WO2018104586A1

WO2018104586A1 - Interface unit and method for controlling stimulation system

Info

Publication number: WO2018104586A1
Application number: PCT/FI2017/050867
Authority: WO
Inventors: Arto Remes; Ingmar GUTBERLET; Jukka Kinnunen
Original assignee: Bittium Biosignals Oy
Priority date: 2016-12-07
Filing date: 2017-12-07
Publication date: 2018-06-14
Also published as: FI20165933L; EP3551286A1

Abstract

The present disclosure describes an interface unit for controlling a stimulation system comprising a stimulator unit for applying stimulation signals to a subject and at least one measurement unit for measuring electric signals from the subject. The interface unit comprises a stimulator interface for sending trigger request signals to the stimulator unit in order to cause the stimulator unit to generate the stimulation signals in response to the trigger request signals, at least one a measurement interface for sending an A/D clock signal to the measurement unit in order to control sampling of an A/D conversion unit in the measurement unit and for receiving measurement data from the measurement unit, and a data interface for sending the measurement data to a control unit. The interface unit is configured to generate the A/D clock signal and the trigger request signals in synchrony such that a phase shift between the sampling of the A/D conversion unit and the stimulation signals remains constant.

Description

I NTERFACE UNIT AND METHOD FOR CONTROLLI NG STIMULATION SYSTEM

FI ELD OF THE I NVENTION

The present invention relatesto measurement of bio-signals of a l iving subject, and more particularly to measuring electric signals from a subject while magneticfield pulses are being applied to the subject.

BACKGROUND I N FORM ATI ON

Transcranial magnetic sti mulation (TMS) is a procedure in which magnetic field pulse are be used for sti mulating regions of the brain. During a TMS procedure, a magnetic field generator in the form of a coil is placed near the head of a subject (e.g. a person). The coil produces small electric currents in the region of the brain of the subject just under the coil viaelectromagnetic induction. The coil is connected to a sti mulator unit which acts as a pulse generator that de- livers electric current to the coil .

It may be desirable to monitor electrical activity of the brain of the subject at the same ti me as the subject is receiving aTMStreatment. For example, Electroencephalography (EEG) of the subject may be monitored during the TMS treatment. EEG is an electrophysiological monitoring method to record electrical activity of the brain over a period of ti me. It is typically non-invasive, with electrodes placed along the scalp of the subject.

However, measurement of electric signals via the electrodes may be disturbed by the magnetic field pulses applied to the subject's head. The disturbances may appear as artifacts in the measurement data. Although there are various algorithms for removing artifacts from data, it may be very difficult to consistently removethem. BRI EF DI SCLOSURE

An object of the present invention is to provide a method and an apparatus for implementing the method so as to alleviate the above disadvantage. The objects of the invention are achieved by a method and an arrangement which are characterized by what is stated in the independent claims. The preferred embod- i ments of the invention are disclosed in thedependent clai ms.

When a fast disturbance is measured at a relatively low sampl ing rate, the shape and characteristics of the artifacts generated by the disturbance may vary significantly even if the disturbance remains the same. This problem may stem from an asynchrony between the pulses and the sampling of measured elec- trie signals. When sampling rate is relatively low, only few samples of the disturbance is produced. If the firing of the pulses and sampl ing of the electric signals are asynchronous, the samples of the disturbance may be sampled each ti me at different poi nts of the disturbance. As a result, each artifact based on the relatively few samples may have a different shape. It is possible to achieve more consistent shapes of the artifacts by increasing the sampl ing frequency. However, this may not be practical since it may increase the cost of the system.

In order to have more consistent shapes of artifacts induced by thedis- turbances, the generation of magnetic pulses and the measurement of electric signals may be synchronized. An interface unit may be used for synchronizing a sti mulator unit generating sti mulus signals and a measurement unit measuring electric signals. The interface unit may generate trigger requests signals that cause the sti mulator unit to generate a sti mul us signal . At the same ti me, the interface unit may generate an N D clock signal for an N D conversion unit in the measurement unit. Sampling of the electric signals may be performed based on the N D clock signal . The trigger request signals and the N D clock signal may be synchronized so that sampl ing of the measured electric signals occurs at the same points of the disturbance every time. As a result, artifacts in the measured data have consistently the same shape and characteristics, and are therefore easier to be removed from the measured data with artifact removal algorithms. Snce sti mulator units typically have a trigger input for externally controll ing the firing of pulses, the interface unit according to the present disclosure allows synchronization without modificationsto the sti mulator unit.

The interface unit may be configured to receive the measurement data from the measurement unit and to send the measurement data to a control unit set up to process the measurement data. The interface unit may further provide ti ming information on the magnetic field pulses to the control unit. The interface unit may receive control signals from the control unit in order to adjust ti ming of firing the magnetic field pulses and/ or sampl ing the measured electric signals. Thus, the interface unit may act as a unified interface for data measurement.

BRI EF DESCRI PTI ON OF TH E DRAWI NGS

In the following the invention will be described in greater detail by means of preferred embodiments with reference to the attached drawings, in which

Figure 1 a and 1 b shows exemplary measurement data on a disturb- ance induced by a sti mulus signal ; and

Figure 2 shows an exemplary embodi ment of a TMS system according to the present disclosure.

DETAI LED Dl SCLOSURE

The present disclosure describes an interface unit for controlling a sti mulation system. The sti mulation system comprises asti mulator unit for applying sti mulation signals in the form of magnetic field pulses to a subject and at least one measurement unit for measuring electric signals from the subject. The sti mulation system may be a transcranial magnetic sti mulation (TMS) system, and the sti mulator unit may be a TMS sti mulator configure to generate magnetic field pulses, for example. The measured electric signals may be measured to determine an EEGof the subject, for example.

In a TMS system, firing of the magnetic field pulses may cause repeating disturbances to the measurements. These disturbances may manifest them- selves as artifacts in measurement data. If the disturbances are fast with respect to the sampl ing rate of the electric signals so that only a few (e.g. 1 - 20) samples the disturbance are generated, and if the firing of the magnetic field pulses and the measurement of the electric signals are not synchronized, the artifacts may vary significantly in shape and characteristics, even if the disturbances them- selves remain the same.

Figure 1 a shows an exemplary measurement data where the firing of magnetic field pulses is not synchronized to sampl ing of measurement. In Figure 1 a, 32 artifacts induced by the disturbance resulting from the firing of the magnetic field pulses are shown. The sampl ing rate of the measurement is 5 kHz in Figure 1 a. The shape of the disturbance itself remains the same for all of the artifacts. However, because a phase shift between the disturbance and the sampling is not constant, the artifacts show high variance.

In contrast, Figure 1 b shows an exemplary measurement data where the same magnetic field pulses are fired in synchrony with sampling of measure- ment. In Figure 1 b, 32 artifacts caused by the disturbance resulting from thefiring of the magneticfield pulses are shown. The sampling rate of the measurement is5 kHz in Figure 1 b. Because a phase shift between the disturbance and the sampling is now constant, the artifacts show low variance in Figure 1 b.

In order to synchronize the firing of the magnetic field pulses and the measurement of electric signals, an interface according to the present disclosure may be used. The interface unit may comprise a sti mulator interface, at least one a measurement interface, and a data interface.

The sti mulator interface may be used for sending trigger request signals to the stimulator unit in order to cause the sti mulator unit to generate the sti mulation signals in response to the trigger request signals.

The at least one a measurement interface may be used for sending an N D clock signal to the measurement unit in order to control sampling of an N D conversion unit in the measurement unit. Further, the measurement interface may be used for receiving measurement data from the measurement unit. The interface unit is configured to generate the N D clock signal and the trigger request signals in synchrony such that a phase shift between the sampl ing of the N D conversion unit and the sti mulation signals remains constant.

The data interface may be used for sending the measurement data to a control unit configured to process the measurement data. The data interface may further comprises mean for receiving a trigger control signal from the control unit, and the interface unit may configured to adjust ti ming of the trigger re- quests on the basis of the trigger control signal . The sti mulator interface may further comprise means for receiving a trigger acknowledgement signal from the sti mulator unit, and the interface unit may be configured to generate timing in- formation on the trigger acknowledgement signals, and to send the ti ming information to the control unit through the data interface.

An interface unit according to the present disclosure may be util ized in aTMSsystem comprising a sti mulator unit, a measurement unit, and the interface unit, for example. Figure 2 shows an exemplary embodi ment of a TMSsystem ac- cording to the present disclosure. In Figure 2, the TMSsystem comprises a sti mulator unit 21 , a measurement unit 22, and an interface unit 23.

The sti mulator unit 21 may be a TMS sti mulator device that controls a current through a coil 21 a positioned in close proxi mity of the head 24 of a subject (e.g. a person) in order to generate magnetic field pulses to the head 24. The sti mulator unit 21 comprises an input for receiving trigger request signals. Each trigger request causes the sti mulator unit 21 to generate a magnetic field pulse. The sti mulator unit 21 may be a separate device.

The measurement unit 22 may be a device that is configured to measure electric signals from the head 24 via at least one electrode pair 22a. The measurement unit 22 may measure electric signals required for generating an EEG of the subject, for example. The electrodes electrode pairs 22a may be con- nected to the scalp of the subject. The measurement unit 22 comprises an Analog/ Digital (A/ D) conversion unit for converting the analog signal or signals from the electrodes into digital measurement data. The N D conversion unit may have one or more measurement channels, one for each electrode pair 22a, for example. The measurement unit 22may comprise a pre-amplifier or pre-ampl ifiers that amplify the analog signals before they are sampled and converter by theA/ D con- version unit. The sampl ing of the analog signals by the A/ D conversion unit is controlled by an N D clock input in the measurement unit 22. The measurement unit 22 may be battery-operated in order to avoid 50/ 60 Hz noise caused by the grid connection. In order to increase common-mode rejection ratio (CMRR) of the measurement, the measurement may drive an active ground attached to the subject (e.g. according to Driven Right Leg principle).

The interface unit 23 may be a separate device that is connected to the sti mulator unit 21 via a sti mulator interface 23a of the interface unit 23. The in- terface unit 23 sends trigger request signals to the sti mulator unit 21 via the sti mulator interface 23a. The sti mulator interface 23a may also be configured to receive trigger acknowledgement signals from the sti mulator unit 21 . The trigger acknowledgements provide ti ming information indicating ti me instants when the sti mulator unit has generated a sti mulation signal .

The measurement unit 22 connects to a measurement interface 23b of the interface unit 23. The interface unit 23 is configured to send an N D clock signal to the measurement unit 22 and receives measurement data from the measurement unit through the measurement interface 23b. By control ling the A/ D clock, the interface unit 23 is able to control the sample rate of the N D conver- sion unit.

Although Figure 2 shows only one measurement interface 23b, an interface unit according to the present disclosure may also comprise a plurality of such measurement interfaces. The measurement interface/ interfaces 23b may be i mplemented in the form of a pluggable optical transceiver/ tranceivers, and the measurement unit 23 be connected to the measurement interface 23a with a fiber optic cable or fiber optic cables, for example. The optical transceiver may be a small form-factor pl uggable (SFP) transceiver, for example. A fiber optic connection provides a galvanic isolation between the interface unit 23 and the measurement unit 22. Further, with a fiber optic connection, large distances between the interface unit 23 and the measurement unit 22. This may bethe casewhen the interface unit 23 and the measurement unit 22 are located in different rooms for patient safety, for example.

In order to mini mizethevariance in the shape and characteristic of the artifacts in the measured data, the interface unit 23 is configured to generate the N D clock signal and the trigger request signals in synchrony such that a phase shift between the sampl ing of the N D conversion unit and the sti mulation signals remains constant. In order to i mplement the functionalities of an interface unit according to the present disclosure, the interface unit 23 may comprise a computing device (such as aprocessor, an FPGA, or an ASI C) and a memory.

The TMS system in Figure 2 may further comprise a control unit 25 as in Figure 2. The control unit 25 may be a computer gathering and/ or processing the measurement data from the measurement unit/ units 22, for example. The control unit 25 may connect to the rest of the TMS system through a data interface 23c in the interface unit 23. The interface unit 23 comprises means for sending the measurement dataoriginating from the measurement unit or units 22 to a control unit 25 through the data interface 23c. The data interface 23c may comprise means for also receiving control signals from the control unit 25. With the control signals, the control unit 25 may control the timing of the trigger requests, for example. The data interface 23c may be i mplemented as an Ethernet interface, for example.

During operation, an interface unit 23 in a TMS system in Figure 2 generates an N D clock signal for the N D con-version unit in the measurement unit 22 in order to control sampl ing of the N D conversion unit. The interface unit 23 further generates trigger request signals for the sti mulator unit. The sti mulator unit 21 then generates the sti mulation signals in response to the trigger re- quest signals. The N D clock signal and the trigger request signals are generated in synchrony such that a phase shift between the sampl ing of the N D conversion unit and the sti mulation signals remains constant.

The trigger requests may originate from the control unit 25. The control unit 25 may generate a control signal , and upon receiving acontrol signal, the interface unit 23 send atrigger request signal to the sti mulator unit 21 . The inter- face unit 23 may delay the generation of the trigger request signal until it has a desired phase shift with respect to the A/ D clock. The interface unit 23 may oper- ate on an internal high-frequency clock, and generate the trigger requests and the N D clock from the internal clock. For example, the interface unit may operate on an internal clock at 20 MHz, and the measurement unit may sample electric signals at 80 KHz/ channel. When the interface unit 23 receives a control signal indi- eating firing of a pulse, it may outputs the trigger pulse to the sti mulator unit 21 at a desired delay in respect to the sampling by the measurement unit 22. Snce sampl ing interval is 12.5 με (at an 80 kHz sampl ing rate) while the resolution provided by the 20MHz clock is 50 ns, the desired delay can be controlled very accurately.

Alternatively, the interface unit 23 may generate the trigger requests autonomously. The interface unit 23 may use its internal clock signal for calculating ti mings of the trigger requests. Even if the interface unit 23 generates trigger requests autonomously, the control unit 25 may send control signals containing ti ming information to the interface unit. For example, the control unit 25 may send control signals that contain ti ming information on a desired period between trigger requests and a ti ming of the initial trigger (e.g. in the form of an initial delay).

The interface unit 23 may receive trigger acknowledgement signals originating from the sti mulator unit 21 . The interface unit 23 may determine ti ming information on the trigger acknowledgements. The interface unit may then send the timing information to the control unit 25 together with the measurement data. In order to facilitate the data transfer from the measurement unit to the control unit, the interface unit may comprise a temporary data storage in the memory of the interface unit, for example.

Although the above embodi ments discuss an interface unit in view of a TMS system, the interface can be used in other kind of sti mulator system where a sti mul us is triggered responsive to a trigger signal . Instead of a TMS sti mulator unit, the sti mulation system may comprise an electrical, optical , heat, cold, or acoustic sti mulator, for example.

It is obvious to a person skilled in the art that the inventive concept can be i mplemented in various ways. The invention and its embodi ments are not limited to the examples described above but may vary within the scope of the clai ms.

Claims

CLAI MS

1 . An interface unit for controlling a sti mulation system comprising a sti mulator unit for applying sti mulation signals to a subject and at least one measurement unit for measuring electric signals from the subject, wherein the interface unit comprises

a sti mulator interface for sending trigger request signals to the sti mulator unit in order to cause the sti mulator unit to generate the sti mulation signals in responseto the trigger request signals,

at least one a measurement interface for sendi ng an N D clock signal to the measurement unit in order to control sampl ing of an N D conversion unit in the measurement unit and for receiving measurement data from the measurement unit, and

a data interface for sending the measurement data to a control unit, wherein

the interface unit is configured to generate the N D clock signal and the trigger request signals in synchrony such that a phase shift between the sampling of the N D conversion unit and the sti mulation signals remains constant.

2. An interface unit according to clai m 1 , wherein

the sti mulator interface comprises means for receiving a trigger acknowledgement signal from the sti mulator unit, and

the interface unit is configured to generate ti ming information on the trigger acknowledgement signals, and send the ti ming information to the control unit.

3. An interface unit according to clai m 1 or 2, wherein

the data interface com prises means for receiving a trigger control signal from the control unit, and

the interface unit is configured to adjust ti ming of the trigger requests on the basis of the trigger control signal .

4. A transcranial magnetic sti mulation (TMS) system comprising a sti mulator unit configured to generate sti mulation signals in the form of magnetic field pulses, a measurement unit, and an interface unit according to any one of clai ms 1 to 3.

5. A method for controlling a transcranial magnetic sti mulation (TMS) system comprising a sti mulator unit and a measurement unit, wherein the method comprises

generating, with an interface unit, an N D clock signal for an N D conversion unit in the measurement unit in order to control sampl ing of the A/ D conversion unit, and

generating, with the interface unit, trigger request signals for the sti m- ulator unit in order to cause the sti mulator unit to generate the sti mulation signals in responseto thetrigger request signals,

wherein the N D clock signal and the trigger request signals are gen- erated in synchrony such that a phase shift between the sampl ing of the N D conversion unit and the sti mulation si gnals remains constant.