Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts

We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm’s ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.Peer ReviewedPostprint (published version

Growth status of children and adolescents with type 1 diabetes mellitus

Background and Objectives: Growth parameters are important indicators of a child′s overall health, and they are influenced by factors like blood glucose control in diabetic children. Data on growth parameters of Indian diabetic children is scarce. This retrospective, cross-sectional, case control study was conducted at diabetes clinic for children at a tertiary care center at Pune, to study growth parameters of diabetic children in comparison with age-gender matched healthy controls and evaluate effect of different insulin regimes and age at diagnosis of diabetes on growth. Materials and Methods: One twenty five diabetic children (boys: 50) and age gender matched healthy controls were enrolled. All subjects underwent anthropometric measurements (standing height and weight). Mean height (HAZ), weight (WAZ) and body mass index (BAZ) for age Z scores were calculated. Diabetes control was evaluated by measuring glycosylated hemoglobin (HbA1C). Statistical analysis was done by SPSS version 12. Results: Mean age of diabetic children and age gender matched controls was 9.7 ± 4.4 years. Diabetic children were shorter (128.3 ± 24.3 cm vs. 133.6 ± 24.7 cm) and lighter (29.2 kg ± 15.3 vs. 31.3 ± 15.4 kg). HAZ (−1.1 ± 1.2 vs. −0.2 ± 0.8) and WAZ (−1.2 ± 1.3 vs. −0.7 ± 1.3) were significantly lower in diabetic children (P 14 years) were comparable to healthy controls. Conclusions: Growth was compromised in diabetic children in comparison to controls. Children diagnosed at younger age need more attention to optimize growth

Modified beer-lambert law for blood flow

We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues

Laser Safety in Fiber-optic Monitoring of Spinal Cord Hemodynamics: A Preclinical Evaluation

The prevention and treatment of spinal cord injury are focused upon the maintenance of spinal cord blood flow, yet no technology exists to monitor spinal cord ischemia. We recently demonstrated continuous monitoring of spinal cord ischemia with diffuse correlation and optical spectroscopies using an optical probe. Prior to clinical translation of this technology, it is critically important to demonstrate the safety profile of spinal cord exposure to the required light. To our knowledge, this is the first report of in situ safety testing of such a monitor. We expose the spinal cord to laser light utilizing a custom fiber-optic epidural probe in a survival surgery model (11 adult Dorset sheep). We compare the tissue illumination from our instrument with the American National Standards Institute maximum permissible exposures. We experimentally evaluate neurological and pathological outcomes of the irradiated sheep associated with prolonged exposure to the laser source and evaluate heating in ex vivo spinal cord samples. Spinal cord tissue was exposed to light levels at ∼18  ×   the maximum permissible exposure for the eye and ∼  (  1  /  3  )    ×   for the skin. Multidisciplinary testing revealed no functional neurological sequelae, histopathologic evidence of laser-related injury to the spinal cord, or significant temperature changes in ex vivo samples. Low tissue irradiance and the lack of neurological, pathological, and temperature changes upon prolonged exposure to the laser source offer evidence that spinal cord tissues can be monitored safely with near-infrared optical probes placed within the epidural space

Bedside measurement of hemodynamic biomarkers with fast diffuse correlation spectroscopy

The objective assessment and characterization of cerebral tissue health at the bedside is a difficult but highly significant problem in the acute care of strokes and other brain injuries. Observational limitations of current technologies, which are better suited for radiological snapshots rather than continuous monitoring of cerebrovascular health, limit bedside optimization/augmentation of care to subjective judgements of observed neurological deficits. In recent years, Diffuse Correlation Spectroscopy (DCS) has proven to be an increasingly popular non-invasive optical technique to solve this technological gap by directly measuring and monitoring deep tissue blood flow. Here, we highlight DCS’s utility as a clinical bedside monitor of acute CBF changes in patients affected with ischemic stroke. In addition, we highlight the development and application of new ‘fast’ DCS instrument that uses conventional DCS sources/detectors, and optimized software computations to measure blood flow ‘waveforms’ at measurement rates of 50-100 Hz. A direct consequence of this new CBF data type is the ability to characterize potentially chronic biomarkers of cerebral tissue health at the bedside. Firs

Dynamic Autoregulation of Cerebral Blood Flow Measured Non-invasively with Fast Diffuse Correlation Spectroscopy

Cerebral autoregulation (CA) maintains cerebral blood flow (CBF) in the presence of systemic blood pressure changes. Brain injury can cause loss of CA and resulting dysregulation of CBF, and the degree of CA impairment is a functional indicator of cerebral tissue health. Here, we demonstrate a new approach to noninvasively estimate cerebral autoregulation in healthy adult volunteers. The approach employs pulsatile CBF measurements obtained using high-speed diffuse correlation spectroscopy (DCS). Rapid thigh-cuff deflation initiates a chain of responses that permits estimation of rates of dynamic autoregulation in the cerebral microvasculature. The regulation rate estimated with DCS in the microvasculature (median: 0.26 s−1, inter quartile range: 0.19 s−1) agrees well (R = 0.81, slope = 0.9) with regulation rates measured by transcranial Doppler ultrasound (TCD) in the proximal vasculature (median: 0.28 s−1, inter quartile range: 0.10 s−1). We also obtained an index of systemic autoregulation in concurrently measured scalp microvasculature. Systemic autoregulation begins later than cerebral autoregulation and exhibited a different rate (0.55 s−1, inter quartile range: 0.72 s−1). Our work demonstrates the potential of diffuse correlation spectroscopy for bedside monitoring of cerebral autoregulation in the microvasculature of patients with brain injury

Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts

We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm’s ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.Peer Reviewe

Cerebral Blood Flow Response During Bolus Normal Saline Infusion After Ischemic Stroke

We quantified cerebral blood flow response to a 500 cc bolus of 0.9%% normal saline (NS) within 96 hours of acute ischemic stroke (AIS) using diffuse correlation spectroscopy (DCS). Materials and Methods: Subjects with AIS in the anterior, middle, or posterior cerebral artery territory were enrolled within 96 hours of symptom onset. DCS measured relative cerebral blood flow (rCBF) in the bilateral frontal lobes for 15 minutes at rest (baseline), during a 30-minute infusion of 500 cc NS (bolus), and for 15 minutes after completion (post-bolus). Mean rCBF for each time period was calculated for individual subjects and median rCBF for the population was compared between time periods. Linear regression was used to evaluate for associations between rCBF and clinical features. Results: Among 57 subjects, median rCBF (IQR) increased relative to baseline in the ipsilesional hemisphere by 17% (-2.0%, 43.1%), P< 0.001, and in the contralesional hemisphere by 13.3% (-4.3%, 36.0%), P < .004. No significant associations were found between ipsilesional changes in rCBF and age, race, infarct size, infarct location, presence of large vessel stenosis, NIH stroke scale, or symptom duration. Conclusion: A 500 cc bolus of .9% NS produced a measurable increase in rCBF in both the affected and nonaffected hemispheres. Clinical features did not predict rCBF response2811NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01 NS060653]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41-EB015893, R25 NS065745