2015/2/16

Sound Medicine
Some contemporary andprospective uses of acoustics inmedicine

Overview: Acoustics
InfrasoundAudible Sound

Therapy

Imaging

Acoustic Frequency

20Hz200Hz

2kHz

20kHz

0.2MHz2MHz20MHz

Greg T Clement

Velocity: ~345 m/s in air, ~1500 m/s in water, ~1540 m/s in tissue, ~3000m/s bone

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Overview: Ultrasound
3Imaging

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Overview: UltrasoundTherapy

2Broadband

MPa

1Continuous
Wave

0-1

High peakpressure-2-3
00.5

1

1.5

2

2.5

Micro-seconds

33.5

4

High intensity

Low timeaverage power

High timeaverage power

High Frequency“Low” Frequency

Philips X7 3D Matrix Probe

2D Echocardiography
Image Courtesy Dr. A Stoylen

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I. BoneOverview: Advantages & Limits‫תהא‬Thou Shalt
beThou Shalt
Not cross

I.
II.

I.
II.

III.
IV.

Fast
Non-ionizing

III.

Cheap
SmallBoneAir

Lord Rayleigh

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I. BoneI. BoneBrain Imaging
Locations of major anatomical structures (e.g. midline falx,
mesencephalic brainstem, ventricle margins, etc.) can already be
accurately and precisely imaged , but only after craniotomy, or inpediatric cranial ultrasound (cUS) through the fontanelle.

Dussik 1942

Ongoing research aims to perform equivalent imaging through the skull.

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I. BoneI. Bone Method 1

Method 1: Mode Conversion

4000

Shear Mode Conversion

3500

0°

3000

m/s

2500
2000
1500
1000

40°

500
0longitudinal speed
shear speed
01

2

3

4

5

6

7

8

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I. Bone Method 1

I. Bone Method 1

Shear Mode Conversion

4000

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Shear Mode Conversion

3500

2822 m/s

3000m/s

2500
2000

1523 m/s

1500
1000

speed of sound in brain

500
0longitudinal speedshear speed
0123456789102822 m/s
1523 m/s
11s

J Ultrasound Med 2009 28: 191-203

Better impedance match  less reflected energy, lowered refraction
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I. Bone Method 1

I. Bone Method 1

Volunteer Study

Volunteer Study
Measurement of the the insular cortex/sylvian fissure (ICSF): US vs MRI

Human Subject Study Comparing MR and US signals over the line shown on right

J Ultrasound Med 2009 28: 191-203

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I. Bone Method 2

Method 2: Aberration Correction

Aberration Correction

Arbitrary plannedsignal

Resulting signal
after planning

Backward-projected totransducerIEEE UFFC 2012 Aug;59(8):1664-73.

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I. Bone Method 2

I. BoneFull Brain Tomography
 Diffraction tomographic approach
PhotoMethod 3: The Next step…

 Replace tomography with more generalized approach

Predicted with phase correction

Predicted, no correction

512 element ring array(1MHz, 1-3 composite with matching layer)

500+ element conformal array (here, unwired)(0.5 MHz, Random Fiber Composite)

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I. BoneMethod 3: The Next step…

Focused Ultrasound Surgery

 Full Inverse Scattering
1540
1530
1520
1510
1500

5λ

“The devise was made in the form of
a double-deck arrangement”

500+ element conformal array (here, unwired) + “generalized” tomography
G.T. Clement Inverse Problems (2014)“Four ultrasound beams could be
brought into coincidence toproduce focal point”
From: Fry et al., J Exp Med. 1956,1;104(3):337-60.

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I. Bone FUS

I. Bone FUS

A resurged interestTherapy

1991 - Magnetic Imaging Guidance and Monitoring
1990’s - High power phased arrays

1. Excellent Targeting2. On-line Temperature Monitoringand Exposure Quantification
3. On-line Tissue Effect Evaluation
4. Array Control & Correction

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I. Bone FUS

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I. Bone FUS

MR-Guided Treatment

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Original Brain array

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I. Bone FUS

I. Bone FUS

Focusing Through Bone

Clinical Brain System

Over 2000
transducer
channels
33222

1

1000-1-1-1-2-2-2y (mm)31-3-3-3-2-10
1x (mm)23No Phasing-3-3-2-10123-3

Model SP7-2-10123

Hydrophone-Phased

Clement & Hynynen, Phys Med Bio. 2002

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I. Bone FUS

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I. Bone FUS

Treatment planning

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Treatment planning

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I. Bone FUS

I. Bone FUS

Clinical trials

6

Transcranial US: Issues, solutions

5.1

Skull heating:Temperature Rise (°C)

4.2

• Distribute energy over as much skull area
as possible• Lower US frequency• Active cooling with circulated water

3.3
2.4
1.6
0.7

Focal shifting/distortion:• Model-based Phased array correction-0.2-1.1-2

Targeting, Monitoring:

Clement & Hynynen, Phys Med Bio. 2002

Initial patients:• Demonstrated focal heating through intact skull without overheating the skull• Sufficient temperatures appeared possible, but somewhat limited by available power
Ongoing:• Clinical studies for Essential Tremors, Brain Cancer, Neuropathic Pain, Parkinson’s• MRI

2 key remaining issues: Variability and “Treatment Envelope”

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I. Bone FUS

I. Bone FUS

PseudoSpectral WVFD
Pressure, 40 mm X 40 mm

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Pressure, 40 mm X 40 mm

PseudoSpectral WVFD
Forward Wave

Backward Wave

0.05

0.1

0.15

0.2

0.25
-0.05

00.05

0.1mMax Temp = 6.27 C

Temp (C)

-0.1m

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I. Bone FUS

I. Bone FUS

Early Clinical trials

Early Clinical trials

Delivery of Doxil (liposomal doxorubicin, rats)

Opening the Blood Brain Barrier• Low-power, pulsed exposures• Combined with ultrasound contrast agent(Optison, Definity)• Temporary (~hours), localized, noninvasive
Trypan blue in rat

Fluorescent image showing targeted
Doxil delivery to the rat brain

rabbitrat

Treat et al., Int J Cancer (2007)

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II. Air

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II. Airp^2/rho cAirAirTissueTissue(reflections omitted for clarity)

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II.AirII.Air

Non-Contact US

Non-Contact US

40 kHz 11-ring array
Pascals

20000-2000
00.5

1

1.5

2

milliseconds

00.5

1

1.5

2

milliseconds

Pascals

0.2
0.1
0-0.1
-0.2

Pascals

0.01
0.005
0-0.005
0.4

0.5

0.6 milliseconds

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II.Air

Non-Contact US
Finally, since phantom data is often not taken seriously some data wereacquired through a hand…One measurement turned to many….

MicrophoneDiaphragmObject1 cmTransducer

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II.AirIII. Rayleigh

Next Steps…

Demonstration at 400kHz in medical (tissue) phantom
Development of sensitive receiver
Improvement of reconstruction methodology

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III.Rayleigh

III.RayleighSub-micron detection at 40 kHz
a.

b.
1

Phase (radians)

Phase (radians)-10-20-30-40

35 mm

10-3

15-42

468-5010

Thickness (wavelengths)
1.2

1

0.2

0.4

0.6

0.8

1

Thickness (wavelengths)

Phase (radians)

Phase (radians)

c.

Mic

d.

2025303540145530

0.8
0.6

0.5

Insert5-2seconds

-50
00-1

50 mm

0532

534536538

micro seconds

540542

0.4
0.2

00

0.002 0.004 0.006 0.008

0.01

Thickness (wavelengths)

000.0002 0.0004 0.0006 0.0008 0.001

Thickness (wavelengths)

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III.Rayleigh

III.RayleighThinning layer

a.

b.

0b.

0

1.2

10

1.2

10
1.030

30

0700

600

900

800

seconds

500

microns

40

0.6
0.4

1020

1.020

0.8

0.8

40
500

0700

600

microns

20

seconds

Thinning layer

a.

900

800

200.230

0.6

“Pop”

0.4100.230040535

540

545

550555560

5650400

micro seconds

51015202530354053545

seconds

540

545

550

55556056505101520

micro seconds

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Fig. 8

III.Rayleigh

2530354045

seconds

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Fig. 7

III.RayleighNear-field Holography

NEXT STEPSInfrasoundThickness/λ = 2.4 X 10

Audible Sound

Therapy

Imaging-4

Acoustic Frequency

200Hz

2kHz

20kHz

0.2MHz

2MHz

20MHz

d/λ

20Hz

Holography

Microscopy

d/λ

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Acknowledgements
University of Electro-communications, Tokyo••T Kamakura, H Nomura, H Adachi
Center for Governmental and Industrial relations

Harvard Medical School•Focused Ultrasound Laboratory

Cleveland Clinic•

US National Institutes of Health Grants R01EB014296 &P01CA174645
More information atwww.focused-ultrasound.org

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