Assessing Cerebral Autoregulation via Oscillatory Lower Body Negative Pressure and Projection Pursuit Regression

The overall goal of the following experiment is to characterize the nature of the relationship between arterial blood pressure and cerebral blood flow fluctuations in healthy individuals. This is achieved using oscillatory lower body negative pressure to create central blood volume shifts and arterial pressure fluctuations, similar to those that occur during standing, but in a controlled and graded manner without accompanying muscle contraction. As a second step projection, pursuit regression is used to quantify the relationship measured arterial pressure and cerebral blood flow.

Next points where the arterial pressure cerebral flow relationship changes are identified and the gain within each region where the relationship is approximately linear are estimated as a measure of the effectiveness of cerebral autoregulation within that region. The results show that as the oscillations of lower body negative pressure becomes slower, arterial pressure fluctuations become larger, while fluctuations in cerebral blood flow are progressively more effectively dampened. The main advantage of this technique over existing methods like transfer function analysis, is that projection pursuit is a non-linear, a theoretical method, meaning that a model is not posited a priority, but drive directly from the observations.

This is a decided advantage to characterize a system whose physiology is not yet defined by explicit models. Demonstrating the procedure will be Jason Hamner, a biomedical engineer from our lab. Be sure to obtain the necessary institutional approvals and subject consent before beginning this procedure, situate the subject comfortably and affix three or more electrodes from an electrocardiography monitor to the torso of the subject to measure heart rate throughout the study.

Then place a custom made neoprene skirt around the subject's chest at the level of the iliac crest. Ensure that the skirt is snug enough to seal the subject into the lower body negative pressure chamber, but does not restrict breathing or interfere with the ECG. Next, have the subject lie supine on the bed and maneuver the lower body pressure chamber underneath them.

Ensure that they are comfortably seated on the bicycle seat. Place a custom plexiglass chamber, cut to the subject's waist size to help seal the chamber. Then use duct tape to seal the neoprene skirt around the lower body negative pressure chamber.

Now connect the lower body negative pressure chamber to a standard pressure transducer and use an empty syringe and figma manometer to calibrate the pressure transducer to millimeters of mercury. Attach the custom built mechanical valve and repeat cycle timer to the lower body negative pressure chamber and adjust the cycle time to the desired oscillatory lower body negative pressure frequency. Next, attach a standard household vacuum cleaner to the mechanical valve.

Then plug the vacuum into a variable transformer to control voltage to the vacuum and turn on the vacuum cleaner. Adjust the transformer until the target lower body negative pressure. Typically 20 to 40 millimeters of mercury is achieved.

To measure arterial pressure, attach a non-invasive photographic arterial pressure cuff to the subject's finger. Then to measure expired carbon dioxide properly, place a nasal cannula attached to an infrared carbon dioxide analyzer on the subject and instruct them to breathe only through their nose. Finally, use a two megahertz pulse wave Doppler probe to intonate the M1 segment of the middle cerebral artery at the temple.

Monitor the signal and alter the probe angle intonation depth gain, and transmission power to maximize the spectral intensity of the signal. Once the optimum signal has been attained, fix the Doppler probe in place with a device that has no back, so that movement artifact is not introduced into the signal as the volunteer moves with negative pressure oscillations. Once the equipment is set up and the subject is ready, set up the analog to digital conversion of arterial pressure, cerebral blood flow, lower body negative pressure chamber pressure, and expired carbon dioxide to acquire at a minimum of 50 hertz per channel.

ECG should be sampled at one kilohertz hertz. Next, turn on the vacuum and ensure that the pressure is stable at around 30 millimeters of mercury. Then set the repeat cycle timer to 33 seconds for 0.03 O solitary, lower body negative pressure, and check the Doppler probe for optimal signal.

Acquire data for a minimum of 15 cycles to ensure confidence in the PR estimates. Now, repeat the procedure for any frequency between 0.03 to 0.08 hertz. By changing the repeat cycle timer duration, it is necessary to process the data to be able to perform project pursuit.

Regression analysis signals are decimated to five hertz and then band pass filtered at the frequency of a solitary lower body negative pressure to decimate the signal open. MATLAB and type the command now shown on the screen where SR is the original sampling rate. This decimate the arterial pressure and cerebral blood flow to five hertz.

Then begin projection pursuit regression estimation in matlab. Enter the command now shown on screen. Then enter the study ID as a three letter study code followed by three numeric characters for subject id.

Enter the study date in the format year, month, day, and enter the numeric measurement number for example, one for day one. Next, enter the arterial pressure measurement entering FP for op press or al for arterial line, enter the vessel type such as M-C-A-A-C-A or PCA, and then enter Y or N to the query. Do you have right MCA measurements and Y or N to the query?

Do you have left MCA measurements? This image shows parameters of the cerebral autoregulation curve derived from PPR analysis of arterial pressure and cerebral blood flow during 0.03 hertz oscillatory lower body negative pressure. This is the classic autoregulatory curve derived from the relationship between static increases and decreases in pressure and steady state cerebral blood flow.

A region of unchanging flow despite changing pressure IE where the slope equals zero, is bounded by regions where increasing and decreasing pressures result in proportional cerebral blood flow changes. This power spectrum shows the magnitude of fluctuations in arterial pressure when O-L-B-N-P frequency is below 0.03 hertz. Note that there are two large peaks in the arterial pressure spectral power at 0.02 and 0.05 hertz.

However, there is only a single peak in the LBNP spectral power at 0.025 hertz. Moreover, the largest fluctuation in pressure is at 0.05 hertz and would confound the interpretation of the cerebral blood flow responses. Here is an example of the effects of oscillatory lower body negative pressure from 0.08 to 0.03 hertz on arterial pressure and cerebral blood flow.

Arterial pressure fluctuations become larger with slower oscillatory, lower body negative pressure, whereas cerebral blood flow fluctuations become smaller. This autoregulatory function is described by the results of the PPR analysis shown in the bottom panels. The autoregulatory region in cerebral blood flow becomes progressively more pronounced with slower oscillatory, lower body negative pressure.

These individual and averaged PPR on autoregulatory curves are derived from 0.03 hertz oscillatory lower body negative pressure data in subjects before and after sympathetic blockade. Note the loss of the narrow auto regulatory region after sympathetic blockade. This is the average of the PPR parameters from 0.03 hertz oscillatory lower body negative pressure data before and after sympathetic blockade.

Sympathetic blockade had a pronounced effect on the cerebral autoregulation curve within the auto regulatory range, markedly increasing the slope. IE more proportional cerebral blood flow changes with pressure changes After this development. This technique paved the way for researchers in the field of cerebrovascular physiology to explore physiologic control as well as pathophysiologic alterations of brain blood flow in humans.