Methods
The Safe Lab is set for simultaneous studies of gait, balance, autonomic, cardiovascular, and respiratory systems, electromyography and cerebral and peripheral blood flow to evaluate dynamics of complex interactions among multiple organ systems during adaptation to standing and walking.
Clinical trials
Investigator initiated and industry-sponsored trials:
- preparation of regulatory documents
- database set up
- physiological measurements
- recruitment, study conduct and management data analysis, reports
Transcranial Doppler ultrasound (TCD)
assessment of cerebral blood flow velocities
vascular reserve and pressure autoregulation.
-Power M-Mode transcranial Doppler technology (PMD-150), 2 channel, Spencer technologies Inc., Seatlle WA.
-Multi-DOP X4, DWL Inc. for 4 channel recordings of cerebral/peripheral blood flow velocities with 2MHz, 4 MHz and 8MHz and 12MHz probes.
- Autonomic and Cardiovascular Function Testing
head-up tilt, Valsalva maneuever with cardiovascular monitoring
(indicated for clinical evaluation of syncope and falls)
treadmill and exercise bike studies
Portable beat-to-beat noninvasive blood pressure monitoring (Finapress, Poratapress (http://www.finapres.com)
ECG monitoring (Spacelabs, Inc)
ME6000 (24 hour ECG recordings)
Capnomac Ultima CO2 (Datex Ohmeda, Inc) multichannel, multigas monitor for respiratory, CO2, O2 monitoring (http://www.datex-ohmeda.com)
24 hour BP monitoring
- 24-hour ambulatory blood pressure monitoring (Dynapulse 5000 Auto, PulseMetric Inc (http://www.pulsemetric.com).
- 24-hour ECG, EMG, gait, activity monitoring (ME6000, Mega Elektronika, Inc)
Gait and balance
Gait assessment – evaluation of gait characteristics and measurements of foot pressure distribution during walking (Pedar Mobile, Novel Inc GE ( HYPERLINK "http://www.novel.de/" http://www.novel.de).
Gait Logger – wearable system for gait and activity monitoring system using B&L foot switches.
Surface Electromyography- 8 channel surface EMG Bagnoli System (http://www.delsys.com).
Balance assessment – measurements of centre of pressure distribution during standing (Kistler force plate, Kistler Inc http://www.kistler.com) and analysis of centre of pressure displacement using traditional and dynamic balance measures.
ME6000 (Mega Elektronica, Inc) –wearable 8 channel system for monitoring ECG, EMG gait and activity up to 24 hours (http://www.meltd.fi).
Software for gait and balance analysis
Traditional measures, time series analysis-stabilogram diffusion analysis, multiscale entropy, etc.
Nonlinear signal analysis
A major challenge in understanding biological systems is to connect the signaling on microscopic levels to the dynamics observed on the integrative, organ system level and functional outcome measures. Physiological recordings exhibit rich and complex dynamical patterns that contain high information content about functional state. Furthermore, loss of these complex dynamics is often correlated with a disease. The following methods for quantification of complex system dynamics are available through collaboration with Dr. Goldbeger and Dr. C.K. Peng (Margret and H.A. Rey Institute for Nonlinear Dynamics at BIDMC/Harvard Medical School ( http://www.physionet.org).
Hilbert-Huang transform: The Hilbert-Huang transform analysis, has been applied to numerous physical and physiological signals to assess non-linear relationship between two signals.
Hilbert-Huang transform: The Hilbert-Huang transform analysis, has been applied to numerous physical and physiological signals to assess non-linear relationship between two signals.
Multimodal Pressure Flow Method (MMPF): The MMPF technique that is based on Hilbert-Huang transform (1), measures coupling between two nonstationary signals. This method was implemented to quantify changes in cerebral autoregulatory dynamics in patients with hypertension, stroke and diabetes using the Valsalva maneuver and spontaneous pressure and flow oscillations (2-4).Cerebral autoregulation in healthy subjects can be characterized by large phase delays pressure and flow oscillations and its absence is an indicator of cerebrovascular disease.
Synchronization Method: Phase synchronization analysis(5) allows to explore the nonlinear feedback interactions between different physiological systems demonstrating complex oscillating behavior (cardiovascular, gait and respiratory).
Multiscale Entropy (MSE)
This method is useful for the complexity analysis of a variety of physiologic time series such as heart beat time series(6).
Modified Wigner distribution (WD): WD has useful properties the evaluation of nonstationary, short data series(7-10), i.e. in electroencephalographic waves, heart rate, blood pressure, respiration, cerebral blood flow, and other physiological signals.
Stabilogram-Diffusion analysis
Postural control is assessed from the center of pressure (COP) displacements using traditional static measures and stabilogram-diffusion analysis that provides dynamics measures of COP fluctuations (11, 12). The COP signals behave as a positively correlated random walk over short-time scales characterized by a Hurst exponent(13).
Mathematical Modeling
Encounters among multiple variables and co-morbidities are common in geriatric clinical research. In collaboration with Dr. M. Olufsen, Dept. of Mathematics, North Carolina State Univ., we use multicompartmental models to distinguish contributions of multiple mechanisms enaged in short-term cardiovascular and cerebrovascular control. The model is used to evaluate effects of aging and hypertension on orthostatic adaptation to standing-up and to predict variables that cannot be measured experimentally (i.. nerve firing, baroreflex firing)(14, 15). Collaborative project with RBGHS group (http://www.uni-graz.at/biomath/Collaboration_group)( Departments of Mathematics at the NC State Univ. (Dr. Olufsen, Dr. Tran), Univ, Roskilde., Denmark (Dr. Ottesen), Univ.Gratz, Austria (Dr. Kappel, Dr. Batzel), and the Safe Lab.
MRI analysis
Evaluation of the relationships between blood flow alterations and structural abnormalities in the brain or other organs, and their impact on functional outcomes requires “registration” alignment of perfusion and anatomical images. Blood flow and vascular reactivity maps are measured non-invasively using Continuous Arterial Spin Labeling and co-registered on high-resolution anatomical images at 3 Tesla to assess perfusion abnormalities and structural defects in gray and white matter. Diffusion tensor imaging is used to assess integrity of white matter pathways. Ultrahigh field MRI at 8 Tesla is used to evaluate for high resolution anatomical imaging (Collaborative project with Dr. D. Alsop, Center for Advanced Magnetic Resonance Imaging, BIDMC; Dr. A. Abduljalil, Center for Magnetic Resonance Imaging, The Ohio State University).
Anatomical morphometrics
MRI: 3 Tesla MP-RAGE and FLAIR images
Main techniques: image segmentation and registration algorithms
Applications:
- Global and regional brain volumetric measures (white matter, gray matter, and cerebrospinal fluid)
- Region of interest measurement, e.g., hippocampus
- Infarct volume and location
- White matter hyperintensities volume and distribution
Vessel Analysis
MRI: 3 Tesla Time of Flight (TOF) image
Main technique: 3D image visualization
Applications:
- Visualization and measurements of diameter and length of main arteries
Cerebral Blood Flow Measurement
MRI: 3 Tesla 3D Continuous Arterial Spin Labeling (CASL)
Main technique: non-invasive blood flow imaging, collaborative project with Dr. D. Alsop, Center for Advanced Magnetic Resonance Imaging, BIDMC
Applications:
- Measurement of cerebral blood flow and its distribution
- Perfusion and vasoreactivity in vascular territories
- Quantitative vascular reactivity and its distribution
Diffusion Tensor Imaging (DTI)
- assessment of white matter integrity
Databases
Safe lab has databases of physiological studies in older people-healthy controls, diabetic, hypertensive and stroke.
- cardiovascular and cerebral blood flow measurements during head-up tilt, standing, walking
- gait and balance measurements with cardiovascular parameters
- magnetic resonance images anatomy and perfusion at 3 Tesla MRI
- ultrahigh field magnetic resonance images at 8 Tesla
- 24 hour ECG, blood pressure, EMG and activity measurements
