OUTLINE PROJECT PROPOSAL TEMPLATE
Title: Comparison of DCE-MRI and DCE-CT in abdominal tumours
Project Objective: I) To develop comparable dynamic contrast enhanced (DCE)
acquisition protocols for CT and MRI; II) to compare the two methods in a small
cohort of patients with abdominal tumours to assess compatibility of results; III) to
investigate the causes of any discrepancy due to water exchange effects in the MRI
data.
Rationale: DCE-MRI is routinely used in phase I/II studies of antivascular therapies
in cancer due to its ability to quantify vascular functional parameters non-invasively1.
DCE-CT has been suggested for these purposes due to its lower cost in comparison
to MRI. However, two challenges need to be overcome before DCE-CT can be used
routinely in clinical drug trials. Firstly, protocols need to be devised that have
sufficiently low radiation dose to make it ethically acceptable for their use in repeat
investigations in clinical drug trials. Secondly, the results produced by the technique
must be shown to be compatible with those produced by DCE-MRI. The first two
objectives of this project will address these issues.
The second rationale for the study is that it has been demonstrated that DCEMRI may suffer from inaccuracies due to the effects of transcapillary water
exchange2. DCE-CT does not suffer from these effects, so a successful comparative
data acquisition will allow these MRI effects to be quantified in vivo for the first time.
Background Information and Previous Literature: DCE-MRI is a method for
determining vascular functional parameters such as capillary permeability surface
area product, blood volume, and blood flow. This is achieved via the application of a
tracer kinetic model3, and has been applied successfully in a number of phase I/II
trials of antivascular agents4,5. DCE-CT has been used successfully for assessment
of microvascular parameters in brain and prostate tumours6,7, but usage has been
limited in comparison with DCE-MRI, and has not to date been applied routinely in a
trial setting.
Transcapillary water exchange has been recognised as a potential confound
for DCE-MRI2,8. Its effect is to reduce the apparent concentration of contrast agent in
a tissue during the first passage of agent, leading to a potentially significant
underestimate of tissue or tumour blood volume. DCE-CT is immune to these effects.
Draft work plan:
month: previous-3 Engage clinical collaborator for recruitment and identify CT
machine for project. Obtain Ethics, and TIU/CRF approval for scanning. Investigate
the need for Radiation Safety Advisory Committee (RSAC) approval. Determine
optimum dosage for CT and MR contrast agents and identify possible CT protocols
from literature.
month: 1-3 Implement DCE-CT protocol on machine (location to be defined).
month: 3-4 Acquire trial MR and CT datasets in single individual. Modify existing
DCE-MRI software to import and analyze DCE-CT data. Perform initial comparative
analyses to provide proof of concept.
month: 3-5 Scan a further 9 patients to obtain useful dataset.
month: 5-6 Patient data will be analysed and a manuscript completed
Number of PDF-months required: 6
Non-staff costs: 10 MR scans at £633 per hour scan = £6330. CT scan costs to be
determined, but will be considerably less than MR costs.
Proposed start and end dates: start: Feb 2005, end: July/August 2005
Milestones: Clinician engaged and CT machine identified; Ethics and other
regulatory documentation; development of DCE-CT protocol; acquisition of first
dataset; establishment of analysis methods; analysis of data; report; manuscript.
Outputs (1) Information sought for AstraZeneca: Assessment of whether
DCE-CT and DCE-MRI outputs are compatible will allow decisions regarding the
utility of DCE-CT in clinical drug trials.
Outputs (2) Publication opportunities: Clinical comparison of potential
publishable interest (radiology journal). Identification of water exchange limitations in
DCE-MRI of publishable interest (radiology or MRI journal). ISMRM and RSNA
submissions likely.
Strategic fit (AstraZeneca): Clinical trials of antivascular agents using DCE-MRI
are costly and the acquisition/analysis methods can be difficult. If DCE-CT can be
shown to be as good/better than DCE-MRI, and that the radiation risks are not
significant, this could lead to a significant cost reduction for trials. Data acquisition
and analysis may be demonstrated to be slightly more straightforward than DCEMRI. Interest in this project has been expressed by Helen Young.
Strategic fit (University): DCE-MRI is of major interest within the University, and
an improved understanding of the limitations of the technique will allow future
improved methods. DCE-CT, if shown to be useful, is likely to be of interest for future
academic studies of tumour microvasculature. Interest in this project has been
expressed by Geoff Parker, Alan Jackson, and David Buckley.
Approvals required (Human subjects, animal subjects, IPR etc): Local
Research Ethics Committee, RSAC, Translational Imaging Unit Approval, CRF
approval.
References
1. Jackson, A., Buckley, D. L. & Parker, G. J. M. (eds.) Dynamic contrastenhanced magnetic resonance imaging in oncology (Springer, Berlin,
2004).
2. Buckley, D. L. Transcytolemmal water exchange and its affect on the
determination of contrast agent concentration. Magnetic Resonance in
Medicine 47, 420-421 (2002).
3. Parker, G. J. M. & Buckley, D. L. in Dynamic contrast-enhanced magnetic
resonance imaging in oncology (eds. Jackson, A., Buckley, D. L. & Parker,
G. J. M.) 81-92 (Springer, Berlin, 2004).
4. Jayson, G. C. et al. Molecular imaging and biological evaluation of
HuMV833 anti-VEGF antibody: Implications for trial design of
antiangiogenic antibodies. Journal of the National Cancer Institute 94,
1484-1493 (2002).
5. Morgan, B. et al. Dynamic Contrast-Enhanced Magnetic Resonance
Imaging As a Biomarker for the Pharmacological Response of PTK787/ZK
222584, an Inhibitor of the Vascular Endothelial Growth Factor Receptor
Tyrosine Kinases, in Patients With Advanced Colorectal Cancer and Liver
Metastases: Results From Two Phase I Studies. Journal of Clinical
Oncology 21, 3955-3964 (2003).
6. Roberts, H. C., Roberts, T. P. L., Lee, T.-Y. & Dillon, W. P. Dynamic,
contrast-enhanced CT of human brain tumors: quantitative assessment of
blood volume, blood flow, and microvascular permeability: report of two
cases. American Journal of Neuroradiology 23, 828-832 (2002).
7. Henderson, E., Milosovic, M. F., Haider, M. A. & Yeung, I. W. T. Functional
CT imaging of prostate cancer. Physics in Medicine and Biology 48, 30853100 (2003).
8. Buckley, D. L. in Dynamic contrast-enhanced magnetic resonance imaging
in oncology (eds. Jackson, A., Buckley, D. L. & Parker, G. J. M.) 69-80
(Springer, Berlin, 2004).