Top Banner
84

Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Sep 07, 2018

Download

Documents

buidat
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical
Page 2: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Quantifying Lymphedema with

Noninvasive Methodology

• Physical Principles

• Practical Aspects

• Potential Limitations

Harvey N. Mayrovitz PhD

Professor of Physiology

College of Medical Sciences

Nova Southeastern University

[email protected]

Page 3: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Why Measure/Quantify?

• Track at-risk patients

• Early detection Early Tx

• Severity stratification

• Treatment outcomes

• Documentation aspects

• Research related

Page 4: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Pre-Surgical

Baseline

Threshold Change Detection

Therapy

Initiation

Periodic Follow-ups

Measures and Criteria

•Limb Volumes and Metrics

•Limb Bioimpedance

•Local Tissue Water

Goal: Earlier Detection and Intervention

A Rationale and Sensible Approach

Dr. HN Mayrovitz

Early Detection of Lymphedema

Page 5: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Methods Applicable to LIMBS

Limb Girth (Circumference)

• Girth Limb Volume or Sum of Girths

Limb Volume

• Water Displacement Limb Volume

Limb fluid content and its change

• Bioimpedance BIA & BIS Whole Limb

• Tissue Dielectric Constant (TDC) Local

Physical and Structural Properties

• Tonometry / Indentometry Various

• Imaging: Ultrasound - MRI - Other

Page 6: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Methods Applicable to MOST Sites

• Head

• Face

• Neck

• Breast

• Trunk

• Foot

• Toe

• etc

Forearm

Biceps

Fluid Content (TDC)Tissue Dielectric Constant

Page 7: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Methods Applicable to MOST Sites

Force

Indentation

(mm)

Physical Properties Tonometry/Identometry

0

40

80

120

160

200

240

280

320

360

400

1 2 3 4 5

F = 108 135 g

r = 0.996, p < 0.001

N = 24 legs

Fo

rce

(F

, g

)

Indentation Depth (, mm)

Healthy legs measured

10 cm proximal to the

medial malleolus

Tissue

“Hardness”

Mayrovitz HN

Lymphology

2009;42:88-98

Indent

(mm)

Measure

Force

Page 8: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

200

220

240

260

280

300

320

340

Pre-Treat Post LLLT

Fo

rce (

g)

Affected Arm

Other Arm

200

250

300

350

400

450

Pre-Treat Post LLLT

Fo

rce (

g)

Treated Leg

Other Leg

Hardness Changes with LLLT

P<0.001

P<0.001

N = 38

Data from:

Mayrovitz HN & Davey S.

Lymphology 2011;44:168-177

Force

Indentation

(mm)

Arms

Legs

N = 38

Page 9: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

200

220

240

260

280

300

320

340

Pre-Treat Post LLLT

Fo

rce (

g)

Affected Arm

Other Arm

200

250

300

350

400

450

Pre-Treat Post LLLT

Fo

rce (

g)

Treated Leg

Other Leg

P<0.001

P<0.001

N = 38

P<0.001

P<0.001

Hardness Changes with LLLT

Data from:

Mayrovitz HN & Davey S.

Lymphology 2011;44:168-177

Force

Indentation

(mm)

Arms

Legs

Page 10: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Commercial Tonometers

Force

Applied

Displacement

Determined

Pallota O. J Lymphoedema 2011;6:34-41

Page 11: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Modified from: Mellor et al. The Breast J. 2004;10:496-503

Gel

Entry

Echo

Dermis

Sub

cutis

0.93 ± 0.13

Normal Lymphedematous

Ventral Forearm US-20 MHz

1.83 ± 1.28

Methods Applicable to MOST Sites

Imaging Ultrasound MRI Other

mm

Page 12: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Metric Measures for LIMBS

Page 13: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Metric Measures for LIMBS

Tape Measure Girth at multiple points

• Measure both limbs

Inter-limb differentials and sequential changes

Mark then Measure

Segment Length

• Measure one limb

Sequential data but miss systemic changes

Page 14: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Limb Girth Volume

Manual

Geometric Model

or Algorithm

Circumferences

@ 4 – 12 cm

intervals

0.95

1

1.05

1.1

1.15

0.4 0.5 0.6 0.7 0.8 0.9 1

= ratio of smaller to larger dimension

Cir

cu

lar

to e

llip

tic

al

vo

lum

e r

ati

o (

VC

/ V

E)

circular

VC/VE =(1/4) (1+ )3 /(1+)

A

B

a

b

L

C1

C2

General FrustumCalculation

Model

<5% difference for ratios > ≈ 0.6 So OK for most Arms & Legs

BUT Not OK for Hands or Feet

Dr HN Mayrovitz

Effect of Degree of Eccentricity

V =L(A2B-a2b)

3(A-a)

Circular/EllipticalVolume Ratio

Volume Tracking

Affected Limb

Contralateral Limb

Edema Volume

V = L/3 ( A1 + A2 + (A1A2)1/2

A1

A2

Page 15: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Foot-Plate

Rail

Frame

Perometer: Girth Volume

IR d

iod

es

Mayrovitz HN et al. Advances in Wound Care 2000;113:272-276

Page 16: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

D1

IR

Diode

Array

D2

Area = KD1D2

Frame

Perometer: Basic Principle

Page 17: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Limb Girth & Volume LE Thresholds

Automated

Manual

GIRTH

If unilateral then lymphedema if

• inter-side differential > C1 cm or

if unilateral or bilateral then

• change from pre-surgery > C2 cm

VOLUME

If unilateral then lymphedema if

• inter-side differential > V1 ml or

• inter-side ratio > g

if unilateral or bilateral then

• change from pre-surgery > V2 ml

Page 18: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0

20

40

60

80

100

12 months 30 months

Lym

ph

ed

em

a R

ate

(%

)

2 cm

200 ml

10% volume

Arm Lymphedema Metric Criteria

Differences • Between sides

• or vs. baseline

Data from: Armer et al. J. Lymphoedema 2009;4:14-18

LE rate dependent on criteria used

Page 19: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Practical Aspects of Limb Girth

Page 20: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Mark in Relation To FLAT Surface

NOT along limb

Source of largeFollow-up error

Minimizing Method Error

Dr HN Mayrovitz

For Reproducibility: Mark along flat

Page 21: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

What Segment Length to Use?

Page 22: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Leg Volume Measured (ml) Volume Reduction

Segment Length Pre-Treatment Post-Treatment (ml) (%)

4 cm 6649 ± 2482* 5465 ± 1969* 1183 ± 778 17.2 ± 7.1

8 cm 6676 ± 2497 5496 ± 1990 1180 ± 782 17.1 ± 7.2

12 cm 6756 ± 2510 5554 ± 2001 1202 ± 781 17.4 ± 7.0

Segment

Length

4 cm

8 cm

12 cm

4000

5000

6000

7000

8000

Leg

Vo

lum

e (

ml)

4 cm 8 cm 12 cm

Pre-treatment Volumes

4000

5000

6000

7000

8000

Leg

Vo

lum

e (

ml)

4 cm 8 cm 12 cm

Post-treatment Volumes

Bilateral lower

extremity lymphedema

> = 10 MLD Tx

What Segment Length to Use?

N = 70

Mayrovitz et al. Physical Therapy 2007; 87: 1362-1368

Page 23: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Limb Shape as a Factor

Page 24: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

If you calculate

on the basis of

THIS

and its really more like

THIS

Then you obtain a volume

greater than the true value

Limb Shape as a Factor

Page 25: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0.0

0.2

0.4

0.6

0.8

1.0

1.2

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2

Ratio (b/a)

Vo

lum

e R

ati

o (

Ve

/Vc

)Limb Shape as a Factor

0.95

1

1.05

1.1

1.15

0.4 0.5 0.6 0.7 0.8 0.9 1

= ratio of smaller to larger dimension

Cir

cu

lar

to e

llip

tic

al

vo

lum

e r

ati

o (

VC

/ V

E)

circular

VC/VE =(1/4) (1+ )3 /(1+)

A

B

a

b

L

C1

C2

General FrustumCalculation

Model

<5% difference for ratios > ≈ 0.6 So OK for most Arms & Legs

BUT Not OK for Hands or Feet

Dr HN Mayrovitz

Effect of Degree of Eccentricity

V =L(A2B-a2b)

3(A-a)

Circular/EllipticalVolume Ratio

C1 = 31.4 cm

C2 = 28.3 cm

L =10 cm

@ b/a 0.68

6.2% volume

deviation

Data from: Mayrovitz HN, Lymphology 2003;31:140-143

Ve

Vc

Ve = 0.938 Vc

Page 26: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Limb & Limb Segment Volumes

Page 27: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Photo from: K. Johansson & E Branje Acta Oncologica 2010;49:166-173

Arm lymphoedema in a cohort of breast cancer survivors 10 years after diagnosis

LE if change in edema volume >= 5% from pre-surgery

Volumes via H2O Displacement

Mostly used

as a so called

gold standard

when comparing

other methods and

in research studies

Page 28: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0

1000

2000

3000

4000

0 1000 2000 3000 4000

Given LAV predict RAV

Line of Identity

95% +Interval

Left Arm Volume (LAV, ml by H2O)

Rig

ht

Arm

Vo

lum

e (

RA

V,

ml)

Normal Arm Volume Differentials

Data from Gebruers N et al . Clin Physiol Funct Imaging 2007; 27:17-22

Line of

Identity

95% +CI

100 RH Females

RAV > LAV (2%)

Page 29: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0

50

100

150

200

250

300

ml

0-10 10 20 20-30 30-40 ARM

Arm Segment (cm)

Dom

NoDom

Normal Arm Volume Differentials

At-risk Arm Is:

Dominant

Non-Dominant

3S

D T

hre

sh

old

s (

ml) If dominant = at-risk

Then

Greater Threshold

Data from: Dylke ES et al Lymphatic Res Biology 2012;10:182-188

N =204

Healthy

Women

Age > 40

Girths via Perometer Volumes via frustum calculation

Page 30: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Hand Volume

Page 31: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Hand Volume: H2O Displacement

Ulna head

Z

Seg Vol = kZ [Ai + Ai+1 + (Ai Ai+1)1/2]

Depth

From: Mayrovitz HN et al. Lymphology 2006;39:95-103

Metrics

Page 32: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

200

250

300

350

400

450

500

550

600

200 250 300 350 400 450 500 550 600

VM = 1.02 Vw – 12.0 ml

r=0.985, p<0.001

N=60 Hands

Algorithm vs. Water Displacement

Volume by water displacement (VW, ml)

Vo

lum

e b

y A

lgo

rith

m

(VM

, m

l)

LOA

± 9.8%

Page 33: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

200

250

300

350

400

450

500

550

with arm LE (n=20) no arm LE (n=20)

Han

d V

olu

me (

ml) Water

Perometer

Hand Volume: H2O vs. Perometer

Data from: Lee MJ et al. Lymphatic Research Biology 2011;9:13-18

Perometer values ~ 7.5%

greater than H2O values

r ~ 0.88

Page 34: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

200

250

300

350

400

450

500

550

with arm LE (n=20) no arm LE (n=20)

Han

d V

olu

me (

ml) Water

Perometer

Hand Volume: H2O vs. Perometer

Data from: Lee MJ et al. Lymphatic Research Biology 2011;9:13-18

Perometer values ~ 7.5%

greater than H2O values

r ~ 0.88

Page 35: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Figure-of-Eight: Hand volume Surrogate

Pellecchia GL J Hand Therapy 2003;16:300-304

Maihafer GC J Hand Therapy 2003;16:305-310

cm (fig-8) vs. H2O displacement (ml)

R = 0.94-0.95 but only normal hands

Tracking ability unproven

Page 36: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Foot Volume

Page 37: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Water

Displacement

Foot Volume: H2O Displacement

4

8

12 cm

0

12

L1

Y

X

A

B

C

D E F

Foot in Water Filled Volumeter

Outflow Tube

L2

Mayrovitz HN et al. Lymphology 2005;38:20-27

Page 38: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Water

DisplacementCompared to

Metric

Measures

Foot Volume: H2O Displacement

4

8

12 cm

0

12

L1

Y

X

A

B

C

D E F

Foot in Water Filled Volumeter

Outflow Tube

L2

Mayrovitz HN et al. Lymphology 2005;38:20-27

Page 39: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Algorithm vs. Water Displacement

N = 60 feet

LOA = ± 9.3%

Mayrovitz HN et al. Lymphology 2005;38:20-27

Page 40: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Water

Displacement

PRO CON

• Direct – Accurate

Limb/Hand/Foot volumes

• Especially for irregularly

shaped limbs

• Impractical for whole limbs

• Bulky equipment

• sterilization procedures

• Patient mobility

• Patient flexibility

• Open wounds

Manual Girth • Low cost

• Portable

• Easy to use

• Whole legs measureable

• Hand & Foot algorithms

• Limited ROM no issue

• Wounds are not an issue

• Multiple measurements

• Time factor

• Volumes from calculations

• Site repeatability

Optoelectronic

(Perometer)• Quick –Easy

• Small segment lengths

• Stored Measurements

• Automatic processing

• Selective processing

• Accuracy depends on

proper positioning

• Patient mobility

• Patient flexibility

• Not portable

• Space requirements

• $$$

Page 41: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Bioimpedance Analysis

• Electrical Impedance of a limb depends

on the limb’s volume and constituents

• Lymphedema increase in low resistance

fluid content of the limb

•Bioimpedance (BIOZ)

•Bioimpedance Spectroscopy (BIS)

•Bioimpedance Analysis (BIA)

•Single Frequency BIA = SFBIA

•Multi-Frequency BIA = MFBIA

Page 42: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Muscle

Bone

Skin

Fat5-10%H2O 70-75% H2O

15-20% H2O

Limb Conducting Structures

1

20

2

Conductivity

@ 5KHz

Relative to Bone

Bone

Muscle

Fat

Page 43: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Basic Operating Principle

No cells

Just salineE

I

R = E/I

Page 44: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

No cells

Just salineE

I

R = E/I

Cell

Membrane

•Polarized

•Charge Separation

•Electrical Capacitance

Basic Operating Principle

Page 45: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

No cells

Just salineE

I

~

Z = E/I

Low

Frequency

High

Frequency

Sinusoidal

Voltage

ExcitationCurrent increases

with frequency

Basic Operating Principle

Page 46: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Cell

Membrane

Cell Interior

Cm

Ri

Re

Frequency Analysis Basis

Cell Exterior

~E

I

Z = E / I

ECW

ICW

Page 47: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0.000000

0.050000

0.100000

0.150000

0.200000

0.250000

0.300000

0.400000 0.500000 0.600000 0.700000 0.800000 0.900000 1.000000 1.100000

Cole-Cole Plot: estimate parameters

increasing

frequency

ReRiRe/(Ri + Re)

Cell

Membrane

Cell Interior

Cm

Ri

Re

Cell Exterior

~E

I

Z = E / IECW

ICW

Low fHigh f

ECW + ICW ECW

MFBIA = BIS

R∞ R0

Page 48: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Current Injecting Electrodes

Voltage Measuring

Electrodes

I

Basic Operating Principle

Mayrovitz HN Clinical Physiology 1998;18:234-242

Z = E/I

E

Page 49: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Leg Volumes: Supine StandL

eg

Vo

lum

e (

ml)

Time (minutes)

Blood volume shift to lower extremities

Supine Standing Supine

-20 -10 0 10 20 30 40 50

2100

2000

1900

1800

Girth-Volume

Measurements

Page 50: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Z Depends on Frequency & Volume

Time (minutes)

|Z|

(W)

Supine Standing Supine

-20 -10 0 10 20 30 40 50

130

120

110

100

090

080

070

Z ~ (1 / volume)

Z ~ (1 / f)

5 KHz

500 KHz

Page 51: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Assessing Arm Lymphedema

Page 52: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

~

V

I

Z = V / I

Assessing Arm Lymphedema

Current

Source

Measured

Voltage

Current

Page 53: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Single Frequency BIA ECW

Page 54: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

R∞

R0

Ri

Ri

R0

R0DOM

R0NONDOM

360.1± 45.8 354.8 ± 45.9

266.5 ± 39.2 257.8 ± 39.4

1052.3 ± 276.2 966.7 ± 264.9

2.988 ± 0.653 2.781 ± 0.595

0.986 ± 0.040

Multi-Frequency BIA

Nondomnant Dominant

Data from: Ward LC et al. Lymphatic Research Biology 2011;9:47-51

172 paired arms

3SD

lymphedema

thresholds

nondom/dom

dom = at-risk

1.134

nondom = at-risk

1.106

Page 55: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

SFBIA = MFBIA for estimating ECW

York SL et al. Breast Cancer Res Treat 2009;117:177-182

Inter-Limb Z Ratios

Arm LEArm controlsLeg LE

Single Frequency Bio-impedance (BIA)

Mu

ltip

le F

req

ue

nc

y B

io-i

mp

ed

an

ce

(B

IS) 2.4

2.2

2.0

1.8

0.8 1.2 1.6 2.0 2.4

Both estimate

Re (Low f)

Page 56: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

So …. Why use MFBIA (BIS)?

ECW

ICW

• If ICW relatively unchanged even with LE then

may not have to depend on inter-arm ratios

• May be approximately true if muscle mass

does not significantly change since the largest

fraction of ICW is associated with muscle

Proposed Concept

Page 57: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0

1

2

3

4

5

6

Normal Arm At-Risk Arm

EC

W /

IC

W

Pre-Surgery

Lymphedema Dx

ECW / ICW Ratios

Data from: Cornish BH et al. Angiology 2002;53:41-47

N = 20

Page 58: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Tissue Dielectric Constant (TDC)

Relative Permittivity (er)

PRINCIPLE

Local Tissue Water Assessment

Page 59: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

H

H

O-

+ +

-

+

+Dipole

What is Dielectric Constant?

H2O Molecule Charge Separation

Page 60: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

What is Dielectric Constant?

H

H

O-

+

+

+

H

H

O-

+

+

+

+

-

+

-

Hydrogen bonding

between water

molecules

2 molecules

“Hook-up”

Page 61: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

What is Dielectric Constant?

+

-

Time varying

electric field

of force - E

Dipole movement

Displacement - D

of various types

D = e E

Dielectric

Constant

= ere0E

er = ratio e/e0 = TDC

H2O @ 32oC er = 76

Page 62: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

• Multi-Probe

• Single Probe (compact)

Measurement Devices

Page 63: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0.5 1.5 2.5 5.0 mm

Effective Measurement Depth

Signal Generation

and Processing

300 MHz

Signal

Reflected Wave yields TDC

Control Unit

10 mm 15 mm 22 mm

Effective Measurement Depths0.5 mm 1.5 mm 2.5 mm

Outer Diameters

Tissue Water via Dielectric Constant

MoistureMeter-D

• Low power 300 MHz

incident wave

• Reflected wave depends

on the tissue’s

dielectric constant

• Dielectric constant

depends on total tissue

water (free + bound)

• Pure water has a

dielectric constant of

about 78

• Calibrated for each

probe from 1 - 80

Penetration Depth (0.5 – 5 mm)

0.5 1.5 2.5 5.0 mm

TDC

readout

Multi-Probe

Page 64: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

20 mm

Display has pressure

bar indicator during

measurement

Effective

measurement

depth is

between

1.5 & 2.5 mm

Multi-Probe

Artery

Nerve

Capillary

Duct

Epidermis

Dermis

Arteriole

Hair

Pore

Fat

Hypo-Dermis

Single Probe (Compact)

Page 65: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Center

ConductorOuter

Conductor

Outer

Conductor

Electric

Field

Lines

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Ele

ctr

ic F

ield

(% o

f S

urf

ace f

ield

)

Depth (mm)

Effective Measurement Depth

2.5 mm depth probe

Tissue Water via Dielectric Constant

MoistureMeter-D

• Low power 300 MHz

incident wave

• Reflected wave depends

on the tissue’s

dielectric constant

• Dielectric constant

depends on total tissue

water (free + bound)

• Pure water has a

dielectric constant of

about 78

• Calibrated for each

probe from 1 - 80

Penetration Depth (0.5 – 5 mm)

0.5 1.5 2.5 5.0 mm

Skin

Effective Measurement Depth

Page 66: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Gel

Entry

Echo

Dermis

Sub

cutis

0.93 ± 0.13

mm

Low water

content

High water

content

Normal Lymphedematous

Ventral Forearm

Interrogation

Depth (2.5 mm)

1.83 ± 1.28

mm

5.0

mm1.5

mm

subcutis

skin

Modified from

Mellor et al.

The Breast J.

2004;10:496-503

Effective Measurement Depth

Page 67: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0

10

20

30

40

50

60

70

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75

TD

C

Calibration Example

(2.5 mm probe)

Water (%)

Y = 0.632 X – 22.1

r2 = 0.998, p < 0.001Ethanol-Water

Mixture

Probe inserted

Into Mixture

Cable to

Control

Unit

TDC dependence on H2O

Page 68: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Skin Water Distribution

Skin Depth (mm)

Skin

Wate

r C

on

ten

t (%

)

aData: Nakagawi N et al. SRT, 2010:16:137-141; Confocal Raman Spectroscopy bData: Gniadecka et al. J Invest Dermatol 1998: 110:393-398 NIR-Raman Spec

20-24 yrs

60-68 yrs

aDermis 70-75% H2O

N = 60

b70-90% Bound

0 50 100 150 200

Epidermis Dermis

Page 69: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Free and Bound Water

Protein

(1 g)

Bound H2O

(0.2 – 0.5 g)

Limited

Mobility H2O

~ 20 g

Free Mobile

Free MobileFree Mobile

Page 70: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Fluid

Protein

Blood

Vessel

Lymphatic Dysfunction

Lymph

Vessel

XBound and immobile

water not readily

measureable with

Standard BIA

Interstitium

Page 71: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Data: Idy-Peretti et al. Int J Dermatol 1998;110:782-787 Hi-Res MRI N=21

Mobile water shows intense

Dermal Water in Lymphedema

1 mm 1 mm

Contralateral Leg Lymphedema calf

40% increase

in Calf

Dermal

Water in

Lymphedema

11 primary LE

10 secondary LE

Page 72: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

TDC Features and Applications

Forearm

Biceps

Signal

Generation

and

Processing

TDC

Value

Display

Foot Dorsum

TDC measurement

Page 73: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

20

25

30

35

40

Fo

reh

ead

Ch

eek

Th

um

b

A.

Fo

rea

rm

D. F

ore

arm

Pa

lm-T

he

nar

Pa

lm-C

en

ter

D. H

an

d C

ntr

1s

t T

oe

Pla

nta

r

A.

Gait

er

1stT

oe

Do

rsu

m

M.

Ga

iter

L.

Ga

iter

D. H

an

d W

eb

D.

Fo

ot

(1-2

)

D.

Fo

ot

(4=

5)

M. M

alleo

lus

TDC @ 1.5 mmTDC Site Variability

32 females

19 - 77 years

1.5 mm Depth

Data From: Mayrovitz HN et al. Skin Research and Technology 2013;19:47–54

Page 74: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

FL

CL

ML

Ophthalmic

Maxillary

Mandibular

42.1 ± 2.942.2 ± 2.5

SUPINE

39.0 ± 5.738.5 ± 5.2

43.7 ± 4.443.8 ± 4.0

N = 30 young adult males (25.0 ± 2.5 years) @ 1.5 mm depth

TDC Site Variability

Data from: Mayrovitz HN et al. Skin Research and Technology 2012;18:504–510

Page 75: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0

10

20

30

40

50

60

35 40 45 50 55 60 65 70 75

Total Body Water (%)

Fo

rea

rm T

DC

@ 5

.0 m

m D

ep

th

N = 130 (50 females)

Age 26.1 ± 3.0 (19-39)

BMI 24.5 ± 4.0 (16-40)

Y = 0.929 X – 22.3

r = 0.740, p < 0.001

Correlation with Total Body Water

Page 76: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

20

22

24

26

28

30

32

34

36

38

40

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5

Measurement Depth , mm)

TDC = 32.44 -0.185

r2 = 0.997, p<0.001

N = 80 females

TDC Depth Dependence: Forearm

TDCPattern of Depth Dependence

May Vary by Site0.5 mm

1.5 mm

2.5 mm

5.0 mm

Compact

Page 77: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

TDC Vascular Component

Page 78: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Skin

Blo

od

Flo

w (

a.u

.)TDC Vascular Component

From: Mayrovitz HN et al.

Clinical Physiology and

Functional Imaging

2013;33:55-61

Large vascular

blood volume

& flow changes

Minor changes

in TDC values

Page 79: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0.6

1.0

1.4

1.8

2.2T

DC

in

ter-

arm

rati

o

PatientsAffected/Control

1.64 ± 0.30

N=18

Premenopausal Postmenopausal1.04 ± 0.04 1.04 ± 0.04

N=15 N=15

Mayrovitz HN Lymphology 2007;40:87-94

TDC Lymphedema Discriminations

Page 80: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

Pre-Surgery Reference TDC Ratios

Cancer Side Healthy Side

Axilla

Biceps

Forearm

1.029 ± 0.196

(1.60)

1.012 ± 0.143

(1.45)

1.003 ± 0.096

(1.30)

N =103

N=80

Thorax0.999 ± 0.119

(1.35)

(3 SD Thresholds)

Page 81: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0.900

0.950

1.000

1.050

1.100

1.150

1.200

pre-surgery 3 6 12 18 24

Th

ora

x T

DC

Ra

tio

(A

t-R

isk

/Co

ntr

ol

Sid

e)

0-3-6-12-18-24 month (N=35)

0-3-6-12-18 month (N=41)

0-3-6-9-12 month (N=47)

0-3-6 month (N=53)

0-3 month (N=60)

**

**** **

** *** * ****

Sequential TDC Ratio Changes

Lateral

Thorax

Page 82: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

0.900

0.950

1.000

1.050

1.100

1.150

1.200

pre-surgery 3 6 12 18 24

Ax

illa

TD

C R

ati

o (

At-

Ris

k/c

on

tro

l)

0-3-6-12-18-24 month (N=35)

0-3-6-12-18 month (N=41)

0-3-6-9-12 month (N=47)

0-3-6 month (N=53)

0-3 month (N=60)

* *****

*

**

** ** ***

Sequential TDC Ratio Changes

Axilla

Page 83: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical

TDC BIA/BIS (Delfin Technologies Ltd) (Impedimed Ltd) Operating principle

Frequency applied EMF 300 MHz 4 - 1000 kHz

Current flowing in the body Very Localized Much of the body

Number of electrodes / probes 1 probe 4 electrodes

Total single measurement time ~ 8 sec ~ 60 sec

Measurement Depth 0.5 – 5 mm Undefined

Measurement quantity Tissue dielectric constant Resistance

Measurement parameter Skin-to-fat tissue fluid Parameter ~ to ECF

Applicability Practically all body sites Limbs

Patient preparation

Patient position Any body position Supine

Arm-leg skin contact No effect Limbs must be abducted

Arm and hand position No restriction Palms flat on surface

Shoe and socks removal Not needed to remove Must be removed

Bladder emptying necessary No Yes

Dominant side affects No Yes

Measurement sites

Hairy skin shaving Yes (very hairy) Yes

Precautions for measurement

Patient metal contact problem No Yes

Methods Features Comparison

Page 84: Quantifying Lymphedema with Noninvasive Methodologyclinsoft.org/drmayrovitz/PRESENTATIONS-ALL/QuantifyingLymphedema... · Quantifying Lymphedema with Noninvasive Methodology •Physical