Application of Signal Advance Technology to Electrophysiology

Medical instrumentation used in diagnosis and treatment relies on the accurate detection and processing of various physiological events and signals. While signal detection technology has improved greatly in recent years, there remain inherent delays in signal detection/ processing. These delays may have significant negative clinical consequences during various pathophysiological events. Reducing or eliminating such delays would increase the ability to provide successful early intervention in certain disorders thereby increasing the efficacy of treatment. In recent years, a physical phenomenon referred to as Negative Group Delay (NGD), demonstrated in simple electronic circuits, has been shown to temporally advance the detection of analog waveforms. Specifically, the output is temporally advanced relative to the input, as the time delay through the circuit is negative. The circuit output precedes the complete detection of the input signal. This process is referred to as signal advance (SA) detection. An SA circuit model incorporating NGD was designed, developed and tested. It imparts a constant temporal signal advance over a pre-specified spectral range in which the output is almost identical to the input signal (i.e., it has minimal distortion). Certain human patho-electrophysiological events are good candidates for the application of temporally-advanced waveform detection. SA technology has potential in early arrhythmia and epileptic seizure detection and intervention. Demonstrating reliable and consistent temporally advanced detection of electrophysiological waveforms may enable intervention with a pathological event (much) earlier than previously possible. SA detection could also be used to improve the performance of neural computer interfaces, neurotherapy applications, radiation therapy and imaging. In this study, the performance of a single-stage SA circuit model on a variety of constructed input signals, and human ECGs is investigated. The data obtained is used to quantify and characterize the temporal advances and circuit gain, as well as distortions in the output waveforms relative to their inputs. This project combines elements of physics, engineering, signal processing, statistics and electrophysiology. Its success has important consequences for the development of novel interventional methodologies in cardiology and neurophysiology as well as significant potential in a broader range of both biomedical and non-biomedical areas of application.

Diffusion tensor imaging of rat spinal cord in vivo

Magnetic resonance imaging, with its exquisite soft tissue contrast, is an ideal modality for investigating spinal cord pathology. While conventional MRI techniques are very sensitive for spinal cord pathology, their specificity is somewhat limited. Diffusion MRI is an advanced technique which is a very sensitive and specific indicator of the integrity of white matter tracts. Diffusion imaging has been shown to detect early ischemic changes in white matter, while conventional imaging demonstrates no change. By acquiring the complete apparent diffusion tensor (ADT), tissue diffusion properties can be expressed in terms of quantitative and rotationally invariant parameters. ^ Systematic study of SCI in vivo requires controlled animal models such as the popular rat model. To date, studies of spinal cord using ADT imaging have been performed exclusively in fixed, excised spinal cords, introducing inevitable artifacts and losing the benefits of MRI's noninvasive nature. In vivo imaging reflects the actual in vivo tissue properties, and allows each animal to be imaged at multiple time points, greatly reducing the number of animals required to achieve statistical significance. Because the spinal cord is very small, the available signal-to-noise ratio (SNR) is very low. Prior spin-echo based ADT studies of rat spinal cord have relied on high magnetic field strengths and long imaging times—on the order of 10 hours—for adequate SNR. Such long imaging times are incompatible with in vivo imaging, and are not relevant for imaging the early phases following SCI. Echo planar imaging (EPI) is one of the fastest imaging methods, and is popular for diffusion imaging. However, EPI further lowers the image SNR, and is very sensitive to small imperfections in the magnetic field, such as those introduced by the bony spine. Additionally, The small field-of-view (FOV) needed for spinal cord imaging requires large imaging gradients which generate EPI artifacts. The addition of diffusion gradients introduces yet further artifacts. ^ This work develops a method for rapid EPI-based in vivo diffusion imaging of rat spinal cord. The method involves improving the SNR using an implantable coil; reducing magnetic field inhomogeneities by means of an autoshim, and correcting EPI artifacts by post-processing. New EPI artifacts due to diffusion gradients described, and post-processing correction techniques are developed. ^ These techniques were used to obtain rotationally invariant diffusion parameters from 9 animals in vivo, and were validated using the gold-standard, but slow, spinecho based diffusion sequence. These are the first reported measurements of the ADT in spinal cord in vivo . ^ Many of the techniques described are equally applicable toward imaging of human spinal cord. We anticipate that these techniques will aid in evaluating and optimizing potential therapies, and will lead to improved patient care. ^