Transcript mri - University of Arizona

Methods to Differentiate Radiation Induced
Necrosis and Recurrent Disease in Gliomas
Lars Ewell
University of Arizona Medical Center
Department of Radiation Oncology
MRI Research Group
2/2/07
Methods to Differentiate Radiation Induced
Necrosis and Recurrent Disease in Gliomas
I.
II.
III.
IV.
V.
VI.
VII.
Introduction: The Problem
Radiation Damage: Brain vs. Tumor
Similarities/Differences
MRS: Metabolite Ratios
DWMRI: ADC
ABRC Grant
Conclusion
2
Radiation Induced Necrosis
• Radiation is one of the few proven currently
known methods to increase survival and
quality of life for glioma (brain tumor)
patients.
• Radiation dose has been correlated with
recurrence.
• Too much radiation can kill normal brain
tissue.
3
Radiation Dose

 m
• Dose
with  the energy imparted by
ionizing radiation to material of mass m .
•  [dose] = Energy/Mass and the SI unit of dose =
Gray = Gy = 1J/Kg.
• Lethal dose is ~4Gy given to the whole body in
~ seconds.
• Typical Rx dose for a glioma is 60Gy given in
30 Fx (2Gy/Fx) over 6 weeks.
• Diagnostic dose (CAT Scan) ~10cGy.
4
Radiation Damage: Cell Survival
• The ‘linear – quadratic’
model of cell survival, w/
S the surviving
fraction, D the dose and
 constants.
• The ratio  has units of
dose, and is used to
determine tissue radiation
reaction.
100
Surviving Fraction
S e
D  D 2
10-1
10-2
4
8
12
Radiation Dose (Gy)
5
Radiation Damage: Early - Late
• The ratio  has been correlated with
response time for radiation damage to
manifest.
• For brain and/or spinal cord,  ~ 2Gy
indicating a late radiation response (months
to years).
• For tumor,  ~ 10 Gy indicating an early
radiation response (weeks to months).
6
RIN/Recurrent Disease
• T1 weighted contrast
enhanced MRI taken
16 months after
completion of
radiotherapy (left).
• Same MRI taken 2
months, 15 days later.
• Biopsy later revealed
no evidence of
recurrent tumor.
Kumar et al., Radiology, 217, 2, November 2000.
7
RIN/Recurrent Disease: Comparison
1. ‘Enhancing lesion’
on MRI.
2. Origin at or near
primary site.
3. Growth over time.
Similarities:
1. Additional radiation
can benefit recurrent
disease.
2. Additional radiation
detrimental to RIN.
Differences:
8
DWMRI to Distinguish RIN and
Recurrent Disease
• Since RIN may have same characteristics as
successfully treated tumor, one may think that
using DWMRI could differentiate RIN from
recurrent disease.
• However, initial studies show little value in using
DWMRI to differentiate RIN and recurrent
disease. Limited resolution of DWMRI one
problem.
• Radial Fast Spin Echo (RFSE) promises better
DWMRI resolution.
9
Magnetic Resonance
Spectroscopy
• MRS, also called Chemical Shift Imaging (CSI),
gets signal from shift in resonance due to
surrounding chemical environment.
• Using MRS, the ratio of brain metabolites such as
Choline (Cho), Creatine (Cr) and NAcetylaspartate (NAA) can be measured.
• These ratios have been shown to have power to
discriminate RIN and recurrent disease.
10
MRS Metabolites
• Cho is a neurotransmitter and is increased in
tumors. Correlated with high cellular
density.
• NAA is a metabolite found in neurons, and
is decreased in tumors.
• Cr is a brain metabolite and is also
decreased in tumors.
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MRS Metabolite Ratios
Metabolite Ratios for Different Tissue *
Ratio
• 2D CSI scans given to
seven patients.
• 16cm FOV, 16x16 and
slice thickness of 1020mm.
• 1 average, scan time of 4
min., 20sec.
• Absence of tumor
confirmed by biopsy in
two patients.
*
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
Cho/Cr
Cho/NAA
NAA/Cr
1
2
3
Recurrent
Tumor
Radiation
Induced Necrosis
White
Matter
*
Weybright et al., Neuroradiology (2004) 46:
541–549
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Magnetic Resonance
Spectroscopy
NAA
Cho
13
Cr
MRS
• ‘Quick and Dirty’
2D multi-voxel
scans taken 1/25/07
– pre and post Gd.
• 3:18 with 2 NEX.
• 3x3cm voxels, 1cm
thick.
• Disease visible in
voxel #2.
14
MRS: Normal vs. Disease
Voxel # 7 - Normal
Voxel # 2 - Disease
15
MRS: Pre vs. Post Gd
Pre Gd
Post Gd
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Magnetic Resonance
Spectroscopy
• Although MRS has been shown to have
discriminating power, there are two
problems associated with it: 1) Low
resolution. 2) Long scan time.
• Imaging protocol will join MRS with RFSE
DWMRI to create synergistic combination.
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Arizona Biomedical Research
Commission
• Grant Awarded: Diffusion Weighted MRI
and Magnetic Resonance Spectroscopy to
Differentiate Radiation Necrosis and
Recurrent Disease in Gilomas (PI LAE).
• Enroll 60 patients diagnosed with a glioma
(metastatic or primary) and follow
longitudinally.
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Imaging Protocol
• Patients eligible to enroll if they have a
reasonable risk of suffering from RIN.
• Published data indicate that patients
receiving a dose of  60Gy in 30 Fx have
between a 5 and 24% chance of developing
RIN.
• Hypo-fractionation and Stereotactic RadioSurgery (SRS) are also forms of radiation
Tx.
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Imaging Protocol: Enrollment Criteria
• Biological Equivalent Dose (BED) used to
determine enrollment criteria for hypofractionation and SRS.
d
 /
• BED = nd(1 +
) with n the
number of fractions, d the dose,  and
 the linear quadratic constants.
• 5 x 6Gy required for hypo fractionation, 21Gy for SRS.
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Imaging Protocol: Enrollment
Criteria
Radiation Type
Number of
Fractions
Minimum
Radiation (Gy)
SRS
1
21
Hypo-fraction
5
30
Normal Fraction
30
60
Re-treatment
varies
varies
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Imaging Protocol: Imaging Sequence
Time from End of
Radiotherapy (days)
Scans Performed
Comments
-5
CT, MRI, DWMRI, MRS
Baseline scans. Used to
plan radiotherapy. CT
and MRI registered using
Brainscan.
30
MRI, DWMRI, MRS
First scan for
comparison.
90
MRI, DWMRI, MRS
Second scan for
comparison. Potential
radiation necrosis.
Check ADCW for change.
22
Imaging Protocol
• VOI centered at center of
resection cavity.
• 2D Multi-voxel CSI with
1cm slice thickness.
7x7cm.
• Three slices, ~8:30 for
each slice, one centered on
lesion and one superior
and inferior.
• MRS will take majority of
time.
Regions to be Longitudinally Monitored
1cm
2cm
Center of Resection Cavity
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Imaging Protocol
• Current ‘Gold Standard’ for confirming glioma
vs. RIN is pathologic examination of biopsy.
• We expect that ~50% of enrolled patients will
undergo biopsy at some point.
• Vector Vision should locate biopsy location to
within ~2mm.
• Biopsy MRI registered with protocol MRI using
Brainscan software.
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Imaging Protocol
• Approved by SRC 11/14/06.
• Third submission to IRB will take place
early next week.
• Expect approval shortly thereafter –
2/13/07
• Patient enrollment thereafter.
25
Conclusion
• DWMRI and MRS are non-invasive forms
of medical imaging that show promise for
differentiation between RIN and recurrent
disease in glioma patients.
• It will take work to realize the full potential
of these complimentary imaging forms.
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Acknowledgement
•
•
•
•
•
Chris Watchman, Russ Hamilton
Dino Stea, Marco Marsella
Thomas Chong
Scott Squire
Jamie Holt
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