ISBE-AstraZeneca Strategic Alliance – Work Plan - Project #43
Comparison of dynamic contrast-enhanced CT (DCE-CT) and
dynamic contrast-enhanced MRI (DCE-MRI) in bladder cancer
Project commencement date:May 2006
Research Project Period: to Dec 2006
Research and Supervisory Staff: GJM Parker, DL Buckley, D McGrath, B Taylor, J
Logue, A Lacey
Name of Supervisor: GJM Parker
Programme of research work (the “Research Project”)
Project Aim
We will investigate the strengths and weaknesses of dynamic contrast-enhanced CT
(DCE-CT) and dynamic contrast-enhanced MRI (DCE-MRI) in the investigation of
bladder tumours. The study will involve 20 patients with primary bladder tumours.
Each patient will be scanned with both DCE-CT and DCE-MRI, with the aim of
determining tumour blood volume, blood flow, capillary wall permeability, and
interstitial volume. We will also investigate the distribution of these properties within
the masses, and establish correspondence between the CT and MRI information.
Rationale and Background
DCE-MRI is the method of choice for monitoring changes in tumour microvascular
functional status due to antiangiogeneic and antivascular treatments (see for example
[Jayson 2002, Morgan 2003, Jackson 2005, Jayson 2005]). However, DCE-CT is an
attractive alternative as it has wider clinical availability, due to which it has attracted
considerable recent interest (see for example [Sahani 2005]). DCE-MRI is known to
have some advantages over DCE-CT – in particular, it is able to provide volume
coverage at high temporal resolution without ionizing radiation. DCE-CT is limited in
the total number of slices and number of time points during the dynamic acquisitions
due to dose restrictions, which means that potentially important information from
spatially heterogeneous tumours may be missed. However, DCE-MRI is thought to
have some accuracy limitations due to its sensitivity to variable rates of water
exchange across capillary walls [Buckley 2002, Buckley & Parker 2005]. We
therefore plan to assess the following key issues in this comparison of methods: 1) Do
significant differences exist between DCE-CT and DCE-MRI in the gross
parameterization of tumour microvascular functional status?; If so, can these be
explained by the limited volume coverage of DCE-CT, or other methodological
differences (for example temporal resolution or data noise level differences),
hindering the extraction of useful summary parameters? 2) Do subtle intra-tumoural
regional differences exist between DCE-CT and DCE-MRI parameterizations? If so,
can these be explained by variable water exchange characteristics (caused by variable
capillary permeability) within the tumours that affects DCE-MRI only? Do these
differences have a significant impact on the accuracy of DCE-MRI?
The provision of answers to the above questions will provide guidance for the design
of future therapeutic studies involving DCE methods. The identification of either
DCE-CT or DCE-MRI as future methods of choice based on the quantitative study we
are proposing will influence the quality of data acquired in future clinical trials, which
in turn has implications for patient groups that may in future benefit from new
therapeutic compounds. If DCE-CT appears inferior to DCE-MRI in our study this
will avoid patients in future studies being exposed without justification to ionizing
radiation. Alternatively, if DCE-CT is identified as being superior or equivalent to
DCE-MRI it then has a strong case for inclusion in future trials due to its relatively
high clinical availability, which will improve trial throughput and therefore
potentially reduce the treatment development time scale, with associated clinical
benefit.
Proposed Work Plan
DCE-CT scanning
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Volunteers will be recruited from suitable patients by J Logue at the Christie
Hospital.
DCE-CT (with Omnipaque 300 (Nycomed)1) will be performed at Christie
Hospital (J Logue and B Taylor)
Conventional CT scanning of the pelvis will also be performed without
contrast agent to identify the location of the mass for the dynamic acquisition.
DCE-CT scanning
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Volunteers will be brought to the University site (WT-CRF) within a time
window of 1 week
The CT information will be used to guide the DCE-MRI volume; the location
of the DCE-CT slices will be incorporated within the 3D DCE-MRI imaging
volume to allow optimal correspondence for comparative analysis
DCE-MRI will be performed on the University of Manchester Philips
Gyroscan 1.5 T system (GJM Parker, D Buckley)
A standard DCE-MRI acquisition protocol will be used (high resolution T2weighted and T1-weighted (pre- and post-contrast) acquisitions plus the DCEMRI time series, which will consist of a 3D gradient echo based technique.
Contrast agent will be administered as a single dose bolus injection of
Omniscan (Nycomed1) for each patient.
Data analysis
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1
The DCE-CT and DCE-MRI data will undergo tracer kinetic modeling, which
will be applied identically to both modalities.
We will apply the adiabatic approximation to the tissue homogeneity (AATH)
model [St. Lawrence & Lee 1998, Sahani 2005], as implemented at our site
[Buckley 2002, Parker 2003, Buckley 2004, Jayson 2005] to provide estimates
within the tumour mass of blood flow, blood volume, capillary permeability
surface area product, and interstitial volume using each modality. These
parameters will be calculated on a pixel-by-pixel basis.
The DCE-CT and DCE-MRI data will be spatially aligned to allow
identification of the areas of overlap between the two acquisitions. The
The Nycomed products Omniscan and Omnipaque 300 will be used for this study, due to the similar
molecular weights and osmotic properties of these compounds, allowing the closest possible
comparison of contrast agent kinetics between the two imaging modalities.
correlation between summary variables (mean, median, standard deviation)
extracted from the tumour within the region of overlap will be assessed across
the patient group to allow assessment of the gross agreement/disagreement
between the modalities.
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The spatial correlation of each variable will be assessed within the region of
overlap of each patient, highlighting any particular regions that may exhibit
inconsistencies that may be indicative of water exchange affects in the DCEMRI data.
Milestones
Outputs (1) Information sought for AstraZeneca:
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Report on comparison
Codes for data analysis
Outputs (2) Publication opportunities:
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ISMRM conference
Journals
Project Management
Payment Schedule
Use of University Intellectual Property/third party Intellectual Property
Ethical/Home Office approvals and authorisations
Subject to approval of ethics committee
SIGNATURE PAGE OVERLEAF
Signed by Dr. Geoff Parker
Signed by Dr Tony Lacey
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______________________________
Title: Lecturer
Title: Senior Informatician
Date:
Date:
Signed by Chris Taylor
Signed by Dr John Waterton
______________________________
______________________________
Title: Professor
Title: Director of Imaging
Date:
Date:
Signed by
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Title:
Date:
References
1. Buckley, D. L., 2002. Transcytolemmal water exchange and its affect on the determination of
contrast agent concentration. Magn. Reson. Med. 47, 420-421.
2. Buckley, D. L., 2002. Uncertainty in the analysis of tracer kinetics using dynamic contrast-enhanced
T1-weighted MRI. Magn. Reson. Med. 47, 601-606.
3. Buckley, D. L., Parker, G. J. M. in Dynamic contrast-enhanced magnetic resonance imaging in
oncology (eds. Jackson, A., Buckley, D. L. & Parker, G. J. M.) 69-80 (Springer, Berlin, 2005).
4. Buckley, D. L., Roberts, C., Parker, G. J. M., Logue, J. P., Hutchinson, C. H., 2004. Vascular
characteristics of prostate cancer: evaluation with dynamic contrast-enhanced T1-weighted MRI initial experience. Radiol. 233, 709-715.
5. Jackson, A., Buckley, D. L., Parker, G. J. M. (eds.) Dynamic contrast-enhanced magnetic resonance
imaging in oncology (Springer, Berlin, 2005).
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Lawrence, J., Carrington, B., Roberts, C., Issa, B., Buckley, D. L., Cheung, S., Davies, K., Watson, Y.,
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K., Ball, H. A., Lee, L., Mietlowski, W., Fuxius, S., Unger, C., O'Byrne, K., Henry, A., Cherryman, G.
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21, 3955-3964.
10. Parker, G. J., Clark, D., Watson, Y., Buckley, D. L., Berrisford, C., Anderson, H., Jackson, A.,
Waterton, J. C., 2003. T1-weighted DCE-MRI applied to lung tumours: Pre-processing and modelling.
Proc. Int. Soc. Magn. Reson. Med., 1255.
11. Sahani, D. V., Kalva, S. P., Hamberg, L. M., Hahn, P. F., Willet, C. G., Saini, S., Mueller, P. R.,
Lee, T.-Y., 2005. Assessing tumour perfusion and treatment response in rectal cancer with multisection
CT: initial observations. Radiol. 234, 785-792.
12. St. Lawrence, K. S., Lee, T.-Y., 1998. An adiabatic approximation to the tissue homogeneity model
for water exchange in the brain: 1. Theoretical derivation. J. Cereb. Blood Flow. Metabol. 18, 13651377.