CN107510900A - A kind of TCD,transcranial Doppler stimulates the device and method of increase neurotrophic factor expression - Google Patents
A kind of TCD,transcranial Doppler stimulates the device and method of increase neurotrophic factor expression Download PDFInfo
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- CN107510900A CN107510900A CN201710986851.1A CN201710986851A CN107510900A CN 107510900 A CN107510900 A CN 107510900A CN 201710986851 A CN201710986851 A CN 201710986851A CN 107510900 A CN107510900 A CN 107510900A
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- tcd
- signal
- stimulates
- signal generator
- transcranial doppler
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0004—Applications of ultrasound therapy
- A61N2007/0021—Neural system treatment
- A61N2007/0026—Stimulation of nerve tissue
Abstract
The invention discloses the device and method that a kind of TCD,transcranial Doppler stimulates increase neurotrophic factor expression, the device includes：First signal generator, for producing the signal of default square wave shape parameter；Secondary signal generator, the pulse signal of default sinusoidal waveform parameter is produced under the triggering for the square wave exported in first signal generator；Power amplifier, for pulse signal caused by the secondary signal generator to be carried out into power amplification, and ultrasonic transducer is encouraged to produce ultrasound stimulation ripple；Ultrasonic transducer, the ultrasound stimulation ripple is produced for receiving the signal of the power amplifier output and changing, the ultrasound stimulation to brain area is realized, the present invention increases the BDNF expressions of hippocampus by stimulating prefrontal lobe, and the treatment for a variety of neurodegenerative diseases provides approach.
Description
Technical field
The present invention relates to TCD,transcranial Doppler to stimulate neuromodulation technical field, and being stimulated more particularly to a kind of TCD,transcranial Doppler increases
The device of neurotrophic factor (Brain Derived Neurotrophic Factor, BDNF) expression
And method.
Background technology
TCD,transcranial Doppler is stimulated as emerging cerebral function control technique, compared to now conventional neuromodulation technology (brain
Deep brain stimulation, through cranium galvanic current stimulation, transcranial magnetic stimulation etc.), have non-invasive, high spatial resolution, penetration depth high, easily
With other technologies are combined the advantages that, targeting stimulation can be carried out to specific function region, therefore cause numerous researchers'
Concern, application prospect are had an optimistic view of extensively.In recent years, ultrasound stimulation technical field of research constantly makes substantial progress, and has tested
Prove TCD,transcranial Doppler stimulate can not only induce or suppress neural electrical activity, can also by stimulate hippocampus increase nerve regeneratl with
And BDNF expression.Research shows that TCD,transcranial Doppler nerve stimulation has extensively as a kind of emerging neuromodulation technology above
Wealthy development and application prospect.
BDNF wide expressions in nervous system, existence, growth, differentiation and function to neuron play important work
With, therefore BDNF can increase and learn, remembers and the neural plasticity on gyrus road that the cognitive function such as stress reaction is related, and
And BDNF can promote the neuron reparation after damage.There are numerous studies to show BDNF to treating alzheimer at present
Disease, schizophrenia, depression, cerebral infarction a variety of neurodegenerative diseases of waiting indefinitely play an important roll.Clinic mainly passes through at present
Drug therapy improves cental system BDNF levels, but complete brain blood barrier hinders BDNF and entered as ripe protein
Enter brain tissue, and then weaken therapeutic effect.Also more difficult directly stimulate exactly is located at deep brain area to existing neuromodulation technology
Hippocampus, improve the horizontal efficiency of BDNF so as to influence it.Therefore, the present invention is proposed by stimulating superficial brain area to be located to increase
A kind of method of the BDNF expression of the hippocampus in deep, so that cental system BDNF is horizontal to provide simple and convenient reliable side to improve
Method.
The content of the invention
To overcome above-mentioned the shortcomings of the prior art, the purpose of the present invention is that providing a kind of TCD,transcranial Doppler stimulates increase
The device and method of neurotrophic factor expression, it is more to increase the BDNF expressions of hippocampus by stimulating prefrontal lobe
The treatment of kind neurodegenerative disease provides approach.
In view of the above and other objects, the present invention proposes that a kind of TCD,transcranial Doppler stimulates the dress of increase neurotrophic factor expression
Put, including：
First signal generator, for producing the signal of default square wave shape parameter；
Secondary signal generator, produced under the triggering for the square wave exported in first signal generator it is default just
The pulse signal of string waveform parameter；
Power amplifier, for pulse signal caused by the secondary signal generator to be carried out into power amplification, and encourage
Ultrasonic transducer produces ultrasound stimulation ripple；
Ultrasonic transducer, the ultrasound stimulation ripple is produced for receiving the signal of the power amplifier output and changing,
Realize the ultrasound stimulation to brain area.
Further, described device also includes transducer-scalp coupling module, for the ultrasound stimulation ripple is accurately fixed
Position is to brain area.
Further, the transducer-scalp coupling module uses collimater, will be low caused by the ultrasonic transducer
Intensity ultrasonic is pin-pointed to brain area by the collimater.
Further, the brain area that TCD,transcranial Doppler stimulates is prefrontal lobe.
Further, first signal generator is function signal generator, the frequency of its output signal for 1kHz~
3kHz。
Further, the secondary signal generator is function signal generator, and the fundamental frequency of its pulse signal exported is
0.35MHz~0.75MHz.
Further, the ultrasound stimulation parameter of the ultrasound stimulation ripple is：Spatial peak pulse peak intensity of sound is 1~8W/
cm2, pulse recurrence frequency is 1kHz~3kHz.
To reach above-mentioned purpose, the present invention, which also provides a kind of TCD,transcranial Doppler, stimulates the side of increase neurotrophic factor expression
Method, comprise the following steps：
Step 1, the voltage signal of pulsed is produced by signal generator；
Step 2, pulse signal caused by step 1 is amplified to the high pressure needed for ultrasonic transducer by power amplifier
Pulse signal；
Step 3, ultrasound thorn is produced under the driving for the high-voltage pulse signal that power amplifier exports using ultrasonic transducer
Shock wave, realize the ultrasound stimulation to brain area.
Further, in step 1, the signal of default square wave shape parameter is produced first with the first signal generator, then
Default sine wave parameter is produced under the triggering for the square wave that first signal generator exports using secondary signal generator
Several pulse signals.
Further, in step 3, using transducer-scalp coupling module by the ultrasound stimulation ripple be accurately positioned to
Brain area.
Compared with prior art, the present invention proposes that a kind of TCD,transcranial Doppler stimulates the nerve factor of influence expression of increase brain source
Method, the voltage signal of pulsed is produced by function signal device, then be amplified to through power amplifier needed for ultrasonic transducer
High-voltage pulse signal, ultrasound stimulation signal is then obtained by ultrasonic transducer, prefrontal lobe brain tissue is stimulated, realized
High spatial resolution and the purpose for non-invasively improving BDNF expression in specific brain area.
Brief description of the drawings
Fig. 1 is the system construction drawing for the device that a kind of TCD,transcranial Doppler of the present invention stimulates increase neurotrophic factor expression；
Fig. 2 is ultrasound parameter schematic diagram in the specific embodiment of the invention；
Fig. 3 is the step flow for the method that a kind of TCD,transcranial Doppler of the present invention stimulates increase BDNF expression
Figure；
Fig. 4 is the protein analysis that the TCD,transcranial Doppler of the present invention stimulates the method for increase BDNF expression
Result figure.
Embodiment
Below by way of specific instantiation and embodiments of the present invention are described with reference to the drawings, those skilled in the art can
Understand the further advantage and effect of the present invention easily by content disclosed in the present specification.The present invention can also pass through other differences
Instantiation implemented or applied, the various details in this specification also can be based on different viewpoints with application, without departing substantially from
Various modifications and change are carried out under the spirit of the present invention.
Fig. 1 stimulates the system construction drawing of the device of increase neurotrophic factor expression, Fig. 2 for a kind of TCD,transcranial Doppler of the present invention
For ultrasound parameter schematic diagram in the specific embodiment of the invention.As shown in Figures 1 and 2, a kind of TCD,transcranial Doppler of the present invention stimulates increase
The system of neurotrophic factor expression, including：First signal generator 101, secondary signal generator 102, power amplifier
103rd, ultrasonic transducer 104.
Wherein, the first signal generator 101, for producing the signal of default square wave shape parameter, of the invention specific real
Apply in example, the first signal generator 101 is function generator, and its design parameter is as follows：Internal trigger pattern, trigger interval be 1s~
3s, the number that pulse signal caused by triggering includes square wave every time is 100~600, and pulse recurrence frequency is 1KHz~3kHz；
Secondary signal generator 102, produced under the triggering for the square wave exported in the first signal generator 101 default
The pulse signal of sinusoidal waveform parameter, in the specific embodiment of the invention, secondary signal generator 102 is also function generator,
Its design parameter is as follows：Sine wave freuqency is 0.35MHz~0.75MHz, selects the frequency to be because this frequency belongs to noninvasive
TCD,transcranial Doppler in optimal ultrasonic frequency range 0.35MHz~0.7MHz, the ultrasonic signal in the frequency range can be in phase
Brain tissue effectively is transferred to through skull in the case of to less decay, stimulates cranial nerve, the sine that individual pulse includes
The number of ripple is 70~250.
Power amplifier 103, for pulse signal caused by secondary signal generator 102 to be carried out into power amplification, and swash
Encourage ultrasonic transducer 104 and produce ultrasound stimulation ripple.Specifically, power amplifier 103 linearly puts the stimulus signal that peak value is 5V
Greatly ultrasound stimulation signal is sent to high-voltage pulse signal, driving ultrasonic transducer 104.
Ultrasonic transducer 104, the signal exported for receiving power amplifier 103 simultaneously changes generation ultrasound stimulation ripple, real
Now to the ultrasound stimulation of brain area.In the specific embodiment of the invention, the sound intensity of ultrasonic wave is 1~8W/cm2(spatial peaks
The peak value of pulse sound intensity), pulse recurrence frequency is 1kHz~3kHz.Because prefrontal lobe region is related to the complicated cognitive behavior of planning,
Participate in memory, judge, analysis, the cognitive activities such as reward system, stress reaction, and with other positions (such as hippocampus) of maincenter
There is extensive nerve connection, position is shallow with respect to table, convenient to stimulate, in the specific embodiment of the invention, the ultrasound thorn of ultrasonic transducer 104
Sharp stimulation location is prefrontal lobe brain area, i.e., low intensity ultrasound reaches prefrontal lobe caused by ultrasonic transducer 104, and in brain table
Face is coated with couplant, so as to stimulate prefrontal lobe brain tissue, to increase the BDNF of hippocampus expression, but needs to illustrate
, the present invention strengthens the horizontal methods of BDNF with ultrasound stimulation and is not limited only to stimulate prefrontal lobe.In the specific embodiment of the invention
In, a length of 15 minute/day during ultrasound stimulation prefrontal lobe is co-continuous to stimulate 14 days.
Preferably, the TCD,transcranial Doppler of the present invention stimulates the device of increase BDNF expression also to include transducing
Device-scalp coupling module, for ultrasound stimulation signal to be accurately positioned to (spatial resolution is up to 2mm) brain area, at this
In invention specific embodiment, transducer-scalp coupling module can use the collimater of different-diameter, by ultrasound stimulation signal essence
It is determined that position is to different brain areas, low intensity ultrasound reaches prefrontal lobe by collimater as caused by ultrasonic transducer, and
Brain surface is coated with couplant, so as to stimulate prefrontal lobe brain tissue, to increase the BDNF of hippocampus expression.
Fig. 3 is the step flow for the method that a kind of TCD,transcranial Doppler of the present invention stimulates increase BDNF expression
Figure.As shown in figure 3, the method that a kind of TCD,transcranial Doppler of the present invention stimulates increase BDNF expression, including it is as follows
Step：
Step 301, the voltage signal of pulsed is produced by signal generator.Specifically, it is sharp first in step 301
The signal of default square wave shape parameter is produced with the first signal generator, recycles secondary signal generator to occur in the first signal
The pulse signal of default sinusoidal waveform parameter is produced under the triggering of the square wave of device output；In the specific embodiment of the invention, the
One signal generator is function generator, and its design parameter is as follows：Internal trigger pattern, trigger interval are 1s~3s, every time triggering
The number that caused pulse signal includes square wave is 100~600, and pulse recurrence frequency is 1KHz~3kHz；Secondary signal occurs
Device is also function generator, and its design parameter is as follows：Sine wave freuqency is 0.35MHz~0.75MHz；
Step 302, pulse signal caused by step 301 is amplified to the height needed for ultrasonic transducer by power amplifier
Pressure pulse signal.Specifically, it is using power amplifier that the stimulus signal Linear Amplifer that peak value is 5V is paramount in step 302
Pressure pulse signal, driving ultrasonic transducer send ultrasound stimulation signal；
Step 303, ultrasound is produced under the driving for the high-voltage pulse signal that power amplifier exports using ultrasonic transducer
Stimulus wave, realize the ultrasound stimulation to brain area.In the specific embodiment of the invention, the sound intensity of ultrasonic wave is 1~8W/cm2
(spatial peak pulse peak intensity of sound), pulse recurrence frequency are 1kHz~3kHz.Because prefrontal lobe region is related to planning complexity
Cognitive behavior, memory is participated in, judges, analyze, the cognitive activities such as reward system, stress reaction, and with other positions of maincenter (such as
Hippocampus etc.) there is extensive nerve connection, position is shallow with respect to table, convenient to stimulate, in the specific embodiment of the invention, ultrasonic transducer
The stimulation location of ultrasound stimulation is prefrontal lobe brain area, i.e., low intensity ultrasound arrival prefrontal lobe caused by ultrasonic transducer, and
Brain surface is coated with couplant, so as to stimulate prefrontal lobe brain tissue, to increase the BDNF of hippocampus expression, but needs
Illustrate, the present invention strengthens the horizontal methods of BDNF with ultrasound stimulation and is not limited only to stimulate prefrontal lobe.Of the invention specific real
Apply in example, a length of 15 minute/day during ultrasound stimulation prefrontal lobe is co-continuous to stimulate 14 days.
Fig. 4 is the protein analysis that the TCD,transcranial Doppler of the present invention stimulates the method for increase BDNF expression
Result figure.Fig. 4 shows in contrast to the brain tissue without ultrasound stimulation, to receive the BDNF expression water of the brain tissue of ultrasound stimulation
It is flat to be obviously improved
In summary, the present invention proposes a kind of method that TCD,transcranial Doppler stimulates the nerve factor of influence expression of increase brain source,
The voltage signal of pulsed is produced by function signal device, then the high-tension pulse needed for ultrasonic transducer is amplified to through power amplifier
Signal is rushed, ultrasound stimulation signal is then obtained by ultrasonic transducer, prefrontal lobe brain tissue is stimulated, realizes high spatial
Resolution ratio and the purpose for non-invasively improving BDNF expression in specific brain area.
Compared with prior art, the invention has the advantages that：
1) the BDNF expressions of hippocampus by blood-brain barrier, need not directly be improved；
2) there is millimetre-sized high spatial resolution；
3) stimulated using low intensity ultrasound；
4) from the 0.5MHz ultrasound stimulation signals for readily penetrating through skull；
5) select the stimulation sites prefrontal lobe shallow with respect to table and reach the BDNF tables for improving the relatively deep hippocampus in position
Up to level, this stimulates the hippocampus for being located at deep more simple and convenient reliable to improve its BDNF expression relative to direct；
6) the invention belongs to the noninvasive ultrasonic neuromodulation technology of safety.
The above-described embodiments merely illustrate the principles and effects of the present invention, not for the limitation present invention.Any
Art personnel can be modified above-described embodiment and changed under the spirit and scope without prejudice to the present invention.Therefore,
The scope of the present invention, should be as listed by claims.
Claims (10)
1. a kind of TCD,transcranial Doppler stimulates the device of increase neurotrophic factor expression, including：
First signal generator, for producing the signal of default square wave shape parameter；
Secondary signal generator, default sine wave is produced under the triggering for the square wave exported in first signal generator
The pulse signal of shape parameter；
Power amplifier, for pulse signal caused by the secondary signal generator to be carried out into power amplification, and encourage ultrasound
Transducer produces ultrasound stimulation ripple；
Ultrasonic transducer, the ultrasound stimulation ripple is produced for receiving the signal of the power amplifier output and changing, is realized
Ultrasound stimulation to brain area.
2. a kind of TCD,transcranial Doppler as claimed in claim 1 stimulates the device of increase neurotrophic factor expression, it is characterised in that：
Described device also includes transducer-scalp coupling module, for the ultrasound stimulation ripple to be accurately positioned to brain area.
3. a kind of TCD,transcranial Doppler as claimed in claim 2 stimulates the device of increase neurotrophic factor expression, it is characterised in that：
The transducer-scalp coupling module uses collimater, low intensity ultrasound caused by the ultrasonic transducer is passed through described
Collimater is pin-pointed to brain area.
4. a kind of TCD,transcranial Doppler as claimed in claim 3 stimulates the device of increase neurotrophic factor expression, it is characterised in that：
The brain area that TCD,transcranial Doppler stimulates is prefrontal lobe.
5. a kind of TCD,transcranial Doppler as claimed in claim 1 stimulates the device of increase neurotrophic factor expression, it is characterised in that：
First signal generator is function signal generator, and the frequency of its output signal is 1kHz~3kHz.
6. a kind of TCD,transcranial Doppler as claimed in claim 1 stimulates the device of increase neurotrophic factor expression, it is characterised in that：
The secondary signal generator is function signal generator, and the fundamental frequency of its pulse signal exported is 0.35MHz~0.75MHz.
7. a kind of TCD,transcranial Doppler as claimed in claim 1 stimulates the device of increase neurotrophic factor expression, it is characterised in that
The ultrasound stimulation parameter of the ultrasound stimulation ripple is：Spatial peak pulse peak intensity of sound is 1~8W/cm2, pulse recurrence frequency is
1kHz~3kHz.
8. a kind of method that TCD,transcranial Doppler stimulates increase neurotrophic factor expression, comprises the following steps：
Step 1, the voltage signal of pulsed is produced by signal generator；
Step 2, pulse signal caused by step 1 is amplified to the high-voltage pulse needed for ultrasonic transducer by power amplifier
Signal；
Step 3, ultrasound stimulation is produced under the driving for the high-voltage pulse signal that power amplifier exports using ultrasonic transducer
Ripple, realize the ultrasound stimulation to brain area.
9. the method that a kind of TCD,transcranial Doppler as claimed in claim 8 stimulates increase neurotrophic factor expression, it is characterised in that：
In step 1, the signal of default square wave shape parameter is produced first with the first signal generator, recycles secondary signal
Device produces the pulse signal of default sinusoidal waveform parameter under the triggering for the square wave that first signal generator exports.
10. the method that a kind of TCD,transcranial Doppler as claimed in claim 8 stimulates increase neurotrophic factor expression, its feature exist
In：In step 3, the ultrasound stimulation ripple is accurately positioned to brain area using transducer-scalp coupling module.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109011225A (en) * | 2018-07-02 | 2018-12-18 | 华中科技大学 | A kind of Biologic analgesia device based on ultrasonic nerve stimulation |
| CN109157768A (en) * | 2018-09-07 | 2019-01-08 | 中国医学科学院生物医学工程研究所 | A kind of TCD,transcranial Doppler and magnetosonic stimulating system and method with mobile rotating device |
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| US20110028867A1 (en) * | 2009-07-29 | 2011-02-03 | Seh-Eun Choo | Apparatus and method for non-invasive delivery and tracking of focused ultrasound generated from transducer |
| CN102791332A (en) * | 2009-11-04 | 2012-11-21 | 代理并代表亚利桑那州立大学的亚利桑那董事会 | Devices and methods for modulating brain activity |
| CN103028202A (en) * | 2012-12-26 | 2013-04-10 | 上海交通大学 | Transcranial ultrasound stimulation cranial-nerve-function-repairing device and method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110028867A1 (en) * | 2009-07-29 | 2011-02-03 | Seh-Eun Choo | Apparatus and method for non-invasive delivery and tracking of focused ultrasound generated from transducer |
| CN102791332A (en) * | 2009-11-04 | 2012-11-21 | 代理并代表亚利桑那州立大学的亚利桑那董事会 | Devices and methods for modulating brain activity |
| CN103028202A (en) * | 2012-12-26 | 2013-04-10 | 上海交通大学 | Transcranial ultrasound stimulation cranial-nerve-function-repairing device and method |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109011225A (en) * | 2018-07-02 | 2018-12-18 | 华中科技大学 | A kind of Biologic analgesia device based on ultrasonic nerve stimulation |
| CN109157768A (en) * | 2018-09-07 | 2019-01-08 | 中国医学科学院生物医学工程研究所 | A kind of TCD,transcranial Doppler and magnetosonic stimulating system and method with mobile rotating device |
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Application publication date: 20171226 |