"In the name of God"

Homework 2

Biomechatronic Systems

Instructor:

Dr. Delrobaei

Student:

Atiye Riasi(9800436)

Spring 2020

1.

Design an implantable-wearable system automatically control

hypertension. How to measure the blood pressure in a semi real-

time manner and send appropriate feedback to the neurostimulator.

Your device need to be unobtrusive and safe.

Keywords

What is Artrial blood pressure?

Diagram of a pulse blood pressure which shows Systolic, Diastolic

and Mean Artrial blood Pressure(MAP)

hypertension High blood pressure

hypotension Low blood pressure

What can cause an increase in blood pressure ?

Blood pressure is a force that blood exerts against the walls of their

vessels. So any reason which increase the volume of blood or

peripheral resistance can increase the blood pressure.

Hypertension can cause heart disease and stroke

It is very important to control the hypertension

How to control hypertension?

Following diagrams shows the role of kidney and nervous system to

control blood pressure in summary.

How baroreceptors decrease blood pressure?

Increasing the blood pressure Stretching the baroreceptors in

wall of carotid sinus Discharging baroreceptors

Sending messages to the vasomotor center in medulla via baro-

receptive afferent fibers including the carotid sinus nerve that fuses

with the glossopharyngeal nerve and the aortic depressor nerve that

runs in the vagal nerve

attenuating the efferent sympathetic nerve firing in response to the

baroreceptor discharge

reducing sympathetic tone/increasing renal function

decreasing peripheral resistance (by vasodilation)/decreasing blood

volume Decreasing blood pressure

What are possible treatments for hypertension?

1. Antihypertension drugs

It is a non-invasive and more acceptable methode

× For some patients blood pressure does not fall

× Blood pressure is reduced insufficiently

× May cause shifting the blood pressure set point (blood pressure

at rest) in a higher level.

2.Artificial stimulation of baroreceptor

is very useful for patients with drug resistance

× it is invasive

History of artificial stimulators

Early models :

1950s: Because of its invasive nature, it was never considered a

front-line and it was used just for patients who underwent neck

dissection for canser, they found out that increasing in the

intensity of electrical stimulation decreases MAP and HR.

Baropacers: the device was placed under the pectoral muscle

and the leads were connected to the carotid sinuses and the

device was turned on or off by placing a magnet over the

device.

Bilateral stimulators

Major limitation of these earlier devices:

Due to lack of ability to individualize for each patient, some patients

developed systemic symptoms such as orthostatic hypertension (a

sudden rise in systolic blood pressure of 20 mmHg or more when

standing), bradycardia and some developed local irritation from

stimulator implantation.

Matching bilateral stimulation frequency to heart rate as

tachycardia could mean an increased sympathetic tone, so the

stimulator did not abolish the body’s innate ability to increase

the sympathetic activity at the time of exercise.

Two major reasons cause this device fall out of favor:

1. Effectiveness and continues of oral anti-hypertensive agents in

1980s and 1990s.

2. Implantation of carotid sinus stimulator is an invasive

procedure.

Baro Activation Therapy(BAT) as an open loop neuro

modulation and long term blood pressure reduction

As the entry of new agents slowed and prevalence of resistance

hypertension increases, new devices such as Rheos

(𝐶𝑉𝑅𝑥,Minneapolis,MN) are developed, they consists of an

implantable pulse generator with leads attached to the carotid sinus

bilaterally.

In contrast to the older devices,

The program in this device could be adjusted after the

implantation.

Electronics have been much miniaturized.

× The most common approach is to set the voltage and the

frequency depending on the prevailing level of blood pressure

and heart rate and the patient’s response to stimulation. it is

necessary to use different settings during daytime and

nighttime. At any rate, it is a matter of trial and error to find

the optimal settings in a particular patient.

closed-loop baroreceptor stimulation lowers blood pressure without

inducing hypotension and adjusting the stimulation pattern in

response to the subject’s physiological state as well as the

environmental condition. Therefore, it would promise ideal blood

pressure control (tested in rats and rabbits)

bionic baroreflex system(BBS) basically consists of an artificial

pressure sensor, a neurostimulator for autonomic nerves and a

regulator that encodes blood pressure into neurostimulation.( New

proposed closed loop system to avoid hypotenstion after controlling

hypertension)

Remember: Bionic means that the device is designed to replicate the

dynamic characteristics of the native system to fully restore the

function

Implementation

It is important to point out that most neuromodulation devices

adopt an open-loop scheme which requires the user to manually

change the stimulation parameters, thus lacking safety, selectivity,

specificity and adaptability. Effective and safe neuromodulation

requires intelligent control to dynamically adjust the stimulation

pattern in response to the subject’s physiological state as well as the

environmental condition.

feasibility of the development of closed-loop blood pressure

control technology

Native baroreflex system

The arterial baroreflex system is a negative feedback system.

Neurostimulation at the afferent limb of the baroreflex inhibits the

efferent sympathetic nervous activity and lowers blood pressure.

Changes in SAP(systolic AP) induced by external disturbance in

pressure (Pd) is sensed by arterial baroreceptors. The change in

pressure initiates a reflex change in vasomotor sympathetic outflow.

Primary reflex center is located in brain stem.

Vasomotor center(controller)

Artificial Baroreflex system

The bionic baroreflex system basically consists of an artificial

pressure sensor, a neurostimulator for autonomic nerves and a

regulator that encodes blood pressure into neurostimulation

𝐻𝑛𝑎𝑡𝑖𝑣𝑒 + +

Pd

SAP

artificial vasomotor center(controller):

In anesthetized rats, bilateral carotid sinus baroreceptive areas

were vascularly isolated with preservation of carotid sinus

nerves

Then a servo-controlled piston pump that can generate real-

time AP in the intracarotid sinus was connected to bilateral

common carotid arteries. Bilateral aortic depressor nerves

were sectioned to eliminate interaction

𝐻𝑆𝐴𝑃−𝑆𝑇𝑀 𝐻𝑆𝑇𝑀_𝐴𝑃

+ +

Pd

SAP

Neurostimulation electrodes were attached to the proximal

end of the sectioned aortic depressor nerves. An AP sensor

was placed in the aortic arc

With this procedure, the ‘‘bionicbaroreflex’’ works through the aortic

depressor nerve, meanwhile the‘‘nativebaroreflex’’works through

the carotid sinus baroreceptor

transfer function from intracarotid sinus pressure to

AP(𝐻𝐶𝑆𝑃−𝐴𝑃) using white noise analysis

transfer function from aortic depressor nerve stimulation to

AP(𝐻𝑎𝑑𝑛𝑆𝑇𝑀−𝐴𝑃)

opening rule for artificial vasomotor center:

𝐻𝐶𝑆𝑃−𝑆𝑇𝑀=𝐻𝐶𝑆𝑃−𝐴𝑃

𝐻𝑎𝑑𝑛𝑆𝑇𝑀−𝐴𝑃

Since the identified HCSP-adnSTM approximated the delta

function, a simple gain as a simplified operating rule is used

set the ‘‘bias’’ stimulation frequency that could maintain AP at

the same level of native closed-loop AP. In other words, the

‘‘bias’’ functions as the modulator of mean AP, whereas the

‘‘gain’’ works as the pressure buffer in reducing pressure

variability.

The bionic baroreceptor therefore allows not only AP lowering

by adjusting the ‘bias’ frequency like BAT therapy but also AP

stabilization by increasing/decreasing stimulation frequency in

response to AP. Thus, the bionic baroreceptor might benefit

hypertensive patients with comorbid orthostatic hypotension.

Practical issues for clinical application

× physical and logical neural interfaces and development of

miniaturized implantable sensor for detecting feedback

signals

× nerve damage due to electrode physical contact and

unpleasant reactions caused by current leakage to

surrounding tissue and nonselective recruitment of the fiber.

× invasive surgical approach to the splanchnic sympathetic

nerve is not practical in humans

× Spinal cord stimulation for blood pressure control therapy

seems more feasible, but the application would be limited to

anesthetized patients because of unpleasant sensation and

muscle twitching. Regarding baroreceptor afferent limb

activation, the baroreflex activation therapy (BAT) system

developed by CVRx Inc. was approved for clinical trial

× we have to introduce a clinically approved, implantable,

durable and safe AP sensors such intravascular pressure

sensor that is used for implanting in the pulmonary artery

FDA approved in 2014

× safety against clot

× it is unclear whether the dynamic transduction from AP to

neurostimulation remains unchanged over time or under the

awake condition

A Wireless Miniaturized Neural Implant system on chip (SoC)

the above mentioned system is not implantable and relies on wires

connecting the stimulator and the pressure sensor with the external

controller, impeding its clinical usage.

For an implantable device we need

to support adaptive power regulation to stabilize the potential

power fluctuation at the implant side due to environment

changes such as coil displacement.

Using inductive powering because of high power transmission

efficiency

Class-E power amplifier with optimized coil pair is used for wireless

power transfer. The loading and/or coupling coefficients change is

dynamically compensated by sensing the implant’s power

information and transmitting it back to the primary power

transmitter in order to adjust the level of delivered power

The unexpected power loss would decrease the efficiency of

the power link and even lead to the malfunction of the implant.

Using a wireless rechargeable battery

a neural implant must be capable of monitoring the electrode-

tissue interface to ensure an effective and safe stimulation

protocol.

An effective approach is time domain analysis on the electrode-

tissue impedance: a biphasic stimulus as a by-product

supported by most stimulators is injected into the electrode-

tissue interface and the electrode potential are measured at

three specific time points to estimate the equivalent circuit

model of the bio-impedance.

Biphasic electrical stimulation is widely adopted to ensure a

zero Faradic charge residual at the stimulation site

the sensed electrode voltage is sent to a proportional-integral-

derivative (PID) controller to precisely control the width of

either the anodic or the cathodic current pulses.

A critical and paramount feature for the closed-loop implant is

the capability of adapting the stimulation parameters in real-

time

The capability of performing selective and focal stimulation to

specific nerves would greatly ameliorate the treatment efficacy.

a multi-channel stimulator should be able to independently

configure the stimulation parameters in each driver and

support various waveforms. This would allow the shaping and

steering of the electric field at the stimulating electrode to

improve the stimulation spatial resolution and accordingly

perform selective nerve stimulation.

Miniaturizing the device to to reduce its surgical invasiveness

would greatly enhance patient acceptability.

There are two approaches widely adopted to execute the control

algorithm for the closed-loop implant:

1) preloading the re-configurable firmware in the implant

2) configuring the algorithm in the external controller that

communicates with the implant