Jurgen H Runge1, Remy Klaassen2, Oliver J Gurney-Champion1,3, Hanneke WM van Laarhoven2, Ralph Sinkus4, Aart J Nederveen1, and Jaap Stoker1
1Radiology, Academic Medical Center, Amsterdam, Netherlands, 2Medical Oncology, Academic Medical Center, Amsterdam, Netherlands, 3Radiation Oncology, Academic Medical Center, Amsterdam, Netherlands, 4Biomedical Engineering, King's College London, London, United Kingdom
Synopsis
Pancreatic cancer remains one the most deadly cancers. New therapeutic agents cause confusion as prior morphological criteria to determine the presence of a response appear to be unreliable. MR Elastography (MRE) is uniquely able to determine tissue stiffness, a property potentially useful for therapy response monitoring. Here we present our first preliminary results of combining MRE with IVIM and DCE MRI.Target audience
Clinicians and scientist interested in cancer research,
pancreas imaging, and MR Elastography.
Purpose
Outcomes for major cancer types (e.g. colorectal cancer) have improved steadily in the last decade(s), but pancreatic cancer
has retained a poor prognosis. It induces a fibrous network
of connective tissue, deposited in and around the cancer (“desmoplastic
stroma”). New chemotherapeutic agents targetting stromal structures may be
able to improve prognosis, but require dedicated monitoring tools different
from current morphology based criteria such as RECIST
1. The stromal
deposition leads to a rise in local viscoelastic properties
2,3.
MR Elastography (MRE) is uniquely able to assess viscoelastic properties by
probing the 3D propagation of shear waves. The intravoxel-incoherent motion (IVIM)-derived
diffusion parameter (
D) is also
related to tissue density and could be a relevant marker for stromal
deposition. Dynamic contrast-enhanced (DCE)MRI derived
Ktrans values relate to
tissue vascularity. Here we present
the first results of a feasibility study in which we added MRE in ongoing
studies of patients with pancreatic cancer and show side-by-side comparisons in
four subjects of DCE MRI, IVIM modelled diffusion MRI and MRE.
Materials & Methods
MRE was added to the scan protocol of four pancreatic
cancer patients (1M/3F, mean age: 67y) who were included in an ongoing study in
which IVIM and DCE were performed on a clinical 3T Ingenia MR Scanner (Philips
Healthcare, The Netherlands)
4. MRE was
performed with a portable transducer placed
either ventrally (pancreas,
n=2),
against the left side of the chest (pancreatic tail,
n=1) or the right side of
the chest (liver,
n=1). In a single
healthy male volunteer (27y), only ventral MRE acquisition of the pancreas was
performed. MRE was performed according to Garteiser et al
5 with in-phase TE=6.9ms,
fMECH=56Hz,
fMEG=160Hz, 4×4×4 mm
3
voxels in four 20s breath holds. Given the limited coverage (32 mm) in the slice direction, we used T1TFE Dixon water-only images to guide placement of the MRE field-of-view
(FOV). Raw phase images were processed in
dedicated software to obtain final elastograms
3. Stiffness (MRE), water
diffusivity
D (IVIM) and
Ktrans (DCE) were assessed in
the tumour (
n=3) and pancreatic liver
metastasis (
n=1) using regions of
interest (ROIs) after co-localising to the high-resolution Dixon water-only,
post-contrast anatomical scan.
Results
Pancreatic cancer
Total measurement time for the MR protocol amounted to circa 45 minutes. All subjects tolerated the additional breath holds and mechanical waves for the MRE acquisition well. Data of patient 1, 2 and 3 are shown in Fig. 1–3, with anatomical image and zoomed images with stiffness, D and Ktrans overlays. For patient 1 (M/72y), the stiffness of the tumour was 2.55 kPa, with D of 1.80∙10-3 mm2/s and Ktrans of 0.32 min-1. For patient 2 (F/74y), this was 3.52 kPa, 1.16∙10-3 mm2/s and 0.35 min-1. Patient 3 (F/52y) had a pancreatic tail cancer with 1.8 kPa, 1.25∙10-3 mm2/s and 0.42 min-1.
Healthy volunteer
The healthy volunteer’s pancreatic stiffness (1.52 kPa) was in concordance with literature values (fMECH=40 Hz: 1.15 ± 0.17 kPa, fMECH=60 Hz: 2.09 ± 0.33 kPa)6. No IVIM or DCE was performed.
Liver metastases
Pancreatic metastases to the liver in patient 4 (F/69y) were stiff, with the largest metastasis at 13.9 kPa. The elastogram showed a relatively spared triangle centrally in the liver, also noted on the anatomical image (Fig. 4). MRE slices were outside the IVIM/DCE FOV, hence no D or Ktrans data were obtained for the metastases.
Discussion
Pancreatic cancers and pancreatic liver metastases were
substantially stiffer than normal pancreatic tissue in three out of four
patients observed. As can be observed in
Fig.
1–3,
D was relatively high for patient 1, but had normal values for
patients 2 and 3 compared to literature values
7.
Ktrans values showed
lower values for the cancers in patient 1 and 2 compared to surrounding
pancreas tissue, in patient 3 this was not as clear. In subsequent patients we
aim to improve spatial coverage and resolution, allowing assessment of the
whole pancreas and small pancreatic lesions and compare MRE results with
histological analysis of surgical (cf.
Klaassen
et al4). This will enable the implementation of MRE as a treatment response monitor tool in pancreatic
cancer. The latter is highly relevant in an era in which new stroma targeting
agents prove difficult to monitor using morphology-based tools such as
RECIST.
Conclusion
MRE of pancreatic cancer patients is feasible with current
MRE equipment and can be added to existing MR protocols incorporating diffusion
weighted imaging and DCE-MR. MRE showed higher stiffness values in three out of
four pancreatic cancer patients. Assessment of its performance in treatment
response monitoring of the new stroma targeting agents should be prioritized.
Acknowledgements
No acknowledgement found.References
1. Miller FH. Tumor Response
Assessment using CT and MRI: Current Clinical Practice. ISMRM 2011;8440. 2. Siegmann KC, Xydeas T,
Sinkus R et al. Diagnostic value of MR elastography in addition to
contrast-enhanced MR imaging of the breast-initial clinical results. Eur
Radiol. 2010;20(2):318-25. 3. Sinkus R, Siegmann KC,
Xydeas T et al. MR elastography of breast lesions: understanding the
solid/liquid duality can improve the specificity of contrast-enhanced MR
mammography. Magn Reson Med. 2007;58(6):1135-44. 4. Klaassen R, Steins A,
Gurney-Champion OJ et al. Correlating post-operative whole mount
immunohistochemistry to functional MRI parameters in pancreatic cancer.
ISMRM 2015;0141. 5. Garteiser P, Sahebjavaher
RS, Ter Beek LC et al. Rapid acquisition of multifrequency, multislice and
multidirectional MR elastography data with a fractionally encoded gradient
echo sequence. NMR Biomed. 2013;26(10):1326-35. 6. Shi Y, Glaser KJ,
Venkatesh SK et al. Feasibility of using 3D MR elastography to determine
pancreatic stiffness in healthy volunteers. J Magn Reson Imaging. 2015;41(2):369-75. 7. Gurney-Champion
OJ, Froeling M, Klaassen R et al. Minimizing the Acquisition Time for
Intravoxel Incoherent Motion MRI Acquisitions in the Liver and Pancreas. Accepted for publication in Invest
Radiol.