Past, Present and Future of Therapeutic THE GOLDEN ERA IN ...Applications of High Intensity Focused...
Transcript of Past, Present and Future of Therapeutic THE GOLDEN ERA IN ...Applications of High Intensity Focused...
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 1
Past, Present and Future of Therapeutic
Applications of
High Intensity Focused Ultrasound
[HIFU]
Narendra T. Sanghvi
Focus Surgery, Inc. 3940 Pendleton Way, Indianapolis, IN 46226[Indiana University School of Medicine, Indianapolis, IN 46204]
THE GOLDEN ERA IN MEDICINE
InvasiveInvasive
Minimally InvasiveMinimally Invasive
NoninvasiveNoninvasive
INTRODUCTION
� History of HIFU• Past Experience
� Present Status • Instrumentation & Clinical Results
� Future of HIFU
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
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 2
1 W/cm2 2000 W/cm2
HIFU Beam
TM
ULTRASOUND ULTRASOUND ---- ADVANTAGESADVANTAGES
� US Can do both Imaging and Treatment
� Quick Tissue Destruction
� Bloodless� Precise and Accurate
� Non-sterile environment
Diagnostic (Imaging) Beam
Temperature at Focus Regionfor Prostate Surgery with HIFU
Focal Zone
Rectal Wall
Peripheral Zone
Time in Seconds
HIFU MECHANISMSHIFU MECHANISMS
� HIFU Therapy Mechanisms:
• Thermal (Coagulative Necrosis)
• Cavitation – (w/wo Chemical Enhancer)
• Mechanical (Shear / Radiation forces)– Changes at molecular level (< 43 C)
Basics ofHigh Intensity Focused Ultrasound
[HIFU]
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 3
HIFU LESION VOLUME CONTROLLING PARAMETERS
� ULTRASOUND FREQUENCY
� TRANSDUCER F -- NUMBER
� ABSORPTION COEFFICIENT
� PEAK INTENSITY
� ON Time & OFF Time
HIFU – Single Beam Focus ZoneLesion Size
HIFU TRANSDUCER
THERMAL LESION BY A SHORT “ON” TIME
SYMMETRICAL LESION GROWTH
BY HEAT CONDUCTION
FOCALSPOT
F n= Radius (R) / Aperture (D) < 2
D
R Temperature Rise = I focus * T on
I focus = (I0 * e -A* Tissue Depth)*GF
GF = Transducer Area / Focal Area
•Tissue Ablation due to Thermal Effect
•Temperature Rise to 70-90 Degrees Cin < 4 Seconds
•Lesions are discrete & symmetrical
• No damage to intervening tissue
HIFU Unique FeaturesLesions In Turkey Tissue
US imagetumor
US slices (from 1 to N) One US slice image
HIFU transducer
One sliceablation
Ablation from 1 to US N-slice
Ablation for all volume of tumor
Volume Lesions form a single lesion
HIFU 3D Conformal Treatment
line slice
Solid (section)solid
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 4
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 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 of
Configurable Size and
Shapes in the Cat Brain
1940’s
HIFU Lesions in Cat Brain with Greater Precision and Placement Of Selected Tissue Type
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 5
HIFU System Integrated with Ultrasound B-Mode Imaging, 1972
Brain Tumor
HIFU Lesion
Ultrasound Images of a Brain during the HIFU treatment
Histology of Dog’s Brain Post HIFU MRI Image of a dog’s brain post HIFU Surgery, June-1989
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 6
32241680
TemperatureRise (oC)
Along the Beam Axis Across the Focus
MRI Temperature maps (PRF shift) during 10 s sonication
in rabbit thigh muscle in vivo
KH 2000
APPLICATIONS OF HIFU FOR
MALIGNANT TISSUE
APPLICATIONS OF HIFU FOR
MALIGNANT TISSUE
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
MedicineIndianapolis, IN
FSI TECHNOLOGY BACKGROUND Significance:Prostate Cancer
Death 31,000 per YearDetection 198,000 per Year
(1/11 men @ age 0f 65 has a chance of developing prostate cancer)
Benign Prostatic HyperplasiaOver 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
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 7
Prostate CancerProstate Cancer� HIFU Subtotal ablation of the prostate
– 83% Success Rate After Two Years– Over 6000 Patients Treated with HIFU– Noninvasive– Less Complications– Lower Cost
Canine Prostate after HIFU Treatment -Bihrle and Sanghvi et al 1994
The The SonablateSonablateTMTM 500 platform500 platform
• 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
SonablateTM 500
SonablateTM Probe TechnologySonablateSonablateTMTM Probe TechnologyProbe TechnologyA 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
Transrectal HIFU Probe
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 8
RF Power RF Power RF Power RF Power
ImagingImagingImagingImaging
and Firingand Firingand Firingand Firing
SystemSystemSystemSystem
ComputerComputerComputerComputer
ElectronicsElectronicsElectronicsElectronics
and safetiesand safetiesand safetiesand safeties
+ Disposable+ Disposable+ Disposable+ Disposable
Endorectal ProbeEndorectal ProbeEndorectal ProbeEndorectal Probe
CoolingCoolingCoolingCooling
MotorsMotorsMotorsMotors
Patient SupportPatient SupportPatient SupportPatient Support
User InterfaceUser InterfaceUser InterfaceUser Interface
Command Command Command Command Command Command Command Command ModuleModuleModuleModuleModuleModuleModuleModule
Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment ModuleModuleModuleModuleModuleModuleModuleModule
Probe ModuleProbe ModuleProbe ModuleProbe ModuleProbe ModuleProbe ModuleProbe ModuleProbe Module
HIFU and Prostate Cancer(Ablatherm device)
HIFU and Prostate CancerTechnical Approach
Transrectal probe:
Imaging mode Firing mode Volume treatment by successive shots
(1)WHAT REGION OF PROSTATESHOULD BE TREATED?
Accurate detection of the cancer regionis very difficult even using TRUS, CT
and/or MRI (endorectal coil)
Whole prostate should be ablated
Slide 15
2D and 3D Treatment Planning:
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 9
Prostate Cancer Treatment Procedure
Is there a complete necrosis of the treated area, in human?
HIFU and Prostate CancerHIFU and Prostate Cancer
CLINICAL CASES
CASE 2 (H.M.), 79 y.o., T2aN0M0
1.35 0.12 0.11 0.11 0.24 0.360.225.41
25.5
46.1
0.19 0.23
13
79.3
0
10
20
30
40
50
60
70
80
90
Jan-
99
Mar
-99
May
-99
Jul-9
9
Sep-
99
Nov
-99
Jan-
00
Mar
-00
May
-00
Jul-0
0
Sep-
00
Nov
-00
Jan-
01
Date
Seru
mPS
A(n
g/m
l)
Negative Biopsies
H H
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 10
CASE 1 (S.S), 78 y.o., T2aN0M0
31.2
15.3
3.82 2.58 5.01 4.46 5.18 6.53 6.9512.2
1.07 0.5
78
15.5
0.750.790.88
0
10
20
30
40
50
60
70
80
90
Jan-
99Fe
b-99
Mar
-99
Apr
-99
May
-99
May
-99
Jun-
99Ju
l-99
Aug
-99
Sep-
99O
ct-9
9N
ov-9
9D
ec-9
9Ja
n-00
Feb-
00M
ar-0
0A
pr-0
0A
pr-0
0M
ay-0
0Ju
n-00
Jul-0
0A
ug-0
0Se
p-00
Oct
-00
Nov
-00
Dec
-00
Jan-
01
Date
Seru
mPS
A(n
g/m
l)
Negative Biopsies
H2H1
Positive biopsy
PRE
PRE 2M
2M 10M
10M
Prostate vol.: 39.9 ml Cavity formation 5.5 mlSerum PSA : 13.0 ng/ml - 0.14 ng/ml
Hypoechoic
G2+2 Necrosis Normal Tissue
MRI...MRI...
MRI & Endoscopy of Prostate Post HIFU Six
Monthsnegative biopsiesnegative biopsies
86,2 %86,2 %86,2 %86,2 %86,2 %86,2 %86,2 %86,2 %Nadir PSA 0,40 ng/mlNadir PSA 0,40 ng/mlNadir PSA 0,40 ng/mlNadir PSA 0,40 ng/mlNadir PSA 0,40 ng/mlNadir PSA 0,40 ng/mlNadir PSA 0,40 ng/mlNadir PSA 0,40 ng/ml
81,8 %81,8 %81,8 %81,8 %81,8 %81,8 %81,8 %81,8 %Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml Nadir PSA 0,26 ng/ml
72,1 72,1 %%%%%%%%Nadir PSA 0,27 ng/mlNadir PSA 0,27 ng/mlNadir PSA 0,27 ng/mlNadir PSA 0,27 ng/mlNadir PSA 0,27 ng/mlNadir PSA 0,27 ng/mlNadir PSA 0,27 ng/mlNadir PSA 0,27 ng/ml
low risk (31,2 %)low risk (31,2 %)T1 T1 -- T2a and PSA T2a and PSA ≤≤ 10 ng/ml and Gleason 10 ng/ml and Gleason ≤≤ 66
middle risk (48,2 %)middle risk (48,2 %)T2b or PSA 10.1T2b or PSA 10.1--20 ng/ml or Gleason = 720 ng/ml or Gleason = 7
high risk (20,6 %)high risk (20,6 %)T2c or PSA > 20 ng/ml or Gleason T2c or PSA > 20 ng/ml or Gleason ≥≥ 88
risk groupsrisk groups
HIFU and Prostate CancerHIFU and Prostate CancerEuropean European MulticenterMulticenter StudyStudy
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 11
EFFICACYEFFICACYEFFICACYEFFICACYEFFICACYEFFICACYEFFICACYEFFICACY
Radical Prostatectomy
52 - 86%
External BeamRadiation
23 - 88%
Brachytherapy
7 - 89%Disease free at 5 years
HIFUHIFUHIFUHIFUAblathermAblathermAblathermAblatherm®®®®
47.5 47.5 47.5 47.5 ---- 84%84%84%84%
Sonablate 50075 - 97%
Disease freeat 1 year
MORBIDITYMORBIDITYMORBIDITYMORBIDITYMORBIDITYMORBIDITYMORBIDITYMORBIDITY
HIFUHIFUHIFUHIFUAblathermAblathermAblathermAblatherm®®®®
4444 ---- 9%9%9%9%
22 22 2222 ---- 66%66%66%66%with n. sp. - without n. sp.
0%0%0%0%
Radical Prostatectomy
5 - 49%
14 - 80%with nerve sparing
2 - 4%
External Beam Radiation
0.7 - 23%
11 - 67%short term - long-term
14 - 63%
Brachytherapy
0 - 18%
20 - 50%short term - long-term
4 - 33%
incontinence
impotence
GI
� Reproducibility: similar results are observed by new users
00.10.20.30.40.50.60.70.80.9
Münich Como 0
0.1
0.2
0.3
0.4
0.5
Münich Como
Münich: 800+ patients - Como: first 127 patients
6-month biopsiesNadir PSA
HIFU and Prostate CancerState of the Art
Therapeutic benefits HIFU Radiotherapy Brachytherapy Surgery
Non-Invasive
Effective
Early Feedback
Quality of Life
Repeatable
Adaptable
No Th. Impasse
Cost Effective
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
N
N
N
N
N
Y
N
Y
N
Y
N
Y
N
N
N
Y
Y
N
N
N
Y
Y
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 12
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.
74
8285
52
35
73
29
3832
8287 85
8175
93
100
87
0
20
40
60
80
100
Brachy XRT CRYO 3D-CRT HIFU
From: John Rucastle, Ph.D. March-2004
HIFU and Prostate CancerConclusion
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
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)
SUMMARYProstate Cancer Clinical Trials
Under the Food and Drug Administration (FDA) Approved Protocol, Phase I clinical studies are conducted at:
Indiana University School of Medicine, Indianapolis, INPI: Dr. M. O. Koch and Dr. T. A. Gardner&Case Western Reserve University, Cleveland, OHPI: 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
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 13
OTHER APPLICATIONS of HIFU
� Tumors --- Liver, Brain,Breast, Pancreas, Rectum
� Heart (TMR-- Trans Myocardial Revascularization)� Acoustic Hemostasis� Targeted Drug Delivery� Blood Brain Barrier
FUTURE PROJECTSFUTURE PROJECTS
� DEVELOPMENT OF FOCUSED ARRAY TRANSDUCERS 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 and Split Focus Beams
Simple HIFU on Schlieren Split Beam on Schlieren
Single Vs. Split Beam Transducer ConfigurationsSingle Vs. Split Beam Transducer Configurations
[mm][mm][mm][mm]
Transducer Transducer GeometryGeometry
Transverse Intensity Plot (Focal Plane)Transverse Intensity Plot (Focal Plane)
[W/cm[W/cm22]]
[mm][mm] [mm][mm]
Transducer Transducer GeometryGeometry
Transverse Intensity Plot (Focal Plane)Transverse Intensity Plot (Focal Plane)
[W/cm[W/cm22]]
Narendra T. Sanghvi
Intracavitory Probes for Ultrasound Therapeutic Applications 14
Quantitative Lesion Imaging By Relative Attenuation Technique
Color-coded M-mode images of a HIFU-created lesion in the turkey breast tissue
Envelope of the backscattered RF data ∆β∆β∆β∆β image
∆β∆β∆β∆β = Relative change in the attenuation coefficient
ON OFF
Results- Continued
(a)
0
2 0
4 0
6 0
8 0
1 0 0
0 2 4 6 8 1 0 12 14 16
T i me (s )
(b)
Temporal evolutions at the focus of the HIFU beam
Temperature ∆β
Spatial profile of ∆βalong the beam axis
Macroscopic view of the HIFU-induced lesions in the turkey breast tissue
AcknowledgmentsAcknowledgmentsAcknowledgments
Indiana University School of Medicine, Indianapolis, IN
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
National Cancer Institute / NIH 1 R 43 DK 59664 - 01
New Energy Development Organization / MITI, Tokyo, Japan
The The Extracorporeal Extracorporeal Treatment of MalignantTreatment of Malignant
Tumors & CancersTumors & Cancerswith HIFUwith HIFU
2002.7
CHONGQING HIFU TECHNOLOGY CO.,LTDTAIHAN METRA CORPORATION