Hugh Harvey1, Jeremie Fromageau2, Veronica Morgan1, Liz Bancroft3, Ros Eeles3, Jeff Bamber2, and Nandita deSouza1
1Radiotherapy & Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom, 2The Institute of Cancer Research, London, United Kingdom, 3Oncogenetics, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom
Synopsis
Location-matched ROI analysis of tissue stiffness (SWE)
and water diffusivity (ADC) in 9 normal prostates demonstrated that both
techniques can adequately differentiate between peripheral and transitional
zonal microenvironments, and that there is a weak negative correlation between
tissue stiffness and water diffusivity in the peripheral zone. This suggests
that factors such as microvascularity, cell size, extracellular matrix and
macromolecules may have a differential effect on tissue stiffness and diffusivity.
Transitional zone stiffness is too heterogeneous to demonstrate significant
inter-modality correlation.Purpose
To ascertain whether zonal prostate tissue stiffness
(quantitatively measured with SWE) negatively correlates to tissue water
diffusion (quantitatively measured with DWI).
Background
The relationship between tissue stiffness and water
diffusivity in the prostate microenvironment has not been formally explored.
Shear Wave Elastography (SWE) interrogates tissue stiffness using low-frequency,
low amplitude ultrasound waves, producing a Young’s modulus estimate (kPa)
which increases as tissue elasticity decreases [1]. Water diffusivity
becomes increasingly restricted as tissues increase in cellularity and density,
and is measured using Diffusion Weighted MRI quantitatively analysed by
calculating Apparent Diffusion Coefficient (ADC mm2/s) maps [2]. Both functional
techniques can be used to detect changes in the prostatic microenvironment, but
it is not known whether a relationship exists between them which could be
exploited in future for differentiating cancerous from non-cancerous regions.
Methods
10 patients with a family history of prostate cancer were
prospectively recruited to a screening trial and underwent SWE (SuperSonic
Imagine, France) and 3T endorectal mpMRI (Achieva, Philips, Best, Netherlands)
in the same session. Two independent operators performed SWE imaging and region-of-interest
(ROI) analysis using 5mm circular ROIs placed in peripheral (PZ) and
transitional zones (TZ) in a sextant pattern at the base, midgland, and apex, as
well in the seminal vesicles. Young’s modulus values were calculated for ROIs
from each observer and interobserver differences documented.
DWI images were obtained in the transverse plane
(single shot EPI, TR 5000ms, TE 54ms, b = 0, 100, 300, 500, 800 s/mm2,
FOV 100 mm, slice thickness 2.2 mm, matrix 80 × 79 extrapolated to 176 × 176). Isotropic ADCall maps were
generated from all b values with the system software using mono-exponential
fitting. Mean ADCall values
were obtained from location-matched 5mm circular ROIs in the same sextant
format as for the SWE studies using a method of cognitive fusion by an operator
for ROI placement.
Paired t-tests were performed between PZ and TZ values for
each modality to ascertain zonal differences for each technique. Pearson’s
correlation between kPa and ADCall values were calculated for each sextant
location, and for the whole gland.
Results
1 patient was excluded from correlation analysis due to
a lack of ADC data (no MRI performed due to claustrophobia). No patients were
found to have clinically significant disease on mpMRI or subsequent biopsy,
therefore all sextants were considered to comprise normal prostate tissue.
Paired t-tests demonstrated significant differences
between PZ and TZ for both modalities (SWE mean difference -18.21 ± 13.24 kPa,
p<0.0001; ADCall mean difference 245 ± 388, p<0.0001) (Table 1),
implying that both techniques can successfully delineate PZ from TZ based on the
functional properties being measured, and that the PZ is more elastic and has
greater diffusion than the TZ. PZ also demonstrated less variation in stiffness than TZ (SD PZ 8.3, SD
TZ 15.8).
Whole gland peripheral zone ADCall and kPa
values demonstrated a weak but significant negative correlation (r= -0.029,
p=0.035, Figure 1), confirming that as tissue stiffness decreases, diffusivity
increases. However, this was not significant at the per-sextant level (Table 2).
Discussion and Conclusions
The functional tissue parameters ADCall and
kPa are not equivalent in their assessment of the microenvironment as shown by
their overall weak correlation in the PZ. This suggests that factors such as
microvascularity, cell size, extracellular matrix and macromolecules may have a
differential effect on the measured parameters. No significant correlation was
found between ADCall and kPa within the TZ (r=0.20, p=0.1375, Figure
2) suggesting that TZ regional heterogeneity is greater than any measurable
correlation. Further studies will investigate
a relationship between stiffness and true diffusion (by excluding low b-values
in the ADC calculation) in order to eliminate perfusional effects from
estimates of diffusivity. An increase in subject numbers would also increase
powering.
It is worth noting that the mean TZ kPa was 39.9 ± 15.8, which is greater than
the cited cut-off value for tumour detection of 35kPa [3], implying that SWE
is likely to be poorly specific for the identification of tumour within the TZ,
but may be adequate in the PZ (mean kPa 21.7 ± 8.3).
Acknowledgements
CRUK
and EPSRC support to the Cancer Imaging Centre at ICR and RMH in association
with MRC & Dept of Health C1060/A10334, C1060/A16464 and NHS funding to the
NIHR Biomedical Research Centre and the Clinical Research Facility in
Imaging. References
1. Woo, S. et al, Shear wave
elastography assessment in the prostate: an intraobserver reproducibility
study. Clinical imaging, 2014.
2. Tamada, T.
et al, Diffusion-weighted MRI and its role in prostate cancer. NMR in
biomedicine, 2014. 27(1): p. 25-38.
3. Correas,
J.-M. et al, Prostate Cancer: Diagnostic Performance of Real-time Shear-Wave
Elastography. Radiology, 2015. 275(1): p. 280-289.