Supplementary material
MRI Protocol
Pre-HIFU and 6-month post-HIFU mpMRI sequence protocol
TR
1. T2 TSE
2. VIBE
TE
5170 92
5.61
Flip
Slice
Matrix
Field of
angle/
thickness
size
view /mm
degrees
(gap)
256x256
180x180
180
2.52 15
Plane
axial,
3mm (10%
coronal
gap)
axial
3mm (20%
with fat sat
Time for scan
3m 54s (ax),
4m18s (cor)
192x192
260x260
gap)
7m at least
(sequential 16s
acquisitions)
3. Diffusion
2200 98
axial
5mm
172x172
260x260
(b values:
5m 44s
(16 averages)
0, 150,
500, 1000)
4.
2200 98
axial
5mm
Diffusion
172 x
320x320
172
3m 39s
(32 averages)
(b=1400)
Early post HIFU mpMRI sequence protocol
TR
1. T2 TSE
TE
5170 92
Flip
Slice
Matrix
Field of
angle/
thickness
size
view
degrees
(gap)
180
Plane
axial
3mm (10%
/mm
256x256
gap)
2. T1 TSE
2. VIBE with
502
5.61
15
150
2.52 15
axial
axial
fat sat
Time for scan
180 x
3m 54s each
180
3mm (10%
256 x
200 x
gap)
256
200
3mm (20%
192x192
260 x
7m at least
260
(sequential 16s
gap)
2m 44s
acquisitions)
4. T1 post
contrast fat
sat
461
19
150
Axial,
3mm
coronal (10% gap)
256 x
200 x
256
200
4m 39s each
Principles of HIFU
Using a cylindrical piezoelectric ceramic transducer, ultrasonic waves are generated and then focused
(using either a spherical plate or a flat plate with an appropriate lens) to a target area determined by the
focal length of the lens. The sound waves are transmitted to the tissues by a coupling mechanism from a
transducer placed either extra-corporeally or transrectally. This is achieved transrectally by placing the
probe within a condom filled with chilled circulating degassed water. The dimensions of the target area are
determined by the focal length of the transducer, the applied frequency, the intensity of the applied power
(W/cm2), and the duration of the shot. The lesion produced is pseudo-ellipsoid in shape and referred to as
the focal zone. Its long axis lies at right angles to the transducer and is greatest in length toward the
transducer. Tissue destruction is produced by thermal, mechanical and cavitation effects to produce a
clearly demarcated region of coagulative necrosis surrounded by “normal” tissue on microscopic
examination.
Thermal energy comes from absorption of mechanical energy. Adequate cell-kill can be
produced by even short exposure (1 second) to temperatures of  60C, which has therefore been adopted
as the minimum target temperature. In practise, this temperature is easily attained with temperatures of
80C recorded during HIFU therapy. Cooling due to tissue perfusion in the focal zone is not a problem as
the rate of heating is greater than that of cooling when the exposure time is within a window of three
seconds. The mechanical effects of HIFU are more complex and involve shear forces, torque and
streaming. They result in destruction through both physical and thermal means. Cavitation results from gas
(bubble) formation within cells. It is caused by heat and mechanical energy deposition causing bubbles to
oscillate.
Supplementary Figure 1. Continence Function (UCLA-EPIC Incontinence Scores) following focal
index lesion high intensity focused ultrasound ablation.
Continence function following focal index lesion high intensity focused ultrasound ablation, measured using
UCLA-EPIC Incontinence questionnaire. (Two-tailed p-values are reported for Wilcoxon signed ranks test
comparing baseline and 12 month scores; median 93.8 (IQR 79.3 - 100) vs 93.8 (IQR 85.5 -100), p=0.74).
0
20
40
60
80
100
Box and whiskers plots indicate median with upper and lower quartile (boxes), range (whiskers).
0
1
3
6
Time(months)
9
12
Supplementary Figure 2. Urinary Function (IPPS Scores) following focal index lesion high intensity
focused ultrasound ablation.
Urinary function following focal index lesion high intensity focused ultrasound ablation, measured using
International Prostate Symptom Score questionnaire. (Two-tailed p-values are reported for Wilcoxon signed
ranks test comparing baseline and 12 month scores). Box and whiskers plots indicate median with upper
and lower quartile (boxes), range (whiskers). IPSS (median 6.5 (IQR 4-12) vs 6.5 (IQR 3-11), p=0.40).
20
10
0
IPSS
30
40
IPSS quality of life scores are detailed in Supplementary Figure 1.
0
1
3
6
Time(months)
9
12
Supplementary Figure 3. Box-and-whisker graphs for validated questionnaire subdomain IPSSquality of life following focal index lesion high intensity focused ultrasound ablation.
Values for median, interquartile range, and Wilcoxon signed ranks test two-tailed p-values comparing
baseline and 12 month scores for individual domains from validated patient questionnaires. IPPS Quality of
Life scores did not significantly deteriorate at 12-months (p=0.23). Calculated p-values indicate significance
levels for 12-month versus baseline outcomes. IPSS-Quality of Life (median 1 (IQR 1-2) vs 1 (IQR -1-0),
0
2
4
6
p=0.23)
0
1
3
6
Time(months)
9
12
Supplementary Figure 4. Sexual Function (Total IIEF-15 Scores) following focal index lesion high
intensity focused ultrasound ablation.
Sexual function following focal index lesion high intensity focused ultrasound ablation, measured using
International Index of Erectile Function-15 questionnaire. (Two-tailed p-values are reported for Wilcoxon
signed ranks test comparing baseline and 12 month scores). Box and whiskers plots indicate median with
upper and lower quartile (boxes), range (whiskers). Total IIEF-15 scores (median 53.5 (IQR 28.8 – 65.3) vs
0
20
40
60
80
42 (IQR 19.8 – 59.3), p=0.05). Other results detailed in Supplementary Figure 2.
0
1
3
6
Time(months)
9
12
Supplementary Figure 5. Box-and-whisker graphs for validated questionnaire subdomain on sexual
function following focal index lesion high intensity focused ultrasound ablation.
Within individual IIEF-15 domains, both orgasmic function (p=0.02) and intercourse satisfaction (p=0.04)
diminished by statistically significant levels between baseline and 12-months. However, erectile function
(p=0.18), sexual desire (p=0.42), and overall satisfaction (p=0.93) scores all returned to baseline.
Calculated p-values indicate significance levels for 12-month versus baseline outcomes.
0
10
20
30
a) IIEF-15 erectile function domain (median 21.5 (IQR 9.8 – 29.0) vs. 16 (IQR 5.0 – 28.0), p=0.18)
0
1
3
6
9
12
Time(months)
0
5
10
15
b) IIEF-15 intercourse satisfaction domain (median 10.0 (IQR 0 – 11.3) vs 7.5 (IQR 0 – 10.3), p=0.04)
0
1
3
6
Time(months)
9
12
0
2
4
6
8
10
c) IIEF-15 orgasmic function domain (median 9.0 (IQR 4.0 – 10.0) vs 6.0 (IQR 3.0 – 9.3), p=0.02)
0
1
3
6
9
12
Time(months)
0
2
4
6
8
10
d) IIEF-15 sexual desire domain (median 6.5 (IQR 6.0 – 8.0) vs 6.0 (IQR 5.0 – 7.0), p=0.42)
0
1
3
6
Time(months)
9
12
0
2
4
6
8
10
e) IIEF-15 overall satisfaction domain (median 8.0 (IQR 4.0 – 8.3) vs 7.0 (IQR 4.0 – 8.0), p=0.93)
0
1
3
6
Time(months)
9
12
Supplementary Figure 6. Quality of Life (FACT-P Trial Outcome Index Scores) following focal index
lesion high intensity focused ultrasound ablation.
Quality of life outcomes following focal index lesion high intensity focused ultrasound ablation, measured
using FACT-P questionnaire. (Two-tailed p-values are reported for Wilcoxon signed ranks test comparing
baseline and 12 month scores). Box and whiskers plots indicate median with upper and lower quartile
(boxes), range (whiskers). Trial Outcome Index (median 93.0 (IQR 83.8 – 97.3) vs 90.0 (IQR 83.8 – 96.0),
20
40
60
80
100
p=0.52). Other results detailed in Supplementary Figure 3.
0
1
3
6
Time(months)
9
12
Supplementary Figure 7. Box-and-whisker graphs for validated questionnaire subdomain on healthrelated quality-of-life following focal index lesion high intensity focused ultrasound ablation.
No significant overall difference was seen between baseline and 12-months on total FACT-P (p=0.66) or
FACT-G (p=0.15). Calculated p-values indicate significance levels for 12-month versus baseline outcomes.
60
80
100
120
140
160
a) FACT-P (median 136.0 (IQR 122.0 – 143.0) vs 137.0 (IQR 124.8 – 144.3), p=0.66)
0
1
3
6
9
12
Time(months)
40
60
80
100
120
b) FACT-G (median 96.0 (IQR 86.5 – 101.0) vs 97.5 (IQR 87.8 – 103.3), p=0.15)
0
1
3
6
Time(months)
9
12
Supplementary Figure 8. Prostate Specific Antigen levels following focal index lesion high intensity
focused ultrasound ablation.
Two-tailed p-value <0.0001, Wilcoxon signed ranks test comparing median values at baseline and 12
month PSA levels, 6.6ng/ml (4.9 – 8.4) vs. 2.4ng/ml (1.6 – 4.1). Box and whiskers plots indicate median
0
5
10
15
20
with upper and lower quartile (boxes), range (whiskers).
0
1
3
6
Time(months)
9
12