HIFU

Clinical
applications

Clinical applications (1)

Prostate tumors:
several devices under ultrasonic guidance
commercially available (Ablatherm, Sonablate
)

Fibroids
MRgHIFU procedures
Exablate (Insightec + GE)- FDA 2004
Philips
CE approuved Dec 2009

Breast cancer
clinical research

Bone tumors
clinical research

Clinical application (2)

Brain
small clinical studies
Limitation: skull (bone) acoustic interface
No motion

Liver:
Haifu under ultrasonic guidance
MRgHIFU procedures: Small clinical studies
Limitation:
aeric

and bone interfaces

Motions

MRI guidance of focused ultrasound

therapy of Uterine fibroids

Uterine fibroids: major

cause of morbidity

Symptomatic in 1/3 of
patients
Bleeding
Mass
effect
Pain

Age years

Lumbiganon

Parazzini

< 30

1,4%

4,7%

30-39

25,1%

22,5%

40-49

61%

61,8%

50

12,5%

10,9%

Fibroids: therapy
Hormonal

Drug transient effect

Progestin
Gonadotrophin-releasing-hormone-agonist
Conservative

approach

(mini-invasive)

Myomectomy
Uterine artery embolization
HIFU outpatient procedure
and very short recovery period
hystrectomy:

First surgery in USA most for fibroids

Uterine Fibroids
Comparing treatment options
Treatment Factors

Hysterectomy

Myomectomy

UF Embolization

MR-HIFU

Procedure count
(USA, 2007)

250.000

25.000

25.000

> 4.000
(total ww)

Hospital stay

2 5 days

1 3 days

2 days

Complication rate

2 50%

2 34%

Peri op: 10%

Post op: 2%

< 3%

28 56 days

44 days

10 days

1-2 day

Future fertility

No

yes
50% increased
risk during
pregnancy

(yes)
Possible ovarian
embolization

(yes)
Exclusion
criteria, but
encouraging
data

Drawbacks/
complications

No future
pregnancy,
emotional stress

30% recurrence
within 5y

effective in 90% of
patients at 1 year
and 80% at 5 years

effectiveness
depends on the
NPV
long-term
monitoring?

Return to
normal activity

MRgHIFU advantages for fibroids

Ambulatory
No

gnral anaesthesia
No cutaneous penetration
Return to work: day 1-2
(hysterectomy: 1-2 month)
Safety (few adverse effects)

MRI: best imaging technique for fibroids

Adnomyosis

MRI: a thermometer!!

Thermal Map
(T C + 37
C)
Y

Module

Phase image
during heating

Temperaturre map based on PRF

d / dT = = 0.01 ppm/C

5%

T = - / ( Bo
TE )

linear and independent of tissue type

Gradient echo with spoiler
Phase 1

zoom x 4

Phase 2

zoom x 4

Phase 2 Phase 1
Relative temp map

zoom x 4

20 mm

MRgHIFU
1MRI: good tracking of the fibroid
2MRI: good targeting of the HIFU in the
fibroids
3 MRI: temperatures changes during
HIFU
4 adjustment of HIFU in real time

MR-HIFU Platform: Sonalleve MR-HIFU

Phased array transducer
256 channels
Focal point size: 1 x 1 x 8 mm3
Frequency 1.2 MHz
Fast electronic focal point steering
Mechanical platform
Large range of displacements
Integrated into a 1.5T Philips Scanner
Anatomical images with Dedicated
SENSE Pelvis coil
Thermal maps

Non-perfused volume

Conscious sedation and analgesia

Outpatient treatment

Light intravenous conscious sedation allowing

communication between patient and treating physician
safety aspect reducing risk of skin burns
Hydroxizine (1mg/kg)
Paracetamol (1 g)
Ketoprofene (100 mg)

Urinary catheter: keeping bladder empty during

treatment
(or reposition)

MRI-controlled HIFU
MR with integrated HIFU

Therapy Planning Console

position,
timing,
& power
control

3D anatomy and
temperature mapping

US
power

thermotherapy

Motor
control
Phased Array Transducer
In Mechanical Positioner

Focused Ultrasound
Electronics

MR is essential for 3D planning and to monitor temperature in real-

MR-HIFU
Traditional ablation concept

Point-by-point ablation

Challenge #1 treatment time

Ablation speed
limit ~1 ml/
min
Excessive cooling times
Long procedure times 3h+

Challenge #2 tissue properties

Local variations in tissue properties
Inhomogeneous absorption,
attenuation, perfusion, diffusion

Irregular heating patterns

Risk of incomplete coverage

New ablation concept

Volumetric heating addressing #1

Volumetric ablation
Increased efficiency
Several volumetric ablation were
performed in order to cover the large
fibroid volume

Cell

Electronic beam steering:

Outwards-moving
concentric circles
4 16 mm

Automatic ablation control

& Thermal
Dose overlays

Temperature

Thermal dose
Temperatur
e
Interuption
threshold

Real time visualization

+
Automatic control
Temp. border > 5457C or Dose > 240
EM
Stop heating
Reliable necrosis size

Variable cell size

4mm

8mm

12mm

16mm

Temp.
[C]

CORONAL

75

2cm

2cm

2cm

SAGITTA
L

2cm

56

47
43
2cm

2cm

2cm

Temperature at the end of sonication

2cm

39

Variable cell size

4mm

8mm

12mm

16mm

Dose
[EM]

CORONAL

480

2cm

2cm

2cm

2cm

240

SAGITTA
L

180
12
0
60
2cm

2cm

2cm

Thermal dose at the end of cool-down

2cm

30

Example of a 12mm sonication

Temp.
[C]
75

56

47
43
39

Dose
[EM]
2
4

Above left: Planning

TSE T2w 3D, FOV250,
1.42x2.10x2.5mm,
Above right: Placing
treatment cells on planning
images. Ultrasound beam cone
and safety margins indicated
Below left: temperature map
real-time, sagittal view
12x30 mm ablation volume
EPI ProSet, 2.5x2.5x7.0 mm
Below right: post treatment
Non Perfused Volume (NPV)
T1 TFE THRIVE 3D SPAIR
C+ FOV200,
1.0x1.10x4.00mm
Treatment time 130 min

25

Patient well-being
No complications or
serious adverse events and
no unintended lesions were
observed.
Hospital stay
Return to normal activity
2.4 1.8 days
Symptoms (SSS) after 1
month
- 13.6 points (26.9%)
(from +10.0% to
-92.3%)

Volumetric Heating with Feedback

Improved efficiency and speed in clinical practice
18

Ablation speed

16

2,5

N=
3

Ablation efficiency
2

12

Ablation efficency [ml/kJ]

Ablation speed [ml/min]

14

10

N=5
7

8
6

N=6
6

4
2

N=
6

0
0

1,5

N=5
7

N=6
6

0,5

N=
6

0
8

12

Cell diameter
[mm]

10x faster ablation than point by

point
Larger cells need 2-3x longer
cooling

16

N=
3

Cell diameter
[mm]

1
2

1
6

16 mm 35x more efficient than 4

mm
Less near field heating, shorter
cooling

Non perfused volume: good correlation between the

ablated volume planned and the NPV

SAGITTA
L

CORONAL

Exemple 1

Exemple 2

CONFIDENTIA

Example of an HIFU treatment outcome

PRE-TREATMENT

DAY OF TREATMENT

1 MONTH FOLLOW-UP

Example of an HIFU treatment outcome

Just after HIFU

Before HIFU

1 month after HIFU

1 year after HIFU

In practice

% of treatment volume and efficiency

Treatment Volume
of Fibroid

< 33 %

< 55%

% of patients with 10 points

improvment (SSS) at 3 months

79%

% of patients with 10 points

improvment (SSS) at 6 months

79%

88%

% of patients with 10 points

improvment (SSS) at 12
months

78%

91%

NPV

16% 16,1

25,7 21,8

Larger treatment volumes are preferred to reduce

fibroid volume as much as possible
Fennessy et al 2007
Radiology

Bone absorbs US more readlily than soft tissue and low energies
are sufficient to heat a bone surface to high temperature.
In this area nerves are adjacent of the bone surface and may be
exposed

Patient to include
A far field margin of 40mm should be
available

Max: 40mm

T2 sagittal

Check that the far field doesnt include sacrum or bowel

Alternatively treat only the anterior part of the fibroid

Patient to exclude

Bowels are located in the beam path

between the fibroid and the gel pad

No sonication possible across air structure or scarves

Air block ultrasound and produce local heating (bowels damage)

Patient to include

Bowels are not located in the beam path

between the fibroid and the gel pad

T2 sagittal
However be careful to avoid bowel when sonicating
Its better to avoid bladder but its possible to sonicate across the

Sonication across the bladder

Patient to exclude?

Patient with too many fibroids?

T1 sagittal before gado

T1 sagittal after gado

Patient to exclude

128mm

T1 sagittal before gado

T1 sagittal after gado

The transducer displacement and maximum focal point is

limited

Patient to include
Fibroid with a mass center at less than 90 mm from the skin could be
treated

Max: 61mm

T2 sagittal

T1 sagittal after gado

Patient to include

Consider the fact that the bladder will be empty during treatment

During pre treatment MRI

During treatment MR-HIFU

Might help to obtain a better far margin relatively to the

sacrum

Patient to exclude
Patient with calcification in or close to the beam path should be
exclude Calcification could be identified by ultrasound echo
image

Calcification

Calcification stops the ultrasound wave (local heating)

and produces local image distortion (wrong treatment planning)

Patient to exclude
Patient with clips in or close to the beam path should be
exclude

Clip

T2 transversal
(after gado)

Clip

T1 transversal

Clips stops the ultrasound wave (local heating), produces local

image distortion (wrong treatment planning)
and induces thermal map instability

Patient to include
Patient with scar in the beam path should be
exclude

Scar

T2 transversal

Scar stops the ultrasound wave (local heating)

Draw two lines with same length to check beam

Patient to include

Consider possibility to fill the bladder to avoid scar

Scar

Scar

Caution, in this case the bladder will continue to fill progressively

Check frequently the fibroid location with markers

Signal of the fibroid

MRHIFU produced a greater volume reduction

in T2 hypointense fibroids than in
hyperintense fibroids

Others applications

Liver

HCC: traitement
Surgery:

liver transplantation+++,
Liver resection but difficult due to cirrhosis:
Percutaneous

therapy

Physique: RF+++
Chimioembolisation

Metastasis from colon carcinoma

One of the K the most frquent
Mtastasis

synchronous: 15-25%,
During the follow up: 50%

Five years survival if M+

Drug only: 5%
Surgery of the metastasis: 30-40%
only10%

by
surgery

of the patient with metastasis can be treated

RF

Transverse

Ablation RF 1

Ablation RF 2

Slice1

Slice1

Slice2

Slice2

Tumour before
RF

Ablation RF N1

Ablation RF N2

T2w

After RF ablation
T1w
Tumour before RF

CE-T1w

HIFU and Liver:

Haifu under ultrasonic guidance
MRgHIFU procedures: Small
clinical studies
Limitation:
aeric

and bone interfaces

Motions

Motions

MR thermometry with motion :

correction
effect
free breathing
10 C

5C

Anatomical
image

standards Dviations
of T (no
correction)

standards Dviations
of T (with
correction)

0C

HIFU and pig liver with motion

correction

Os

University Childrens Hospital, Zurich,

Switzerland

Local Drug Delivery

via permeability enhancement

Focal BBB Opening using High Intensity Ultrasound in

rabbit

T1- weighted contrast enhanced scan

Hynynen et al.
Boston

Subtraction Image:
TD1-w: After Before Contrast
Injection

Combined MR contrast agents for

imaging/therapy

Target specific part

MAB (fragments)
Peptides
Aptamers (short
DNA/RNA strings)

Heat sensitive Linkage

Contrast agent (multiple)

Gd
Iron particle

Drugs

MRI guided FUS for spatio-temporal control of gene expression

under control of a heat sensitive promoter

Heated region

Analysis of Green
Fluorescent Protein gene
Expression using Confocal
Microscope
Fluorescence
Image Transmission Image

Conclusion
Mini-invasive

therapy particularly

attractive
for patient
A lot of applications