvelles techniques pouvant améliorer la localisation du foyer épileptique chez les patients avec épilepsie focale réfractaire considérés candidats potentiels à une chirurgie d’épilepsie : l’IRM à haut champ, la spectroscopie proche infrarouge (SPIR) et la magnétoencéphalographie (MEG). Dans une première étude, nous avons évalué si l’IRM de haut champ à 3 Tesla (T), présentant théoriquement un rapport signal sur bruit plus élevé que l’IRM conventionnelle à 1,5 T, pouvait permettre la détection des lésions épileptogènes subtiles qui auraient été manquées par cette dernière. Malheureusement, l’IRM 3 T n’a permis de détecter qu’un faible nombre de lésions épileptogènes supplémentaires (5,6 %) d’où la nécessité d’explorer d’autres techniques. Dans les seconde et troisième études, nous avons examiné le potentiel de la SPIR pour localiser le foyer épileptique en analysant le comportement hémodynamique au cours de crises temporales et frontales. Ces études ont montré que les crises sont associées à une augmentation significative de l’hémoglobine oxygénée (HbO) et l’hémoglobine totale au niveau de la région épileptique. Bien qu’une activation contralatérale en image miroir puisse être observée sur la majorité des crises, la latéralisation du foyer était possible dans la plupart des cas. Une augmentation surprenante de l’hémoglobine désoxygénée a parfois pu être observée suggérant qu’une hypoxie puisse survenir même lors de courtes crises focales. Dans la quatrième et dernière étude, nous avons évalué l’apport de la MEG dans l’évaluation des patients avec épilepsie focale réfractaire considérés candidats potentiels à une chirurgie. Il s’est avéré que les localisations de sources des pointes épileptiques interictales par la MEG ont eu un impact majeur sur le plan de traitement chez plus des deux tiers des sujets ainsi que sur le devenir postchirurgical au niveau du contrôle des crises.Epilepsy is the most common chronic neurological disorder after stroke. The major form of treatment is long-term drug therapy to which approximately 30% of patients are unfortunately refractory to. Brain surgery is recommended when medication fails, especially if magnetic resonance imaging (MRI) can identify a well-defined epileptogenic lesion. Unfortunately, close to a quarter of patients have nonlesional refractory focal epilepsy. For these MRI-negative cases, identification of the epileptogenic zone rely heavily on remaining tools: clinical history, video-electroencephalography (EEG) monitoring, ictal single-photon emission computed tomography (SPECT), and a positron emission tomography (PET). Unfortunately, the limited spatial and/or temporal resolution of these localization techniques translates into poor surgical outcome rates. In this thesis, we explore three relatively novel techniques to improve the localization of the epileptic focus for patients with drug-resistant focal epilepsy who are potential candidates for epilepsy surgery: high-field 3 Tesla (T) MRI, near-infrared spectroscopy (NIRS) and magnetoencephalography (MEG). In the first study, we evaluated if high-field 3T MRI, providing a higher signal to noise ratio, could help detect subtle epileptogenic lesions missed by conventional 1.5T MRIs. Unfortunately, we show that the former was able to detect an epileptogenic lesion in only 5.6% of cases of 1.5T MRI-negative epileptic patients, emphasizing the need for additional techniques. In the second and third studies, we evaluated the potential of NIRS in localizing the epileptic focus by analyzing the hemodynamic behavior of temporal and frontal lobe seizures respectively. We show that focal seizures are associated with significant increases in oxygenated haemoglobin (HbO) and total haemoglobin (HbT) over the epileptic area. While a contralateral mirror-like activation was seen in the majority of seizures, lateralization of the epileptic focus was possible most of the time. In addition, an unexpected increase in deoxygenated haemoglobin (HbR) was noted in some seizures, suggesting possible hypoxia even during relatively brief focal seizures. In the fourth and last study, the utility of MEG in the evaluation of nonlesional drug-refractory focal epileptic patients was studied. It was found that MEG source localization of interictal epileptic spikes had an impact both on patient management for over two thirds of patients and their surgical outcome