Detection of Metastatic Brain Tumours Using Dynamic Glucose Enhanced MRI After D-glucose Injection
This project will compare two MRI contrast agents in metastatic brain tumours in humans.
More specifically, the investigators will compare the tumour contrast obtained using glucose
versus the current standard gadolinium-based contrast agent (GBCA, gadobutrol, trade name
Gadovist, will be used).
First, participants will receive a glucose bolus injection followed by glucose enhanced MRI.
Second, participants will receive a Gd-DTPA bolus injection followed by Gd-DTPA enhanced
MRI. Both contrast studies will be performed during the same MRI study, which will be under
one hour long.
- Integral tumour contrast generated by GBCA and glucose experiments will be assessed using Area Under Curve (AUC).
- Maximum instantaneous tumour contrast generated by GBCA and glucose experiments will be assessed.
Purpose: To quantitatively compare glucose-enhanced MRI with the current standard GBCA
enhanced MRI in participants with metastatic brain tumours prior to receiving radiation therapy
from British Columbia Cancer Agency at Vancouver Cancer Centre.
Hypotheses: 1) Glucose enhanced MRI will highlight malignant metastatic brain tumours with
comparable contrast to noise compared to GBCA and 2) Glucose enhancements in brain tumours
will offer unique and complementary information, when compared to GBCA enhanced MRIs.
Justification: The current standard MRI contrast agent for metastatic brain tumours, GBCA,
is limited by low specificity since GBCA accumulates in regions with disrupted blood brain
barrier due to cancer as well as radiation necrosis and pseudo-progression after
radiation therapy. It is important for radiation oncologists to reliably identify recurrent
cancer, necrosis and post-treatment inflammation; and GBCA does not allow this. Therefore, a
clinical need exists for an MRI technique that offers improved specificity for
characterization of metastatic brain tumours before and after therapy. Glucose enhanced MRI
represents a new technique that could offer improved specificity for detecting metastatic
Justification for number of participants included: The magnitude of signal enhancement is
expected to vary between participants because 1) metastatic brain tumours exhibit a variety
of enhancements patterns including ring, solid and nodular and 2) metastatic brain tumours
will range in size. Therefore, 20 participants is considered sufficient to provide a
reasonably accurate estimation of the expected mean tumour contrast as well as the expected
variance in tumour contrast for future clinical trials. One additional healthy participant
will be included in the study to perform a 'test-run' for the complicated MRI and infusion
1. Compare area under curve (AUC) maps calculated with glucose and GBCA in tumour and
contralateral brain areas over different time intervals.
2. Compare post-injection contrast enhanced MRIs displaying maximum tumour contrast for
single images to compare the 'instantaneous' contrast from both glucose enhanced and
GBCA enhanced MRI.
Research Design and Statistical Analysis:
Participant recruitment: Recruitment will begin with collaborating radiation oncologists
asking suitable patients if they are interested in participating in a MRI research study.
The study will be described and if patients are still interested, consent will be taken and
the screening forms will be completed. Participants will be scheduled for routine blood work
to screen for eligibility (blood glucose status and renal function). Participants will also
be scheduled for an MRI appointment at UBC MRI research centre.
Participants will be asked to fast the night before the MRI scan. They will be suggested
to:"Eat a normal dinner and then not eat and only drink water from midnight until after the
MRI scan, which will be scheduled in the morning to minimize the fasting duration."
MRI study details: To be performed at the UBC MRI research centre using a 3T Philips Achieva
Intravenous catheter preparation: Patients will arrive and an intravenous catheter will be
placed in one arm by a qualified nurse or physician. Fasting glucose levels will be measured
with a glucometer using a 1-2 mL sample of blood. Only participants with normal fasting
blood glucose levels (70-125 mg/dL) will proceed with the study. The first intravenous
catheter will be used to monitor blood glucose every 10 minutes after bolus injection until
it returns to normal. A second intravenous catheter is placed on the opposite arm for
glucose infusion and GBCA (gadobutrol) infusion.
Glucose infusion protocol: This will occur when the participant is lying in the MRI. The
protocol mimics the intravenous glucose tolerance test. Bolus injection of hospital grade
25g of 50% dextrose solution over 1 minute is used to increase blood glucose concentrations
to approximately 3-4 times the normal level. Blood glucose levels should return to normal
levels within 30 to 60 minutes according to previous studies.
GBCA infusion protocol: This will also occur when the participant is lying in the MRI and
approximately 20 minutes after glucose infusion. Standard intravenous bolus injection of
0.1mM/kg of gadobutrol (Gadovist) at an injection rate of 5 mL/sec.
MRI timeline: Metastatic tumours will be initially detected using standard 3D T2-weighted
MRI. Then a slice of interest containing maximum tumour coverage will be selected for the
remainder of the study. In participants with multiple metastases, the largest untreated
lesion will be the focus and multiple lesions will be included if feasible.
MRI scans will include: 1) Scouts and magnetic field shimming; 2) 3D T2 weighted MRI; 3)
Magnetic field maps (B0 & B1); 4) Pre- glucose injection Z-spectrum; 5) Begin serial glucose
enhanced MRI; [glucose infusion after 3 minutes]; 6) Post- glucose injection Z-spectrum
after 10 minutes; 7) Begin serial T1-weighted gadobutrol enhanced MRI; [gadobutrol infusion
after 3 minutes]; 8) Continue Gd-enhanced MRI scans until 10 minutes post-injection.
MRI data analysis will be performed using well documented, standard techniques using
custom-built Matlab software.
Statistics: Mean and standard deviation statistics will be calculated for both glucose
enhanced and gadobutrol enhanced data. Tumour contrast to noise will be calculated using AUC
curves as well as single MR images. These metrics will help to quantify the tumour detection
sensitivity of glucose enhanced MRI relative to GBCA enhanced MRI. The investigators expect
that both techniques will offer similar contrast to noise in metastatic tumours, based on
previously reported results in human participants with glioma tumours.
View this trial on ClinicalTrials.gov