Kartikeya Murari

Bio: Kartikeya Murari is an academic researcher from University of Calgary. The author has contributed to research in topics: Endomicroscopy & Speckle pattern. The author has an hindex of 19, co-authored 72 publications receiving 1431 citations. Previous affiliations of Kartikeya Murari include Johns Hopkins University School of Medicine & Johns Hopkins University.

Micropower CMOS Integrated Low-Noise Amplification, Filtering, and Digitization of Multimodal Neuropotentials

Abstract: Electrical activity in the brain spans a wide range of spatial and temporal scales, requiring simultaneous recording of multiple modalities of neurophysiological signals in order to capture various aspects of brain state dynamics. Here, we present a 16-channel neural interface integrated circuit fabricated in a 0.5 mum 3M2P CMOS process for selective digital acquisition of biopotentials across the spectrum of neural signal modalities in the brain, ranging from single spike action potentials to local field potentials (LFP), electrocorticograms (ECoG), and electroencephalograms (EEG). Each channel is composed of a tunable bandwidth, fixed gain front-end amplifier and a programmable gain/resolution continuous-time incremental DeltaSigma analog-to-digital converter (ADC). A two-stage topology for the front-end voltage amplifier with capacitive feedback offers independent tuning of the amplifier bandpass frequency corners, and attains a noise efficiency factor (NEF) of 2.9 at 8.2 kHz bandwidth for spike recording, and a NEF of 3.2 at 140 Hz bandwidth for EEG recording. The amplifier has a measured midband gain of 39.6 dB, frequency response from 0.2 Hz to 8.2 kHz, and an input-referred noise of 1.94 muV rms while drawing 12.2 muA of current from a 3.3 V supply. The lower and higher cutoff frequencies of the bandpass filter are adjustable from 0.2 to 94 Hz and 140 Hz to 8.2 kHz, respectively. At 10-bit resolution, the ADC has an SNDR of 56 dB while consuming 76 muW power. Time-modulation feedback in the ADC offers programmable digital gain (1-4096) for auto-ranging, further improving the dynamic range and linearity of the ADC. Experimental recordings with the system show spike signals in rat somatosensory cortex as well as alpha EEG activity in a human subject.

A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy

Abstract: We report the development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues and demonstrate its utility for monitoring the remodeling of cervical collagen during gestation in mice. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. SHG endomicroscopic imaging of ex vivo murine and human cervical tissues through intact epithelium has also been performed. Our findings demonstrate the feasibility of SHG endomicroscopy technology for staging normal pregnancy, and suggest its potential application as a minimally invasive tool for clinical assessment of abnormal cervical remodeling associated with preterm birth.

VLSI Potentiostat Array With Oversampling Gain Modulation for Wide-Range Neurotransmitter Sensing

Abstract: A 16-channel current-measuring very large-scale integration (VLSI) sensor array system for highly sensitive electrochemical detection of electroactive neurotransmiters like dopamine and nitric-oxide is presented. Each channel embeds a current integrating potentiostat within a switched-capacitor first-order single-bit delta-sigma modulator implementing an incremental analog-to-digital converter. The duty-cycle modulation of current feedback in the delta-sigma loop together with variable oversampling ratio provide a programmable digital range selection of the input current spanning over six orders of magnitude from picoamperes to microamperes. The array offers 100-fA input current sensitivity at 3.4-muW power consumption per channel. The operation of the 3 mm times3 mm chip fabricated in 0.5-mum CMOS technology is demonstrated with real-time multichannel acquisition of neurotransmitter concentration

Which Photodiode to Use: A Comparison of CMOS-Compatible Structures

Abstract: While great advances have been made in optimizing fabrication process technologies for solid state image sensors, the need remains to be able to fabricate high quality photosensors in standard CMOS processes. The quality metrics depend on both the pixel architecture and the photosensitive structure. This paper presents a comparison of three photodiode structures in terms of spectral sensitivity, noise and dark current. The three structures are n+/p-sub, n-well/p-sub and p+/n-well/p-sub. All structures were fabricated in a 0.5 mum 3-metal, 2-poly, n-well process and shared the same pixel and readout architectures. Two pixel structures were fabricated-the standard three transistor active pixel sensor, where the output depends on the photodiode capacitance, and one incorporating an in-pixel capacitive transimpedance amplifier where the output is dependent only on a designed feedback capacitor. The n-well /p-sub diode performed best in terms of sensitivity (an improvement of 3.5 times and 1.6 times over the n+/p-sub and p+/n-well/p-sub diodes, respectively) and signal-to-noise ratio (1. 5times and 1.2 times improvement over the n+/p-sub and p+/n-well/p-sub diodes, respectively) while the p+/n-well/p-sub diode had the minimum (33% compared to other two structures) dark current for a given sensitivity.

Contrast-enhanced imaging of cerebral vasculature with laser speckle

Abstract: High-resolution cerebral vasculature imaging has applications ranging from intraoperative procedures to basic neuroscience research. Laser speckle, with spatial contrast processing, has recently been used to map cerebral blood flow. We present an application of the technique using temporal contrast processing to image cerebral vascular structures with a field of view a few millimeters across and approximately 20 μm resolution through a thinned skull. We validate the images using fluorescent imaging and demonstrate a factor of 2-4 enhancement in contrast-to-noise ratios over reflectance imaging using white or spectrally filtered green light. The contrast enhancement enables the perception of approximately 10%-30% more vascular structures without the introduction of any contrast agent.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

Abstract: Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

Miniaturized integration of a fluorescence microscope

Abstract: The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

Optical coherence tomography today: speed, contrast, and multimodality.

Abstract: In the last 25 years, optical coherence tomography (OCT) has advanced to be one of the most innovative and most successful translational optical imaging techniques, achieving substantial economic impact as well as clinical acceptance. This is largely owing to the resolution improvements by a factor of 10 to the submicron regime and to the imaging speed increase by more than half a million times to more than 5 million A-scans per second, with the latter one accomplished by the state-of-the-art swept source laser technologies that are reviewed in this article. In addition, parallelization of OCT detection, such as line-field and full-field OCT, has shortened the acquisition time even further by establishing quasi-akinetic scanning. Besides the technical improvements, several functional and contrast-enhancing OCT applications have been investigated, among which the label-free angiography shows great potential for future studies. Finally, various multimodal imaging modalities with OCT incorporated are reviewed, in that these multimodal implementations can synergistically compensate for the fundamental limitations of OCT when it is used alone.

Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice

Abstract: Developments in miniaturized microscopes have enabled visualization of brain activities and structural dynamics in animals engaging in self-determined behaviors However, it remains a challenge to resolve activity at single dendritic spines in freely behaving animals Here, we report the design and application of a fast high-resolution, miniaturized two-photon microscope (FHIRM-TPM) that accomplishes this goal With a headpiece weighing 215 g and a hollow-core photonic crystal fiber delivering 920-nm femtosecond laser pulses, the FHIRM-TPM is capable of imaging commonly used biosensors (GFP and GCaMP6) at high spatiotemporal resolution (064 μm laterally and 335 μm axially, 40 Hz at 256 × 256 pixels for raster scanning and 10,000 Hz for free-line scanning) We demonstrate the microscope's robustness with hour-long recordings of neuronal activities at the level of spines in mice experiencing vigorous body movements

Review of laser speckle contrast techniques for visualizing tissue perfusion.

Abstract: When a diffuse object is illuminated with coherent laser light, the backscattered light will form an interference pattern on the detector. This pattern of bright and dark areas is called a speckle pattern. When there is movement in the object, the speckle pattern will change over time. Laser speckle contrast techniques use this change in speckle pattern to visualize tissue perfusion. We present and review the contribution of laser speckle contrast techniques to the field of perfusion visualization and discuss the development of the techniques.