LD TECHNOLOGY SYMPOSIUM CANCUN 2008

Welcome to LD TECHNOLOGY

We are listening the body signals

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Medical devices Positioning Diagnosis /Monitoring

• GENERAL INFORMATION’S• ACCURACY

DIAGNOSIS DEFINITION*

Diagnosis is the identification, by

process of elimination, of the nature of anything.

*Wikipedia

Process of elimination in medical diagnosis

• Clinical context : signs, symptoms, history, current treatments………………..

• Specific Examinations : Medical devicesImagingIn vitro Laboratory testsIn vivo Physiological measurements

.Physician’s Knowledge and interpretation

Medical devices

• features : Provide Indicators necessary for the process of elimination for diagnosis

• A medical device do not make a diagnosis, only a Physician can make a diagnosis.

• According to the investigation site, each medical device is providing specific indicators in same or different direction.

• The cross analysis of all indicators are necessary in the process of elimination for diagnosis and interpretation and knowledge of the physician

Accuracy of the Medical devices

Depend of the Specificity and Sensitivity of the Indicators provided.

Specificity and sensitivity

Diagnosis are hypothesis

• After the process of elimination , the cross analysis of the clinical context and supplementary examinations , the physician make a hypothesis of diagnosis: because the human body is a complex of balance and all the dysfunctions or diseases have implications in all the body systems

Treatment choiceHypothesis of diagnostic

Adapted Treatment of the diagnosed diseases issues from the clinical investigations

Improvement of the clinical context

Improvement of the results of the

supplementary examinations

No Improvement of the results of the

supplementary examinations

Or Improvement or no improvement of the

clinical context

MONITORING

Validation of the diagnosis hypothesis

No validation , misdiagnosis or no

responses dues to inter individual difference

Side effect over the benefits of the

treatment

EIS SYSTEM TECHNOLOGY

• FEATURES• BACKGROUND

EIS Measurement

EIS SYSTEM Features : Impedance plethysmography

1.Measurement of the conductivity in DC* of 22 segments of the human body.

*The conductivity in DC ( way from anode (+) to cathode (-) ) is proportional with the :

I.S.F volume I.S.F Ionic concentration and in particular the Na+ concentration Blood flow Conductivity measurement accuracy +/-3.5%2. Modeling** of the Human body according to the conductivity of the 22

segments by mathematical application of the Venn diagram and the normal positioning extrapolation of the body systems.

**Accuracy of the modeling ( p<0.001) for the cerebral frontal lobes, digestive system Prostate and thyroid.

EIS Features

-150

-100

-50

0

50

100

150pat1

pat2

pat3

pat4

pat5

pat6

pat7

pat8

pat9

pat10

pat11

pat12

pat13

pat14

pat15

Sequence of the measurement of the 22 body segments

ESG graphic: conductivity of the 22 segments

ESG normal range values

EIS Features (2)

Venn diagram calculation

Maxwell equation’ s calculationModeling

CONDUCTIVITY

Min

Max

The current is carrier by the ions . The Current is sending from the Anode (+) to Cathode (-) , and therefore the Na+ ( most significant concentration of positive ions in the IF) are moving to the negative pole .

The conductivity is proportionally increased with the Na+ concentration and the volume of the interstitial fluid

1.28 V

Na+

Na+

Na+

Na+

Na+

EIS / EFFECT OF THE DC CURRENT IN INTERSTITIAL FLUID

Na+/K+ pump Na+/H+ anti porterNa+/ATP Production

Na+

Na+Na+

Na+Na+

Na+Na+ Na+

Na+

Na+H+

ATP

Interstitial fluid volume and Oxygen delivery

Effect of inter capillary distance on relation between oxygen delivery BMJ. 1998 November 14; 317(7169): 1370–1373. Copyright © 1998, British Medical

Journal

EIS MODELING PARAMETERS

• I.SF volumeRelated with the Oxygen delivery and osmotic/

hydrostatic pressure• I.SF [Na+]Related with [K+] (2/3), [H+] and ATP production. • Blood flow Related with the Blood viscosity and the Blood

velocity.

EIS –BF SYSTEM

• CLINICAL INVESTIGATIONS

• UPDATE VERSION 10

EIS- BF Clinical Investigations

Accuracy for Monitoring of the following treatment (p< 0.001) : Sp 94% No sensitivity

• Thyroid substitute treatment• Hypo tensors ( Beta blockers and CEI)• Anticoagulants• Antidepressants SSRIAccuracy in Adjunct in conventional diagnosis of

the ADHD children: (p< 0.0001) : Sp 95% / Se 78%

Visit 1 : No treatmentVisit 2: Dosage 100 µgVisit 3: Dosage 120 µgVisit 4: Dosage 150 µgVisit 5: Dosage 100 µg

Visit 1 :-40 Visit 2: -10Visit 3: 0Visit 4: +20Visit 5: -5

Visit 1Visit 2: 6Visit 3: 3Visit 4: 0Visit 5: 2

Thyroid value in EIS Modeling

TSH measured in lab tests

N=52(r=0.79, P<0.001,

and r=0.80, P<0.001, respectively).

N=52(r=0.81, P<0.001,

and r=0.73, P<0.001, respectively).

N=52(r=0.79, P<0.001, and r=0.80, P<0.001,).

N=52(r=0.79, P<0.001, and r=0.80, P<0.001,).

N=52

(r=0.79, P<0.001, and r=0.80, P<0.001,).

N=52

(r=0.79, P<0.001, and r=0.80, P<0.001,).

N=52

(r=0.79, P<0.001, and r=0.80, P<0.001,).

N=52

(r=0.79, P<0.001, and r=0.80, P<0.001,).

ADHD Children Profile

EIS BF Results Version 10

Digestive system Indicators

Brain Indicators

Cardiovascular Indicators

HORMONAL INDICATORS

RESPIRATORY INDICATORS

General metabolic indicators

Uro genital and renal indicators

Follow up of all the indicators

Medications monitoring indicators

Antidepressant (SSRI) Follow up

Before treatment Response

No response

Follow up of the Cerebral neurotransmitters

Medications monitoring indicators

Follow up of thyroid treatment

Before treatment Monitoring and results

Over doses Under doses

Medications monitoring indicators

Anti agregants and anticoagulants follow up

Before treatment Effective treatment

No effective

Medications monitoring indicators

Beta blockers follow up

Before treatment No effective treatment

Overdosis and side effects Good treatment

CEI Follow up

Before treatment Good treatment

Overdose and side effect No effective

ADHD Children profile and diagnosis in adjunct with the clinical context

Indicator of ADHD Children

Lack Dopamine and Serotonin and signs and symptoms from clinical context children less 17 y.o

EIS POSITIONING

• QUALITY SYSTEM IN MEDECINE

EIS System: May be a possibility for help the quality system requirements in medicine

Positioning of the EIS in the Quality System Requirements

Risk management

/Patient'

compliance Patient' needs

Consultation

Supplementary

examinations

Diagnostics

Treatments

Control

Corrective actions

Control

EIS SYSTEM ADHD

Why a quality system with the EIS System

• No invasive, quick, usability, Low cost• For the patient : Understanding of the treatment

and goal of the treatment• For the practitioner Early visualization of the

therapies and early possibility of corrective action• Because a disease treatment requires drug,

sometime surgery and always lifestyle change• Because , the major diseases cannot be treated by

lifestyle change or alternative medicine.

Benefits of the quality system in medicine

• For the patient: Visualization / motivation/ compliance• For the practitioner:Organization , save time Better understanding of the intended use and side

effects of the treatments usedCorrective actions that the patient can understand Referrals Income increased

NEW PRODUCTS

• WHY?

New products

• EIS• BWS: Wellness and lifestyle • ES Teck: Estimated of the ANS activity and of

cardiovascular indicators. 510k in progress Nr K083229• ES Teck Complex : Combination EIS /ES Teck• ITM Breast imaging by electro impedance.

EIS New application : BSW (Body Scan Wellness)

• Why BSW?Because There is not good or bad diet for every people,

there is good or bad diet for each personThe change of nutrition need to be monitoring

and the good nutrition for each person is not available all his life.

Based on the EIS and BC device measurement

Why the E S Teck

• Because HRV ( ANS activity estimation) Photoelectrical Plethysmograph ( Vascular

estimation)body composition and the phase Angle

measurementCan give new indicators in the process of

elimination of the physician’s diagnosis

Why the ES Teck Complex

Combination of the EIS and the ES Teck:Because :The cross analysis of the indicators issue from 4

different technologies will increase the sensitivity and therefore the accuracy of a medical device

Why the ITM

• Because • The positive predictive value of mammography for breast

cancer ranges from 20% in women under age 50.• The tissue conductivity has a high sensitivity (> 80%) for

the cancer.• The ITM as an adjunct to mammography in patients who

have equivocal mammographic findings within ACR BI-RADSTM categories 3 or 4 provides the radiologist with additional information to guide a biopsy recommendation and increase the sensitivity of the examination from 20 % to 80 % in women under age 50.

BODY SCAN WELLNESS

• New application of the EIS Technology

BWS Measurement

BSW Results

Body Composition

Nutritional and micro nutrional program Analysis

Body composition

Acid base Conductivity

Nutritional Analysis ReportAll results should be considered in the clinical context of the patient's case history, symptoms, known diagnosis, current

medications, treatment plan and therapies. This diet analysis does not replace the advice of your practitioner.The estimated body composition is made according to the James equation and the formulas from the peer reviews.

Nutritional Analysis Report (2)

Body Composition Follow up

ES TECK SYSTEM

• GENERAL INFORMATION’S

ES Teck System (Cardiology)

• HRV Photoelectrical Plethysmograph

HRV ( short time)

HRV Reference: Task Force of The European Society

of Cardiology and The North American Society of Pacing and Electrophysiology (1996)

SpO2 and Photoelectrical Plethysmograph

References:• Nichols WW, O’Rourke MF. McDonald’s : Blood Flow in Arteries:Theoretical, Experimental

and Clinical Principles. London: Arnold, 1998.• Takazawa, Kenji; Tanaka, Nobuhiro; Fujita, Masami; Matsuoka, Osamu; Saiki, Tokuyu;

Aikawa, Masaru; Tamura, Sinobu; Ibukiyama, Chiharu :Assessment of Vasoactive Agents and Vascular Aging by the Second Derivative of Photoplethysmogram Waveform Hypertension: Volume 32(2)August 1998pp 365-370

• IToshiaki OTSUKA , Tomoyuki KAWADA , Masao KATSUMATA , Chikao IBUKI , and Yoshiki KUSAMA ndependent Determinants of Second Derivative of the Finger Photoplethysmogram among Various Cardiovascular Risk Factors in Middle-Aged Men Hypertens Res Vol. 30, No. 12 (2007)

• Toshiaki Otsuka, , Tomoyuki Kawada, Masao Katsumata,Chikao Ibuki, :Utility of Second Derivative of the Finger Photoplethysmogram for the Estimation of the Risk of Coronary Heart Disease in the General Population Circ J 2006; 70: 304 – 310

• Alberto Avolio : The finger volume pulse and assessment of arterial properties .Journal of Hypertension 2002, 20:2341–2343

• Oximeter Guidelines 1998

ES Teck Measurements

Heart Rate and sinus node depolarization

Autonomic Nervous System and Heart rate variability

SpO2 AND Photoelectrical Plethysmography

SpO2 Probe

Infra red/ Red 660/905 nm

Photo diode

SpO2%

PR

Vascular waves

SpO2 ANALYSISOxygen - hemoglobin Affinity Changes.The functions of hemoglobin are oxygen pickup and delivery. The hemoglobin has an

affinity (the strength of bond between oxygen and hemoglobin) that can be increased or decreased due to various situations. If hemoglobin has an increased affinity, it is highly saturated; but oxygen is less available for release to the tissues due to the strong bond. The reverse is also true.

Vascular Wave Analysis

Analysis by Acceleration and Second derivative

Analysis of the Second derivative with age

Analysis of the second derivative and diseases : b/a

Analysis of the second derivative and diseases : d/a

Specificity and sensitivity of the b/a and d/a indicators

Specificity and sensitivity of the b/a and d/a indicators

Ref. Toshiaki OTSUKA , Tomoyuki KAWADA , Masao KATSUMATA , Chikao IBUKI , and Yoshiki KUSAMA Independent Determinants of Second Derivative of the Finger Photoplethysmogram among Various Cardiovascular Risk Factors in Middle-Aged Men Hypertens Res Vol. 30, No. 12 (2007)

Results of ES Teck

HRV STATISTICAL RESULTS

SpO2 and Photoelectrical Plethysmograph results

E.S TECK COMPLEX

• GENERAL INFORMATION’S

ES TECK COMPLEX THE NATURAL EIS UPDATE

ES Teck Complex Measurements

CROSS ANALYSIS

CrossAnalysis

• HRV module: To analyze the basic rhythms of the NN or RR intervals in electrocardiograms, both in the time domain and in the frequency domain (short time 5 minutes)

• It only provides numerical analyses of the input electrocardiogram. • Estimate of the parasympathetic and sympathetic system stimulation. • PP module: Analyze the pulse waveform by photoelectric

plethysmography and Pulse rate. • Evaluation of Large and small artery

• EIS module: • Monitoring of diseases, functional and lifestyle ‘ treatments

• Adjunct to conventional diagnosis of ADHD children• BIA module :• Calculation and Historical Tracking of body composition

E.S TECK COMPLEX INTENDED USES

Body Impedance Analysis (BIA)Measurement of the Resistance

and Reactance in Tetra polar mode with a frequency of 50

KHz

Resistance and Reactance measurements

• Resistance is a measure of how difficult it is for electricity to flow through an object.

• ReactanceMost objects have some capacitance, which is a

measure of ability to store an electrical charge. The more capacitance the object has, or the faster the current changes direction, the less the object will “react” to the current.

EIS B I A

Peer reviews formula • Total Body Water :TWB5-19 y.o Davies et al 1988 20-80 y.o Lukaski and Bolonchuk 1988 Adult obese subjects: Segal et al 1988 • Fat free fat mass:7-15 y.o Deurenberg et al 1991 16-83 y.o Deurenberg et al 1991• Extra cellular water volume : EWCSergi G, et al 1994

Phase Angle

Impedance Components

X

LX

C

R

Z Z

Z

RX

XC

L

Phase Angle

Xc = 1 / (2 * PI * F * C), C – Capacity [Farad]

Phase Angle = Arctan (Xc / R)

Clinical application in survival in colorectal cancer

The survival curves for the 2 categories of phase angle are shown.

Patients with a phase angle < 5.57 had a median survival of 8.6 mo (95% CI: 4.8, 12.4; n = 26), and those with

a phase angle > 5.57 had a median survival of 40.4 mo (95% CI: 21.9, 58.8; n = 26); this difference was

significant (P = 0.0001).

Impact of phase angle in liver cirrhosis

NEW INTERFACE

E.S TECK RESULTS

EIS ANALYSIS

HRV STATISTICAL RESULTS

HRV RECORDS

HRV GEOMETRICAL ANALYSIS

SpO2 RESULTS AND MANAGEMENT OF THE PHOTOELECTRICAL WAVE

PHOTOELECTRICAL PLETHYSMOGRAPH ANALYSIS AND RESULTS

Vascular Indicators

• PH : Relation with blood flow of small artery • EEI : Relation with LV ejection and elasticity of

large artery - LV Ejection Insufficiency• DDI : Relation with contraction and tension of

small artery - Hypertension & Arteriosclerosis• DEI : Relation with blood flow to vein system. • Etc (Estimated Cardiac Ejection time) :

260~380 Function of left ventricle

BODY COMPOSITION RESULTS

Body Composition follow up

E.S TECK COMPLEX

• CROSS ANALYSIS • MODELING AND BODY SYSTEMS’ INDICATORS

DIGESTIVE SYSTEM INDICATORS

BRAIN INDICATORS

CARDIOVASCULAR INDICATORS

HORMONAL INDICATORS

RESPIRATORY SYSTEM INDICATORS

GENERAL METABOLIC INDICATORS

UROGENITAL AND RENAL INDICATORS

Follow up of all the indicators

Follow up of the Cerebral neurotransmitters

Medications monitoring indicators

Medications monitoring indicators

Medications monitoring indicators

Medications monitoring indicators

ADHD Children profile and diagnosis in adjunct with the clinical context

Chiropractor Indicators and monitoring treatment

Advices for Lifestyle and exercises and monitoring

Advices for Lifestyle and exercises and monitoring

Advices for Lifestyle and exercises and monitoring

Exercises

Sport men condition Evaluation and improvement

Statistical risk analysis

• No access before 5 measurements. The accuracy increased with the number of measurements.

• Statistical analysis of the indicators of each body systems and metabolic general indicators

• It is not a diagnosis , but help for the physician in the process of elimination

I.T.M Impedance Tomography

Mammography

• GENERAL INFORMATION’S

ITM ADJUNCT TO THE MAMMOGRAPHY

• BI-RADS

MAMOGRAPHY IMAGES AND MRI IMAGES

MAMMOGRAPHY AND ITM IMAGES

Mammography accuracy

• specificity from 90% to 95%• The positive predictive value of mammography for

breast cancer ranges from 20% in women under age 50 to 60% to 80% in women age 50-69. Randomized clinical trials (RCTs) have demonstrated a 30% reduction in breast cancer mortality in women 50-69 years who are screened annually or biennially with mammograms. (4) The data on women under age 50 are less clear.

Breast Cancer tissue and conductivity

• The studies of T-Scan and ITM devices are demonstrated the evidence between the breast cancer tissue and the increased of conductivity. The sensitivity is > at 80 %

MRI and Ultrasound

• The specificity of these techniques are inferior to the mammography and do not increased the sensitivity of the screening

ITM in adjunct to the Mammography

• Increase the sensitivity of the breast cancer diagnosis from 20% to 80% for the women under 50 y.o and therefore reduce the number of no necessary biopsies

Intended Uses• In Gynecology:The ITM is intended for use as: Early detection of mastopathy and monitoring of the mastopathy treatment. Estimated the lactation function for the pregnant women• In Oncology: The ITM is intended for use as an adjunct to mammography in patients who have

equivocal mammographic findings within ACR BI-RADSTM categories 3 or 4. This device provides the radiologist with additional information to guide a biopsy

recommendation.The device is intended for use on women age > 20 years old and increase the

sensitivity of the diagnosis of breast cancer in particular for the women under 50 y.o

The system will be use by licensed practitioner and the interpretation will be made by radiologists who have satisfactorily completed the training phase of the ITM system.

Contra Indications

•None known to date•No Invasive and Safe•No Compressive

The ITM Device

ITM Data acquisition sequence

Last electrodefor measuring?

Last electrodefor injecting?

Connect first matrix electrode to voltmeter

Connect first matrix electrode to current source

Inject current andmake measurement

Connect next matrixelectrode to current source

End of measurements

Connect next matrixelectrode to voltmeter

No

No

Yes

YesResult is 65536 pulsesIn 22 seconds

ReconstructionDevice Slice 1 . . . Slice n

Electrical impedance tomography with planar array enables imaging of three-dimensional distribution of electrical conductivity in subsurface areas (~ 5-cm depth) using flat matrix of 256 electrodes. For the convenience of viewing, the results are represented as the set of

I

E

ReR

P(x,y,z)

Lx y

z

i iyxL

rmr

iyxL

dllElElElWdllW

zWzyxP),,(

2

),,(

2

1 )())()()(()(

1)(1),,(

222242 )()(1/1 zyyxxRW ll

mE

rE- measured electric intensity

- reference electric intensity

ITM Calculation of the electric field intensity

: electrodes: grid, where Ex is defined

mE

1yE 2yE

2xE

4xE

1V 2V

3V 4V

: grid, where Ey is defined

x1

y2

,341 VVEx ,452 VVEx

,141 VVEy ,252 VVEy

,)1(

)1()1)(1(

411311

211111

xx

xxmx

EyxEyx

EyxEyxE

1. Finite-difference approximation on staggered grids:

2. Two-dimensional linear interpolation of each component:

3yE 4yE

1xE

3xE

5V

6V 7V 8V,673 VVEx ,784 VVEx

,473 VVEy .584 VVEy

.)1(

)1()1)(1(

422322

222122

yy

yymy

EyxEyx

EyxEyxE

,5.021 xx 5.012 yy

2211 ,,, yxyx position inside corresponding grid cell

1

The T-Scan 2000 First application of the Impedance Mammography

The T-Scan™ 2000 is an electrical impedance scanning device that received approval for marketing from the U.S. Food and Drug Administration (FDA) in 1999, with the following labeled indication: "The T-Scan™ 2000 is intended for use as an adjunct to mammography in patients who have equivocal mammographic finding with ACR Bi-RADS™ categories 3 or 4…”

Electrical impedance studies are used as an adjunct to mammography to improve patient selection for biopsy in patients with equivocal indications..

Image quality is rigidly limited in T-Scan by the physics of the current flow. The collected data set is poor and no data processing is applicable.In ITM system there are no hard limitations of image quality. The number of electrodes, accuracy of measurements and complexity of reconstruction algorithm are limiting factors. The collected data set is full for given geometry of electrodes.

~V

A A AAAA

T-Scan measurements

~I

V V V V V

ITM measurements

0

ITM Versus T-Scan 2000

ITM Versus T-Scan 2000

8 images for each breast and only 2 depth slides. 42 electrodes and 2 frequencies

1 image for each breast and 7 depth slides . 256 electrodes and 7 frequencies

IMAGES’ PRESENTATION

BREAST NORMAL RANGE OF CONDUCTIVITY

ITM Clinical investigation protocol performed in accordance with trial protocol approved by the Western Institutional

Review Board (WIRB) in Olympia, Washington

Specificity = Mammography + ITM diagnosis is malignant | Biopsy is malignant) = 13/14 = 0.926Specificity = only Radiology diagnosis is malignant | Biopsy is malignant) = 13/14 = 0.926Note that the specificity for malignant biopsy (cancer) is the same for both Mammography + ITM and diagnostic only radiology.

Sensitivity Mammography + ITM diagnosis is benign | Biopsy is benign) = 17/26 = 0.654 Similarly, the conditional probability that defines specificity for diagnostic radiology is as follows: Sensitivity only Radiology diagnosis is benign | Biopsy is benign) = 3/26 = 0.115

CLINICAL CASES

FIBRO ADENOMA

FIBRO ADENOMA CONDUCTIVITY

Mastopathy : Multiple cysts of the left and the right breasts

Multiple cysts of the left and the rights breasts

Left Breast Cancer

Left Breast Cancer : Conductivity analysis

TECHNICAL SUPPORT

Remote Technical Support Assistance

Remote Technical Support Assistance

Installation problemsN Description or message Solution

1 Windows can’t find USB device Driver

Read User’s manual and install driver’s according to instruction step by step,Call Technical Support Assistance

Software problemsN Description or message Solution1 GDI Error Reinstall EIS software2 Visual C++ Runtime error… on

3D imageInstall new Graphic Driver

3 Version Open GL less then 1.2 Install new Graphic Driver4 EIS Software works very slowly Switch computer’s Power

Option to High Performance5 Login or Password is incorrect Call Technical Support

Assistance6 Software requires a new PIN

codeCall Technical Support Assistance

7 Right or Left Electrode is not connected during scan process ..

See Hardware Problems

Hardware problemsN Description or message Solution1 Device is disconnected … Check Driver’s installation in Device

Manager, Reconnect USB cable, restart the computer

2 Channels Test or Power Test is not OK 1. Disconnect the cables for electrodes from device, make the test again

3 Channels Test or Power Test is not OK 2. Check the device is connected directly to USB port and there are not any USB HUBs

4 Channels Test or Power Test is not OK 3.Call Technical Support Assistance5 Right or Left Electrode is disconnected during

scan and some volumes are very low (-100)1.Check and remove film protection from electrode’s surface

6 Right or Left Electrode is disconnected during scan and some volumes are very low (-100)

2. Make cable’s test, Connection Wizard Test, Disconnect all cables and connect again

7 Right or Left Electrode is disconnected during scan and some volumes are very low (-100)

3.Call Technical Support Assistance

NETWORK

Contract of MaintenanceFree the first year

And then US$ 500 / Year If no maintenance contract :

Update price : US$ 400Each technical support intervention: US$ 80

BILLING SYSTEM

BILLING SYSTEM NETWORK