Narendra T. Sanghvi
THE GOLDEN ERA IN
MEDICINE
Past, Present and Future of Therapeutic
Applications of
High Intensity Focused Ultrasound
Noninvasive
[HIFU]
Minimally Invasive
Narendra T. Sanghvi
Focus Surgery, Inc. 3940 Pendleton Way, Indianapolis, IN 46226
[Indiana University School of Medicine, Indianapolis, IN 46204]
INTRODUCTION
History of HIFU
• Past Experience
Present Status
• Instrumentation & Clinical Results
Future of HIFU
Intracavitory Probes for Ultrasound
Therapeutic Applications
Invasive
Features of Advanced Medical
Technology for Noninvasive Treatment
Image Guided ---- [See What , Where & When
You Treat, i.e. Must have FeedBack]
Plan Treatment At The Patient Table
Control Energy To Create Desired Effect
No Residual Effect On Treated Organ and
Surrounding Tissues
Must be Easy To Use
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Narendra T. Sanghvi
ULTRASOUND -- ADVANTAGES
2
1 W/cm
Temperature at Focus Region
for Prostate Surgery with HIFU
2
2000 W/cm
Focal Zone
TM
Peripheral Zone
US Can do both Imaging
and Treatment
Rectal Wall
Quick Tissue Destruction
Bloodless
Precise and Accurate
HIFU Beam
Non-sterile environment
Diagnostic (Imaging) Beam
Time in Seconds
HIFU MECHANISMS
HIFU Therapy Mechanisms:
• Thermal (Coagulative Necrosis)
• Cavitation
– (w/wo Chemical Enhancer)
Basics of
High Intensity Focused Ultrasound
[HIFU]
• Mechanical (Shear / Radiation forces)
– Changes at molecular level (< 43 C)
Intracavitory Probes for Ultrasound
Therapeutic Applications
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Narendra T. Sanghvi
HIFU – Single Beam Focus Zone
Lesion Size
HIFU LESION VOLUME
CONTROLLING PARAMETERS
THERMAL LESION BY
A SHORT “ON” TIME
F n = Radius (R) / Aperture (D) < 2
ULTRASOUND FREQUENCY
TRANSDUCER F -- NUMBER
FOCAL
SPOT
D
I focus = (I0 * e -A* Tissue Depth)*GF
ABSORPTION COEFFICIENT
GF = Transducer Area / Focal Area
PEAK INTENSITY
R
Temperature Rise = I focus * T on
SYMMETRICAL LESION
GROWTH
BY HEAT CONDUCTION
ON Time & OFF Time
HIFU TRANSDUCER
Lesions In Turkey Tissue
Volume Lesions form a single lesion
HIFU Unique Features
•Tissue Ablation due to Thermal Effect
US slices (from 1 to N)
•Temperature Rise to 70-90 Degrees C
in < 4 Seconds
tumor
One US slice image
US image
•Lesions are discrete & symmetrical
line
slice
solid
Solid (section)
Ablation from
1 to US N-slice
• No damage to intervening tissue
HIFU 3D
Conformal
Treatment
One slice
ablation
Ablation for all
volume of tumor
HIFU transducer
Intracavitory Probes for Ultrasound
Therapeutic Applications
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Narendra T. Sanghvi
How & When HIFU Started
1927 Wood & Loomies: Biological Effects of
Ultrasound
1942 - Lynn et al: Proposed Focused
Ultrasound for Tissue Treatment
1945 - Fry et al: Brain Treatment
HIFU Lesions
of
Configurable
Size and
Shapes in the
Cat Brain
1940’s
Intracavitory Probes for Ultrasound
Therapeutic Applications
Prof. William J. Fry, Bioacoustic Research Laboratory, University of Illinoise, IL
First HIFU System with four transducers to produce sufficient acoustic power for the
treatment of brain disorders.
HIFU Lesions in Cat Brain with Greater Precision
and Placement Of Selected Tissue Type
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Narendra T. Sanghvi
HIFU Lesion
Brain Tumor
HIFU System Integrated with Ultrasound B-Mode Imaging, 1972
Histology of Dog’s Brain Post HIFU
Intracavitory Probes for Ultrasound
Therapeutic Applications
Ultrasound Images of a Brain
during the HIFU treatment
MRI Image of a dog’s brain post HIFU Surgery, June-1989
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Narendra T. Sanghvi
MRI Temperature maps (PRF shift)
during 10 s sonication
in rabbit thigh muscle in vivo
APPLICATIONS OF HIFU
FOR
MALIGNANT TISSUE
Temperature
Rise (oC)
32
24
16
8
0
Along the Beam Axis
Across the Focus
KH 2000
FSI TECHNOLOGY BACKGROUND
Illustration of a Prostate HIFU Probe
Based on Success of
Lithotripsy in 1984,
HIFU Project was Started in
1986 at the
Department of Urology,
Indiana University School of
Medicine
Indianapolis, IN
Significance:
Prostate Cancer
Death 31,000 per Year
Detection 198,000 per Year
(1/11 men @ age 0f 65 has a chance of developing prostate cancer)
Benign Prostatic Hyperplasia
Over 7 Millions Men suffer from BPH
(Very high probability of developing BPH above the age of 55)
Both diseases are prevalent & costly
Effect Family & Quality of Life
Intracavitory Probes for Ultrasound
Therapeutic Applications
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Narendra T. Sanghvi
Prostate Cancer
The Sonablate 500 platform
TM
HIFU Subtotal ablation of the prostate
– 83% Success Rate After Two Years
– Over 6000 Patients Treated with HIFU
– Noninvasive
– Less Complications
– Lower Cost
• High Frequency & 3D Volume Imaging
• BPH and Prostate Cancer Treatment
• Totally Digital Platform (Windows NT)
• Upgradeable Probes & Software (3D Imaging /
Treatment planning, Treatment Feedback, ...)
• Multiple Focal Depths / Transducers
• Split-Beam Technology
•Adjustable Power Level During Treatment
• REDUCED TREATMENT TIME
Canine Prostate after HIFU Treatment Bihrle and Sanghvi et al 1994
SonablateTM Probe Technology
SonablateTM 500
Transrectal HIFU Probe
A patented technology that combines both imaging
and therapy elements on a single ultrasound crystal.
• Therapy Element: 4.0 MHz, Curved Rectangular
• Imaging Element: 4.0/6.0 MHz, Curved Circular
Intracavitory Probes for Ultrasound
Therapeutic Applications
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Narendra T. Sanghvi
HIFU and Prostate Cancer
(Ablatherm device)
Command
Module
User Interface
Treatment
Module
Probe Module
Electronics
Imaging
and safeties
and Firing
RF Power
HIFU and Prostate Cancer
Technical Approach
Transrectal probe:
System
Motors
Cooling
+ Disposable
Computer
Patient Support
Endorectal Probe
Imaging mode
Firing mode
Volume treatment
by successive shots
2D and 3D Treatment Planning:
(1)WHAT REGION OF PROSTATE
SHOULD BE TREATED?
Accurate detection of the cancer region
is very difficult even using TRUS, CT
and/or MRI (endorectal coil)
Whole prostate should be ablated
Slide 15
Intracavitory Probes for Ultrasound
Therapeutic Applications
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Narendra T. Sanghvi
Prostate Cancer Treatment Procedure
HIFU and Prostate Cancer
Is there a complete necrosis of the treated
area, in human?
CASE 2 (H.M.), 79 y.o., T2aN0M 0
90 79.3
70
60
46.1
50
Negative Biopsies
40
25.5
30
2013
Jan-01
Sep-00
0.36
N ov-00
0.23
0.24
Jul-00
M ar-00
Jul-99
M ay-99
Jan-99
M ar-99
HH
0.19
0.22
M ay-00
0.11 0.11
Jan-00
0.12
0
N ov-99
5.41
1.35
10
Sep-99
CLINICAL CASES
S erum P SA (ng/ml)
80
Date
Intracavitory Probes for Ultrasound
Therapeutic Applications
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Narendra T. Sanghvi
PRE
CASE 1 (S.S), 78 y.o., T2aN0M0
90
2M
Hypoechoic
10M
78
80
S e ru m P S A (n g /m l)
70
60
50
Prostate vol.: 39.9 ml
Serum PSA : 13.0 ng/ml
40 31.2
Positive biopsy
30
PRE
15.515.3
3.82
10
5.01
2.58
2M
10M
6.95
6.53
5.18
4.46
5.5 ml
0.14 ng/ml
Negative Biopsies
12.2
20
Cavity formation
-
1.07
0.5
0.88
0.79
0.75
J a n -0 1
O c t-0 0
D e c-0 0
S e p -0 0
N o v -0 0
J u l-0 0
J u n -0 0
H2
Date
A u g -0 0
A p r-0 0
A p r-0 0
M a y -0 0
J a n -0 0
M a r-0 0
F e b -0 0
O c t-9 9
D e c-9 9
N o v -9 9
J u l-9 9
S e p -9 9
J u n -9 9
A u g -9 9
A p r-9 9
M a y -9 9
M a r-9 9
H1
M a y -9 9
F e b -9 9
J a n -9 9
0
G2+2
MRI & Endoscopy of
Prostate Post HIFU Six
Months
MRI...
Necrosis
Normal Tissue
HIFU and Prostate Cancer
European Multicenter Study
risk groups
negative biopsies
low risk (31,2 %)
T1 - T2a and PSA
10 ng/ml and Gleason
middle risk (48,2 %)
T2b or PSA 10.110.1-20 ng/ml or Gleason = 7
high risk (20,6 %)
T2c or PSA > 20 ng/ml or Gleason
Intracavitory Probes for Ultrasound
Therapeutic Applications
8
6
86,2 %
Nadir PSA 0,40 ng/ml
81,8 %
Nadir PSA 0,26 ng/ml
72,1 %
Nadir PSA 0,27 ng/ml
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Narendra T. Sanghvi
MORBIDITY
EFFICACY
HIFU
Ablatherm®
Disease free
at 5 years
47.5 - 84%
Radical
Prostatectomy
52 - 86%
External Beam
Radiation
Brachytherapy
23 - 88%
7 - 89%
HIFU
Ablatherm®
Radical
Prostatectomy
External Beam
Radiation
incontinence
4 - 9%
5 - 49%
0.7 - 23%
0 - 18%
impotence
22 - 66%
14 - 80%
11 - 67%
20 - 50%
with n. sp. - without n. sp.
with nerve sparing
short term - long-term
short term - long-term
0%
2 - 4%
14 - 63%
4 - 33%
GI
Disease free
at 1 year
Sonablate 500
75 - 97%
HIFU and Prostate Cancer
State of the Art
Reproducibility: similar results are
observed by new users
Therapeutic benefits
0.9
0.5
0.8
0.7
0.4
0.6
0.5
0.3
0.4
0.3
0.2
0.2
0.1
0
Brachytherapy
0.1
Münich
Como
6-month biopsies
0
Münich
Como
Nadir PSA
Münich: 800+ patients - Como: first 127 patients
Intracavitory Probes for Ultrasound
Therapeutic Applications
HIFU
Radiotherapy
Brachytherapy
Surgery
Non-Invasive
Y
Y
N
N
Effective
Y
Y
Y
Y
Early Feedback
Y
N
N
Y
Quality of Life
Y
N
Y
N
Repeatable
Y
N
N
N
Adaptable
Y
N
Y
N
No Th. Impasse
Y
N
N
Y
Cost Effective
Y
Y
N
Y
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Narendra T. Sanghvi
100
100
93
80
82
87
85
82
74
85
87
81
75
73
HIFU and Prostate Cancer
Conclusion
60
HIFU treatment for prostate cancer is increasingly
accepted and used by the medical community. This is a
result of a fruitful collaboration between a biomedical
company, physicists, and clinicians
52
40
38
35
29
32
20
0
Brachy 3D-CRT
XRT
CRYO
HIFU
Figure 1. Comparison of negative biopsy results of brachytherapy (Brachy), 3-dimensional conformal
radiation therapy (3D-CRT), external beam radiation therapy (XRT), cryoablation (CRYO) and HIFU.
From: John Rucastle, Ph.D. March-2004
Prostate Cancer Clinical Trials
SUMMARY
1. Total prostate should be ablated
2. No severe complications
3. Possible one night stay or outpatient clinic ?
4. Non-sterile procedure
5. HIFU can be repeated (Local recurrence after Rd, Px
and/or Ho)
Intracavitory Probes for Ultrasound
Therapeutic Applications
Under the Food and Drug Administration (FDA) Approved Protocol, Phase I clinical
studies are conducted at:
Indiana University School of Medicine, Indianapolis, IN
PI: Dr. M. O. Koch and Dr. T. A. Gardner
&
Case Western Reserve University, Cleveland, OH
PI: Dr. M. Resnick and Dr. A. Seftel
Initially, patients with prostate cancer confined within the gland (T1/T2) or who have
recurrent prostate cancer will be treated under these protocols.
For more detailed information about these studies please contact:
Focus Surgery, Inc. at 317-541-1580 or visit our web-site:
www.focus-surgery.com
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Narendra T. Sanghvi
OTHER APPLICATIONS of HIFU
Tumors --- Liver, Brain,Breast,
FUTURE PROJECTS
DEVELOPMENT OF FOCUSED ARRAY TRANSDUCERS
Pancreas, Rectum
Heart (TMR-- Trans Myocardial Revascularization)
Acoustic Hemostasis
Targeted Drug Delivery
Blood Brain Barrier
FOR PROSTAE TREATMENT
QUANTITATIVE ULTRASOUND IMAGING & THERAPY
SYSTEMS For Increased Efficacy and Safety
DEVELOP SECOND GENERATION HIFU SYSTEMS
– Utilize Chemicals with HIFU to treat Cancer tissue at
Lower Power Levels
Single Vs. Split Beam Transducer Configurations
Single and Split Focus Beams
Transducer
Geometry
Transverse Intensity Plot (Focal Plane)
[W/cm2]
[mm]
Transducer
Geometry
[mm]
Transverse Intensity Plot (Focal Plane)
[W/cm2]
Simple HIFU on Schlieren
Split Beam on Schlieren
Intracavitory Probes for Ultrasound
Therapeutic Applications
[mm]
[mm]
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Narendra T. Sanghvi
Quantitative Lesion Imaging By Relative
Attenuation Technique
Results- Continued
Temporal evolutions at the focus of the HIFU beam
Color-coded M-mode images of a HIFU-created lesion in the turkey breast tissue
(a)
100
80
60
40
ON
OFF
20
0
0
2
4
6
8
10
12
14
16
T i me (s )
Temperature
(b)
Envelope of the backscattered RF data
image
= Relative change in the attenuation coefficient
Acknowledgments
Indiana University School of Medicine,
Indianapolis, IN
Spatial profile of
along the beam axis
Macroscopic view of the HIFU-induced
lesions in the turkey breast tissue
The Extracorporeal
Treatment of Malignant
Tumors & Cancers
with HIFU
Partial Funding was provided by:
National Cancer Institute / NIH 1 R 43 CA 83244 - 01
National Cancer Institute / NIH 2 R 43 CA 83244 - 02
2002.7
National Cancer Institute / NIH 1 R 43 DK 59664 - 01
New Energy Development Organization / MITI, Tokyo, Japan
Intracavitory Probes for Ultrasound
Therapeutic Applications
CHONGQING HIFU TECHNOLOGY CO.,LTD
TAIHAN METRA CORPORATION
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