Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

MethodologiesMethodologies and and instrumentsinstruments

forfor the the characterizationcharacterization of the of the

Parkinson Parkinson diseasedisease

Computer Computer EngineeringEngineering FacultyFaculty

THESIS DEGREETHESIS DEGREE

AuthorAuthor::

Alfonso IsolaAlfonso Isola

SupervisorSupervisor

Chiar.mo Prof. Ing. P. ArenaChiar.mo Prof. Ing. P. Arena

CoCo--SupervisorsSupervisors::

Chiar.mo Prof. P. MazzoneChiar.mo Prof. P. Mazzone

Ing. Adriano BasileIng. Adriano Basile

Ing. Davide LombardoIng. Davide Lombardo

Ing. Guido VagliasindiIng. Guido Vagliasindi

2/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

�� Project Project CooperationCooperation�� Cooperation among the DIEES of the Università degli Studi di CatCooperation among the DIEES of the Università degli Studi di Catania, the ania, the

STMicroelectronics of Catania and the Orthopedic Surgery Center STMicroelectronics of Catania and the Orthopedic Surgery Center of the of the A. Alesini HospitalA. Alesini Hospital-- RomaRoma..

�� Technology usedTechnology used�� DBS Activa Therapy and LFP recordings (DBS Activa Therapy and LFP recordings (furnishedfurnished byby MedtronicMedtronic))�� This therapy is a big scientific opportunityThis therapy is a big scientific opportunity

�� ObjectivesObjectives�� Design a DataDesign a Data--Logger for the Logger for the massmass--storagestorage of the neuro celebral signals of the neuro celebral signals

taken from Basal Ganglia taken from Basal Ganglia nucleusesnucleuses by means of DB leads.by means of DB leads.

�� Possible ApplicationsPossible Applications�� Medical Research and careful characterization of the Parkinson Medical Research and careful characterization of the Parkinson diseasedisease�� AutoAuto--settingsetting of the of the neurostimolator’neurostimolator’s s parametersparameters

IntroductionIntroduction

3/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

The Parkinson The Parkinson diseasedisease

�� The The Parkinson Parkinson diseasedisease ((MPMP) ) isis anan evolutionevolution progressive progressive illnessillness withwith unknownunknowncausescauses ((idiopathicidiopathic), ), correlatedcorrelated toto a a neuralneural degenerationdegeneration of the of the SubstantiaSubstantia NigraNigra..

�� The The mainmain clinicalclinical symptomssymptoms are:are:�� BradikinesiaBradikinesia ((slownessslowness of movement)of movement)�� AkinesiaAkinesia ((lacklack of movement)of movement)�� Tremor Tremor �� RigidityRigidity�� Postural instabilityPostural instability

�� TherapyTherapy�� PharmaceuticalPharmaceutical (L(L--DOPA)DOPA)

�� LossLoss of of effictiveneseffictivenes after 5 after 5 yearsyears�� Clinic Clinic therapytherapy uselessuseless in some in some patientspatients�� LTDS (LTDS (Long Term Dopa SyndromeLong Term Dopa Syndrome) )

�� SurgicalSurgical lesionslesions ((PallidotomyPallidotomy surgerysurgery))�� These lesions are executed in the STN or GPiThese lesions are executed in the STN or GPi�� Invasive Irreversible Therapy Invasive Irreversible Therapy

�� ElectricElectric stimulation at high stimulation at high frequencyfrequency (DBS)(DBS)�� ItIt succedssucceds in in attenuatingattenuating the the symptomssymptoms�� UnknownUnknown workingsworkings, , maybemaybe itit forcesforces the the neuronsneurons of the of the stimulatedstimulated zone zone toto work at high work at high freqfreq..

31%

50%

74%

0%

10%

20%

30%

40%

50%

60%

70%

80%

3-5 yrs

5-7 yrs

10-12 yrs

Percentage of patientsthat suffer of LTDS

4/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

The The BasalBasal GangliaGanglia nucleusesnucleuses�� The The BasalBasal GangliaGanglia nucleusesnucleuses

consistconsist of of severalseveral subcorticalsubcorticalstructuresstructures denselydensely interconnectedinterconnected

�� TheThe main four nucleuses are:main four nucleuses are:

�� thethe Striated (Putamen & Striated (Putamen & Caudate)Caudate)

�� the the GlobusGlobus Pallidus (GP)Pallidus (GP)

�� thethe Substantia NigraSubstantia Nigra (SN)(SN)

�� The Subthalamic nucleus (STN)The Subthalamic nucleus (STN)

�� The The Globus PallidusGlobus Pallidus consist of :consist of :

�� Internal Globus Pallidus (GPi) Internal Globus Pallidus (GPi) �� External Blobus Pallidus (GPe)External Blobus Pallidus (GPe)

�� The The SubstantiaSubstantia NigraNigra consistconsist of: of:

�� reticularreticular partpart ((SNrSNr))

�� compact compact partpart ((SNcSNc))

5/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

The “The “boxesboxes and and arrowsarrows” Model ” Model

�� The direct and The direct and indirectindirect pathspaths�� The Direct The Direct pathpath isis positive in the positive in the PutamenPutamen –– Talamo actionTalamo action�� The The IndirectIndirect pathpath isis negative “ “ “negative “ “ “

Indirect Direct

Cortex

Putamen

SNc

GPe

STN

Talamo

GPi

SNr

Indirect Direct

Cortex

Putamen

SNc

GPe

STN

Talamo

GPi

SNr

Ec D1Inib D2

Physiological activity of the B.G. nucleusesPhysiological activity of the B.G. nucleuses Pathological activity of the B.G. nucleusesPathological activity of the B.G. nucleuses

6/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

Deep Brain StimulationDeep Brain Stimulation

�� The The neurostimolatorneurostimolator isis plantedplanted completelycompletely under under skinskin; the ; the leadsleads are are plantedplanted inside inside the GPi or the STN, the GPi or the STN, onlyonly laterlater having identified the objective nucleus through MRIhaving identified the objective nucleus through MRI..

�� The The neurostimolatorneurostimolator hashas twotwo electrodeselectrodes, one , one forfor eacheach partpart of the brain of the brain �� WeWe havehave toto tunetune neurostimulatorneurostimulator parametersparameters ((VoltageVoltage toto bebe appliedapplied, , DDutyuty CycleCycle

squaresquare wavewave, , etcetc..).).�� EachEach electrodeelectrode hashas 4 terminal 4 terminal contactscontacts

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SignalsSignals AnalysisAnalysis

�� PatientsPatients ExerciseExercise ProtocolProtocol usedused� Go-no-go� Free movement

�� SpectralSpectral AnalysisAnalysis TecniquesTecniques usedused� Short Time Fourier analysis (STFT)� Power Spectral Density (PSD)

�� SynchronousSynchronous and and asyncronousasyncronousactivitiesactivities�� Inside the Inside the ββ bandband (10(10÷÷40 Hz)40 Hz)�� CloseClose the 70 Hz (the 70 Hz (onlyonly forfor the STN) the STN)

�� The The NeuronalNeuronal Gate Gate TheoryTheory in STNin STN

8/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

SignalsSignals AnalysisAnalysisThe effects of the L-Dopa on the PSD of the signal rSTN12:

9/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

SignalsSignals AnalysisAnalysis

We have verified that during a patient voluntary movement and without dose of L-Dopa, inside the β band the signal rSTN12 PSD reduces its amplitude, whiledoesn’t appear the high-frequencysynchronization (typical of the L-Dopa case).

The

mov

emen

t Effe

cts

10/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

SignalsSignals AnalysisAnalysis� Degradation of the signals in case of re-quantization of data from 12 to 8 bits:

ThisThis lastlast analysisanalysis isis usefulusefulin in orderorder toto reachreach the the aimaim of of

thisthis work, or work, or betterbetter totodesign a Data Logger design a Data Logger forfor

the the massmass--storagestorage of of neurocerebralneurocerebral signalssignals. . ItIt consistconsist of one of one ST7

microcontrollormicrocontrollor, , whichwhich isisfurnishedfurnished of a 8 of a 8 bitsbits ADC.ADC.

The final The final resultsresults of of thisthisstudystudy, , allowallow toto underlineunderline asas

the the reductionreduction of the of the quantizationquantization bitsbits doesn’doesn’t t

cause the cause the lossloss of of anyanysignalsignal intrinsicintrinsic

characteristiccharacteristic bothboth in the in the time time domaindomain and the and the frequencyfrequency domaindomain..

11/15THESIS DEGREE

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Limits of the Limits of the analyzedanalyzed recordingsrecordings

�� MeasurementsMeasurements executedexecuted withwith differentdifferent exerciseexercise protocolsprotocols

�� DifferentDifferent SignalsSignals amplificationamplification and and SamplingSampling frequecyfrequecy

�� DifferentDifferent and and boundedbounded measurementsmeasurements durationduration

((ImplementationImplementation of a DBS of a DBS signalssignals Data Logger)Data Logger)

�� Need to have DB measurements related to the Need to have DB measurements related to the mostmostvariedvaried conditionsconditions in in whichwhich the the patientpatient can can bebe duringduring hishisday. day. (Future (Future implementationimplementation of of anan adaptiveadaptive and and autonomousautonomousDBS DBS ParametersParameters Control System)Control System)

12/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

Data LoggerData Logger�� The The developmentdevelopment card card choicechoice in in orderorder toto implementimplement the Data Logger the Data Logger hashas beenbeen

the the ST7F265 Mass Storage Evaluation Kit.ST7F265 Mass Storage Evaluation Kit.

INDART-STxSTVD 7

13/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

The The recordingrecording FirmwareFirmware

main()

Media_check()

Signal_Record()

USER_application()

End

BeginThe recording routine Signal_Record()

exploits a timer interrupt routine in order totake a signal sample (1 byte) every ∆t seconds (ex. ∆t =125µs if Fs=8KHz).

This sample is saved inside one of the 512 bytes recording buffers available.

Just one of the buffers is full by means of the DTC (Data Transfer Coprocessor) unitthe buffer is downloaded inside a file wave

held in a SD-MMC memory.

14/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

The The NeurocerebralNeurocerebral signalssignals MassMass--storagestorage

SystemSystem

Circuit ofSignal

adaptation

Data Logger

ADC 8 bit

DTC

RAM

ST

7F265 M

CU

01001001

1 byte

Buffer_0

512 Byte

The data are saved inside a WAVE file held inside a SD-MMC memory.

15/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

Future Future developmentsdevelopments�� ImplementationImplementation of of anan adaptiveadaptive and and autonomousautonomous Control System Control System forfor the the

DBS DBS technicaltechnical parametersparameters..

CONTROL

16/15THESIS DEGREE

Dipartimento di Ingegneria Elettrica Elettronica e dei Sistemi - Università di Catania

ThanksThanks

�� SupervisorSupervisor of Università degli Studi di Catania, of Università degli Studi di Catania, Prof. P. ArenaProf. P. Arena

�� CoCo--SupervisorsSupervisors of of UniveristàUniveristà di Catania, Ing. D. di Catania, Ing. D. Lombardo e Ing. Lombardo e Ing. G.VagliasindiG.Vagliasindi, and of ST , and of ST Microelectronics di Catania Ing. Adriano BasileMicroelectronics di Catania Ing. Adriano Basile

�� Prof. P. Mazzone (Prof. P. Mazzone (Centro Traumatologico Centro Traumatologico OrtopedicoOrtopedico dell’Ospedale dell’Ospedale A. Alesini A. Alesini -- Roma)Roma)