There are few medical devices currently utilized that have not had, at the very least, a second iteration. Medical device companies continually strive to improve their product to make it the best on the market. Medical devices are often optimized by defining the size of the device, making it more efficient and/or improving the device to tissue interface. Using the capabilities of the Visible Heart ® Laboratories various cardiac devices can be implanted in reanimated swine and human hearts for the assessment of the various aforementioned parameters. After the implantation of these devices and assessment in functional anatomies, specimens were perfusion-fixed and then a micro-CT scanner was utilized to take high-resolution scans of the resultant device and tissue interfaces. These scans are used to generate high-resolution (∼20 microns) 3D models of the numerous implanted devices, measurement analyses, device simulations, and the creation of virtual reality scenes. All can then be used for detailed visual analyses. These abilities to render high-resolution models will allow medical device designers to closely evaluate their designs, in order to optimize their next iterations.

Complex, unstable inflow jet has been linked to aneurysm growth and rupture. However, methodologies to characterize this inflow jet have not been well established. Our previous works (Le et al., J. Biomech. Engr., 2010 and Le et al., Annals Biomedical Eng., 2013) have shown a possible transition from the stable mode (cavity) to the unstable mode (vortex ring) of this jet. We have proposed the use of a non-dimensional index called Aneurysm Number to characterize this transition (Le et al., 2013). However, the quantification of such a transition is lacking. Currently, there have no efforts in quantifying unstable flows in intracranial aneurysms, which is essential in stratifying rupture risks. In this work, the aneurysmal geometries from three patients at Sanford Health, North Dakota are reconstructed from Magnetic Resonance Angiogram and Digital Subtraction Angiogram data. Using our in-house CFD code (Virtual Flow Simulator), high-resolution flow data is obtained via numerical simulation. We perform modal analysis of blood flow dynamics for these cases using Proper Orthogonal Decomposition. Our results show that there are up to five dominant modes in the flow arising from the interaction of the incoming jet and the aneurysm dome. The spatial distribution of these modes reflect the characteristics of the inflow jet and can be used to quantify flow unsteadiness. Future works will be needed to apply the same procedure for a larger population of patients to examine its relevance in clinical practice.

Medical device designers must develop catheters that avoid harming the vascular pathway during therapy delivery. To better characterize the necessary design features to minimize damage to central and peripheral vessels, the vascular pathway used for femoral delivery of a cardiac device is studied through high resolution, computed tomography images of fresh, human cadavers. Comparisons of the amount and location of vessel calcification are made between specified anatomical sections. Though the potential complications may be less fatal, the descending aorta and iliac regions were found to be most susceptible to embolism in our analysis.

Bioprinting is a 3D fabrication technology used to accurately dispense cell-laden biomaterials for the fabrication of complex 3D functional living tissues. A syringe-based extrusion (SBE) deposition method comprising of multiple nozzles is integrated into the system. This allows for a wider selection of biomaterials that can be used for the formation of the extracellular matrix (ECM). The 3D bioprinting system presented in this paper aims to facilitate the process of 3D bioprinting through its ability to control the environmental parameters within an enclosed printing chamber. The primary objective of this research is to print viable 3D tissue constructs seeded with cells with high structural integrity and high resolution.

Microinjection of genetic components and dye into organotypic slices provides excellent single cell resolution for unraveling biological complexities, but is extremely difficult and time consuming to perform manually resulting in low yield and low use in the developmental biology field. We developed a computer vision guided platform to inject specimen with mRNA, and/or dye and investigated the efficiency of the process using organotypic slices of the mouse developing neocortex. We demonstrate that the system significantly increases yield of injection relative to manual use by an order of magnitude, allows for cell tracking over 0, 24, and 48 hours post injection in culture, and enables mRNA translation of injected product. The autoinjector platform thus can open the door to new types of experiments including investigating effects of mRNA concentration, and composition on cell fate, and tracking these effects on cell reprogramming and lineage.

We are engineering neurotechnologies for large-scale cellular resolution activity mapping of the mammalian cortex. We have developed ‘brain windows’ — 3D-printed transparent cranial prostheses for chronic, optical access to the whole cortex. Using compatible imaging methodologies, we have demonstrated the pan-cortical activity map at multiple spatial scales — cellular to the mesoscale.

Magnetic resonance (MR) imaging (MRI) has become the preferred method for medical diagnosis due to high resolution images and lack of ionizing radiation. Recently, the potential for using MRI to obtain real-time image feedback for targeted therapeutic procedures such as targeted biopsies and injections has been explored [1]. Some devices designed for intra-MRI use exist and more such devices are currently being developed and researched. Procedures often require precise positional targeting, such as injections and biopsies, and an MRI safe controlled-motion stepper motor is an ideal choice for actuating these mechanical devices. Some such drivers have been developed, but for various reasons, none are considered to be the standard for MRI use at this time. Therefore, a new design combining certain aspects of previous motors has been developed, making use of newer three-dimensional (3D) printers with extreme accuracy. Presented is a small, low-cost plastic four-cylinder piston stepper motor which is actuated by pressurized air. Connected to a plastic gearbox, this motor is capable of driving a rotational shaft at torques of up to 20 N·mm by increments of 3.6 degrees.

There has been an emerging interest in high intensity focused ultrasound (HIFU) for therapeutic applications. By means of its thermal or mechanical effects, HIFU is able to serve as a direct tool for tissue ablation, or an indirect moderating medium to manipulate microbubbles or perform heating (hyperthermia) for the purpose of targeted drug delivery. The development and testing of HIFU based phased arrays is favorable as their elements allow for individual phasing to steer and focus the beam. While FDA has already approved tissue ablation by HIFU for the treatment of uterine fibroids (2004) and pain from bone metastases (2012), development continues on other possible applications that are less forgiving of incomplete treatment, such as thermal necrosis of malignant masses. Ideally, each element, of such an array must have its own fully programmable electrical driving channel, which allows the control of delay, phase, and amplitude of the output from each element. To enable full control, each channel needs a waveform generator, an amplification device, and an impedance matching circuit between driver and acoustic element. Similar projects utilizing this approach to drive therapeutic arrays include a 512-channel therapy system which was built at the University of Michigan using low cost Field-Programmable Gate Arrays (FPGA) microcontroller and highly efficient MOSFET switching amplifiers [1]. However, this system lacks the ability to drive both, continuous wave (CW) and transient short duty-cycle high power pulses. This paper presents a hybrid system, which is able to perform CW and transient short duty-cycle high power excitation. In the following we will describe the design, programming, fabrication, and evaluation of this radiofrequency (RF) driver system as used in our laboratory for a 1.5 MHz center frequency, 298-element array (Imasonic SA, Besancon, France) [2], FPGA-controlled amplifier boards and matching circuitry. Advantages of our design include: 1. Inexpensive components (<$15/channel); 2. Ability to program/drive individual output channels independently; 3. Sufficient time and amplitude resolution for various acoustic pattern design; 4. Capability of hybrid switching between low power CW and short duty cycle, high instantaneous power.

Prostate cancer is the most common cancer among males, leading to approximately 27,000 deaths in the United States [1]. Focal laser ablation (FLA) has been shown to be a promising approach for prostate cancer treatment with the advantage of efficiently ablating the cancer cells while inflicting less damage on the surrounding tissues. In current FLA procedures, a rigid template — with holes spacing of 5mm — guides the FLA catheter to the target position. Drawbacks of the conventional approach for catheter targeting are 1) limited degrees of freedom (DoF) and 2) a low insertion resolution. In addition, the targeting capability of the rigid template is compromised when the pubic arch or nerve bundles intersect the catheter trajectory. We hypothesized that a compact design of an MRI-conditional robot with two active planar DoFs, one passive rotation DoF, and remote catheter insertion capacities could enhance the clinical workflow required for MRI-guided FLA prostate procedures.

Bioprinting technology has been rapidly increasing in popularity in the field of tissue engineering. Potential applications include tissue or organ regeneration, creation of biometric multi-layered skin tissue, and burn wound treatment [1]. Recent work has shown that living cells can be successfully applied using inkjet heads without damaging the cells [2]. Electrostatically driven inkjet systems have the benefit of not generating significant heat and therefore do not damage the cell structure. Inkjets have the additional benefit of depositing small droplets with micrometer resolution and therefore can be used to build up tissue like structures. Previous attempts at tracking and drawing on a hand include either direct contact with the hand [3] or tracking the hand only in two degrees of freedom [4]. In this work we present an approach to track a hand with three degrees of freedom and accurately apply a substance contact free to the hand in a desired pattern using a bioprinting compatible inkjet. The third degree of freedom, in this case depth from the hand surface, provides improved control over the distance between the inkjet head and object, thus increasing deposition accuracy.

The recent and rapid developments of immersive, interactive 3D environments have been critical in advancing interfaces for entertainment, design, and education. For cardiovascular research, our laboratory and others have been able to use such software tools for the construction of heart models from DICOM files. These models can then be printed in hard or soft plastic from a 3D printer. In general, such models are considered useful for surgical planning and education; these modalities are being applied as critical tools in the field of cardiovascular research. Recently, the development of virtual reality (VR) has introduced a new modality for exploring 3D virtual structures with high resolution, high flexibility, and fast turn-around times. Until recently, the adoption of these technologies has been hindered by the high costs of VR goggles and the complexities in their setup. New developments in phone software and hardware, however, have alleviated some of these difficulties by allowing smartphone screens, graphics units, and gyroscopes to provide the necessary technologies for VR. In this way, phones can be placed inside a headset holder and used freely, without being connected to the computer. Here we explore the utility of using this VR setup in the context of internal heart anatomy visualization.

Epilepsy is a prevalent neurological disorder affecting 65 million people globally [1]. Anti-epileptic medications fail to provide effective seizure control for 30% of patients, placing them at a 7–17% risk of Sudden Unexplained Death in Epilepsy and recurrent seizures. Surgical resection of the seizure focus is a potentially curative treatment for patients with seizures that electrophysiologically correlate to a focal lesion. For these patients, focal surgical resection can result in 60–70% seizure-freedom rates [2]. However, open resection carries the risk of cognitive impairment or focal neurologic deficit [3]. Recent innovations in MRI enable high resolution soft tissue visualization, and real-time temperature monitoring, making MR-guided ablation therapy a promising minimally invasive technique to restrict the tissue destruction to just the seizure focus. Commercial products (e.g., Visualase, Medtronic Inc.; ClearPoint, MRI Interventions Inc.; NeuroBlate, Monteris Inc.) have recently been introduced for MR-guided laser-based thermal ablation. These products require the physician drill a hole into the skull for ablation probe placement, and may not always be able to ablate the entire seizure focus when the structure has a curved shape (such as the hippocampus) [4]. Incomplete ablation of the seizure focus would lead to seizure recurrence. We have recently proposed concentric-tube steerable needles as a means to address these challenges [4–7]. They enable nonlinear trajectories and offer the potential to enter the brain through the patient’s cheek via a natural opening in the skull base (i.e. the foramen ovale). We have designed and fabricated an MR-compatible robotic system to provide high resolution actuation for helical needle deployment [5]. We have shown in simulation that the curved medial axis of hippocampus can be accessed via a helical needle that delivers the ablation probe into the brain [4]. These preliminary results suggest that MR-guided robotic transforamenal thermal therapy could potentially provide a less invasive approach for potentially curative epilepsy treatment. In this paper we present our first results delivering heat along curved paths in brain phantoms and imaging the resulting treatment zones using MRI.

This work presents development and testing of image processing algorithms for the automatic detection of landmarks within ultrasound images. The aim was to automate ultrasound analysis, for use during the process of epidural needle insertion. For epidural insertion, ultrasound is increasingly used to guide the needle into the epidural space. Ultrasound can improve the safety of epidural and was recommended by the 2008 NICE guidelines (National Institute for Health and Care Excellence). Without using ultrasound, there is no way for the anaesthetist to observe the location of the needle within the ligaments requiring the use of their personal judgment which may lead to injury. If the needle stops short of the epidural space, the anaesthetic is ineffective. If the needle proceeds too deep, it can cause injuries ranging from headache, to permanent nerve damage or death. Ultrasound of the spine is particularly difficult, because the complex bony structures surrounding the spine limit the ultrasound beam acoustic windows [1]. Additionally, the important structures for epidural that need to be observed are located deeper than other conventional procedures such as peripheral nerve block. This is why a low frequency, curved probe (2–5 MHz) is used, which penetrates deeper but decreases in resolution. The benefits of automating ultrasound are to enable real-time ultrasound analysis on the live video, mitigate human error, and ensure repeatability by avoiding variation in perception by different users. Previous ultrasound image processing for epidural research used speckle image enhancement with canny and gradient based methods for bone detection [2]. A clinical trial with 39 patients had success detecting the ligamentum flavum (LF) from ultrasound by algorithms in 87% of patients. Echogenic needles and catheters are now becoming available which are enhanced for extra ultrasound visibility. The Epimed UltraKath ULTRA-KATH™ [3] has a patented design to maximize visibility under ultrasound [4]. The Echogenic Tuohy Needle also includes imprints on the needle tip that reflects ultrasound, allowing for better visualization. Curved needles can also be detected in 2D ultrasound images [5].

Stents are most commonly used in the relief of coronary artery stenosis, but in the last decade have found increasing applications in the treatment of other cardiovascular disease and in particular in heart valve replacement [1]. In transcatheter valve implantation, acquisition of high temporal and spatial resolution images during stenting procedure and patients’ follow-up is required to help the correct positioning of the device and to assess the mechanical performance over time. The imaging techniques routinely used for this purpose are 2D X-ray fluoroscopy and 3D computed tomography (CT), and recent studies have demonstrated their value as diagnostic tools [1–3]. However, these image modalities carry errors and the resulting information might not be accurate enough to be employed in engineering analyses of stent deformations, mechanics, dynamics and fracture. In this study, we aim to evaluate the errors of conventionally used clinical images (fluoroscopy and CT) and post-processing by comparison with ultra-high resolution micro-CT (μCT) as gold standard. Additionally, an optical image acquisition method and a high-radiation CT scan were evaluated as potential techniques to acquire geometrical data that could be used for computational and in-vitro engineering experiments.

A numerical suspension flow solver is presented that can accurately quantify blood damage in cardiovascular flows. This method is capable of high spatiotemporal resolution simulations with optimal parallel computing. In addition, the method models realistic platelets for more accurate damage quantification compared to alternative methods. The numerical tool is tested on a baseline case of a St. Jude Medical bileaflet mechanical heart valve, and blood damage results are analyzed in both Lagrangian and Eulerian viewpoints.

We introduce a lensless high-throughput fluorescent detection modality that can simultaneously image micro-objects and labeled cells over an ultra-wide field-of-view (FOV) of ∼8cm 2 without the use of any lenses, thin-film filters and mechanical scanners. This lensfree platform utilizes total-internal-reflection (TIR) to block the excitation light, and an inexpensive absorption filter to remove the weakly scattered light that does not obey TIR. The emitted fluorescent light from the objects is then detected on the same chip without the use of any lenses. A digital deconvolution algorithm is used to resolve overlapping fluorescent spots, enabling a resolution of ∼40–50 μm over the entire field-of-view. Such an ultra wide field-of-view lensfree fluorescent imaging modality might be very valuable for high-throughput screening applications as well as quantification of rare cells such as circulating tumor cells using ultra-large microfluidic devices.

This study aims at the design, implementation, and verification of a near infrared (NIR) diffuse optical tomography (DOT) electro-optical imaging system based on a measuring instrument with scanning mechanism of synchronous multi-point detection and an image reconstruction scheme implemented on an off-line PC. The developed measurement instrument possesses a high degree of angular resolution and can be operated in a continuous-intensity or intensity modulation scheme to acquire output NIR radiance signals. Experimental trials are conducted using both homogeneous and heterogeneous phantoms made of high-scattering Intralipid. Promising results have been obtained with a superior spatial resolution, especially for absorption image, compared with the system with fixed number of detection channels.

Diffuse optical tomography (DOT) is a recently emerging technique that uses arrays of sources and detectors to obtain spatially dependent optical parameters of tissue. DOT techniques have been applied for a wide range of applications, especially for breast and head as well as animal imaging. We have developed an integrated dynamic MR/DOT imaging system. This combined system can acquire MR and optical data simultaneously with a high temporal resolution. Hence, the enhancement kinetics of multiple MR and optical contrast agents can be monitored independently.

There is a need in medical and biological research to probe cells with high spatial resolution. We have developed a method for fabricating integrated carbon nanopipes with diameters ranging from 10’s to 100’s of nanometers to form carbon nanopipettes (CNPs) without the need for cumbersome assembly. CNPs are easily adapted to standard cell physiology equipment and simultaneously provide an accessible nanoscale channel for mass transport and a conductive pathway for electrical measurements. We present the fabrication method, the characterization of the device, and their ability to inject fluids into cells, specifically, calcium mobilizing second messengers.

Shock wave lithotripsy (SWL) has been used to treat kidney stones for decades. However, there is growing recognition that shock waves induces trauma to kidney tissue [1, 2]. The poor understanding of stone comminution mechanisms means that the design of new lithotripters is principally a practice of empiricism [3]. A mechanistic understanding of stone comminution would provide a criterion to develop new lithotripsy systems. In this work, a three-dimensional finite-difference time-domain (FDTD) solution to the linear elastic equations was employed [4] to investigate the stress and displacement fields of kidney stones subject to lithotripsy shock waves. The kidney stone models were obtained from micro-computed tomography images (resolution of 20 μm) and have diameters from 2 mm to 5 mm.