Reengineering Biomedical Engineering Curricula: A New Product Development Approach

Product development engineers in medical industries have created design control procedures to ensure high quality designs that are as error-free as possible. The reason is simple; companies must adhere to certain engineering and manufacturing best practices in order to obtain certification of their devices for sale in the US and abroad. We describe here an ongoing effort to apply these industrial best practices to the design and implementation of a novel sequence of undergraduate biomedical computing courses within the Department of Bio-medical Engineering at Marquette University (Milwaukee, Wisconsin). We have tightly integrated our industrial advisory board into this design and development effort. The board has contributed to significantly to the orderly generation of curricular requirements, the development of course implementation designs and the evaluation of these designs per requirements

A Pneumatically Actuated Manipulandum for Neuromotor Control Research

Functional magnetic resonance imaging (fMRI) techniques have great potential for identifying which neural structures are involved in the control of goal-directed reaching movements. However, fMRI techniques alone are not capable of probing the neural mechanisms involved in acquisition of novel motor behaviors because such studies require that the moving limb be perturbed in a controlled fashion. We outline a plan to design and develop a non-metallic, pneumatically actuated tool that, along with systems identification techniques and functional magnetic resonance imaging (fMRI), will characterize and quantify how the human central nervous system uses sensory information during practice-based motor learning

Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake Rats

Background: Neuronal interactions are fundamental for information processing, cognition and consciousness. Anesthetics reduce spontaneous cortical activity; however, neuronal reactivity to sensory stimuli is often preserved or augmented. How sensory stimulus-related neuronal interactions change under anesthesia has not been elucidated. Here we investigated visual stimulus-related cortical neuronal interactions during stepwise emergence from desflurane anesthesia. Methods: Parallel spike trains were recorded with 64-contact extracellular microelectrode arrays from the primary visual cortex of chronically instrumented, unrestrained rats (N=6) at 8%, 6%, 4%, 2% desflurane anesthesia and wakefulness. Light flashes were delivered to the retina by transcranial illumination at 5-15s randomized intervals. Information theoretical indices, integration and interaction complexity, were calculated from the probability distribution of coincident spike patterns and used to quantify neuronal interactions before and after flash stimulation. Results: Integration and complexity showed significant negative associations with desflurane concentration (N=60). Flash stimulation increased integration and complexity at all anesthetic levels (N=60); the effect on complexity was reduced in wakefulness. During stepwise withdrawal of desflurane, the largest increase in integration (74%) and post-stimulus complexity (35%) occurred prior to reaching 4% desflurane concentration – a level associated with the recovery of consciousness according to the rats\u27 righting reflex. Conclusions: Neuronal interactions in the cerebral cortex are augmented during emergence from anesthesia. Visual flash stimuli enhance neuronal interactions in both wakefulness and anesthesia; the increase in interaction complexity is attenuated as post-stimulus complexity reaches plateau. The critical changes in cortical neuronal interactions occur during transition to consciousness

Comparison of Randomized Multifocal Mapping and Temporal Phase Mapping of Visual Cortex for Clinical Use

fMRI is becoming an important clinical tool for planning and guidance of surgery to treat brain tumors, arteriovenous malformations, and epileptic foci. For visual cortex mapping, the most popular paradigm by far is temporal phase mapping, although random multifocal stimulation paradigms have drawn increased attention due to their ability to identify complex response fields and their random properties. In this study we directly compared temporal phase and multifocal vision mapping paradigms with respect to clinically relevant factors including: time efficiency, mapping completeness, and the effects of noise. Randomized, multifocal mapping accurately decomposed the response of single voxels to multiple stimulus locations and made correct retinotopic assignments as noise levels increased despite decreasing sensitivity. Also, multifocal mapping became less efficient as the number of stimulus segments (locations) increased from 13 to 25 to 49 and when duty cycle was increased from 25% to 50%. Phase mapping, on the other hand, activated more extrastriate visual areas, was more time efficient in achieving statistically significant responses, and had better sensitivity as noise increased, though with an increase in systematic retinotopic mis-assignments. Overall, temporal phase mapping is likely to be a better choice for routine clinical applications though random multifocal mapping may offer some unique advantages for selected applications

Monosynaptic Functional Connectivity in Cerebral Cortex During Wakefulness and Under Graded Levels of Anesthesia

The balance between excitation and inhibition is considered to be of significant importance for neural computation and cognitive function. Excitatory and inhibitory functional connectivity in intact cortical neuronal networks in wakefulness and graded levels of anesthesia has not been systematically investigated. We compared monosynaptic excitatory and inhibitory spike transmission probabilities using pairwise cross-correlogram (CCG) analysis. Spikes were measured at 64 sites in the visual cortex of rats with chronically implanted microelectrode arrays during wakefulness and three levels of anesthesia produced by desflurane. Anesthesia decreased the number of active units, the number of functional connections, and the strength of excitatory connections. Connection probability (number of connections per number of active unit pairs) was unaffected until the deepest anesthesia level, at which a significant increase in the excitatory to inhibitory ratio of connection probabilities was observed. The results suggest that the excitatory–inhibitory balance is altered at an anesthetic depth associated with unconsciousness

Microfocal X-Ray Computed Tomography Post-Processing Operations for Optimizing Reconstruction Volumes of Stented Arteries During 3D Computational Fluid Dynamics Modeling

Restenosis caused by neointimal hyperplasia (NH) remains an important clinical problem after stent implantation. Restenosis varies with stent geometry, and idealized computational fluid dynamics (CFD) models have indicated that geometric properties of the implanted stent may differentially influence NH. However, 3D studies capturing the in vivo flow domain within stented vessels have not been conducted at a resolution sufficient to detect subtle alterations in vascular geometry caused by the stent and the subsequent temporal development of NH. We present the details and limitations of a series of post-processing operations used in conjunction with microfocal X-ray CT imaging and reconstruction to generate geometrically accurate flow domains within the localized region of a stent several weeks after implantation. Microfocal X-ray CT reconstruction volumes were subjected to an automated program to perform arterial thresholding, spatial orientation, and surface smoothing of stented and unstented rabbit iliac arteries several weeks after antegrade implantation. A transfer function was obtained for the current post-processing methodology containing reconstructed 16 mm stents implanted into rabbit iliac arteries for up to 21 days after implantation and resolved at circumferential and axial resolutions of 32 and 50 μm, respectively. The results indicate that the techniques presented are sufficient to resolve distributions of WSS with 80% accuracy in segments containing 16 surface perturbations over a 16 mm stented region. These methods will be used to test the hypothesis that reductions in normalized wall shear stress (WSS) and increases in the spatial disparity of WSS immediately after stent implantation may spatially correlate with the temporal development of NH within the stented region

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

BACKGROUND: The phase-space relationship between simultaneously measured myoplasmic [Ca(2+)] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca(2+)] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca(2+ )sensitivity responsible for alterations in Ca(2+)-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. METHODS: We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca(2+)] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. RESULTS: We found that IR injury resulted in reduced myofilament Ca(2+ )sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca(2+ )sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca(2+ )sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca(2+ )sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca(2+ )affinity and cross-bridge kinetics only after ischemia. CONCLUSION: Estimated model parameters reveal mechanistic changes in Ca(2+)-contraction coupling due to IR injury, specifically the inefficient utilization of Ca(2+ )for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca(2+)-contraction coupling before and after IR injury

A NOVEL CURRICULUM TO PREPARE UNDERGRADUATE BIOMEDICAL ENGINEERS FOR INDUSTRIAL OPPORTUNITIES

ABSTRACTThe Biomedical Engineering Program at MarquetteUniversity has integrated a novel two-year curriculum intotheir undergraduate industrial cooperative (co-op) educationand summer internship program. The new curriculum isdesigned to prepare students for industrial opportunities at thecompletion of their sophomore year.Keywords: cooperative education, internship, freshman,training, career1 halama

A novel curriculum to prepare undergraduate biomedical engineers for industrial opportunities

ABSTRACTThe Biomedical Engineering Program at MarquetteUniversity has integrated a novel two-year curriculum intotheir undergraduate industrial cooperative (co-op) educationand summer internship program. The new curriculum isdesigned to prepare students for industrial opportunities at thecompletion of their sophomore year.Keywords: cooperative education, internship, freshman,training, career1 Lemba