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Bioinginerie

Andrei Barborica

andrei.barborica@fizica.unibuc.ro

Introducere

Inginerie biomedicala (BME


BME))
aplicarea
li
principiilor
i i iil ingineriei
i i i i in
i medicina
di i sii
biologie

Subdomenii:
S bd
Subdomenii
ii:
Electronica (bio)medicala
(bio)medicala
Protezare
Protezare,, mecatronica medicala
Interfete creiercreier-masina (subset al protezarii si mecatronicii,
mecatronicii,
care include comunicatia electrica cu sistemele neuronale
neuronale))

Biomateriale
Bionica (aplicarea principiilor din biologie in tehnologie ex: ciulini -> velcro)
velcro)
Inginerie genetica,
genetica, celulara,
celulara, si a tesuturilor
Imagistica medicala
Bionanotehnologie

Electronica medicala
Orice

dispozitiv medical care:

masoara in mod direct biopotentialele


stimuleaza
prelucreaza alte semnale fiziologice nee
nee-electrice convertite in marimi electrice cu
ajutorul traductorilor
foloseste semnale electrice (de ex
tomografele))
tomografele

Electronica medicala
Biopotentialele

Sursa biopotentialelor o constituie neuronii


si alte celule excitabile,
excitabile, precum fibrele
musculare

Inregistrarea biopotentialelor
Microscala
Microscala:: intracelular
intracelular,, extracelular
Mesoscala
Mesoscala:: extracelular,
extracelular, pe suprafata mai
mare (multi( lti-unit),
(multi
it) LFP
Macroscala
Macroscala:: pe suprafata (cortical, scalp,
piele))
piele

Originea
g
potentialelor bioelectrice
p

Potenialele electrice i au originea la nivel celular,


celular,
din diferena concentraiilor ionilor de sodiu i potasiu
(n principal) n spaiul intraintra-celular i interinter-celular

Interiorul celulei

Spaiul extracelular

[ Na + ]int
1

[N + ]ext 10
[Na

Na+
K+

[K + ]int 30

+
[K ]ext
1

[A + ]ext
RT
V=
logg +
zF
F
[A ]int

RT
61.6 mV
zF
F
10
+60 mV
1
1
VK = 61.6 log
90 mV
30

VNa = 61.6 log

Curentii ionici

Prin membrana ionii se deplaseaza prin intermediul

canalelor ionice
Na+

K+

Canale ionice

Na+ K+

Pomp ionic

Canalele
Ca a e e ionice
o ce de au o permeabilitate
pe eab a e ce depinde
dep de de
potentialul transmembranar aplicat pentru ionii de
Na+ si K+,(voltage gated channels) si este relativ
constanta pentru alti
l ioni,
ioni, cum ar fi
f Cl- (passive
channel).
Gradientul
G di t l de
d concentratie
t ti este
t mentinut
ti t prin
i
intermediul pompelor ionice

Curentii transmembranari

Cei mai semnificativi curenti transmembranari


transmembranari:: Na+ si K+

V VNa
I Na =
= g Na (V VNa )
RNa
V VK
IK =
= g K (V VK )
RK

Desi exista un gradient de concentratie semnificativ al ionilor de


Cl--, canalele de clor au o permeabilitate mult mai mica,
Cl
mica deci
contributia lor la curentul transmembranar si potentialul de
repaus este mica

PK : PNa : PCl = 1.0 : 0.04 : 0.45


[ P ] = cm / s

Potentialul de repaus

La echilibru
echilibru,, curentii transmembranari prin canalele ionice sunt
egali cu cei prin pompele ionice
ionice.. Potentialul de membrana este
dat de ecuatia lui Goldman:

PK [K + ]ext + PNa [ Na + ]ext + PCl [Cl ]ext


RT
Vm =
log
PK [K + ]int + PNa [ Na + ]int + PCl [Cl ]int
F

Dat fiind ca la repaus permeabilitatea maxima este pentru de


ionii de K, acest potential electrochimic determina potentialul
transmembranar::
transmembranar
Vm0 VK 90 mV

In momentul in care apare un potential de actiune


actiune,,
permeabilitatile canalelor,
canalelor, se modifica semnificativ:
semnificativ:

PK : PNa : PCl = 1.0 : 20 : 0.45

Circuitul electric echivalent


Exteriorul celulei

gK

gNa
Membrana

_
+

La repaus:
repaus
p
:

+
E Na

EK

Interiorul celulei

I K + I Na = 0
V VNa
= g Na (V VNa )
RNa
V VK
IK =
= g K (V VK )
RK
I Na =

Vm0 =

g NaVNa + g KVK
g Na + g K

Regimul dinamic (tranzitoriu)

Membrana poate fi considerata ca un


strat dielectric p
plasat ntre doua solutii
electrolitice conductoare, formndu
formndu--se
astfel un condensator
Exteriorul celulei

gK

gNa
Membrana

_
+

+
E Na

EK

dV
= I K I Na
dt

Interiorul celulei

Potentialul de actiune
Vm (mV
V)

+20
0

-20
-40
-60
P t iiall de
Poten
d repaus
+20 mV

1 mS

0 mV

gK

Variatia conductantei la
aplicarea unui potential
transmembranar
constant
co
sta t p
prin metoda
etoda
patch clamp

-20 mV
-40 mV

t
+20 mV
0 mV

gNa

-20 mV
-40 mV

Potentialul de actiune
Evolutia libera a potentialului de actiune
la aplicarea unui stimul:
stimul:
Vm

Vm , gNa , gK

Vrepaus

1 mS

gNa
0

gK

Scala spatiala
p
a inregistrarilor
g
de
scalp, corticale si de adancime

EEG d
de scalp
l necesita
i ~7cm
7 2 de
d cortex cu activitate
i i
sincrona
i
ECoG and SEEG necesita ~10mm2 de cortex
Microconductori (microwires
microwires)),
microwires),
) o sfera cu raza R~150
R~150
R
150m
150
Electrozi extracelulari sau intracelulari un singur neuron / AP
Worrell et al, Progress in Neurobiology, 2012

Proprietatile Neuronului
(scurta recapitulare)

1
t
0

intrari/iesiri
i t i/i i i binare:
bi
neuronull genereaza potentiale
t ti l
de actiune a caror amplitudine exacta nu este
relevanta Conteaza doar depasirea unui anumit
relevanta.
prag de tensiune al pulsurilor generate.
Informatia este codificata in secventa temporala a
pulsurilor,, sau simplist vorbind, in frecventa
pulsurilor
acestora.

LORETA

Nivel sistem:

Neurostiinta sistemica

(Systems Neuroscience)
Studiaza the organizarea functionala a sistemului
nervos central
Creierull este considerat
d
ca fiind
f d constituit din
d diferite
df
arii functionale
functionale,, care sunt interconectate
Ariile functionale sunt interconectate intr
intr--o strucura
ierarhica,, in care prelucrarea se face secvential
ierarhica
Ariile functionale
functionale,, impreuna
p
cu interconexiunile intre
ele formeaza cai de procesare a informatiei (
(neural
neural
pathways)
pathways
)
Elementul
El
t l aflat
fl t la
l baza
b
acestor
t structuri
t t i este
t
neuronul considerat o cutie neagra cu anumite
proprietati
p
p
(functionale
functionale)) de semnalizare,
semnalizare, insa nimic
mai mult nu este cunoscut despre structura interna
interna..

Metode generale de investigare


sistemica

Ce studiem ?
(sub)sisteme senzoriale: cum raspund
neuronii la p
prezentari ale diferitilor stimuli
(sub)sisteme motorii: cum raspund
neuronii in timpul pregatirii si executarii
miscarilor

Sistem simplu
simplu, sistem complex

Sisteme simple (ex: musca, broasca ):


Relatii de determinare directe (sa cablate) intre informatia
senzoriala si comortament (actiunile motrice)
Informatia senzoriala (associatii simple) comportament

Sisteme complexe:
Implica
p
luarea de decizii
asociatii complexe

Informatia senzoriala

memorie

gandire
gandire

comportament

analiza complexa a features reprezentari mentale

Interfata creier
creier--masina (BMI
BMI))
Receptor

Creier

Efector

Output
Input brainbrain
brain
brainRobot
-Cyborg
machine
-machine
! interface
interface

Input/Output BMI

Principalele probleme in interfata creier


creier--masina:
Alegerea corespunzatoare a ariilor corticale cu care se
face interfatarea
Cunoasterea codurilor care pe care le folosesc
neuronii
Codarea/decodarea informatiei in timp real
Realizarea unei conexiuni fizice compatibila biologic si
stabila intre circuitele electronice si neuroni

Arii corticale pentru


p
conectarea BMI

Input BMI
cortexul
t
l senzorial
i l primar
i
(V1 etc)
t )

Output
p BMI
preluarea comezilor:

cortexul motor

preluarea intentiilor:

cortexul pre
pre--motor
cortexul prepre-frontal

Comenzi vs. Intentii


in Output BMI

Comenzi:

16,000

hand
activity

15,000

Serruya et al. (Nature 2002)

14,000
3.5deg/1,000units

13,000
8,000

9,000

10,000

11,000

O maimuta rhesus a fost antrenata sa miste un cursor:


cu mana, folosind un touch
touch--screen
cu ajutorul unei arii de electrozi implantata in aria corticala
spcifica mainii a cortexului motor primar

Problema: comenzile motorii tind sa evoce miscari ale


mainii
i ii care au fost
f t incomplete
i
l t sau suprimate
i t volunatar,
l
t
fapt care genereaza semnale de feedback contradictorii.

Comenzi vs. Intentii


in Output BMI

Preluarea intentiilor:
Trebuie sa ne conectam in cortexul prefrontal
(PFC)

Intrebari
Reprezinta cortexul prefrontal o alegere mai buna
decat cortexul motor ?
Poate furniza un semnal la fel de precis ca si
cortexul motor ?

Input/Output BMI

The major problems in brain


brain--machine interfaces:
choosing the proper processing areas to connect to
knowing
kno ing the codes the ne
neurons
ons a
are
e using
sing
encoding/decoding the information in real time
making reliable and stable physical connections
between electronic circuits and neurons

Codurile care pe care le


folosesc neuronii

Intentii: planificarea miscarilor catre


ti t invisibile/imaginare
tinte
i i ibil /i
i
in absenta feedback
feedback-ului optic

Intrebari:
Cum sunt reprezentarile mentale in PFC ale
obiectelor
bi t l imaginare
i
i
?
Mediul in care traim este unul in continua
schimbare:
hi b
care este
t dinamica
di
i
reprezentarilor mentale ?

Frontal Eye Fields (FEF)


Proiectii anatomice dinspre ariile
parietale ce proceseaza miscarea
obiectelor vizuale
(Schall et al. 1995)

Creierul maimutei rhesus

FEF posterior PFC:


Planificarea miscarilor oculare
Scanarea spatiului vizual
Memorie spatiala

Obiecte temporar invizibile


Exista o reprezentare interna a
obiectelor ce devin invizibile pentru
scurt timp
timp?
p?
Este aceasta reprezentare actualizata in
mod continuu ?
Putem folosi aceasta reprezentare
p
pentru output BMI?

Motion Prediction Task

Stimuli vizuali in miscare pe un ecran


ecran,, ce
devin temporar invizibile

Maimute Rhesus sunt antrenate sa execute


miscari oculare saccadice catre locatia
extrapolata a stimulilor,
stimulilor, dupa ce devin
invizibili

Saccadele sunt facute catre o tinta imaginara,


imaginara,
fara nici un reper vizual
vizual,, pe baza unor
estimari ce iau in considerare viteza si directia
de miscare a tintelor
tintelor,, cand erau vizibile

Motion Prediction Task


Vi ibl ttargett
Visible
Invisible target

Motion Prediction Task


Vi ibl ttargett
Visible
Invisible target

Motion Prediction Task

Motion Prediction Task

How does the monkeyy


solve this task ?

Hypothesis 1: he updates a mental


representation of a moving target

Hypothesis 2: he learns a complex set


of stimulusstimulus-response associations

Error correction without visual


feedback

Error correction without visual


feedback
f db k

Error correction without visual


feedback
f db k

How does the monkeyy


solve this task ?

Hypothesis 1: he updates a mental


representation of a moving target

Hypothesis 2: he learns a complex set


of stimulusstimulus-response associations

Probing Internal Representations

II :

Neural responses in FEF


FEF electrical microstimulation

cue

occ

sacc
+
track

Late
L t Vi
Visible
ibl
Full Visible

sp/s
sec

144.9

Occlusion Trials

Time (ms)

2500

180

TRACK

SAC C

OC C

66.9 sp /sec

CU E

BK G

90

Late
L t Vi
Visible
ibl
Full Visible

sp//sec

144.9

Occlusion Trials

180o

0o

Time (ms)

2500

270

TRACK

SACC

OCC

BKG

120.0 sp/sec

CUE

90

10
00 ms

10
00 ms

10
00 ms

10
00 ms

10
00 ms

10
00 ms

10
00 ms

Tuning Dynamics
0.5 s

Response tuning rotation


saccade

1000ms
900ms
800ms

500ms
400ms
300ms
200ms
100ms

MEM cue

OCC cue

tim

600ms

700ms

Dynamical features encoding:

T
Target
tS
Speed
d

Equal cue duration

a
20

Equal cue path

Cue
Early delay
Late delay
Presaccade

20

Esstimated spe
eed (/s)

Motion extrapolation with different target speeds


Target speed can be reconstructed from neural responses

Esstimated spe
eed (/s)

15

10

15

10

5
5

10

15

Actual speed (/s)

20

10

15

Actual speed (/s)

Barborica A, Ferrera VP. Nat Neurosci. 2003 Jan;6(1):66Jan;6(1):66-74.

20

Response Intervals
Equal
Different
path
paths

slow

cue

occ

Different
Equal duration
durations

sacc
+
track

slow

cue

occ

fast

fast

Space

Time

sacc
+
track

Encoding
E
di off Target
T
tS
Speed
d
Equal cue duration

Estima ted speed (/s)

20

Cue
Early delay
Late delay
Presaccade

20

Estima ted speed (/s)

Equal cue path

15

10

15

10

5
5

10

15

Actual speed (/s)


( /s)

20

10

15

Actual speed (/s)


( /s)

Barborica A, Ferrera VP. Nat Neurosci. 2003 Jan;6(1):66Jan;6(1):66-74.

20

Estimated Target Speed


Based On Saccade Amplitude

Probing
g Internal Representations
p
II
FEF Electrical Microstimulation
Evokes spatially accurate eye
movements
Evoked movements are modified by
visual cues, motor plan, and locus of
attention (Kustov and Robinson 1996)
Are EE saccades modified during
g
covert tracking ?

Experiment
p

We selected FEF sites where saccades were evoked by electrical


stimulation*
ti l ti * during
d i a simple
i l fixation
fi ti task
t k
We arranged the target trajectory to be orthogonal to the
direction of EE saccades during
g fixation
We applied microstimulation at random times during the
occlusion interval
We analyzed
anal ed the de
deviation
iation of the EE saccade vectors.
ecto s

Stimulation: biphasic pulses, t=70ms, f=350Hz, i<=100microamps

Saccade Deviation
cue

sacc

When electrical stimulation was applied:


early during the occlusion interval:
EE saccades were deflected towards the cue

late during the occlusion interval:


EE saccades were deflected towards the
planned eye movements

Early Stimulation

Stimulation during fixation with no moving target: average amplitude 5.2 deg, direction 193 deg.

Late Stimulation

FEF stimulation site

1
0
-3

-2
-1
0
1
2
Horizontal Eye Position (deg)

-20

-40

200
400
Delay (ms)

***

***

***

Delay=600 ms
Diff=47.7

20

***

0
180

40

***

Saccade Diirection Diffe


erences (de
eg)

Vertica
al Eye Positiion (deg)

600

All 110 sites / 2 monkeys


0
180

0
180

All Monkeys
10
5
0
-5

-15

200

400

Delay (ms)

***

***

***

***

***

-10

***

Saccad
de Direction
n Differences
s (deg)

15

600

Spatial Memory Task


180

15

12 sites

10
5
0
-5

200
400
Delay (ms)

***

***

***

-20

***

-15

***

-10

***

No target motion
Cue and saccade have same
location

0
180

Monkey C

***

Sacca
ade Directio
on Differencces (deg)

20

600

Dynamic update

To program saccades to invisible targets


diff
different
t strategies
t t i may b
be used:
d
Static: wait for the GO signal, then combine the
available
il bl information
i f
ti to
t execute
t saccade
d
Dynamic: requiring a continuous update of an
internal target representation
representation, then make a catch
catch-up saccade to this mental target

FEF Microstimulation:

Conclusions

FEF microstimulation may be used to probe


i t
internal
l object
bj t representations
t ti
Electrically evoked saccades are modified
during covert tracking as if there is a sliding
attentional window
The saccade deviation is quasiquasi-linear, following
the constant motion of the invisible target.
g
This suggests that there is a continuous
update
p
of an internal representation.
p

Input/Output BMI

The major problems in brain


brain--machine interfaces:
choosing the proper processing areas to connect to
learning
lea ning mo
more
e abo
aboutt the codes ne
neurons
ons are
a e using
sing
encoding/decoding the information in real time
making reliable and stable physical connections
between electronic circuits and neurons

Real--Time Encoding/Decoding
Real
g/
g
of Neural Activity

We have developed a DSP


DSP--based system for
realreal
l-time
ti
processsing
i off neurall signals
i
l
Multiprocessing: each neuron is assigned a
powerful
f l 3232-bit FP processor th
thatt runs complex
l
algorithms in real time
flexible architecture
architecture, can implement various
input/output BMI algorithms stored in its internal
FLASH memory
can be scaled easily with increasing number of
channels

System Architecture

A Multichannel System

BMI Device Design? Not an easy task! Medical device standards:


IEC 60601
60601--1 Medical electrical equipment Part 1:
General requirements for basic safety and essential performance
Scope, object and related standards...............................................................................29
1.1 * Scope .................................................................................................................29
.................................................................................................................29
1.2 Object ..................................................................................................................
...................................................................................................................29
.29
1 3 * Collateral standards ............................................................................................29
1.3
29
1.4 * Particular standards ............................................................................................31
2 * Normative references ...................................................................................................31
...................................................................................................31
3 * Terminology and definitions .........................................................................................39
4 General requirements .....................................................................................................79
.....................................................................................................79
4.1 * Conditions for application to ME EQUIPMENT or ME SYSTEMS..................................79
4.2 * RISK MANAGEMENT PROCESS for ME EQUIPMENT or ME SYSTEMS ..............................79
4.3 * ESSENTIAL PERFORMANCE .....................................................................................81
4.4 * EXPECTED SERVICE LIFE ........................................................................................81
4.5 * Equivalent safety for ME EQUIPMENT or ME SYSTEMS .............................................83
4.6 * ME EQUIPMENT or ME SYSTEM parts that contact the PATIENT .................................83
4.7 * SINGLE FAULT CONDITION for ME EQUIPMENT...........................................................83
4.8 Components of ME EQUIPMENT ...............................................................................85
4.9 * Use of COMPONENTS WITH HIGHHIGH-INTEGRITY CHARACTERISTICS in ME EQUIPMENT .......85
4.10 * Power supply ......................................................................................................87
4.11 Power input ...........................................................................................................89
...........................................................................................................89
5 * General requirements for testing ME EQUIPMENT ...........................................................91
5.1
5 1 * TYPE TESTS..........................................................................................................91
TESTS
91
5.2 * Number of samples .............................................................................................91
5.3 Ambient temperature, humidity, atmospheric pressure...........................................91
5.4 Other conditions ....................................................................................................91
5.5 Supply voltages, type of current, nature of supply, frequency ................................93
5.6 Repairs and modifications .....................................................................................93
5.7 * Humidity preconditioning treatment .....................................................................93
5.8 Sequence of tests .................................................................................................95
5.9 * Determination of APPLIED PARTS and ACCESSIBLE PARTS .......................................
.......................................95
95

IEC 6060160601-1 General requirements for basic safety and essential performance
6 * Classification of ME EQUIPMENT and ME SYSTEMS ...........................................................99
6.1 General .................................................................................................................
.................................................................................................................99
99
6.2 * Protection against electric shock.........................................................................99
6.3 * Protection against harmful ingress of water or particulate matter ...................... 101
6.4 Method(s) of sterilization ..................................................................................... 101
6 5 Suitability
6.5
S it bilit for
f use in
i an OXYGEN RICH ENVIRONMENT .............................................. 101
6.6 * Mode of operation ............................................................................................. 101
7 ME EQUIPMENT identification, marking and documents ................................................... 101
7.1 General ............................................................................................................... 101
101
7.2
7 2 Marking on the outside of ME EQUIPMENT or ME EQUIPMENT parts .......................... 105
7.3 Marking on the inside of ME EQUIPMENT or ME EQUIPMENT parts ........................... 113
7.4 Marking of controls and instruments .................................................................... 117
7.5 Safety signs ........................................................................................................ 119
7.6 Symbols
y
.............................................................................................................. 121
121
7.7 Colours of the insulation of conductors ................................................................ 121
7.8 * Indicator lights and controls .............................................................................. 123
7.9 ACCOMPANYING DOCUMENTS.................................................................................. 123
8 * Protection against electrical HAZARDS from ME EQUIPMENT ........................................... 135
8.1 Fundamental rule of protection against electric shock.......................................... 135
8.2 Requirements related to power sources............................................................... 137
8.3 Classification of APPLIED PARTS ............................................................................ 137
8.4 Limitation of voltage, current or energy................................................................ 139
8.5
8 5 Separation
Sep tion of p
parts
t .............................................................................................. 145
8.6 * Protective earthing
earthing,, functional earthing and potential equalization of
ME EQUIPMENT...................................................................................................... 161
8.7 LEAKAGE CURRENTS and PATIENT AUXILIARY CURRENTS ........................................... 167
8 8 Insulation ............................................................................................................ 201
8.8
201
8.9 * CREEPAGE DISTANCES and AIR CLEARANCES......................................................... 213
8.10 Components and wiring ....................................................................................... 243
8.11 MAINS PARTS, components and layout .................................................................. 247

IEC 6060160601-1 General requirements for basic safety and essential performance
9 * Protection against MECHANICAL HAZARDS of ME EQUIPMENT and ME SYSTEMS ................ 259
9.1 MECHANICAL HAZARDS of ME EQUIPMENT
Q
................................................................ 259
9.2 * HAZARDS associated with moving parts.............................................................. 261
9.3 * HAZARD associated with surfaces, corners and edges........................................ 271
9.4 * Instability HAZARDS ............................................................................................ 271
9.5 * Expelled parts HAZARD ...................................................................................... 281
9.6 Acoustic energy (including infrainfra- and ultrasound) and vibration ........................... 281
9.7 * Pressure vessels and parts subject to pneumatic and hydraulic pressure.......... 285
9.8 * HAZARDS associated with support systems ........................................................ 291
10 * Protection against unwanted and excessive radiation HAZARDS .................................. 301
10.1
10 1 XX-Radiation
R di ti ......................................................................................................... 301
10.2 Alpha, beta, gamma, neutron and other particle radiation .................................... 303
10.3 Microwave radiation ............................................................................................ 303
10.4 * Lasers and light emitting diodes (LEDs) ............................................................ 303
10.5
10 5 Other visible electromagnetic radiation
radiation................................................................ 303
10.6 Infrared radiation................................................................................................. 305
10.7 Ultraviolet radiation ............................................................................................. 305
11 * Protection against excessive temperatures and other HAZARDS................................... 305
11.1 * Excessive temperatures
p
in ME EQUIPMENT..........................................................
Q
305
11.2 * Fire prevention.................................................................................................. 313
11.3 * Constructional requirements for fire ENCLOSURES of ME EQUIPMENT .................... 323
11.4 * ME EQUIPMENT and ME SYSTEMS intended for use with flammable anaesthetics ........ 329
11.5 * ME EQUIPMENT and ME SYSTEMS intended for use in conjunction with flammable agents .......9
11.6 Overflow, spillage, leakage, ingress of water or particulate matter, cleaning,
disinfection, sterilization and compatibility with substances used with the ME EQUIPMENT
EQUIPMENT...............
............... 329
11.7 Biocompatibility of ME EQUIPMENT and ME SYSTEMS ............................................... 333
11.8 * Interruption of the power supply / SUPPLY MAINS to ME EQUIPMENT ...................... 333

IEC 6060160601-1 General requirements for basic safety and essential performance
12 * Accuracy of controls and instruments and protection against hazardous outputs ........ 333
12.1
12 1 Accuracy of controls and instruments .................................................................. 333
12.2 USABILITY............................................................................................................. 333
333
12.3 Alarm systems..................................................................................................... 333
12.4 Protection against hazardous output.................................................................... 333
13 * HAZARDOUS SITUATIONS and fault conditions................................................................ 337
13.1 Specific HAZARDOUS SITUATIONS ........................................................................... 337
13.2 SINGLE FAULT CONDITIONS ..................................................................................... 339
14 * PROGRAMMABLE ELECTRICAL MEDICAL SYSTEMS (PEMS) .................................................. 351
14.1 * General............................................................................................................. 351
351
14.2 * Documentation.................................................................................................. 351
14.3 * RISK MANAGEMENT plan ...................................................................................... 353
14.4 * PEMS DEVELOPMENT LIFELIFE-CYCLE .......................................................................... 353
14.5 * Problem resolution ............................................................................................ 353
14.6 RISK MANAGEMENT PROCESS.................................................................................. 353
14.7 * Requirement specification ................................................................................. 355
14.8 * Architecture ...................................................................................................... 35
355
5
14.9 * Design and implementation ............................................................................... 357
14.10
14 10 * VERIFICATION .................................................................................................... 357
14.11 * PEMS VALIDATION .............................................................................................. 357
14.12 * Modification ..................................................................................................... 35
359
9
14.13 * Connection of PEMS by NETWORK/DATA COUPLING to other equipment ................ 359
15 Construction of ME EQUIPMENT ...................................................................................... 359
15.1 * Arrangements of controls and indicators of ME EQUIPMENT................................. 359
15.2 * Serviceability .................................................................................................... 35
359
9
15.3 Mechanical strength ............................................................................................ 361
15.4 ME EQUIPMENT components and general assembly............................................... 369
15.5 * MAINS SUPPLY TRANSFORMERS of ME EQUIPMENT and transformers providing
separation in accordance with 8.5 ....................................................................... 379

IEC 6060160601-1 General requirements for basic safety and essential performance
16 * ME SYSTEMS ............................................................................................................... 387
16 1 * General requirements for the ME SYSTEMS ......................................................... 387
16.1
16.2 * ACCOMPANYING DOCUMENTS of an ME SYSTEM ..................................................... 389
16.3 * Power supply .................................................................................................... 391
16.4 ENCLOSURES ........................................................................................................ 391
16.5 * SEPARATION DEVICES.......................................................................................... 391
16.6 * LEAKAGE CURRENTS............................................................................................ 393
16.7 * Protection against MECHANICAL HAZARDS ............................................................ 395
16.8 Interruption of the power supply to parts of an ME SYSTEM ................................... 395
16.9 ME SYSTEM connections and wiring ...................................................................... 395
17 * Electromagnetic compatibility of ME EQUIPMENT and ME SYSTEMS ................................ 399
Annexes
Annex A (informative) General guidance and rationale....................................................... 401
Annex B (informative)
f
Sequence off testing ........................................................................ 613
Annex C (informative) Guide to marking and labelling requirements for ME EQUIPMENT
and ME SYSTEMS..................................................................................................................
SYSTEMS.................................................................................................................. 621
Annex D (informative) Symbols on marking........................................................................ 629
Annex E (informative) Examples of the connection of the measuring device (MD) for
measurement of the PATIENT LEAKAGE CURRENT and PATIENT AUXILIARY CURRENT .................. 647
Annex F (informative) Suitable measuring supply circuits................................................... 651
Annex G (normative) Protection against HAZARDS of ignition of flammable anaesthetic
mixtures.....................................................................................................................
mixtures........................................................................................................................
.........
...... 657
Annex H (informative) PEMS structure, PEMS DEVELOPMENT LIFELIFE-CYCLE and
documentation ...............................................................................................................
..................................................................................................................
.....
.. 687
Annex I (informative) ME SYSTEMS aspects ......................................................................... 713
Annex J (informative) Survey of insulation paths ................................................................ 725
Annex K (informative) Simplified PATIENT LEAKAGE CURRENT diagrams ................................ 731
Annex L (normative) Insulated winding wires for use without interleaved insulation............ 737

IEC 6060160601-1 General requirements for basic safety and essential performance
16 * ME SYSTEMS ............................................................................................................... 387
16 1 * General requirements for the ME SYSTEMS ......................................................... 387
16.1
16.2 * ACCOMPANYING DOCUMENTS of an ME SYSTEM ..................................................... 389
16.3 * Power supply .................................................................................................... 391
16.4 ENCLOSURES ........................................................................................................ 391
16.5 * SEPARATION DEVICES.......................................................................................... 391
16.6 * LEAKAGE CURRENTS............................................................................................ 393
16.7 * Protection against MECHANICAL HAZARDS ............................................................ 395
16.8 Interruption of the power supply to parts of an ME SYSTEM ................................... 395
16.9 ME SYSTEM connections and wiring ...................................................................... 395
17 * Electromagnetic compatibility of ME EQUIPMENT and ME SYSTEMS ................................ 399
Annexes
Annex A (informative) General guidance and rationale....................................................... 401
Annex B (informative)
f
Sequence off testing ........................................................................ 613
Annex C (informative) Guide to marking and labelling requirements for ME EQUIPMENT
and ME SYSTEMS..................................................................................................................
SYSTEMS.................................................................................................................. 621
Annex D (informative) Symbols on marking........................................................................ 629
Annex E (informative) Examples of the connection of the measuring device (MD) for
measurement of the PATIENT LEAKAGE CURRENT and PATIENT AUXILIARY CURRENT .................. 647
Annex F (informative) Suitable measuring supply circuits................................................... 651
Annex G (normative) Protection against HAZARDS of ignition of flammable anaesthetic
mixtures.....................................................................................................................
mixtures........................................................................................................................
.........
...... 657
Annex H (informative) PEMS structure, PEMS DEVELOPMENT LIFELIFE-CYCLE and
documentation ...............................................................................................................
..................................................................................................................
.....
.. 687
Annex I (informative) ME SYSTEMS aspects ......................................................................... 713
Annex J (informative) Survey of insulation paths ................................................................ 725
Annex K (informative) Simplified PATIENT LEAKAGE CURRENT diagrams ................................ 731
Annex L (normative) Insulated winding wires for use without interleaved insulation............ 737

Input/Output BMI

The major problems in brain


brain--machine interfaces:
choosing the proper processing areas to connect to
knowing
kno ing the codes the ne
neurons
ons a
are
e using
sing
encoding/decoding the information in real time
making reliable and stable physical connections
between electronic circuits and neurons

acute multiple electrode recordings

chronic recordings

Conclusions

We have addressed some of the points in brainbrain-machine


complex problem:
prefrontal cortex may be a plausible candidate for output BMI
we have learned more about the FEF neural codes for dynamical
y
mental representation
we have developed a hardware platform thats able to process
the information in real time

Open Issues:
making reliable and stable physical connections between
electronic circuits and neurons
learning more about the codes for input BMI

References

Anatomical projections from parietal areas: Schall, J.D., Morel, A., King, D.J. &
Bullier, J. Topography of visual cortex connections with frontal eye field in
macaque: convergence and segregation of processing streams. J. Neurosci. 15,
4464--4487 (1995).
4464
Motion extrapolation by macaque monkeys: Filion C. M., Washburn D. A. &
Gulledge J. P. Can monkeys (Macaca mulatta) represent invisible displacement?
J Comp.
J.
Comp Psychol.
Psychol 110,
110 386386-395 (1996).
(1996)
Saccade errors introduced downstream from the SC: Stanford T.R., Sparks D.L.
Systematic errors for saccades to remembered targets: evidence for a
dissociation between saccade metrics and activity in the superior colliculus,
Vision Research 34
34,, 9393-106 (1994).
Reconstrcting target speed: Barborica A, Ferrera VP. Estimating invisible target
speed from neuronal activity in monkey frontal eye field. Nat Neurosci. 6(1):66
6(1):66-74 (2003).
Biasing of EE saccades (FEF) by moving dot cues: Gold J.I., Shadlen
MN.Representation of a perceptual decision in developing oculomotor
commands. Nature 404
404,, 390390-394 (2000).
Bi i off EE saccades
Biasing
d (SC) by
b stationary
t ti
spatial
ti l cues: Kustov
K t A
A.A.,
A Robinson
R bi
D.L. Shared neural control of attentional shifts and eye movements. Nature
384,, 74384
74-77 (1996).

More Issues !

Number of neurons required to encode actions:


primary motor areas encoding is more precise, less
neurons required (n>5)
prefrontal area fuzzier encoding, more neurons
may be required.

Input BMI specific: almost no studies of


microstimulation codes !!!!!

Abstract
Creating an output brain
brain--machine interface may require that a mental
representation has to be translated into a real object or action. In order
to perform this translation, we have to learn more about the neural
codes underlying mental representations. A likely candidate cortical
area for maintaining mental representations of objects and actions is
the frontal eye field (FEF). In a systems neuroscience approach, we
study neural responses in FEF of macaque monkeys during a motion
prediction task,
task where moving targets presented on a display are
rendered temporarily invisible. The monkeys are required to make eye
movements to the predicted target location (while invisible). By using
electrical microstimulation of frontal eye
y fields we show that the mental
representation is dynamic, being continuously updated. Our data shows
that FEF responses can be used to reconstruct not only targets static
properties, but also their dynamicsdynamics-related features, like speed. A DSPDSPbased system for online analysis of neural activity is proposed for
implementing a realreal-time brain
brain--machine interface for projecting mental
representations into the real world.

Contact:

andrei.barborica@fizica.unibuc.ro

Electrozi pentru masurarea


biopotentialelor
Andrei Barboric

Electrozi de p
pentru masurarea
biopotentialelor
Electrozi si microelectrozi interni
Sunt n general realizai din fire
foarte subiri (50
(50-100mm)
100mm) dintr-un
dintr un
metal rezistent: oel, platin sau
wolfram. Poriunea activ a
electrodului p
poate fi acoperit
p
cu
un strat metalic bun conductor (Pt
poroasa, Au, Ag etc), iar cea
inactiv cu un strat izolator (de
exemplu un polimer sau o pelicul
subire de sticl). Vrfurile acestor
electrozi au totui dimensiuni mari
n comparaie cu dimensiunile
celulare, de aceea se folosesc
pentru nregistrri extracelulare.

Tub metalic
(de tip hipodermic)
Tub izolator
(polimer)
Fir de platin

Strat de sticl

Vrf

Arii de microelectrozi
Suport de siliciu
izolat cu SiN

Contact aurit

Electrod
El
t dd
de siliciu
ili i
izolat cu SiN

Traseu metalic

Suport de siliciu

Zone active

Vrf acoperit cu Pt

Microelectrozi interni

Microelectrozi solizi

Depunere metalic

Vrf expus

Microelectrozi lichizi

0.5 mm

Fibr de carbon

Fir conductor

Suport de sticl
Suspensie de past
de carbon n rin

Izolaie de rin

Capilar
p
de sticl
Fir de cupru

Electrolit
20 mm

Micropipet
p p de sticl

Electrozi de suprafata
p

Electrozi externi (de suprafata):


Solizi (sau uscai) - sunt realizai n general din Ag, Ag/AgCl, W, Pt,
Au sau Ni
Ni-Cr.
Cr
Ionii prezenti pe suprafata pielii (in principal Na,Cl) intra in
reactie cu suprafata electrodului, ducand la aparitia unui
potential de electrod
electrod.
O condiie pe care trebuie sa o ndeplineasc electrozii este
aceea ca metalele (sau materialele) din care sunt confecionai
s nu fie solubile n electroliii prezeni pe suprafaa pielii
pielii, sau
sau,
dac sunt solubile, reaciile chimice aprute s fie total
reversibile la aplicarea unui potenial electric pe electrozi.

Electrozi de suprafata
p

(continuare)

electrozii din metale inerte, greu solubile:


Exemplu: electrodul de Au
Conductivitate foarte mare
-> zgomot redus
Inert -> reutilizabil
Potential de contact mai mare
-> artefacte de miscare mai mari
Utilizat in special in EEG

electrozii nemetalici, din polimer conductiv


realizati din material care este in acelasi timp si conductiv
conductiv, si adeziv
polimerul devine conductiv prin adaugarea de ioni monovalenti
nu necesita gel
rezistenta
i t t de
d contact
t t mare -> zgomott ridicat
idi t

Electrozi reversibili

electrozii din metal n contact cu un electrolit ce conine proprii si ioni:

M + + e

electrozii nemetalici n contact cu un electrolit:


1
2

(electrozi de suprafata, solizi, continuare)

H2

H + + e

electrozii compui dintr-un metal i o sare greu solubil a acestui metal n


electrolitul cu anion comun cu sarea metalului. Exemplul tipic pentru aceast
categorie de electrozi este electrodul de argint clorurat - Ag/AgCl. Pentru acest
tip de electrod, metalul este Ag, sarea greu solubil este AgCl si electrolitul cu
anion comun cu sarea metalului este NaCl (soluie salin) care componenta
pricipal n secreiile epidermei. Reaciile reversibile care au loc la interfaa
electrod-electrolit
l t d l t lit sunt:
t
Ag/AgCl/NaCl Ag + + e
Ag + /AgCl/NaCl + e
Ag

Electrozi reversibili
A. Electrod metalic

Caracteristici:
rezistena de contact:
n gama 1-10 M.
capacitatea de contact:
n jur de 10 F/cm2.

Electrod

Obinerea unui electrod de Ag/AgCl se


f
face
prin
i tratarea
t t
unuii electrod
l t d de
d A
Ag n
modul urmtor:
se introduce electrodul de Ag ntro baie electrochimic ce conine o
soluie de electrolit de NaCl cu o
concentraie de 0,9%.
se menine electrodul circa 2
minute la polul pozitiv al bii
electrochimice la o densitate de
curent ntre 1 i 3 mA/cm2.

Electrolit

Strat electric dublu, ce duce la apariia unui


potenial ntre electrod i electrolit.

B. Electrod de argint clorurat (Ag/AgCl)


Ag

Electrod
de Ag

AgCl

Cl

Cl

Ag

Ag
Ag

Cl

Electrolit

Cl

AgCl va da natere att la ioni pozitivi (Ag+),


ct i la ioni negativi (Cl-), mpiedicnd formarea stratului dublu.

Potentiale de electrod

Metal Reacie reversibil


Al
Al = Al3+ + 3eZn
Zn = Zn2+ + 2eZn(Hg) Zn = Zn2
Zn2+ + Hg + 2e
2eCr
Cr = Cr3+ + 3eFe
Fe = Fe2+ + 2eCd
Cd = Cd2+ + 2eNi
Ni = Ni2+ + 2e
2ePb
Pb = Pb2+ + 2ePt(H2) H+
Ag
Ag + Cl- = AgCl + eCu
Cu = Cu2+ + 2eCu
Cu = Cu+ + eHg
2 Hg = Hg2+ + 2eAg
Ag = Ag
Ag+ + e
ePt
Pt = Pt2+ + 2eAu
Au = Au3+ + 3eAu
Au= Au+ + e-

Potenial la 25C (V)


-1,662
-0,7628
-0,7627
0,7627
-0,744
-0,4402
-0,4029
-0,250
0 250
-0,126
0
+0,2225
+0,337
+0,521
+0,788
+0
0,7991
7991
~ +1,2
+1,498
+1,691

Coeficient de temp. (mV/C)


+1,375
+ 0,962
+1,339
+0,923
+0,778
+0 93
+0,93
+0,420
+0,213
+0,879
+0,813
-0
0,129
129
-

El t i lichizi
Electrozi
li hi i

Electrozii lichizi au avantajul de a avea o rezisten de contact mai


mic dect a electrozilor solizi. Sunt electrozi de unic folosin i
constau dintr-un electrod metalic plasat ntr-o cavitate umplut cu un
electrolit care de regul este o soluie de KCl
2

1
4
3

Electrod cu jonciune lichid: 1 - soluie de electrolit (coninnd KCl); 2 electrod (Ag/AgCl); 3 - piele; 4 - band adeziv sau ventuz de
cauciuc; 5 - conductor;

Circuitul echivalent
Rpiele

Econtact
t t

Ccontact
Rcontact

R esut
Piele

Electrod

Cpiele
=

Rpiele

Econtact

Ccontact
Rcontact

Fara contact
Camer TV

Lentil

Diafragm
Lamp halogen

Splitter
Filtru interferenial
Lentil
Montur din oel inoxidabil
implantat n craniu

Fereastr
Tuburi prin care se injecteaz colorantul
Craniu
Cortex

Prelucrarea semnalelor

Analogica
Semnal analogic: continuu in timp si in domeniul valorilor
In
I aparatura
t
analogica,
l i
semnalele
l l bioelectrice
bi l t i
sau obinute
bi t
prin intermediul unor traductori, sunt prelucrate analogic
cu ajutorul unor etaje tipice ca: amplificatoare, filtre,
comparatoare, detectoare de amplitudine, faz sau frecven,
.a.m.d.
Digitala
Semnal digital:
g
discret in timp
p si/sau
/
domeniul valorilor
Semnalele in forma digitala (numerica) sunt prelucrate cu
ajutorul microprocesoarelor sau procesoarelor dedicate
Digital Signal Processor (DSP)
In aparatura numeric, necesitatea folosirii blocurilor
analogice nu a fost nlturat complet. Semnalele nu sunt
convertite direct n valori numerice, ci mai nti sunt
amplificate,
lifi t
filt t
filtrate,
eventual
t l aplicate
li t ii alte
lt prelucrri
l
i
analogice, iar numai dup aceea sunt convertite n valori
numerice.

Prelucrarea analogica semnalelor

Electrozi si traductorii:
Traductori pasivi furnizeaza la iesire o tensiune sau un
curent
Traductori activi necesita o sursa externa de semnal sau de
alimentare pentru a putea functiona: rezisten, inductan
sau capacitate variabil etc.
etc
Conectarea traductorilor activi:
OUT
AMP
~
Direct, unipolar
Trad izolati electric
+

AMP

Diferential (bipolar)
Masurarea
M
potentialelor
i l l bioelectrice
bi l
i

OUT

Conectarea Traductorilor

Traductor pasiv (rezistiv, inductiv, capacitiv)


se folosesc elemente adiionale, care s duc la apariia
unui semnal (tensiune, curent etc) pe elementul pasiv. Dup
cu am reprezentat i n figura de mai jos, elementul adiional
poate o fi o surs de tensiune sau de curent continuu sau
alternativ.
- Conectare directa:
~
R,
L,
C

AMP

OUT

- n
punte:
t
a. de semnal continuu:
TR
R

AMP
TR'

OUT

Conectarea Traductorilor

n punte
de semnal alternativ cu detectie in amplitudine sau faza:
TR

AMP
TR'

Detectia in amplitudine
D t ie
Detec
i

Filt
Filtrare

OUT

Conectarea Traductorilor

Detectia in faza
REF

COMPARATOR
C
DE
FAZ

IEIRE

Preamplificatoare i amplificatoare de semnal

Amplificator inversor
VOUT

R2
VIN
R1

R2

R1
VIN

VO UT

Z IN R1

Amplificator neinversor
R
VOUT 1 + 2 VIN
R1
OPAMP
Z IN = Z IN

VIN

VO UT

R2
R1

Caz particular:
R1 = , R2 = 0 - repetor de tensiune : Av=1
VIN

Z IN = Z

OPAMP
IN

VO UT=VIN

Preamplificatoare
p
i
amplificatoare
p
de semnal

amplificator diferenial de instrumentatie


VIN

VOUT

R
2 VIN+ VIN
R1

R2

R1
VOUT
R1

OPAMP
Z IN = Z IN

R2

VIN+

VOUT =

Ad VIN+

VIN

)+ A

(V

+
IN

+ VIN
2

Ad reprezint amplificarea de mod diferenial (Ad=R2/R1 pentru


amplificatorul de mai sus), iar Ac reprezint amplificarea de mod
comun.
Ideal, Ad=mare, Ac=mic.
CMRR - Common Mode Rejection Ratio
Ad

CMRR =

Ac

Preamplificatoare i amplificatoare de semnal

Amplificatoarele de curent
R

VOUT = RI IN

IIN

VO UT

Operaii matematice simple


cu circuite analogice

Vout

Rf

Sumarea
Rf
Rf
Rf

V2 + L +
= V1 +
Vn
R2
Rn
R1

R1
VIN1
R2
VIN2

Rn
VINn

Scderea se p
poate face:
inversnd polaritatea semnalului care se scade i apoi
sumndu-l cu cel din care se face scderea
folosind un amplificator diferenial care furnizeaz la ieire
un semnal proporional cu diferena tensiunilor pe cele dou
intrri.

VOUT

Operatii
p
matematice

(continuare)

Integrarea
Amplificator inversor cu condensator in bucla de reactie
C
t

Vout
IN
OUT

Q
1
= = I in ( ) d
C
C0
t

1
Vout (t ) =
Vin ( )d
RC 0

Derivarea
Amplificator inversor cu condensator in serie cu intrarea
R

Vin =

C
IN

Q
C

dVin 1 dQ 1
=
= I in
dt
C dt C

OUT

Vout = RI in = RC

dVin
dt

Filtrarea semnalelor
Orice semnal care are o frecven ce nu se situeaz n banda de
frecven a semnalului fiziologic - semnal parazit care poate fi
suprimat prin filtrare in frecventa.
Zgomot
Semnal util

0
-3

S (dB)

-20

-40

10

100

(Hz)

1000

10000

Filtrarea semnalelor
Filtru trece-sus de ordin I

Filtru trece-jos de ordin I


C

+Vcc R

+Vcc

IN

IN

R
OUT

OUT

-Vcc

-Vcc

20
db
/de
ca
da
1

10

-20

100

(Hz)

0 1000

10000

-40
10

da
ca
/de
db
-20

-20

-40

H (dB)

0
-3

H (dB)

0
-3

100

1000

(Hz)

10000

100000

Filtrarea semnalelor

C2

Filtru trece-band de ordin I

R2
+Vcc

IN

R1

-Vcc
Filtru opreste-band
Suprima o semnalele dintr-o anumita banda de frecventa
Exemplu
E
l d
de utilizare
tili

Zgomot

0
-3

-3

Semnal util

Semnal util

S (dB)

-20

-40

Caracteristica filtrului

S (dB)

OUT

C1

-20

10

100

1000

10000

-40
40

(Hz)

semnal + zgomot de banda ingusta

10

100

(Hz)

semnal filtrat

1000

10000

Filtrarea semnalelor

Caracteristici de frecventa abrupte


filtre de ordin superior conectarea in cascada a mai
j de filtrare
multor etaje
Filtru trece-sus de tip Butterworth de ordin 6
Pentru fs=480 Hz, R=33kW, C=10 nF
R

IN

+V
+Vcc

C
2k24

+Vcc

C
19k3

-Vcc
V

+Vcc

OUT

R
48k9

-Vcc
R

-Vcc
R

Filtru trece-jos de tip Butterworth de ordin 6


Pentru fs=7200 Hz, R=10kW, C=2.2 nF
C

+Vcc

+Vcc

+Vcc

IN

R
680

C
-Vcc

R
5k9

C
-Vcc

OUT

R
C

14k8
-Vcc

Conversia Analog-Digitala

Semnalul analogic: continuu in timp si in domeniul valorilor


O reprezentarea fidela a semnalului ar presupune o infinitate de
valori numerice
Se folosesc aproximari ale semnalului, care pot fi reprezentate in
secvente finite de date

Aproximari:
1. Esantionarea in timp:
Aproximarea semnalului analogic prin valori constante pe
intervalele de timp intre doua esantioane ale semnalului
2. Cuantificarea:
Aproximarea valorilor continue ale semnalului printr-un set finit
de valori

Conversia Analog-Digitala
g g

Esantioarea in timp
aproximarea semnalului analogic prin valori constante pe intervalul
d esantionare
de
ti
semnalul fiind continuu, valorile sunt arbitrare este nevoie de o
reprezentare cu un numar infinit de biti -> esantionarea nu rezolva
problema reprezentarii semnalului printr-un volum finit de date
x
x(3T )
0

x(4T )
0

x(5T )
0

x(2T )

x(6T )

x(T )

x(7T )
0

T0

2T0

3T0

4T0

5T0

6T0

7T0

Conversia Analog-Digitala (continuare)


Cuantificarea:
Aproximarea valorilor continue ale semnalului printr-un numar
finit de valori distincte
De obicei numarul de valori i este o putere a lui 2:
i = 28 = 256 cuantificare pe 8 biti
i = 212 = 4096 cuantificare pe 12
12 biti
biti
i = 2n cuantificare pe n biti

x
x
x
x
x
x
x

i+6

i+5

i+4

i+3

i+2

i+1

x
x
x

i-1

i-2

Conversia Analog-Digitala (continuare)

Caracteristica de transfer a unui cuantizor

Semnalul cuantificat + esantionat

x
x
x
x
x

i+6

i+5

i+4

i+3

x
x

i+2

i+1

x
x
x

i-1

i-2

T0

2T0

3T0

4T0

5T0

6T0

7T0

8T0

Prelucrarea Digitala a Semnalelor

Prelucrarea digitala a semnalelor digitizate preia o serie de functii


implementate anterior in blocul analogic:
Filtrarea in frecventa
Sumarea, scaderea
Integrarea, derivarea
In mod suplimentar, semnalelor le pot fi aplicati algoritmi mai
complecsi greu sau imposibil de implementat cu ajutorul circuitelor
complecsi,
analogice:
Filtrarea adaptiva
Suprimarea/introducerea
S i
/i t d
ecoului
l i sii a reverberatiei
b ti i ((ptt efecte
f t audio)
di )
Compresia
g
nu este identic cu cel original,
g
ci este o aproximare.
Semnalul digitizat
De aceea, pentru aplicarea diferitilor algoritmi si a modului in care
actioneaza asupra semnalului, trebuie sa cunoastem relatiile exacte
intre proprietatile semnalului initial si a celui digitizat

Recapitulare: Transformarea Fourier

De multe ori reprezentarea in domeniul timp (numit si spatiul direct) nu


este cea mai adecvata pentru reprezentarea si prelucrarea semnalelor.
De aceea in mod frecvent se face o reprezentare a semnalelor intr
intr-un
un
alt spatiu, numit deseori reciproc, de exemplu spatiul frecventelor.
Trecerea de la spatiul direct la cel reciproc se face prin intermediul unor
transformari ortogonale
ortogonale. Acestea presupun existenta:
unui produs scalar intre doua functii:

< f (t ),
) g (t ) >=

f (t ) g * (t )dt

unei baze de ortogonale de functii ui :

ui 2 i = j
< ui , u j >=
0
i j
unde am notat cu ui norma vectorului ui.
atat functiile, cat si baza, trebuie sa fie integrabile in modul patrat

(de clasa L2 ):
2

f (t ) dt <

Recapitulare: Transformarea Fourier

Orice funcie f aparinnd acestui spaiu se va putea reprezenta sub


forma unei combinatii liniare intre functiile bazei:

< f , ui >
f =
ciui
ci =
2
u
i =
i
unde coeficienii ci se numesc coeficieni Fourier.
Daca vrem sa facem o transformare din spatiul timp in spatiul
frecventelor, putem alege ca baza o functie periodica complexa,
caracterizata de frecventa :
2

( u (t ) = 1 )
u (t ) = e t +
+
c =< f (t ), u (t ) >= f (t )u* (t )dt = f (t )e - jt dt

Functia definita de setul coeficientilor c , pentru valori continue ale ,


se numeste Transformata Fourier F a semnalului
+

F{ f (t )}() = f (t )e

- j t

dt

Recapitulare: Transformarea Fourier

Proprietati ale transformatei Fourier:


liniaritate:
F{ f + g} = F{ f } + F{g}

F{ f g} =
+ +

= f ( ) g (t ) d e jt dt =

teorema convolutiei
F{ f (t ) g (t )}() = F{ f (t )}() F{g (t )}()
F{ f (t ) g (t )}() = 1 F{ f (t )}() F{g (t )}()
2

+ +

f ( ) e

g (t )e j( t ) ddt =

j
g (t )e j( t ) dt d

f
(
)
e

1
44424443

t - t ' ,

F{ g }

= F{ f } F{ g}

deplasarea n domeniul timp:


F{ f (t + )}() = e jF{ f (t )}()
deplasarea n domeniul frecven
Modulatia cu semnal periodic:

F{ f (t )}( + ) = F{e
0

schimbarea de scala
conjugarea complexa
teorema derivarii
teorema integrarii:
g

j 0 t

f (t )}()

F{e

j 0 t

F{ f (at )}() = 1 F{ f (t )}
a

F{ f (t )}() = F{ f (t )}()

F df (t ) () = jF{ f (t )}()
dt

F{ f (t )dt}() =

1
F{ f (t )}()
j

f (t )}() = F{ f (t )}( 0 )

Recapitulare: Transformarea Fourier

Transformata Fourier a unor functii si distributii importante:


functie f para, F este reala:
f ( t ) = f (t )

F()

functie f impara, F este pur imaginara

f ( t ) = f (t ) Re( F() ) = 0

functia Dirac:

F{(t )}() = 1
constanta:
semnal periodic

F{e

F{1}() = ()
j 0 t

}() = ( 0 )

suma de functii Dirac echidistante (functie pieptene):

F{ (t kT0 )}() = 1
T
k =

( k ),

k =

tot pieptene, in domeniul frecventa

0 =

2
T0

Prelucrarea digitala a semnalelor

Esantionarea semnalelor analogice


xe (t ) = x(t )(t kT0 )
k =

Spectrul de frecventa (transformata Fourier) al semnalului

original:
- j t

F() = F{x(t )}() = x(t )e

eantionat:

1
2

k =

k =

2 1

=
{
}

F
x
(
t
)
(
)
k

T0 T0
k =

F + 2T

3
T0

jkT0

2
T0

0
T0

2
2

T0 k =
T0

{
}

F
x
(
t
)
k

T0
k =

F 4T

F 2T

k =

F{(t kT )} = e

F{x (t )} = F{x(t )} F{(t kT )}


e

F{xe (t )} = 1
T0

dt

T0

2
T0

3
T0

4
T0

5
T0

Esantionarea semnalelor

Teorema esantionarii
Explica posibilitatea suprapunerii spectrelor (aliasing)
Frecventele peste jumatate din frecventa de esantionare apar
in spectrul semnalului de frecvente mai mici

F + 2T

3
T0

2
T0

0
T0

T0

F 4T

2

T0

2
T0

3
T0

4
T0

5
T0

jumatate din frecventa de esantionare = frecventa


frecventa Nyquist
Nyquist
Pentru prevenirea suprapunerii, semnalul trebuie filtrat inainte de
esantionare

Semnale finite n timp. Ferestre de ponderare

Transformarea Fourier presupune


existenta unui semnal infinit in timp si
calcularea unei integrale pe un domeniu
infinit
In realitate, nu putem analiza decat
g
secvente finite, de lungime
predeterminata
Operatia echivalenta este aceea de
p
a unui semnal infinit in
multiplicare
timp cu o fereastra finita in timp
functie pondere
Intrebari:
Care este relaia ntre spectrul
Fourier al semnalului iniial i cel al
semnalului ponderat ?
Ct de departe de spectrul real al
semnalului iniial este spectrul
estimat pe baza considerrii numai a
unui eantion finit n timp ?

x (t )

-T

fp(t)

-T

xp(t)

-T

Semnale finite n timp. Ferestre de ponderare

Functia ponderata:

xp = x f p

f *g =

f ( ) g (t ) d

Teorema convolutiei (curs analiza matematica


matematica, an I)
I), mai exact
reciproca:

1
F{x p } = F{x f p } = F{x} F{f p }
2
spectrul de Fourier al semnalului ponderat se obine din spectrul
semnalului iniial prin convoluie cu spectrul Fourier al funciei
fereastr.

Semnale finite n timp. Ferestre de ponderare

fereastra dreptunghiulara centrata n origine, de lrgime 2T are


spectrul de frecven :

sin(T )
S () = 2T
T
S()
2T

|S()|
2T

/T

2/T

/T

2/T

Semnale finite n timp. Ferestre de ponderare

Exemplu:
semnal (co)sinusoidal de
frecven 0, (i perioad
T0=2/0)
spectrul Fourier al
semnalului infinit in timp
- o pereche de funcii
Dirac centrate pe 0
se alege o poriune
pori ne coninnd
patru sinusoide (funcia
fereast se extinde de la -2T0
la +2T0),
)
spectrul Fourier al poriunii
respective va fi egal suma a
doua spectre ale funciei
fereastr, centrate pe
frecvenele 0

-2T0

-T0

T0

2T0

-1

F(cos(t))()
0

0
S()

0
F()

Semnale finite n timp. Ferestre de ponderare

Exemplu (continuare)
Un spectru al semnalului mai apropiat de cel original se poate
obine

lrgind
g
fereastra dreptunghiular.
p
g
Acest lucru are ca efect ngustarea lobilor laterali ai spectrului
fereastr.
p
semnalului obinut

p
prin utilizarea unei ferestre de 4 ori
Spectrul
mai largi dect cea utilizat n exemplul precedent:

F()
0

Concluzie:
spectrul
t l semnalului
l l i este
t cu att
tt maii apropiat
i t de
d
cel iniial cu ct funcia fereastr are lobii
laterali mai nguti i descrete mai repede spre
zero

Semnale finite n timp. Ferestre de ponderare

Fereastra dreptunghiular

1 t [ T ,+T ]
f (t ) =
n rest
0

S () = 2T

t [ T ,0]
t [0,+T ]

sin(T / 2)
S () = T
T / 2

Fereastra cosinus

S () =

sin(T )
T

n rest

T T
cos(2t / T ) t ,+
f (t ) =
4 4

0
n rest

|S(

Fereastra triunghiular (Bartlett):


T + t
T

T t
f (t ) =
T
0

S()
2T

0 = 2 / T

T sin ((0 )T / 4 ) sin ((0 + )T / 4 )


+

4 (0 )T / 4
(0 + )T / 4

/T

2/T

Fereastra cosinus ptrat


2
T T
cos (2t / T ) t ,+
f (t ) =
4 4

0
n rest

Fereastra Hanning
1 + cos(t / T )
f (t ) =
2


1
2

S () =
sin
1 + 2
2 0 + 2 20

t [ T ,+T ]
n rest

sin (T ) sin ((0 )T ) sin ((0 + )T )


S () = T
+
+

T
(
)
T
(0 + )T
0

F
Fereastra
t Hamming
H
i
0.54 + 0.46 cos(t / T ) t [ T ,+T ]
f (t ) =
0
n rest

sin ((0 )T ) sin ((0 + )T )


sin (T )

+
+ 0.92 *
S () = T 1.08 *

T
T
T
(
)
(
)
0
0

Fereastra Gauss
f (t ) = e

12
(
T
/
2
)

T T
t ,+
2 2

Fereastra Bartlett-Hann

F
Fereastra
t Blackman
Bl k


1
2

sin
S () =
1 + 2
2
2 0 +
20

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Serii Fourier

Reprezentarea semnalelor periodice

x ( t ) = C0 + Cn cos( nt ) + Sn sin( nt )
n =1

1
C0 =
T

t 0 +T

x(t )dt

t0

n =1

2
Cn =
T

t 0 +T

x(t ) cos(nt )dt

t0

2
T

2
Sn =
T

t 0 +T

x(t ) sin(nt )dt

t0

Aplicatie: semnal dinte de


fierastrau
x(t ) = t

T T
t ,
2 2

C0 = 0
T /2
T /2
sin(nt ) T / 2 T / 2 sin(nt )
2
cos(
n

t
)
Cn =
t cos(nt )dt = t

dt = 0 +
=0
2

T T/ 2
n

(
)
T / 2
T / 2
T / 2

T /2
T /2
T /2
T /2

2
2 cos(nt )
cos(nt ) (1) n sin(nt )
(1) n +1

Sn =
t sin(nt )dt =
t
+
dt = 2
+
=2
2
n

T T/ 2
T
n T / 2 T/ 2 n
(
n
)
n

T / 2

Serii Fourier

Aplicatie 2: semnal triunghiular

4t

+
1

T
x(t ) =
3 4t

x ( t ) = C0 + Cn cos( nt ) + Sn sin( nt )
n =1

1
C 0 = x(t )dt
T 0

n =1

2
C n = x(t ) cos(nt )dt
T 0

T
t 0,
2
T
t ,T
2

2
=
T

1
T

0
-1

T/2

2
S n = x(t ) sin(nt )dt
T 0

C0 = 0
2
Cn =
T

T /2

4t
2
4t

1 + cos(nt )dt + 3 cos(nt )dt =


T
T T /2
T

-8/2

T /2
T /2
T
T
T /2
T
2 sin( nt )
4 sin( nt )
sin( nt ) sin( nt )
4 sin( nt )
sin( nt )
t
t
=
+

dt + 3


dt =

T
n 0
T
n 0
n
n
T
n

n
/
2
/
2
T
T
0
T
/
2

T /2
T
2
4
cos((nt )
4
cos((nt ) 8
=
= 0 +
0+
+0
0+
( n ) 2 0
T T
T
n T / 2 T 2

2
Sn =
T

T /2

2
2
32
8
(n) 2 (n) 2 = (2n) 2 = (n) 2

4t
2
4t

1 + sin(nt )dt + 3 sin(nt )dt =


T
T T /2
T

T /2
T /2
T
T
T /2
T
2 cos(nt )
4 cos(nt )
cos(nt ) cos(nt )
4 sin( nt )
sin( nt )
dt 3
dt = 0

t
+
=
+
t
+

n
n
T n 0
T
n 0
n
n
T

/
2
/
2
T
T
0
/
2
T

Transformarea Fourier
Di
Discreta
t

Fie un semnal esantionat, de durata finita (n esantioane la interval fix T0)

x = ( x0 , x1 , x2 , K, xn 1 )

Integrala Fourier se transforma intr-o suma


+

F{x}() = x(t )e
t kT0

j t

dt

n 1

1
F{x}() = X () = 1
x(kT0 )e jkT0
n k =0 23

2
,
in general se alege m = m0 / n = m
nT
T0
xk

si deci

1 n 1
X m = xk e j 2 m k / n
n k =0

1 n 1
X () = xk e jkT0
n k =0
0 = 2 / T0

m=0,1,2,,n-1

X = ( X 0 , X 1 , X 2 , K, X n 1 )

Transformarea Fourier Discreta

Nota: spre deosebire de transformata Fourier a semnalelor continue, care


pentru existenta necesita ca functia ((semnalul)) sa fie de clasa L2,
p
transformarea Fourier discreta a semnalelor de durata finita exista
intotdeauna !
Aplicatie:
p
1
0 . 8
0 . 6
0 . 4
0 . 2
0
- 0 . 2
- 0 . 4
- 0 . 6

0.5

- 0 . 8
- 1

0 . 0 0 2

0 . 0 0 4

0 . 0 0 6

0 . 0 0 8

0 . 0 1

0 . 0 1 2

0 . 0 1 4

0.4

0 . 1 6
0 . 1 4

0.3

0 . 1 2
0 . 1
0 . 0 8

0.2

0 . 0 6
0 . 0 4

0.1

0 . 0 2
0

0 . 2

0 . 4

0 . 6

0 . 8

1 . 2

1 . 4

1 . 6

1 . 8

2
x

1 0

100
80

0
-0.1

60
40

-0.2

20

-0.3

0
-2 0

-0 4
-0.4

-4 0
-6 0

-0.5

-8 0
-1 0 0

0.2

0 .4

0.6

0 .8

1 .2

1.4

1 .6

1.8

2
x 10

500

1000

1500

2000

2500

3000

3500

4000

Transformarea Fourier Discreta

The values u = 0, 1, 2, , M-1 correspond to samples of the


continuous transform at values 0, u, 2u, , (M-1)u.
(
)

i.e. F(u) represents F(uu), where:

1
u =
Mx

Transformarea Fourier Discreta

Urmarim sa ajungem la o forma implementabila in cod:

e j = cos( ) + j sin( )
1 n 1
X m = xk [cos(2 m k / n) j sin(2 m k / n)]
n k =0

Transformata Fourier este in general o functie complexa:

X = R + jI

R = ( R0 , R1 , R2 , K, Rn 1 ) I = ( I 0 , I1 , I 2 , K, I n 1 )

X = X e j
X = [ R 2 + I 2 ]1/ 2
I
= tan
R
1

1 n 1
Rm = xk cos(2 m k / n)
n k =0
1 n 1
I m = xk sin(2 m k / n)
n k =0

Transformarea Fourier Discreta


|X| (magnitudinea) este spectrul Fourier al x si faza.

Modulul patrat al transformatei Fourier a semnalului se numeste si


spectru de putere sau densitate spectrala (de putere)
2

P = X = R2 + I 2

Transformarea Wavelet

f (t ) = ck k (t )
k =0

k (t ) = e

ik0t

ck = f (t ), k (t ) =

f (t )

*
k

(t )dt =

f (t )e

ik0t

f (t ) = c j ,k j ,k (t )

dt

k =0

j ,k (t ) =

j
k

1
2

j/2

(2 j t k )

= wavelet-ul mama
= indice
i di d
de scala
l
= indice de translatie

Sisteme Liniare
(preambul la filtrarea numerica)
x(t )

y (t )

H
H
x(t )
y (t )

Liniaritate
H
x1 (t ) + x2 (t )
y1 (t ) + y2 (t )
H
a x(t )
a y (t )

I
Invarianta
i t in
i timp
ti
H
x(t T )
y (t T )

x(t ) = x t =

x()(t )d

H
x(t ) = (t )
h(t )
+

raspuns la impuls

operatorul H nu actioneaza decat


asupra functiilor ce depind de t (nu
si de )

H
x
(

(
t

)
d

x()h(t )d = x * h

y = x*h

Filtrarea numerica

In domeniul frecventa, raspunsul unui sistem liniar este:

F{y} = F{x h} = F{x} F{h}


Y () = X () H ()
transformata Fourier a semnalului de iesire este egala cu produsul
intre transformata Fourier a semnalului de intrare multiplicata cu
transformata Fourier a raspunsului la impuls al filtrului raspunsul in
frecventa al filtrului

Proiectarea unui filtru numeric:


se alege raspunsul in frecventa dorit H()
se aplica transformata Fourier inversa si se determina h(t)
pentru a obtine semnalul de iesire
iesire, se calculeaza calculeaza
convolutia intre semnalul de intrare si h(t).

Filtrarea numerica

Forma discreta a relatiilor precedente:

x = ( x1 , x2 , K, xn )
( f g ) n = f k g nk
k

Semnalul la iesire este o convolutie, care pentru semnale discrete se scrie:


n

yn = xk hn k
k =1

facem schimbarea de indice

k nk
n 1

yn = xn k hk
k =0

yn = h0 xn + h1 xn 1 + h2 xn 2 + L + hn 1 x1

Prelucrari specifice fiecarui tip de


semnall bi
bioelectric
l ti

Prelucrarea potentialelor de actiune


masurate
t intracelular
i t
l l sau extracelular
t
l l

Informatia este codificata in timp/frecventa, nu in amplitudinea sau forma


potentialelor
i l l d
de actiune
i
(AP)
Importanta este determinarea momentului in timp al aparitiei al unui potential
de actiune
Semnalele continand potentialele de actiune ale unui neuron sunt afectate de:
1. Zgomote provenind de la lantul electronic de amplificare a semnalului
2 Alte potentiale de actiune provenite de la neuroni aflati in vecinatate
2.
3. Zgomote datorate interferentelor electromagnetice
Zgomotele de tip 1 sunt stationare, in timp ce cele de tip 2 si 3 sunt
nestationare

Detectia AP

Pentru detectia unui semnal ce contine doar


un AP si zgomotul electronicii, este suficient
un prag de detectie (threshold)

Pentru detectia unui semnal ce contine si alte


AP sau zgomote nestationare, este necesara
separarea
p
sau discriminarea p
potentialelor de
actiune folosind diferite caracteristici ale
semnalului

Vpeak

Neuron 1

Vap

FWHM

~1 mS

Neuron 1+2

Neuron 2

Vvalley

Discriminarea AP

Feature vs Feature reprezentare


in spatiul caracteristicilor (sau
(
fazelor)

Electrocardiografie
g
((ECG/EKG))

Masoara activitatea electrica a muschiului cardiac


Istoric: 1887- Augustus Waller masoara pentru prima data potentialele
EKG ffolosind
l i d electrometrul
l t
t l capilar
il
Una dintre cele mai folosite metode clinice, data fiind frecventa
disfunctiilor cardiace
Are o importanta foarte mare in stabilirea diagnosticelor

2. Ventricular
depolarization

1. Atrial
depolarization

3. Ventricular repolarization

ECG

Triunghiul Einthoven - trei axe orientate la


aproximative
p
60 g
grade:
Electrod I RA(-) LA(+)
Electrod II RA(-) LL(+)
Electrod III LA(-)
LA( ) LL(+).
LL(+)
Se poate obtine un set de semnale unipolare prin
inregistrarea potentialului unui electrod fata de media
celorlalti
l l lti d
doi:i
aVR:
(LA+LL)/2 (-) RA (+)
aVL:
(RA+LL)/2 (-) LA (+)
aVF:
(RA+LA)/2 (-) LL (+)
Exista o relatie vectoriala intre E I, E II, E III si
semnalele unipolare: aVR, aVL, aVF:

ECG

Pentru obtinerea unui maxim de detaliu in


masurarea activitatii cardiace, se mai plaseaza inca
6 electrozi in zona pectorala, obtinandu-se in total
12 derivatii:
I,II,II, aVR, aVL, aVF, V1,V2,V3,V4,V5,V6
Sistemul cu 12 derivatii, probabil cel mai folosit in
clinica,, insa numai din ratiuni istorice un sistem
cu 3 electrozi poate descrie aproximativ 90% din
activitatea cardio-electrica
Exista pentru sistemul cu 12 puncte un o baze de
date foarte cuprinzatore, precum si retete de
interpretare a inregistrarilor.

Caracteristicile
semnalului ECG

Amplitudine:
Banda de frecventa:

1-5
1
5 mV
0.05-100 Hz

Cele mai importante surse de erori:


Artefactele de miscare
Interferenta cu liniile de
alimentare de 50/60 Hz

Applicatii:
Diagnosticare ischemiei
cardiace
Aritmii
A i ii
Defecte de conductie

Electroencephalografie (EEG)
Masoara activitatea electrica a
creierului reflectata la nivelul scalpului
Semnalul EEG este rezultatul activitatii
mediate a miliarde de neuroni
Amplitudine:
A lit di
0 001 0 01 mV
0.001-0.01
V
Banda de frecventa: 0.5-40 Hz
E
Erori:i
Zgomotul preamplificatorului
Interferenta cu liniile de
alimentare
li
t
de
d 50/60 H
Hz
Interferenta cu surse RF
Artefacte de miscare, in principal
a ochilor
hil
Aplicatii:
Studierea somnului
Detectarea crizelor epileptice

Masurarea EEG

Sistem standardizat (10-20) de


puncte in care se face plasarea
electrozilor
Anumite repere anatomice sunt
folosite ca puncte de referinta
P iti
Pozitionarea
unuii numar mare
de electrozi poate dura, de
aceea de multe ori se folosesc
casti elastce sau plase pe care
electrozii sunt pre-pozitionati
In cercetare (insa rar in clinica),
se pot face inregistrari pe un
numar de pana la 256 sau 512
canale.

Sistemul standardizat 1020 pentru masurarea EEG (1958).

El t
Electromiografia
i
fi - EMG
Definitii:

Semnalelul electric associat cu contractia unei fibre musculare


este numita electromiograma (EMG)

Studiul semnalelor EMGs


EMG s se numeste electromiografie
electromiografie.

Electromiografie
Istoric:
1838 Matteucci descrie pentru prima oara detectarea de impulsuri
electrice provenite de la muschi.
pentru inregistrare
g
1929 este introdus electrodul coaxial p
intramusculara
Caracteristicile semnalului EMG
Relaxarea fibrei musculare nu este insotita generarea de semnale
electrice. Doar contactia genereaza semnale EMG.
Magnitudinea semnalului EMG creste o data cu tensiune musculara
Factori care influenteaza semnalul EMG
Viteza de contractie/relaxare
Ob
l
Oboseala
Activitatea reflexa
.

Originea semnalelor EMG


Tesutul muscular consta in
elemente contractile (active)
elemente pasive de conectare a fibrelor
Curba forta-lungime a unui element contractil (Fc)

Influenta tesutului pasiv ce inconjoara elementele


contractile (Fp).
Forta pasiva apare la elongarea fibrei peste lungimea
de repaus l0 , nu si la repaus sau contractie.

Viteza de contractie

Vmax

Forta musculara

F0

Forta descreste cu viteza de contractie

Impulsul
p
muscular
Cum raspunde fibra musculara la un impuls electric ?
La aplicarea unui impuls electric scurt,
scurt raspunsul mecanic F(t) este:

unde:
T este o constanta numita timpul de contractie, ce corespunde timpului dupa care
forta/tensiunea atinge valoarea maxima
maxima.
F0 este o constanta de magnitudine, ce depinde de caracteristicile fibrei motoare

T este mai mare pentru fibre cu raspuns lent, F0 creste cu marime fibrei
Ex: muschii membrelor superioare au in general T mai mic decat cel
al mambrelor inferioare:

T creste cu scaderea temperaturii.


Ex: Biceps brachialis
T=54 ms la 370
T=124 ms la 230.

Forma fortei musculare in timpul contractiei si relaxarii

Turn-on
Turn
on time
(~ 200 ms)

Turn off time


Turn-off
(~ 300 ms)

Modele ale muschiului


Modelele incearca furnizarea de relatii analitice cat mai exacte pentru relatia
intre tensiune si elongatie. Fibra musculara este modelata ca o serie de:
elemente contractile
elemente elastice liniare si nelineare (cu rol de amortizor)
LINIAR: Element elastic (spring)

NELINIAR: Amortizor cu fluid vascos (damper)

Modelul visco-elastic:

Relatii de echivalenta,
echivalenta similare cu
cele ale circuitelor electrice

Semnalele generate in fibrele musculare se numesc potentiale


d actiune
de
ti
musculare
l
(MUAP motor
t unit
it action
ti potential)
t ti l)
Electrozii p
plasati ppe suprafata
p
unui unui muschi ori in interiorul muschiului,
vor inregistra suma tuturor MUAP care sunt transmise de-a lungul fibrelor
musculare.
Terminologie:
Muschi consta din fibra musculara sau unitati motorii (motor units)
Fiecare unitate motoare este controlata de catre un neuron motor ((motor neuron))
Contact terminal - jonctiunea sinaptica intre un neuron motor si o unitate motorie
(motor end plate)
Depolarizarea post-sinaptica a membranei faza initiala a activarii unei unitati motorii
de catre neuronul motor.
Unda de depolarizare (depolarization wave) unda care se propaga pe lungimea fibrei
musculare care rezultat al depoarizarii post-sinaptice initiale.
Unda de repolarizare (repolarization wave) unda care se propaga pe lungimea fibrei
musculare ce are ca rezultat repolarizarea fibrei (revenirea la potentialul de repaus).

Procesul de contractie a muschiului


Neuronii motorii alpha (cei care dau comanda
initiala) incep sa genereze potentiale de actiune
(NUAP nerve unit AP)
O data cu cresterea fortei, are loc un proces de
activare selectiva recrutare a mai multor
motoneuroni, pornind de la cei mai mici, la cei
mai mari
Tensiunea in muschi creste (eventual insotita de
contractie)
Semnalul EMG creste.

Principiul activarii sau recrutarii


neuronilor motori
Recrutarea neuronilor motori (MN - motoneuron) are la
baza marimea si tensiunea in muschi:
Marimea
M i
MN ((sii corespunzator
t a MU) activate
ti t lla un
moment dat creste cu tensiunea din fibra musculara.
Cu cresterea tensiunii
tensiunii, primele unitati selectate sunt
cele mai mici, iar cele mai mari la forta maxima

Potentialul de actiune muscular (MUAP) creste o data


cu marimea
i
fib
fibreii musculare
l
cu care este asociat.
i
Doua tipuri de MU: Tip I si Tip II

Potentialul unui electrod de suprafata

d adancimea fibrei musculare


a aria sectiunii transversale a fibrei
unde:
V potentialul electrodului
m amplitudinea undei de depolarizare
K o constanta de proportinalitate
unghiul solid subntins la punctul de contact al
electrodului de sectiunea frontului de depolarizare (sectiunea fibrei)

Depolarization
p
p
process
quite rapid process
The leading edge of the wavefront is quite sharp
The magnitude of the m.a.p quite big.

Repolarization process
quite comparatively slow process
The leading edge of the wavefront is not sharp
The magnitude
g
of the m.a.p
p qquite small.

Most EMGs require two electrodes over the muscle site.


The voltage waveform that is recorded, is the difference in
potentials between the two electrodes.

diff
difference
iin potentials
t ti l
between the two electrodes.

The voltage waveform at each electrode is almost the same but is


shifted in time.
time
The similarity between both waveforms is higher when the
electrodes are closer.
The
Th differential
diff
ti l signal
i l between
b t
electrodes
l t d is
i smaller
ll in
i case off
nearly located electrodes.

Applicatiile studiului semnaelelor EMG:


Diagnosticul functionarilor muschilor
Controlul protezelor si ortezelor
FES

Electrozi pentru studiul EMG


Doua tipuri:
1.
2.

Intramusculari - invazivi.
De suprafata neinvazivi

( )
(a)

Exemple de electrozi tip ac (needle electrodes):


((a)) Electrod monopolar
p
cu contact in varf.

( )
(a)

(b)

Exemple de electrozi tip ac:


((b)) Monopolar
p
coaxial,, cu contact central ((fir conductor intr-un tub hipodermic)
p
)

( )
(a)

(b)

(c)

Exemple de electrozi tip ac :


((c)) Electrod bipolar
p
cu doua contacte alaturate (fire
(
paralele
p
inserate intr-un tub hipodermic)
p
)

( )
(a)

(b)

(c)

(d)

Exemple de electrozi tip ac :


( ) Electrod monopolar
(d)
p
cu contact lateral. Acest tipp de electrod poate
p
fi folosit la detectia
MUAP al fibrelor individuale.

( )
(a)

(b)

(c)

(d)

(e)

Exemple de electrozi tip ac:


((e)) Electrod bipolar
p
cu doua contacte laterale.

Concentric
electrode

The concentric needle consists of a cannula with an insulated


wire (or wires) down the middle.
The active electrode is the small tip of the center wire,
wire and
the reference electrode is the outside cannula.
Concentric needles may have two central wires (bipolar), in
which
hi h case the
th active
ti
and
d reference
f
electrodes
l t d are att the
th tip
ti and
d
the outside cannula acts as the ground.

Monopolar electrode

Two electrodes are used

Single fiber electrode

The electrode consists of a 0.5-0.6 mm stainless steel cannula with a 25


m fine platinum wire inside its hollow shaft.
In a side port 3 mm behind its tip, the cut end of the platinum wire is
exposed.

Very small pick-up range

Wire electrodes
Fine electrodes with about the diameter of human hairs.
Hypodermic needle is used to insert the wire electrode.

Microelectrodes
Capillary glass microelectrode

IInsulated
l d metall
microelectrode

Solid-state
multisite recording
microelectrode

Electrozi de suprafata
Constau in discuri metalice, aplicate pe
epiderma in zona adiacenta muschiului
investigat
Ag/AgCl (silver chloride); ~1cm
diametru.
Inregistreaza
I
i
media
di activitatatii
i i
ii unuii numar
mare de fibre aflate in vecinatatea
electrodului
Sunt deseori folositi ca electrozi de
referinta pentru inregistrarile cu electrozi
hipodermici
p

Durata pulsurilor EMG


Semnalul (MUAP) depinde de:
- suprafata electrodului
- durata depinde de viteza de propagare a frontului de unda al MUAP.
Viteza de propagagare. ~ 4 m/s

Relatia intre semnalul EMG si tensiunea/contractia


musculara
Intre semnalul EMG si tensionarea/contractia
muschiului se observa o intarziere de cateva zeci
de milisecunde (30-80 ms) electromechanic
delay.

Contractii izometrice (fara modificarea lungimii muschiului)


- dependendenta cvasi-liniara intre semnalul EMG si tensiune
Contractii izotonice ( forta constanta,, cu modificarea lungimii
g
muschiului)
- dependendenta neliniara intre semnalul EMG si tensiune. Semnalul
depinde de lungimea muschiului
muschiului.
Contractii ciclice - Oboseala musculara
- Activitatea
A ti it t electrica
l t i a muschiului
hi l i creste
t cu oboseala
b
l

Kinesiologia
g EMG
Studiul si prezicerea contractiei musculare pe
baza detectiei si analizei semnalelor EMG.
Urmareste
U
t corelatiile
l tiil intre
i t semnalele
l l EMG
si tensiunea/contractia segmentelor analizate
Presupune
p
inregistrarea
g
simultana a
semnalelor EMG si parametrii miscarii.

Semnalul EMG
Caracteristicile semnalului EMG
Amplitudine:
1-10 mV
Banda de frecvente:

20-2000 Hz

Termenul semnal EMG curat se refera la:


S
Semnal
l putin
ti catt maii putin
ti distorsionat
di t i t sii catt maii putin
ti afectate
f t t de
d zgomott
si interferente.
Semnal nedistorsionat
Amplificare liniara atat semnalele mici cat si cele mari trebuie sa
fie amplificate in mod egal. Ex: saturatia amplificatorului rezulta intr-o
distorsionare a semnalului (clipping)

Zgomot
zgomot biologic (de exemplu semnal EKG/ECG cules de electrozi EMG
in zona muschilor toracici)
interferente datorate liniilor cu alimentare cu tensiune (50/60 Hz)
interferente cauzate de alte aparate (ex telefon mobil)
artefacte de semnal (de exemplu datorita aplicarii de pulsuri electrice de
stimulare asupra pacientului)

Consideratii majore la proiectarea


amplificatoarelor de semnal EMG
1.
2.
3
3.
4.

Amplificarea
p
si gama
g
dinamica
Impedanta de intrare
Raspunsul in frecventa
Rejectia modului comun

Prelucrarea semnalelor EMG

Filtrarea in frecventa:
Trece-jos (low-pass)
Trece-sus (high-pass)
Trece-banda (band-pass)
Filtru de rejectie (notch)

Prelucrarea semnalelor EMG

Prelucrari in domeniul timp


Redresarea (full-wave rectify)
Detectia anvelopei (detectia liniara, modul patrat/RMS,
integrarea/IEMG)
Normalizare
Onset/offset

Detectia liniara a anvelopei semnalului redresat

Prelucrarea semnalelor EMG

Prelucrari in domeniul timp (continuare)


Filtrarea liniara trece-jos (netezirea) anvelopei (smoothing EMG)

Efectul
f
filtrarii
f
trece-jos
j asupra
p anvelopei
p semnalulului

Corespondenta intre semnalul netezit si tensiuna musculara

Prelucrarea semnalelor EMG

Prelucrari in domeniul timp (continuare)


Alte metode de netezire:
Integrarea (medierea) - IEMG

1
IEMG(t ) =
T

t+
+T
T

EMG() d
t

Valoarea medie patratica - RMS

1
RMS (t ) =
T

t +T

2
EMG
()d

Prelucrarea semnalelor EMG

Prelucrari in domeniul frecventa


Spectrul de putere:
Frecventa caracteristica - cu amplitudinea ce mai mare
Frecventa mediana 50% din puterea cumulativa
Frecventa medie a spectrului de putere

P
Putere

Pu
utere cum
mulativa

Frecventa (Hz)

Electrooculografie (EOG)

Semnale bioelectrice rezultate in urma miscarilor globilor oculari


provin din sumarea activitatilor muschilor ce deplaseaza globul ocular,
precum si a nervilor ce ii comanda
Potential este in mare proportional cu amplitudinea of the miscarii
oculare
Amplitudine:
0.01-0.1 mV
Banda de frecventa:
DC-10 Hz
Sursele primare de eroare includ potentialul EEG si artefactele de
miscare ale pielii
AplicatiI: corectitudinea positionarii ochilor, patologia somnului, reflexul
vestibulo ocular
vestibulo-ocular

Electro
lectroCo
Cortico
rticoG
Grafie
ECoG
Curs Bioinginerie
Andrei Barborica: andrei.barborica@fizica.unibuc.ro

Electro
lectroCo
Cortico
rticoG
Grafie - ECoG

Inregistrari invazive de semnale


bioelectrice direct pe suprafata
corticala
Sursa semnalelor bioelectrice o constituie
neuronii corticali

S l spatiala
Scala
ti l a inregistrarii
i
i t ii ECoG
EC G mm2

Sursa de semnal si inregistrare scale spatiale diferite ECoG


inregistreaza rezultatul activitatii colectiva a neuronilor

Scale spatiale
Microscala
Microscala:: intracelular
intracelular,, extracelular

Mesoscala:
Mesoscala: extracelular
extracelular,, pe suprafata mai mare (multi(multi-unit),
unit) LFP
Macroscala
Macroscala:: pe suprafata (cortical, scalp, piele)
piele)

Scala spatiala
p
a inregistrarilor
g
de
scalp, corticale si de adancime

EEG d
de scalp
l necesita
i ~7cm
7 2 de
d cortex cu activitate
i i
sincrona
i
ECoG and SEEG necesita ~10mm2 de cortex
Microconductori (microwires
microwires)),
microwires),
) o sfera cu raza R~150
R~150
R
150m
150
Electrozi extracelulari sau intracelulari un singur neuron / AP
Worrell et al, Progress in Neurobiology, 2012

Spectrul
p
de frecvente

Inregistrarile pe arii mari limiteaza spectrul de frecvente din


semnal prin mediere spatiala cu efect in domeniul timp
Neuronul genereaza potentiale de actiune (AP) cu o durata de ordinul
milisecundei spectru f <10 kHz
10 ms

ECoG,
ECoG, SEEG - inregistrari invazive pe suprafete de
ordinul 1-10 mm2 spectru f < 1 kHz

58

59

60
Time (s)

61

62

Scalp 0.50.5-1 cm2 spectru f < 100 Hz


P4-O2

ECoG

Inregistrari pre
pre-- sau intra
intra--operatorii folosind gridgrid-uri bidimensionale sau
stripuri unidimensionale de electrozi pentru

Localizarea focarelor epilpeptice


Localizarea zonelor functionale (functional mapping)

ECoG inregistreaza:
inregistreaza:

Activitatea inter-ictala
inter ictala spontana.
spontana
Markeri patologici: varfuri
rapide (spikes), eventual
descarcari
desca
ca repetitive
epe
e

Activitatea ictala (crize) numai


pentru monitorizari de lunga
p
g
durata (cateva zile)

Intraoperator,
p
, necesita decizii
rapide timp limitat de
inregistrare

Electroencefalograf
g

ECoG

Varfuri inter
inter--ictale spikes
Varf inter-ictal (spike)

22
20
18

Conta
act

16
14
12
10
8
6
646

647

648
Time (s)

649

650

*Aceasta pozitionare a gridului este cu titlu exemplificativ, nu ete cea care sa corespunda
inregistrarii din stanga

ECoG

Varfuri inter
inter--ictale harta activitatii

ECoG

Varfuri inter
inter--ictale harta activitatii cu
pseudocolorare

ECoG

Varfuri inter
inter--ictale filmul activitatii

ECoG

Spike--uri se pot propaga


Spike

ECoG

Propagarea spike
spike--urilor - animatie

Contact:

andrei.barborica@fizica.unibuc.ro

Filtrarea EEG
Curs Bioinginerie
Andrei Barborica: andrei.barborica@fizica.unibuc.ro

Artefacte in filtrarea EEG

Tranzientii din semnalele EEG produc artefacte la filtrarea


trece--sus,
trece
sus, trecetrece-jos (si trece banda
banda))
Ex: Urresterazu et al, Brain 2007 au raportat oscilatii in
gama 8080-500Hz in varfuri interinter-ictale

Urrestarazu E, Chander R, Dubeau F, Gotman J. Interictal high


high--frequency oscillations (100(100-500 Hz) in the
intracerebral EEG of epileptic patients. Brain.
Brain. 2007 Sep;130(Pt
Sep;130(Pt 9):2354
9):2354--66. Epub 2007 Jul 11.

Benar et al, Clin


Clin.. Neurophysiol
Neurophysiol.. 2010 au aratat ca oscilatiile
identificate in aceste varfuri sunt de fapt artefacte de filtrare

Bnar CG, Chauvire L, Bartolomei F, Wendling F. Pitfalls of high


high--pass filtering for detecting
epileptic oscillations: a technical note on "false" ripples. Clin Neurophysiol
Neurophysiol.. 2010

Mar;121(3):301--10. doi:
Mar;121(3):301
doi: 10.1016/j.clinph.2009.10.019. Epub 2009 Dec 1.

Surse de tranzienti:
tranzienti:
Fiziologici

Spikepike-uri inter
inter--ictale (varf/spike
varf/spike < 70ms, unda
unda/wave
/wave > 70 ms)
ms)

Artefacte musculare (EMG)

Ne
Ne--fiziologici

Interferente
Trunchierea//segmentarea semnalului
Trunchierea

Artefacte in filtrarea EEG

Artefactele vizibile in mod deosebit la filtrarea la frecvente mari


((HFO>100Hz))
HFO un biomarker al epileptogenicitatii

Urrestarazu E,, Chander R,, Dubeau F,, Gotman J. Interictal highhigh


g -frequency
q
y oscillations (100(100
(
-500 Hz)) in the intracerebral EEG of
epileptic patients. Brain. 2007 Sep;130(Pt
Sep;130(Pt 9):2354
9):2354--66. Epub 2007 Jul 11.

Artefacte in filtrarea EEG


Benar et al,, 2012
Simulated spike in
EEG resulted in false
HFOs
HFO

Bnar CG, Chauvire L, Bartolomei F, Wendling F. Pitfalls of highhigh-pass filtering for detecting epileptic oscillations: a technical
note on "false" ripples. Clin Neurophysiol.
Neurophysiol. 2010 Mar;121(3):301
Mar;121(3):301--10. doi:
doi: 10.1016/j.clinph.2009.10.019. Epub 2009 Dec 1

Bnar CG, Chauvire L, Bartolomei F, Wendling F. Pitfalls of highhigh-pass filtering for detecting epileptic oscillations: a technical
note on "false" ripples. Clin Neurophysiol.
Neurophysiol. 2010 Mar;121(3):301
Mar;121(3):301--10. doi:
doi: 10.1016/j.clinph.2009.10.019. Epub 2009 Dec 1

Artefacte in filtrarea EEG

C.G. Bnar et al. / Clinical Neurophysiology 121 (2010) 301


301
310

Artefacte in filtrarea EEG

C.G. Bnar et al. / Clinical Neurophysiology 121 (2010) 301


301
310

Artefacte in filtrarea EEG

Explicatia
p
p
proprietatiele
p
transformatei Fourier
+

F{ f (t )}( ) = f (t )e

- jt

dt

F
Functie
ti Gaussiana
G
i
normata
t

1
g ( x) =
e
2

x2
2 2

g ( x)dx = 1

Transformata Fourier: Gaussiana

G ( ) = e

2 2
2

Trransformata
a Fourrier a u
unei G
Gaussiiene

Artefacte in filtrarea EEG

Impulsul Dirac

(t )

Transformata Fourier functia unitate - 1

F{ (t )}( ) = 1

Dirac - Functie Gaussiana 0

(definitia nu e unica)
unica)

x2

( x) = lim
0

T
Transformata
f
t Fourier
F i

1 2 2
e
2

li G ( ) = lim
lim
li e

2 2
2

= e0 = 1

Cu cat pulsul este mai ingust


ingust,, cu atat sunt mai bine reprezentate frecventele
inalte in spectru.
spectru. La limita,
limita, pentru un puls Dirac, toate frecventele sunt egal
reprezentate in spectru

Artefacte in filtrarea EEG

Tranzienti::
Tranzienti
Effectul Gibbs oscilatii (ringing)
rezultate
lt t din
di reconstructia
t ti semnalului
l l i
folosind un numar limitat de termeni
Fourier

Descoperit de
d Henry Wilbraham
lb h
(1848
1848)) si redescoperit de J. Willard
Gibbs (1899
1899))

Semnal dreptunghiular reconstituit din 5 armonici

Ex semnal dreptunghiular de
pulsatie :

1
1
f (t ) = sin(t ) + sin(3t ) + sin(5t ) + ...
3
5

Semnal dreptunghiular reconstituit din 5 armonici

Reconstructia Fourier

Semnal Dreptunghiular

Semnal Triunghiular

Concluzii

Filtrarea in frecventa poate introduce artefacte


Trebuie cunostinte solide de analiza Fourier si de analiza
semnalelor,, in general, pentru a evita erorile
semnalelor
De multe ori sunt necesare analize complexe
p
pentru a discrimina
p
semnalele reale de artefacte

C.G. Bnar et al. / Clinical Neurophysiology 121 (2010) 301


301
310

Contact:

andrei.barborica@fizica.unibuc.ro

Stereoelectroencephalography
in Presurgical Evaluation of Focal Epilepsy

Andrei Barborica
andrei.barborica@fizica.unibuc.ro

We are aiming at identifying


the epileptogenic network
Patients with drugdrug-resistant focal epilepsy

Epileptogenic Zone:
Zone:
the minimum amount of cortex that must be resected
(inactivated or completely disconnected) to produce seizure freedom
Luders et al., 2006
S
Symptomatogenic
t
t
i zone

F
Functional
ti
l deficit
d fi it

area of cortex which, when activated, produces the


initial ictal symptoms or signs

area of cortex that is not functioning


normally in the interictal period

Seizure Propagation
Eloquent Cortex

Seizure
Onset
S i
O
t Zone
Z
area of cortex that initiates clinical seizures

Epileptogenic
p p g
lesion (if
( present)
p
)
Irritative zone
area of cortex which generates interictal spikes

macroscopic lesion which is causative of the epileptic seizures because the


lesion itself is epileptogenic (e.g. cortical dysplasia) or by secondary
hyperexcitability of adjacent cortex

After Luders et al 2006


& Kahane, AES 2012

Why Stereoencephalography?
Stereoencephalography?

The only technique that provides direct access to


electrophysiological recordings in the seizure onset zone,
when located in deep brain structures

Allows determination of the depth of epileptogenic areas

Requires insertion of depth electrodes (7(7-14)

Electrode placement is achieved through stereotactic


techniques

Stereotaxy
Uses a 3D
3 coordinate
di
system to locate
l
brain structures
Requires a stereotactic positioning device
MultiMulti
u t -modal
oda imaging
ag g (CT,
(C , MRI,,
Angiography etc)
etc) that allows visualization
patient anatomyy and coco-registration
g
of p
with the stereotactic frame

Electroencephalographic depth recordings

High specificity / spatial resolution

High frequencies well evidenced

Stable, no EMG artifacts

Spatial scale of scalp, cortical


and
d depth
d th recordings
di

Scalp EEG requires a ~7cm2 patch having synchronous activity


ECoG and SEEG require ~10mm2 of cortex
Mi
Microwires,
Microwires
i , a sphere
h
having
h i R~150
R~150
R 150m
After Worrell et al, Progress in Neurobiology, 2012

Goals of SEEG investigation

Confirming that brain regions suspected of being involved


in seizure onset and propagation show the expected ictal
pattern.

Delineating
g the border of the epileptogenic
p p g
zone as
precisely as possible, to perform the minimum cortical
resection.

Assessing whether the complete removal of the


epileptogenic zone will be possible or not by performing
stimulation mapping of the eloquent areas.
areas

Evaluating the precise relationships between an


anatomical
t i l lesion
l i (when
( h present)
t) and
d the
th epileptogenic
il t
i
zone.
After Kahane et al, 2004

Implantation patterns

Follow a certain hypothesis,


yp
, based on the anatomical
evidence (if any), ictal semiology and scalp EEG.

O
Q

A
I

R
W
C

B
E

A - Amygdala; B Anterior Hippocampus; C Posterior Hippocampus;


E Entorhinal Cortex; U Superior Temporal Gyrus
Gyrus;; D - Retrosplenial cortex;
I Temporal Pole; O - Orbitofrontal; F - Fusiform gyrus;
gyrus; R Rolandic Operculum;
W Wernicke;

Stereotactic planning
Preoperative MRI with contrast
Patient anatomy, vasculature

Stereotactic planning
A i
Angiography
h
Virtual angiography from contrastcontrast-enhanced MRI through3D Frangi
vesselness filtering
g

Safe electrode placement


1

0.8

Entry S

T arget S

0.9

Safety index:0.83
Traj 6: S
Frangi scales =[0.85 1.35]
3D smoothing =2.00

0.6

SI

Norm
malized MRA level

07
0.7

0.5
04
0.4
0.3
0.2
0.1
0
-20

-10

10

20
30
40
Distance from target (mm)

50

60

70

80

Safe electrode placement


Entry S

0.8

Target S

1
0.9

Traj 5: S
Frangi scales =[0.85 1.35]
3D smoothing =2.00

0.7
Normalized
d MRA level

Safety index:0.90

0.6
0.5
0.4
0.3
0.2
0.1
0

10

20

30
40
50
Distance from target (mm)

60

70

80

Stereotactic frame Leksell

Stereotactic devices
StarFix techology
techology,, FHC Inc
No adjustable components

Waypoint Navigator, FHC Inc

Stereotactic devices

StarFix,, personalized fixture


StarFix

Personalized Stereotactic Frame

Advantages:
g
Simplicity - no adjustable parts, thus minimizing
risk of human error
Reduces OR time with a factor of two
Two
Two--step procedure (anchor
(anchor implant
implant,, actual
surgery) spaced one to two weeks
Surgical planning can be performed in the
generous interval between the two steps. It does
not have to be performed the day of the surgery
Frame coordinates match anatomical coordinates
(centered on MCP and aligned with mid
mid--plane),
plane)
making targeting more consistent across patients.

Electrode Implantation
Percutaneous Hole Drilling
Dura Electrocoagulation
g
Anchor placement
Stylet insertion
Electrode Insertion

Postoperative CT

Verification of electrode p
position,, hemorrhages
g

B01-B03 Hippocampus
B01pp
p
B04--B05
B04
Parahippocampal gyrus
B06--B08 WM
B06
B11--B12 Middle
B11
Temporal Gyrus (T2)

SEEG Recordings
and Stimulation

1-3 weeks video EEG monitoring


g
Continuous recording using wireless
amplifier
p
Several ictal events captured

Various stimulation protocols for:


Eliciting responses characteristic to interinter-ictal or ictal
patterns
Functional mapping of eloquent cortex, to delineate
the area that can be resected with minimal deficit

Typical SEEG Signals

R7--R8 Brocas area


R7
speech arrest on stimulation (f=50 Hz, I=2mA)

Typical SEEG Signals

O2--O3 Orbitofrontal Cortex


O2
Low amplitude Delta

Typical SEEG Signals

P10--P1 - Parietal
P10

Typical SEEG Signals

U4--U5 Infrasylvian Operculum


U4

Typical SEEG Signals

F5--F6 Fusiform Gyrus


F5

Typical SEEG Signals

D1--D2 Retrosplenial Cortex


D1

Typical SEEG Signals

D1--D2 Retrosplenial Cortex


D1
Propagation from Amygdala

Typical SEEG Signals

O1--O2 Supra
O1
Supra--Calcarine

Typical SEEG Signals

F2--F3 Fusiform Gyrus


F2
inter
inter--ictal spikes

Seizure onset on SEEG

Time--frequency map
Time

Seizure propagation

Electrical Stimulation
Stimulationprotocols:
l
l
1Hz,3ms biphasicpulses,15mA,40s
50Hz,1ms
50 Hz 1 ms biphasicpulses,13mA,5s
biphasic pulses 1 3 mA 5 s
Amigdala seizure reproduction

Electrical Stimulation

A1-2 (Amygdala), 50 Hz, 1 ms biphasic


A1pulses, 1
p
1--3 mA, 5 s seizure reproduction
p

10.Tailoredresections

Temporallobe
poleresection

Conclusions

Despite its complexity, SEEG method


can provide invaluable information
regarding:
3-D llocalization
li ti off the
th seizure
i
onsett zone
in deep brain structures
propagation
ti paths
th off th
the ictal
i t l discharges
di h
functional mapping of eloquent cortex for
delineating the resection

Acknowledgments

SEEG Team:
Ioana Mindruta,, Jean Ciurea,, Alin Rasina,
Rasina, Bogdan
g
Balanescu

Stereotactic mT Platform design:


Ron Franklin

Funding::
Funding
UEFISCDI PNPN-II
II--ID
ID--PCEPCE-2011
2011--3-0240

Institutions
Bucharest
B h
tU
University,
i
it Physics
Ph i Dept,
D t, Biomedical
Dept
Bi
di l Engineering
E i
i
University Emergency Hospital, Bucharest
Bagdasar
Bagdasar--Arseni Emergency Hospital

Intracranial
Direct Electrical Stimulation
in
StereoElectroEncephaloGraphy
(SEEG)
Andrei Barborica

andrei.barborica@fizica.unibuc.ro

Identifying
y g the
epileptogenic network
Epileptogenic Zone:
the minimum amount of cortex that must be resected
(inactivated or completely disconnected) to produce seizure freedom
S
Symptomatogenic
t
t
i zone

F
Functional
ti
l deficit
d fi it

area of cortex which, when activated, produces the


initial ictal symptoms or signs

area of cortex that is not functioning


normally in the interictal period

Luders et al., 2006

Seizure Propagation
Eloquent Cortex

Seizure
Onset
S i
O
t Zone
Z
area of cortex that initiates clinical seizures

Epileptogenic
p p g
lesion (if
( present)
p
)
Irritative zone
area of cortex which generates interictal spikes

macroscopic lesion which is causative of the epileptic seizures because the


lesion itself is epileptogenic (e.g. cortical dysplasia) or by secondary
hyperexcitability of adjacent cortex

After Luders et al 2006


& Kahane, AES 2012

StereoElectroEncephaloGraphy
SEEG
Provides direct access to electrophysiological
recordings in the seizure onset zone
zone, when located in
deep brain structures
Allows delineation of the epileptogenic area in 3D
volume
Provides excellent time & space resolution

Direct Electric Stimulation (DES)

Stim

Uses different stimulation protocols to map


epileptogenicity and brain connectivity
Functional mapping of eloquent cortex
Delayed Response

SEEG + DES
Each zone has specific EEG markers
- during spontaneous activity - ictal or inter-ictal
- as a response to stimulation
Analysis of the electrophysiological responses to DES:
Its major advantage is that it covers the full spectrum of events (spikes,
ripples and fast ripples) that can be used to delineate the epileptogenic
cortex without depending on their spontaneous occurrence and the
occurrence of seizures.
- van t Klooster et al, 2011
Symptomatogenic zone
Auras

Functional deficit
Low responses

Eloquent
El
t Cortex
C t
Clinical Symptoms,
Functional Deficit (or enh.!)

Seizure Onset Zone


Afterdischarges, Seizures, Delayed SPES
Responses, HFOs

E il t
Epileptogenic
i lesion
l i (if present)
t)
Irritative zone
Afterdischarges, Delayed
SPES Responses, HFOs

No responses (hypoexcitability)
SOZ-Like responses (hyperexcitability)

Imaging the Seizure Onset Zone


MRI shows anatomical data based on probing the
response of protons (H
(H+)) in the water using variable
magnetic fields applied in various sequences and
radiofrequency signals
DES could show functional data electrophysiological
responses to electrical stimulation, imaging the
epileptogenic areas.

U W
B C

I A

DES Protocols
Repetive
p
low- ((1Hz)) and highg
frequency (50 Hz) stimulation
Single Pulse Electric Stimulation
(SPES)

intracranial electrodes, Monophasic


pulse, 0.3 - 3ms pulse width, 5-30 s
interpulse interval, up to 8mA currents

Early Responses (ER) and sometimes


Delayed Responses (DR)
DR are a marker specific to seizure
onset zone - SOZ (2002, Valentin et. All)

subdural grid electrodes, similar


stimulation protocol

Similar
Si il results
lt (2009,
(2009 Flanagan
Fl
ett al.)
l)

DES Protocols
SPES

Grid electrodes, monophasic square wave, 0.3


ms pulse width, 1 s interpulse interval, 1
10mA currents
Results:
Response amplitude varies with current
amplitude (2010, Iwasaki et. All)

Grid electrodes, biphasic pulse, 0.3 ms pulse


width, 1 s interpulse interval, 1 15mA
currents
Results:
Response amplitude varies with current
amplitude (2012, Enatsu et. All)

2010, Iwasaki et. All

Subjects and Methods


Subjects:
4 patients with refractory epilepsy
Stimulation done during
gp
presurgical
g
evaluation
Equipment used:
Nicolet wireless 64channel amplifier
Programmable
P
bl
stimulator (Guideline
LP+, FHC Inc)

Methodology
gy
SEEG electrodes
Data recorded using
64 channels
Sampling rate 4096 Hz
- allows visualization of
High-Frequency
Oscillations (HFO) with
f>100 Hz

A - Amygdala; B Anterior Hippocampus;


C Posterior Hippocampus;
E Entorhinal Cortex; U Superior Temporal Gyrus;
D - Retrosplenial cortex; S - Suprasylvian;
I Temporal Pole; O - Orbitofrontal; F - Fusiform gyrus;
R Rolandic Operculum; W Wernicke;

U W
B C

I A

Methods
Stimulation protocols:
1 Hz: biphasic
biphasic, 3 ms pulse width,
width
40 s stimulation length, 0.5 - 3 mA
current range

50 Hz functional mapping: biphasic, 1 ms pulse width,


5 s stimulation length, 0.5 - 3 mA current range
SPES: monophasic & biphasic,
biphasic 3 ms pulse width,
width 15 s
interpulse interval, currents in the 0-5mA range
(0.25mA step)
Paired Pulse (PP) : biphasic, 3 ms pulse width, 10200ms pair delay, 1 mA current
Variable Pulse Width (VPDES):
(
S) biphasic, 0
0.25
2 3ms
3
pulse witdh (0.25ms step), 15 s interpulse interval, 1 mA
current

Methods

5
4
3

SPES
biphasic, 3 ms pulse width,
biphasic
width 15
s inter-pulse interval,
variable amplitude in the 05mA range (0.25mA step)
pseudo-random sequence for a
total of 5 min to factor out time

Am
mplitude (mA)

2
1
0
-1
-2
-3
-4
-5

50

100

150

200
250
Time (s)

300

peri-stimulus
i ti
l
response: early,
l
delayed, HFOs
stimulus response-curves

350

400

450

1 Hz Stimulation

Common practice
Used for mapping brain connectivity
(electric responses) (2012, Enatsu

et all.)

Sometimes a seizure can occur:


E1-E2 Entorhinal Cortex stimulated
(see attached video)

50 Hz Stimulation

Common practice
Used for functional mapping (clinical responses)
Can produce auras and seizures
Oth clinical
Other
li i l response: muscle
l contractions,
t
ti
auditory / visual / olfactive hallucinations, verbal
arrest,etc

Case study: (see attached video)

Wernicke stimulation causes verbal arrest


Entorhinal Cortex stimulation causes aura during
stimulation
1 mA a mild aura
2 mA a stronger aura like the one before seizure

SPES

High frequency oscillations (HFO, 100-250Hz)


strong marker for epileptogenic area. (2012

Enatsu et all.; 2012 da Silva et all.)

A4 Amygdala

C2 Posterior Hippocampus

E1-E2 Entorhinal

SPES
E1-E2 Entorhinal Cortex

C2 Posterior Hippocampus

SPES HFO ((100-250 Hz))

E1-E2 Entorhinal Cortex

C2 Posterior Hippocampus

SPES Fast Ripples


pp
(>250
(
Hz))
E1-E2 Entorhinal Cortex
SPES biphasic

Fast Ripples (FR, >250Hz)


are even more specific to
the epileptogenic area
than HFOs (2012 Cho et

all.)

C2 Posterior Hippocampus

DES Case Study


Symptomatogenic
zone
Auras

Functional
F
nctional
deficit
Low responses

Eloquent Cortex
Clinical Symptoms,
Functional Deficit (or
enh.!)

Seizure Onset Zone


Afterdischarges, Seizures, Delayed
SPES Responses, HFOs

Irritative zone

Epileptogenic lesion (if


present)

Afterdischarges,
Delayed
D l
d SPES
Responses, HFOs

No responses (hypoexcitability)
SOZ-Like responses
(hyperexcitability)

Seizure Onset Zone


A - Amygdala;
B Anterior Hippocampus;
C Posterior Hippocampus;
Irritative zone:
E Entorhinal Cortex;

Functional Deficit:
I Temporal Pole;
F - Fusiform gyrus;
Eloquent Cortex:
R Rolandic Operculum;
W Wernicke;
No responses:
O - Orbitofrontal;
U Superior Temporal Gyrus;

SPES Monophasic

Monophasic pulse

Biphasic pulse

Our data showed that brain responses are similar for both
monophasic and biphasic SPES (results are shown on a future slide)

VPDES
B1 B2 Hippocampus
VPDES 1.5mA

A4 Amygdala

C2 Posterior Hippocampus

SPES vs. VPDES


Injected current or charge per
phase is the most relevant
parameter in SPES
p

A7 Amygdala

C2 Posterior Hippocampus

SPES vs. VPDES


Injected current or charge per
phase is the most relevant
parameter in SPES
p

B5 Hippocampus

B6 Hippocampus
Hippocampus

Conclusions
Intracranial Direct Electric Stimulation (iDES )
helps in delineating the epileptogenic network
Evaluation of stimulus-response curves as well
as oscillations in various frequency bands
triggered by iDES provide valuable
complementary information to recording
spontaneous activity.
Th
The mostt relevant
l
t parameter
t iin SPES iis th
the
injected current (charge per phase)

Analiza activitatii
neuronilor individuali
Introducere
Curs Bioinginerie
Andrei Barborica: andrei.barborica@fizica.unibuc.ro

Analiza potentialelor de actiune masurate


intracelular sau extracelular

Informatia este codificata in timp/


timp/frecventa,
frecventa, nu in amplitudinea sau
forma potentialelor de actiune (AP)
Importanta este determinarea momentului in timp al aparitiei al unui
potential de actiune
Semnalele continand potentialele de actiune ale unui neuron sunt
afectate de:
1.
2.
3
3.

Zgomote provenind de la lantul electronic de amplificare a semnalului


Alte potentiale de actiune provenite de la neuroni aflati in vecinatate
Zgomote datorate interferentelor electromagnetice
Zgomotele de tip 1 sunt stationare
stationare,, in timp ce cele de tip 2 si 3 sunt
nestationare

Discriminarea AP (Action Potentials)

Raza volumului inregistrat 50 - 100 m (Gerstein and Clark, 1964; Buzsaki, 2004)

Discriminarea AP

Pentru detectia unui semnal ce contine doar


un AP si zgomot,
zgomot
g
, este suficient un prag
p g de
detectie (threshold)
Pentru detectia AP intrintr-un semnal ce contine si
alte AP sau zgomote nestationare
nestationare,, este
necesara separarea sau discriminarea
di i i
potentialelor de actiune folosind diferite
caracteristici ale semnalului
Vpeak
Neuron 1

Vapp
FWHM

~1 mS

Neuron 1+2

Neuron 2

Vvalley

Discriminarea AP

(Action Potentials)

Achizitie biosemnal

AP provenind de la
doi sau mai multi neuroni diferiti (r~100m)

Filtrare semnal (i)


Filtrare in frecventa (300Hz(300Hz-6kHz)
Filtrare adaptiva
p
Filtrare avansata - wavelet

Detectie AP (ii)
prag (threshold) de amplitudine
tipuri de erori:
erori:

alarme false, false


false positives
positives tip I
omisiuni,, misses
omisiuni
misses tip II

Sortarea
Extragere de caracteristici ale AP ce
diferentiaza neuronii (iii)
Gruparea in functie de caracteristici
caracteristici,,
clustering
clustering,
, (iv)

Quiroga et al. (2004)

Filtrarea AP
A l i
Analogica

Filtre cauzale
cauzale

valorile iesirii depind


numai de valorile
prezente si trecute ale
semnalului

Numerica

Filtre cauzale
Non--cauzale valorile
Non

iesirii depind si de valorile


viitoare ale semnalului
Ex: convolutia cu o
gaussiana a unui
semnal numeric

Sortarea AP
Discriminator cu 1 fereastra
slope--height windows discriminator
discriminator
slope

Sortarea AP

Discriminator cu ferestre
rectangulare
t
l
boxes
b
boxes

Sortarea AP

Potrivirea cu sablon template matching


matching

Sortarea AP

Vpeak

FWHM

Vap

Feature vs Feature
reprezentare in spatiul
caracteristicilor (sau fazelor)

~1 mS
S

t
Vvalley

Sortarea AP

Analiza folosind componentele


principale ale semnalului
Componentele principale un set de forme de
unda ortogonale
g
(d.p.d.v
p
al operatorului
p
de
convolutie)) care surprind variabilitatea maxima
convolutie
din semnal (Glaser and Marks 1968, Glaser 1971,
Gerstein et al1983)
al1983).

Sortarea AP

PCA scorul fiecarui AP

Clustering:

Sortarea AP

Proiectiile pe 3 componente principale


principale::
reprezentare 3D

Sortarea AP

Probleme::
Probleme
Suprapunerea spike
spike--urilor

template matching =
potrivirea cu sablon ?????

Opriti masacrarea
terminologiei de specialitate
din limba engleza!
De acum inainte vom folosi
numai limba engleza.

Contact:

andrei.barborica@fizica.unibuc.ro

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