A Wearable Transcranial Doppler Ultrasound Phased Array System.

OBJECTIVE: Practical deficiencies related to conventional transcranial Doppler (TCD) sonography have restricted its use and applicability. This work seeks to mitigate several such constraints through the development of a wearable, electronically steered TCD velocimetry system, which enables noninvasive measurement of cerebral blood flow velocity (CBFV) for monitoring applications with limited operator interaction. MATERIALS AND METHODS: A highly-compact, discrete prototype system was designed and experimentally validated through flow phantom and preliminary human subject testing. The prototype system incorporates a custom two-dimensional transducer array and multi-channel transceiver electronics, thereby facilitating acoustic beamformation via phased array operation. Electronic steering of acoustic energy enables algorithmic system controls to map Doppler power throughout the tissue volume of interest and localize regions of maximal flow. Multi-focal reception permits dynamic vessel position tracking and simultaneous flow velocimetry over the time-course of monitoring. RESULTS: Experimental flow phantom testing yielded high correlation with concurrent flowmeter recordings across the expected range of physiological flow velocities. Doppler power mapping has been validated in both flow phantom and preliminary human subject testing, resulting in average vessel location mapping times <14 s. Dynamic vessel tracking has been realized in both flow phantom and preliminary human subject testing. CONCLUSIONS: A wearable prototype CBFV measurement system capable of autonomous vessel search and tracking has been presented. Although flow phantom and preliminary human validation show promise, further human subject testing is necessary to compare velocimetry data against existing commercial TCD systems. Additional human subject testing must also verify acceptable vessel search and tracking performance under a variety of subject populations and motion dynamics-such as head movement and ambulation.

Tissue perfusion pressure enables continuous hemodynamic evaluation and risk prediction in the intensive care unit.

Treatment of circulatory shock in critically ill patients requires management of blood pressure using invasive monitoring, but uncertainty remains as to optimal individual blood pressure targets. Critical closing pressure, which refers to the arterial pressure when blood flow stops, can provide a fundamental measure of vascular tone in response to disease and therapy, but it has not previously been possible to measure this parameter routinely in clinical care. Here we describe a method to continuously measure critical closing pressure in the systemic circulation using readily available blood pressure monitors and then show that tissue perfusion pressure (TPP), defined as the difference between mean arterial pressure and critical closing pressure, provides unique information compared to other hemodynamic parameters. Using analyses of 5,988 admissions to a modern cardiac intensive care unit, and externally validated with 864 admissions to another institution, we show that TPP can predict the risk of mortality, length of hospital stay and peak blood lactate levels. These results indicate that TPP may provide an additional target for blood pressure optimization in patients with circulatory shock.

Deconvolution-Based Partial Volume Correction for Volumetric Blood Flow Measurement.

Ultrasound-based blood flow (BF) monitoring is vital in the diagnosis and treatment of a variety of cardiovascular and neurologic conditions. Finite spatial resolution of clinical color flow (CF) systems, however, has hampered measurement of vessel cross Section areas. We propose a resolution enhancement technique that allows reliable determination of BF in small vessels. We leverage sparsity in the spatial distribution of the frequency spectrum of routinely collected CF data to blindly determine the point spread function (PSF) of the imaging system in a robust manner. The CF data are then deconvolved with the PSF, and the volumetric flow is computed using the resulting velocity profiles. Data were collected from phantom blood vessels with diameters between 2 and 6 mm using a clinical ultrasound system at 2 MHz insonation frequency. The proposed method yielded a flow estimation bias of 0 mL/min, standard deviation of error (SDE) of 22 mL/min, and a root-mean-square error (RMSE) of 22 mL/min over a 150 mL/min range of mean flows. Recordings were also obtained in low signal-to-noise ratio (SNR) conditions using a skull mimicking element, resulting in an estimation bias of -13 mL/min, SDE of 23 mL/min, and an RMSE of 26 mL/min. The effect of insonation frequency was also investigated by obtaining recordings at 4.3 MHz, yielding an estimation bias of -16 mL/min, SDE of 16 mL/min, and an RMSE of 22 mL/min. The results indicate that our technique can lead to clinically acceptable flow measurements across a range of vessel diameters in high and low SNR regimes.

Non-Invasive Evaluation of a Carotid Arterial Pressure Waveform Using Motion-Tolerant Ultrasound Measurements During the Valsalva Maneuver.

This work details the non-invasive evaluation of a carotid arterial blood pressure (ABP) waveform during the Valsalva maneuver. Unfocused and wide acoustic beams are insonated on the carotid artery to achieve motion-tolerant measurements with a simple two-element ultrasound scanner. Arterial flow and distension waveforms are reliably estimated from spectral Doppler and M-mode ultrasound images whose qualities are consistently maintained in different phases of the maneuver despite possible displacements of the artery. A local pulse wave velocity is estimated using a flow-area method, and it is then combined with the distension waveform to produce the ABP waveform. Human subject validation on seven healthy subjects shows that the bias in pulse pressure estimates across subjects is 0.47 ± 13.1 mmHg. The average root mean square deviations of the ultrasonically measured waveform across subjects is 10.1 ± 2.43 mmHg, excluding the strain phase of the Valsalva maneuver, and 17.7 ± 6.30 mmHg in all phases. The mean correlation coefficient between the ultrasonically measured and reference waveform is calculated to be 0.92 ± 0.04 across subjects. Detailed morphological features and their changes across different phases are observed as reported. This uninterrupted central ABP waveform monitoring under hemodynamics changes supports the idea of a novel stress test to evaluate the health and dynamics of the cardiovascular system at a spot check in clinical settings.

Measuring Saccade Latency Using Smartphone Cameras.

OBJECTIVE: Accurate quantification of neurodegenerative disease progression is an ongoing challenge that complicates efforts to understand and treat these conditions. Clinical studies have shown that eye movement features may serve as objective biomarkers to support diagnosis and tracking of disease progression. Here, we demonstrate that saccade latency-an eye movement measure of reaction time-can be measured robustly outside of the clinical environment with a smartphone camera. METHODS: To enable tracking of saccade latency in large cohorts of patients and control subjects, we combined a deep convolutional neural network for gaze estimation with a model-based approach for saccade onset determination that provides automated signal-quality quantification and artifact rejection. RESULTS: Simultaneous recordings with a smartphone and a high-speed camera resulted in negligible differences in saccade latency distributions. Furthermore, we demonstrated that the constraint of chinrest support can be removed when recording healthy subjects. Repeat smartphone-based measurements of saccade latency in 11 self-reported healthy subjects resulted in an intraclass correlation coefficient of 0.76, showing our approach has good to excellent test-retest reliability. Additionally, we conducted more than 19 000 saccade latency measurements in 29 self-reported healthy subjects and observed significant intra- and inter-subject variability, which highlights the importance of individualized tracking. Lastly, we showed that with around 65 measurements we can estimate mean saccade latency to within less-than-10-ms precision, which takes within 4 min with our setup. CONCLUSION AND SIGNIFICANCE: By enabling repeat measurements of saccade latency and its distribution in individual subjects, our framework opens the possibility of quantifying patient state on a finer timescale in a broader population than previously possible.

Feasibility of Fingertip Oscillometric Blood Pressure Measurement: Model-Based Analysis and Experimental Validation.

The most commonly used oscillometric upper-arm (UA) blood pressure (BP) monitors are not convenient enough for ambulatory BP monitoring, given the large size of the arm cuff and the compression of UA during the measurement. Finger-worn oscillometric BP devices featuring miniaturized finger cuff have been developed and researched as an alternative solution to the UA-based measurement, yet the reliability of the finger-based measurement is still questioned. To investigate the feasibility of oscillometric BP measurements at the finger position, we performed model-based analysis and experimental validation to explore the underlying issues associated with extending the cuff-based oscillometric approach from UA to other alternative sites. The simulation results revealed that a larger bone-to-tissue volume ratio produced a lower pressure transmission efficiency, which can account for the inter-site measurement discrepancies of mean blood pressure (MBP). We also experimentally compared the oscillometric MBP measurements at UA, middle forearm, wrist, finger proximal phalanx, and finger distal phalanx (FD) of 20 young adults, and each position was matched with a cuff of appropriate size and kept at the same height with the heart. The experimental results demonstrated that FD could be a superior alternative position for oscillometric BP measurement, as it requires the smallest cuff size while providing the most consistent MBP with the UA. Our analysis also suggested that further study is demanded to identify the appropriate oscillometric algorithm for reliable systolic blood pressure and diastolic blood pressure measurements at FD.

Electrode Placement for Calf Bioimpedance Measurements During Hemodialysis.

Congestive Heart Failure (CHF) is a chronic medical condition that causes reduced exercise tolerance, shortness of breath, and fluid buildup in the lungs, legs, and abdomen. Monitoring patient fluid status using non-invasive techniques such as bioimpedance may help reduce CHF related read- mission rates. Bioimpedance measurements were performed in a controlled environment (hemodialysis) at two locations on the calf (side and back) to determine ideal electrode placement for monitoring changes in fluid status. Changes in calf bioimpedance were heterogeneous. Three out of seven patients had higher changes at the back of the calf compared with the side of the calf for the bioimpedance parameter $R_{0}$ (the resistance measured at low frequency that is related to extracellular water). These data suggest there are differences in resistivity within the calf. Simulations showed that the use of point electrodes weights tissue nearest the electrodes more heavily, but that this dependence can be eliminated through the use of ring electrodes, effectively averaging resistivity around the calf.

Monitoring of Pulse Pressure and Arterial Pressure Waveform Changes during the Valsalva Maneuver by a Portable Ultrasound System.

This work presents non-invasive evaluation of the arterial blood pressure (ABP) waveform during the Valsalva maneuver. Ultrasound scanning is conducted to acquire blood flow and arterial distension signals. Motion-tolerant ultrasound measurement schemes are employed by using two wide rectangular transducers. Pulse pressure (PP) estimated at the common carotid artery is compared to that of a finger waveform measured by a volume clamping device. The changes of PP are correlated between the two measurements. A more depressed dicrotic notch during the Valsalva strain is observed, and beat-to-beat variations of PP and a pulse rate caused by respiration and baroreflex is observed during the control. This validation suggests novel opportunities to investigate the pathophysiology of cardiovascular diseases through the noninvasive ABP waveform monitoring during the stress test.

Motion Tolerant Unfocused Imaging of Physiological Waveforms for Blood Pressure Waveform Estimation Using Ultrasound.

This paper details unfocused imaging using single-element ultrasound transducers for motion tolerant arterial blood pressure (ABP) waveform estimation. The ABP waveform is estimated based on pulse wave velocity and arterial pulsation through Doppler and M-mode ultrasound. This paper discusses approaches to mitigate the effect of increased clutter due to unfocused imaging on blood flow and diameter waveform estimation. An intensity reduction model (IRM) estimator is described to track the change of diameter, which outperforms a complex cross-correlation model (C3M) estimator in low contrast environments. An adaptive clutter filtering approach is also presented, which reduces the increased Doppler angle estimation error due to unfocused imaging. Experimental results in a flow phantom demonstrate that flow velocity and diameter waveforms can be reliably measured with wide lateral offsets of the transducer position. The distension waveform estimated from human carotid M-mode imaging using the IRM estimator shows physiological baseline fluctuations and 0.6-mm pulsatile diameter change on average, which is within the expected physiological range. These results show the feasibility of this low cost and portable ABP waveform estimation device.

A Column-Row-Parallel Ultrasound Imaging Architecture for 3-D Plane-Wave Imaging and Tx Second-Order Harmonic Distortion Reduction.

We propose a column-row-parallel imaging front-end architecture for integrated and low-power 3-D medical ultrasound imaging. The column-row-parallel architecture offers linear-scaling interconnection, acquisition, and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data/control interface to a 2-D array. A capacitive micromachined ultrasonic transducer (CMUT)-application-specific integrated circuit (ASIC) column-row-parallel prototype is fabricated and assembled with a flip-chip bonding process. It facilitates the 3-D plane-wave coherent compounding algorithm for volumetric imaging with a fast frame rate of 62.5 Hz and 46% improved lateral resolution with 10-angle compounding and a field of view volume of 2.3 mm in both azimuth and elevation, 8.5 mm in depth. At a hypothetically scaled up array size, the frame rate can still be kept at 31.2 Hz for a volume of 40 mm in both azimuth and elevation, 150 mm in depth. An interleaved checkerboard pattern with in-phase ( ) and quadrature ( ) excitations is also demonstrated for reducing CMUT second-harmonic distortion emission by up to 25 dB at the loss of 3-dB fundamental energy reduction. The method reduces nonlinear effects from both transducers and circuits and is a wide band technique that is applicable to arbitrary pulse shapes.

A Column-Row-Parallel Ultrasound Imaging Architecture for 3D Plane-wave Imaging and Tx 2nd-Order Harmonic Distortion (HD2) Reduction.

We propose a Column-Row-Parallel imaging frontend architecture for integrated and low-power 3D medical ultrasound imaging. The Column-Row-Parallel architecture offers linear-scaling interconnection, acquisition and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data / control interface to a 2D array. A 16×16 CMUT-ASIC Column-Row-Parallel prototype is fabricated and assembled with a flip-chip bonding process. It facilitates the 3D plane-wave coherent compounding algorithm for volumetric imaging with a fast frame rate of 62.5 Hz and 46% improved lateral resolution with 10-angle compounding and a field of view volume of 2.3mm in both azimuth and elevation, 8.5mm in depth. At a hypothetically scaled up 64x64 array size, the frame rate can still be kept at 31.2 Hz for a volume of 40mm in both azimuth and elevation, 150mm in depth. An interleaved checker board pattern with in-phase (I) and quadrature (Q) excitations is also demonstrated for reducing CMUT second harmonic distortion (HD2) emission by up to 25 dB at the loss of 3 dB fundamental energy reduction. The method reduces nonlinear effects from both transducers and circuits and is a wide band technique that is applicable to arbitrary pulse shapes.

Low-Power, 8-Channel EEG Recorder and Seizure Detector ASIC for a Subdermal Implantable System.

EEG remains the mainstay test for the diagnosis and treatment of patients with epilepsy. Unfortunately, ambulatory EEG systems are far from ideal for patients who have infrequent seizures. These systems only last up to 3 days and if a seizure is not captured during the recordings, a definite diagnosis of the patient's condition cannot be given. This work aims to address this need by proposing a subdermal implantable, eight-channel EEG recorder and seizure detector that has two modes of operation: diagnosis and seizure counting. In the diagnosis mode, EEG is continuously recorded until a number of seizures are recorded. In the seizure counting mode, the system uses a low-power algorithm to track the number of seizures a patient has, providing doctors with a reliable count to help determine medication efficacy or other clinical endpoint. An ASIC that implements the EEG recording and seizure detection algorithm was designed and fabricated in a 0.18 µm CMOS process. The ASIC includes eight EEG channels and is designed to minimize the system's power and size. The result is a power-efficient analog front end that requires 2.75 µW per channel in diagnosis mode and 0.84 µW per channel in seizure counting mode. Both modes have an input referred noise of approximately 1.1 µVrms.

Noninvasive and continuous blood pressure measurement via superficial temporal artery tonometry.

The measurement of blood pressure is an important cardiovascular health assessment, yet the current set of methodologies is limited in resolution, repeatability, accuracy, simplicity, and safety. This paper presents the design and prototype implementation of a novel and easy-to-use medical device for noninvasive and continuous blood pressure monitoring through tonometry at the superficial temporal artery (STA). The device features a stable form factor inspired by over-ear headphones that adjusts easily from person to person using a combination prismatic and rotational joint. A stepper motor and pressure sensor, built into the device, apply a controlled force to flatten the artery and measure the wearer's blood pressure. The design is fully wireless, using Bluetooth communication to connect to a custom control and monitoring interface on the user's laptop that allows for easy calibration and real-time measurement. Preliminary testing of the device showed a percentage error from a blood pressure cuff mean arterial pressure measurement of 7.7% (7.0 mmHg). This was also compared to a Nexfin vascular unloading device, which showed a percentage error from the blood pressure cuff of 7.3% (6.6 mmHg).

Carotid arterial blood pressure waveform monitoring using a portable ultrasound system.

This work presents a non-invasive arterial blood pressure (ABP) waveform monitoring technique using ultrasound. A portable ultrasound system to excite ultrasound transducers and acquire data is designed with off-the-shelf components. The insonation angles are identified using a vector Doppler technique based on the cosine dependency of the Doppler signals. The pulse pressure of an estimated waveform at the left common carotid artery is compared to the standard sphygmomanometer measurement in a clinical test. The estimated carotid ABP waveform shows excellent agreement to the finger ABP waveform with expected discrepancy of the systolic peak shape due to different measurement sites. The proposed method also tracks slow blood pressure fluctuations. This validation on human subjects shows potential for a noninvasive blood pressure waveform monitoring device at central arterial sites.

A 58 nW ECG ASIC With Motion-Tolerant Heartbeat Timing Extraction for Wearable Cardiovascular Monitoring.

An ASIC for wearable cardiovascular monitoring is implemented using a topology that takes advantage of the electrocardiogram's (ECG) waveform to replace the traditional ECG instrumentation amplifier, ADC, and signal processor with a single chip solution. The ASIC can extract heartbeat timings in the presence of baseline drift, muscle artifact, and signal clipping. The circuit can operate with ECGs ranging from the chest location to remote locations where the ECG magnitude is as low as 30 µV. Besides heartbeat detection, a midpoint estimation method can accurately extract the ECG R-wave timing, enabling the calculations of heart rate variability. With 58 nW of power consumption at 0.8 V supply voltage and 0.76 mm (2) of active die area in standard 0.18 µm CMOS technology, the ECG ASIC is sufficiently low power and compact to be suitable for long term and wearable cardiovascular monitoring applications under stringent battery and size constraints.

Head ballistocardiogram based on wireless multi-location sensors.

Recently a wearable BCG monitoring technique based on an accelerometer worn at the ear was demonstrated to replace a conventional bulky BCG acquisition system. In this work, a multi-location wireless vital signs monitor was developed, and at least two common acceleration vectors correlating to sitting-BCG were found in the supine position by using head PPG signal as a reference for eight healthy human subjects. The head side amplitude in the supine position is roughly proportional to the sitting amplitude that is in turn proportional to the stroke volume. Signal processing techniques to identify J-waves in a subject having small amplitude was also developed based on the two common vectors at the head side and top.

A Low-Power, Dual-Wavelength Photoplethysmogram (PPG) SoC With Static and Time-Varying Interferer Removal.

This paper presents a low-power, reflectance-mode photoplethysmogram (PPG) front end with up to 100 µA of static interferer current removal and 87 dB attenuation of time-varying interferers. The chip nominally consumes 425 µW including signal chain circuits, red and IR LED drive power, clocks, digitization and I/O. Measured data shows the noise of the PPG signal to be dominated by the photodiode sensor photon shot noise.

Noninvasive arterial blood pressure waveform monitoring using two- element ultrasound system.

This work details noninvasive arterial blood pressure (ABP) waveform estimation based on an arterial vessel cross-sectional area measurement combined with an elasticity measurement of the vessel, represented by pulse wave velocity (PWV), using a two-element ultrasound system. The overall ABP waveform estimation is validated in a custom-designed experimental setup mimicking the heart and an arterial vessel segment with two single element transducers, assuming a constant hemodynamic system. The estimation of local PWV using the flow-area method produces unbiased elasticity estimation of the tube in a pressure waveform comparison. The measured PWV using 16 cardiac cycles of data is 8.47 + 0.63 m/s with an associated scaling error of -1.56 + 14.0% in a direct pressure waveform comparison, showing negligible bias error on average. The distension waveform obtained from a complex cross-correlation model estimator (C3M) reliably traces small pressure changes reflected by the diameter change. The excellent agreement of an estimated pressure waveform to the reference pressure waveform suggests the promising potential of a readily available, inexpensive, and portable ABP waveform monitoring device.

An Ear-Worn Vital Signs Monitor.

This paper presents a wearable vital signs monitor at the ear. The monitor measures the electrocardiogram (ECG), ballistocardiogram (BCG), and photoplethysmogram (PPG) to obtain pre-ejection period (PEP), stroke volume (SV), cardiac output (CO), and pulse transit time (PTT). The ear is demonstrated as a natural anchoring point for the integrated sensing of physiological signals. All three signals measured can be used to obtain heart rate (HR). Combining the ECG and BCG allows for the estimation of the PEP, while combining the BCG and PPG allows for the measurement of PTT. Additionally, the J-wave amplitude of the BCG is correlated with the SV and, when combined with HR, yields CO. Results from a clinical human study on 13 subjects demonstrate this proof-of-concept device.

A wearable cardiac monitor for long-term data acquisition and analysis.

A low-power wearable ECG monitoring system has been developed entirely from discrete electronic components and a custom PCB. This device removes all loose wires from the system and minimizes the footprint on the user. The monitor consists of five electrodes, which allow a cardiologist to choose from a variety of possible projections. Clinical tests to compare our wearable monitor with a commercial clinical ECG recorder are conducted on ten healthy adults under different ambulatory conditions, with nine of the datasets used for analysis. Data from both monitors were synchronized and annotated with PhysioNet's waveform viewer WAVE (physionet.org) [1]. All gold standard annotations are compared to the results of the WQRS detection algorithm [2] provided by PhysioNet. QRS sensitivity and QRS positive predictability are extracted from both monitors to validate the wearable monitor.