Therapeutic UltrasoundTherapeutic Ultrasound

Setting the Stage for Evidence Setting the Stage for Evidence Based Clinical TrialsBased Clinical Trials

Johns LD, Straub SJ, *Johns LD, Straub SJ, *LeDetLeDet EG, * Howard S and Zaino A:EG, * Howard S and Zaino A:Quinnipiac University, Hamden Connecticut and Quinnipiac University, Hamden Connecticut and

OndaOnda Corporation*, Sunnyvale, California.Corporation*, Sunnyvale, California.

Funded by Quinnipiac University, EATA & NATAFunded by Quinnipiac University, EATA & NATA--REFREF

Clinical Indications: Inferential

MethodsMethods ResultsResultsCell Biology Studies: Cell Biology Studies: Strong SupportStrong Support

Clinical Trials: Clinical Trials: InconclusiveInconclusive

Tissue Heating:Tissue Heating: Conclusive ‘BUT’Conclusive ‘BUT’VariableVariable

Clinical VariabilityClinical VariabilityHuman Human ––vsvs-- TechnologyTechnology

TechniqueTechnique–– Treatment Area, Coupling MediumTreatment Area, Coupling Medium

Differences between manufacturersDifferences between manufacturers–– Ultrasound field producedUltrasound field produced–– BNR, ERA, crystals, Technology, etcBNR, ERA, crystals, Technology, etc–– Calibrations Calibrations ++ 1515--20 % of baseline20 % of baseline

3030--40% difference between heads40% difference between heads

Or….more fundamental issues?Or….more fundamental issues?

Clinical AssumptionClinical Assumption

Equality Between:Equality Between:1.1. ManufacturersManufacturers2.2. Various Heads within a ManufacturerVarious Heads within a Manufacturer

BNR and ERA are PredictiveBNR and ERA are Predictive

TrueTrue or or FalseFalse

0.633.8 oC1.6 cm61.5<6.0` Dynatron

0.623.7 oC1.6 cm61.5<4.0` Excel

1.006.0 oC1.6 cm61.53.9` Omnisound

0.393.9 oC1.2 cm101.02.3" Forte

0.585.8 oC1.2 cm101.03.7" Omnisound

oC/minTempDepthMinW/cm2BNR

“Holcomb etal 2003, JAT 38(1):24-27. 49% difference in heating rate` Merrick etal 2003, JOSPT 33:379-385. 59 & 61% difference in heating rate

Variability Between ManufacturersVariability Between Manufacturers

3 MHz3 MHz N=1 HeadN=1 Head

Variability Between Heads???Variability Between Heads???

^ Draper, etal. JOSPT. 21(3) 1995, page 153-157

~ Rose,etal., JAT, 31(2) 1996, pages 139-143

Difference Difference in heating in heating raterate

39%39%1 MHz1 MHz

0.393.9 oC5.0 cm10.01.52.2^Omnisound

0.283.5 oC5.0 cm12.31.51.8~Omnisound

oC/minTempDepthMinW/cm2BNR

Clinical AssumptionClinical Assumption

Equality Between:Equality Between:1.1. ManufacturersManufacturers2.2. Various Heads within a ManufacturerVarious Heads within a Manufacturer

BNR and ERA are PredictiveBNR and ERA are Predictive

Appear to be FalseAppear to be False

2 Possible Factors Leading to Variability in 2 Possible Factors Leading to Variability in Clinical OutcomClinical Outcomes

1) Determination of SAI1) Determination of SAI W/cmW/cm22

–– Total PowerTotal PowerDisplay of total power Display of total power ––vsvs-- actual total power producedactual total power producedSAI variability (SAI variability (++ 20%) 20%)

–– ERA ERA group means in the software to determine SAIgroup means in the software to determine SAISAI variability (SAI variability (++ 2020--25%) 25%)

2) Distribution of acoustical amplitudes2) Distribution of acoustical amplitudes–– Variability in tissue heatingVariability in tissue heating

Range of Potential SAI Values Range of Potential SAI Values While Staying Within Manufacturer LimitsWhile Staying Within Manufacturer Limits

1.42.00*1.671.333.00.750.751.501.25*1.004.00.51.201.000.80*5.0

Rate6.05.04.0ERA cm2

*HeatingWatts + 20%

Digital indicator on machines reads 1.25 W/cm2

3 MHz Heating Rate oC/min in muscle (based upon Draper)150% difference between high and low SAI

Field Testing of Clinical UnitsField Testing of Clinical Units44% Failed Calibration or Electrical Safety (N=45) 44% Failed Calibration or Electrical Safety (N=45)

Daniel & Rupert, Daniel & Rupert, J.Man.Phys.TherJ.Man.Phys.Ther 26(3):17126(3):171--175, 2003175, 2003

39% Failed Calibration Standard (N=32)39% Failed Calibration Standard (N=32)ArthoArtho, , etaletal, Physical Therapy82(3):257, Physical Therapy82(3):257--263, 2002263, 2002

69% Failed Calibration Standard (N=85)69% Failed Calibration Standard (N=85)PyePye & Milford, Ultrasound, Med Biol. 23:347& Milford, Ultrasound, Med Biol. 23:347--359, 1994359, 1994

56% Failed Calibration Standard (N=43)56% Failed Calibration Standard (N=43)Lloyd & Evans, Physiotherapy, 74:56Lloyd & Evans, Physiotherapy, 74:56--61, 198861, 1988

81% Failed Calibration Standard (N=26)81% Failed Calibration Standard (N=26)Snow, Physiotherapy Canada, 34:185Snow, Physiotherapy Canada, 34:185--189, 1982189, 1982

85% Failed Calibration Standard (N=58)85% Failed Calibration Standard (N=58)Stewart, Stewart, etaletal, Phys , Phys TherTher, 54:707, 54:707--715, 1974715, 1974

Clinical AssumptionClinical Assumption

New transducers are more accurate?New transducers are more accurate?

Buy new transducers and testBuy new transducers and test

Experimental DesignExperimental DesignChattanoogaChattanooga IntellectIntellectModel #Model # 7804778047Frequency:Frequency: 1 & 3 MHz1 & 3 MHzHead size: Head size: 5 cm5 cm22

N=N= 7 Heads7 Heads

Manufacturer ReportedManufacturer Reported–– BNR:BNR: 4:1 Max4:1 Max–– ERA:ERA: 4.0 cm4.0 cm22

Independent Analysis ofIndependent Analysis ofUltrasound Transducers at 1.0 MHzUltrasound Transducers at 1.0 MHz

4.18 + 1.141.3 + 0.105.30 + 0.234.03 + 0.27Mean

5.851.45.43.8537954

4.481.35.54.3437953

5.091.25.04.1337952

4.511.35.14.0435986

2.871.25.44.3835664

2.791.45.63.8835663

3.651.45.13.6235661

Planar BNRSAI in W/cm2Watts ERA in cm2Transducer

Manufacturer reported ERA 4.00 + 1.0Watts calibrated to 5.0 + 0.75 or 15%SAI, digital indicator on machines reads 1.2 W/cm2

0.83 + 0.06^4.42 + 0.205.35 + 0.285.00 + 1.00Dynatronics

0.99 + 0.164.95 + 0.385.03 + 0.584.45 + 0.67Omnisound

1.09 + 0.134.28 + 0.433.97 + 0.254.00 + 1.00Chattanooga

1.12 + 0.155.14 + 0.234.61 + 0.495.00 + 0.75Xltek

1.19 + 0.074.57 + 0.233.83 + 0.215.00 + 1.00Rich-Mar

1.36 + 0.111.26 + 0.44

5.45 + 0.203.97 + 0.41

4.01 + 0.343.16 + 0.66

5.00 + 1.004.00 + 1.00

MettlerChatt.New

MeasuredMeasuredMeasuredReported

SAITotal PowerERAERA1 MHz

DynatronicsDynatronics ERA was larger than all others (ERA was larger than all others (PP<0.05)<0.05)XltekXltek and and OmnisoundOmnisound ERA was larger than ERA was larger than MettlerMettler, Chattanooga and Rich, Chattanooga and Rich--Mar (Mar (PP<0.05)<0.05)Overall ERA at 1MHz was smaller than at 3MHz (Overall ERA at 1MHz was smaller than at 3MHz (PP<0.005)<0.005)

ERA in cm2, Total Power in Watts and SAI in W/cm2

*SAI when the ultrasound generator reads 1.0 Watts/cm2

Transducer Profiling of ERA and Generation of Watts at 1 MHz

0.83 + 0.06^4.42 + 0.205.35 + 0.285.00 + 1.00Dynatronics

0.99 + 0.164.95 + 0.385.03 + 0.584.45 + 0.67Omnisound

1.09 + 0.134.28 + 0.433.97 + 0.254.00 + 1.00Chattanooga

1.12 + 0.155.14 + 0.234.61 + 0.495.00 + 0.75Xltek

1.19 + 0.074.57 + 0.233.83 + 0.215.00 + 1.00Rich-Mar

1.36 + 0.111.26 + 0.44

5.45 + 0.203.97 + 0.41

4.01 + 0.343.16 + 0.66

5.00 + 1.004.00 + 1.00

MettlerChatt.New

MeasuredMeasuredMeasuredReported

SAITotal PowerERAERA1 MHz

**MettlerMettler SAI was higher than all others (SAI was higher than all others (PP<0.05) <0.05) ^̂DynatronicsDynatronics SAI was lower than all others (SAI was lower than all others (PP<0.05). <0.05). SAI range across all 66 transducers at 1 MHz was SAI range across all 66 transducers at 1 MHz was 0.76 to 1.560.76 to 1.56

ERA in cm2, Total Power in Watts and SAI in W/cm2

*SAI when the ultrasound generator reads 1.0 Watts/cm2

Transducer Profiling of ERA and Generation of Watts at 1 MHz

% Difference in Mean SAI: 1 MHz% Difference in Mean SAI: 1 MHz

0%0.83Dynatronics

19%0%0.99Omnisound

31%10%0%1.09Chattanooga

35%13%3%0%1.12Xltek

43%20%9%6%0%1.19Richmar

64%37%25%21%14%0%1.36Mettler

0.830.991.091.121.191.36

DynatronicsOmnisoundChattanoogaXltekRichmarMettler

SAI = W/cm2SAI = W/cm2

%Difference Between High and Low SAI, 1 MHz

SAI = W/cm2SAI = W/cm2

24%7%9%-3%-14%-20%0.94Dynatronics

50%30%33%18%5%-3%1.14Omnisound

71%48%51%34%19%11%1.30Chattanooga

86%60%64%45%29%21%1.41XlTeck

71%48%51%34%19%11%1.30Rich-Mar

105%77%81%61%43%33%1.56Mettler

0.760.880.860.971.091.17

DynatronicsOmnisoundChattanoogaXlTekRich-MarMettler

Independent Analysis of Ultrasound Independent Analysis of Ultrasound Transducers at 3.3 MHzTransducers at 3.3 MHz

3.42 + 0.731.3 + 0.165.4 + 0.444.22 + 0.35Mean

2.851.24.83.9137954

3.131.35.74.3437953

3.041.35.74.4437952

4.561.55.63.7435986

4.061.45.64.0435664

2.511.35.64.3135663

3.811.04.74.7635661

Planar BNRSAI in W/cm2Watts ERA in cm2Transducer

Manufacturer reported ERA 4.00 + 1.0 SAI of 1.0 = 0.6 oC/min >> 6.6 min >> 55%Watts calibrated to 5.0 + 0.75 or 15% SAI of 1.5 = 1.0 oC/min >> 4.0 minSAI, digital indicator on machines reads 1.2 W/cm2

Transducer Profiling of ERA and Transducer Profiling of ERA and Generation of Watts at 3 MHzGeneration of Watts at 3 MHz

0.81 + 0.063.94 + 0.294.64 + 0.444.00 + 1.00Chattanooga0.93 + 0.045.16 + 0.225.56 + 0.155.00 + 0.75Xltek

0.97 + 0.075.49 + 0.195.64 + 0.305.00 + 1.00Mettler

1.02 + 0.094.95 + 0.414.56 + 0.624.46 + 0.39Omnisound

1.04 + 0.074.72 + 0.204.55 + 0.335.00 + 1.00Rich-Mar

1.08 + 0.241.06 + 0.10

4.09 + 0.365.11 + 0.44

3.79 + 0.724.83 + 0.11

4.00 + 1.005.00 + 1.00

Chatt.NewDynatronics

MeasuredMeasuredMeasuredReported

*SAITotal PowerERAERA3 MHz

MettlerMettler and and XltekXltek ERA, were larger than ERA, were larger than Chattanooga, Chattanooga, DynatronicsDynatronics, , OmnisoundOmnisound and Richand Rich--Mar Mar ((PP<0.001) <0.001)

ERA in cm2, Total Power in Watts and SAI in W/cm2

*SAI when the ultrasound generator reads 1.0 Watts/cm2

Transducer Profiling of ERA and Transducer Profiling of ERA and Generation of Watts at 3 MHzGeneration of Watts at 3 MHz

0.81 + 0.063.94 + 0.294.64 + 0.444.00 + 1.00Chattanooga0.93 + 0.045.16 + 0.225.56 + 0.155.00 + 0.75Xltek

0.97 + 0.075.49 + 0.195.64 + 0.305.00 + 1.00Mettler

1.02 + 0.094.95 + 0.414.56 + 0.624.46 + 0.39Omnisound

1.04 + 0.074.72 + 0.204.55 + 0.335.00 + 1.00Rich-Mar

1.08 + 0.241.06 + 0.10

4.09 + 0.365.11 + 0.44

3.79 + 0.724.83 + 0.11

4.00 + 1.005.00 + 1.00

Chatt.NewDynatronics

MeasuredMeasuredMeasuredReported

*SAITotal PowerERAERA3 MHz

SAI of Chattanooga was lower than all otherSAI of Chattanooga was lower than all otherSAI range across all 77 transducers at 3 MHz was SAI range across all 77 transducers at 3 MHz was 0.69 to 1.68

ERA in cm2, Total Power in Watts and SAI in W/cm2

*SAI when the ultrasound generator reads 1.0 Watts/cm2

% Difference in Mean SAI: 3 MHz% Difference in Mean SAI: 3 MHz

SAI = W/cmSAI = W/cm22

0%0.81Chattanooga

15%0%0.93Xltek

20%4%0%0.97Mettler

26%10%5%0%1.02Omnisound

28%12%7%2%0%1.04Rich-Mar

31%14%9%4%2%0%1.06Dynatronics

0.810.930.971.021.041.06

ChattanoogaXltekMettlerOmnisoundRich-MarDynatronics

%Difference Between %Difference Between High and Low SAI, 3 MHzHigh and Low SAI, 3 MHz

Comparative analysis depends on which ultrasound heads we comparComparative analysis depends on which ultrasound heads we compareeSAI = W/cmSAI = W/cm22

29%1%3%0%-6%1%0.89Chattanooga48%16%19%15%7%16%1.02Xltek58%24%27%22%15%24%1.09Mettler68%32%35%30%22%32%1.16Omnisound68%32%35%30%22%32%1.16Rich-Mar72%35%38%34%25%35%1.19Dynatronics0.690.880.860.890.950.88

ChattanoogaXltekMettlerOmnisoundRich-MarDynatronics

ConclusionsConclusions

Significant variability in SAI existsSignificant variability in SAI exists–– Within manufacturerWithin manufacturer–– Between manufacturersBetween manufacturers

Two factors contribute to wide variabilityTwo factors contribute to wide variability–– Utilization of Group mean ERA in the calculation of Utilization of Group mean ERA in the calculation of

SAISAI–– ++ 20% power calibrations20% power calibrations

RecommendationsRecommendationsERA should be reported ERA should be reported –– Transducer specificTransducer specific–– Frequency specificFrequency specific

Improved accuracy of power measurementImproved accuracy of power measurement–– Incorporation into SAI calculationsIncorporation into SAI calculations

Incorporation of these finding by manufacturers Incorporation of these finding by manufacturers and clinicians may increase consistency in and clinicians may increase consistency in applied treatmentsapplied treatments

2 Possible Factors Leading to Variability in 2 Possible Factors Leading to Variability in Clinical OutcomClinical Outcomes

1) Determination of SAI1) Determination of SAI W/cmW/cm22

–– Total PowerTotal PowerDisplay of total power Display of total power ––vsvs-- actual total power producedactual total power producedSAI variability (SAI variability (++ 20%) 20%)

–– ERA ERA group means in the software to determine SAIgroup means in the software to determine SAISAI variability (SAI variability (++ 2020--25%) 25%)

2) Distribution of acoustical amplitudes2) Distribution of acoustical amplitudes–– Variability in tissue heatingVariability in tissue heating

Primary ObjectivePrimary Objective

1.1. Develop Novel Method Develop Novel Method WHOLE FIELD characterizationWHOLE FIELD characterizationNot dependent on BNR and ERANot dependent on BNR and ERA

2.2. Establish a General Beam Profile of a Establish a General Beam Profile of a Single ManufacturerSingle Manufacturer

SchlierenSchlieren ImageImage

Describes the interaction of light and soundDescribes the interaction of light and sound

–– Optical index of refractionOptical index of refraction

–– Shows field variationsShows field variations

High Intensity Focused High Intensity Focused UltrasoundUltrasound

Experimental Set up forExperimental Set up forSchlierenSchlieren MeasurementsMeasurements

0.00

0.40

0.80

1.20

1.60

2.00

1 cm 2 cm 3 cm 4 cm 5 cm 6 cm 7 cm

Distance from Transducer

Bea

m W

idth

in c

m 80%40%

SchlierenSchlieren Image andImage andData AnalysisData Analysis

3 MHz: General Images3 MHz: General Images

UL – Chattanooga & RichmarUR – Dynatronics, Mettler & XltekLL - Omnisound

1 MHz: General Images1 MHz: General Images

UL – DynatronicsUR – Xltek, Rich-Mar, Omnisound, ChattanoogaLL - Mettler

1 MHz Images1 MHz Images

3 MHz Images3 MHz Images

Take Home MessageTake Home Message

Utilized a Novel Method for Therapeutic Ultrasound Whole Utilized a Novel Method for Therapeutic Ultrasound Whole Field CharacterizationField Characterization

ERA & BNR are a component of beam profilingERA & BNR are a component of beam profilingBut appear to be insufficientBut appear to be insufficient

Demonstrated variability within manufacturerDemonstrated variability within manufacturer–– Variability between heads (3 profiles)Variability between heads (3 profiles)

3.3 MHz is significantly wider than 1.0 MHz3.3 MHz is significantly wider than 1.0 MHz–– Clinical effects of this are unknownClinical effects of this are unknown

LimitationsLimitations–– Beams in waterBeams in water–– Effects of Tissue on profileEffects of Tissue on profile

Refraction & ReflectionRefraction & ReflectionPreliminary studies underway Preliminary studies underway

Therapeutic UltrasoundTherapeutic Ultrasound

Setting the Stage for Evidence Setting the Stage for Evidence Based Clinical TrialsBased Clinical Trials

Johns LD, Straub SJ, *Johns LD, Straub SJ, *LeDetLeDet EG, * Howard S and Zaino A:EG, * Howard S and Zaino A:Quinnipiac University, Hamden Connecticut and Quinnipiac University, Hamden Connecticut and

OndaOnda Corporation*, Sunnyvale, California.Corporation*, Sunnyvale, California.

Funded by Quinnipiac University, EATA & NATAFunded by Quinnipiac University, EATA & NATA--REFREF