Methods to Differentiate Radiation Induced Necrosis and Recurrent Disease in Gliomas

1
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
2
Methods to Differentiate Radiation Induced
Necrosis and Recurrent Disease in Gliomas

• Introduction The Problem
• Radiation Damage Brain vs. Tumor
• Similarities/Differences
• MRS Metabolite Ratios
• DWMRI ADC
• ABRC Grant
• Conclusion

3
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.

4
Radiation Dose

• ? 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.

5
Radiation Damage Cell Survival
100

• The linear quadratic model of cell survival,
  w/ S the surviving fraction, D the dose and
  ???? constants.

10-1
Surviving Fraction

• The ratio ??? has units of dose, and is used to
  determine tissue radiation reaction.

10-2
4
8
12
Radiation Dose (Gy)
6
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).

7
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.
8
RIN/Recurrent Disease Comparison

• Enhancing lesion on MRI.
• Origin at or near primary site.
• Growth over time.

Similarities

• Additional radiation can benefit recurrent
  disease.
• Additional radiation detrimental to RIN.

Differences
9
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.

10
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
  N-Acetylaspartate (NAA) can be measured.
• These ratios have been shown to have power to
  discriminate RIN and recurrent disease.

11
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.

12
MRS Metabolite Ratios

• 2D CSI scans given to seven patients.
• 16cm FOV, 16x16 and slice thickness of 10-20mm.
• 1 average, scan time of 4 min., 20sec.
• Absence of tumor confirmed by biopsy in two
  patients.

Weybright et al., Neuroradiology (2004) 46
541549
13
Magnetic Resonance Spectroscopy
NAA
Cho
Cr
14
MRS

• Quick and Dirty 2D multi-voxel scans taken
  1/25/07 pre and post Gd.
• 318 with 2 NEX.
• 3x3cm voxels, 1cm thick.
• Disease visible in voxel 2.

15
MRS Normal vs. Disease
Voxel 7 - Normal
Voxel 2 - Disease
16
MRS Pre vs. Post Gd
Pre Gd
Post Gd
17
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.

18
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.

19
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 Radio-Surgery
  (SRS) are also forms of radiation Tx.

20
Imaging Protocol Enrollment Criteria

• Biological Equivalent Dose (BED) used to
  determine enrollment criteria for
  hypo-fractionation and SRS.

• 5 x 6Gy required for hypo - fractionation, 21Gy
  for SRS.

21
Imaging Protocol Enrollment Criteria
22
Imaging Protocol Imaging Sequence
23
Imaging Protocol

• VOI centered at center of resection cavity.
• 2D Multi-voxel CSI with 1cm slice thickness.
  7x7cm.
• Three slices, 830 for each slice, one centered
  on lesion and one superior and inferior.
• MRS will take majority of time.

24
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.

25
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.

26
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.

27
Acknowledgement

• Chris Watchman, Russ Hamilton
• Dino Stea, Marco Marsella
• Thomas Chong
• Scott Squire
• Jamie Holt