Difficulties in Glioma Diagnosis/Monitoring: Apparent Diffusion Coefficients, Magnetic Resonance Spectroscopy and th

1. Difficulties in Glioma Diagnosis/Monitoring: Apparent Diffusion Coefficients, Magnetic Resonance Spectroscopy and the Role of Uncertainty Saturday, 8/29/09 Lars Ewell Department of Radiation Oncology, University of Arizona Medical Center

2. Ted Kennedy 1932-2009

3. 3 Difficulties in Glioma Diagnosis/Monitoring: ADCs, MRS and the Role of Uncertainty • Introduction • Treatment Efficacy/Radiation Necrosis • Apparent Diffusion Coefficients • Comparison of Different Diffusion Techniques: Image Distortion vs. Signal to Noise Ratio • Magnetic Resonance Spectroscopy • Conclusion Outline

4. 4 Glioma Tx: Radiation • Typical Tx: Resection (if possible) followed by 60Gy radiation to de-bulked region, Temozolomide. • Poor prognosis: 14.6 months median survival for GBM1, which constitute ~1/2 of all gliomas. • Brain tissue is considered to be late responding to radiation → Months to years before radiation effects are manifest. 1: NEJM , Stupp et al., 352(10): 987-996, 3/10/2005

5. 5 Tx Efficacy vs Differential Dx Two Questions Being Addressed: • Is radiation therapy effective? • Months/Years after therapy, is enhancing lesion on contrast enhanced MRI radiation necrosis or recurrent disease?

6. 6 Diffusion Weighted MRI: Apparent Diffusion Coefficient • Isotropic diffusion weighting sensitizes MRI signal to H2O Mobility. • If tumor is successfully treated, disease site could exhibit an increase in H2O Mobility. • The Apparent Diffusion Coefficient can, in principal, quantify this increase (or lack thereof).

7. 7 Diffusion Weighted MRI: Apparent Diffusion Coefficient • Diffusion weighting of image decreases signal intensity. • Diffusion weighted images less robust to magnetic susceptibility inhomogeneitities near, e.g., paranasal sinus cavities. Two problems

8. 8 Apparent Diffusion Coefficient:Sulci Density Maps • Sulci filled with CSF, which, through volume averaging, may affect ADC calculation. • Correlate sulci density with SD of pixel intensity. • See L.A. Ewell et al. / Magnetic Resonance Imaging 26 (2008) 20–25 Medial Slice Lateral Slice

9. 9 Apparent Diffusion Coefficient • Disease site contoured by clinician on, e.g., a T2 FLAIR MRI in preparation for radiation therapy. • Lesion transcribed to DWMRI scans in order to calculate ADC. • ADC monitored longitudinally as surrogate for tumor response.

10. 10 Apparent Diffusion Coefficient: Uncertainty with Different DW Techniques • Image distortion, especially near inhomogeneities (e.g. para-nasal sinus cavities). • Noise and the signal to noise ratio (SNR). • Radial Diffusion more robust wrt distortion, but has lower SNR. • Echo planar (most common) more susceptible to distortion. • T2 FLAIR for comparison.

11. 11 ADC: How to Quantify Uncertainty? • SNR Straightforward (see, e.g., Firbank et. al, Phys. Med. Biol. 44 (1999) . • with μ the signal intensity in the ROI (lesion) and σair the SD of the background

12. 12 ADC: How to Quantify Uncertainty? • Image distortion less straightforward than SNR. • Image Registration via Mutual Information (MI). • Can plot MI vs. slice number to see dependence. DWMRI(RD) DWMRI (EP) T2FLAIR

13. 13 ADC: How to Quantify Uncertainty?

14. 14 ADC: How to Quantify Uncertainty? • Compare normalized SNR difference (EP – RD) vs. normalized MI difference (EP – RD) and plot vs. slice number. • Submitted Image Distortion vs. Noise in DWMRI Scans: Different Diffusion Weighting Techniques Compared via Image Registration to the journal MRI (Elsevier).

15. 15 ADC – Longitudinal Monitoring Radial Diffusion vs. Echo Planar Echo Planar Radial Diffusion

16. 16 Magnetic Resonance Spectroscopy • Metabolite ratios have been show to have the ability to differentiate recurrent tumor from radiation necrosis. • MRS has at least two challenges associated with it: 1) Resolution and 2) Uncertainty. Metabolite Ratio Weybright et al., Neuroradiology (2004) 46: 541–549 Recurrent Tumor Radiation Necrosis White Matter

17. 17 Magnetic Resonance Spectroscopy • Multivoxel grid allows for contra-lateral comparison. • Initially used 1x1x1cm voxel grid in imaging protocol. • Switched to 2x2x1cm grid (displayed) due to spectra quality.

18. 18 Magnetic Resonance Spectroscopy • Various different phenomena, e.g., lactate/lipid peaks and background selection affect peak area. • Subtraction of background allows for more straightforward ratio calculation. • Labor intensive. • Still assessing how to quantify uncertainty.

19. 19 Difficulties in Glioma Diagnosis/Monitoring: ADCs, MRS and the Role of Uncertainty Conclusions • Uncertainty is an important, and often overlooked, consideration when using DWMRI to asses disease diagnosis/monitoring. • Image registration with a non-diffusion weighted image is a useful way to quantify image distortion. • Image distortion and noise should be compared to see which may have the largest effect. • Uncertainty in MRS is a challenging part of using this imaging modality.

20. 20 Acknowledgement University of Arizona Amarjeet Bhullar(PhD) Baldassarre Stea (MD, PhD) Department of Electrical/Computer Engineering Naren Vijayakumar (MS) Joshua Kim (MS) Jeffrey Rodriguez (PhD) King College, Bristol TN Morgan Gillie (BS) Department of Radiation Oncology This work funded by a grant from the Arizona Biomedical Research Commission

21. 21 Echo Planar Adjustment: PROPELLER • Pipe JG, Farthing VG, Forbes KP. Multishot diffusion-weighted FSE using PROPELLER MRI. Magn Reson Med 2002;47(1):42–52. • PROPELLER – Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction

22. Radial Diffusion • Fourier data collected along radial lines. • See Sarlls et al. Isotropic Diffusion Weighting in Radial Fast Spin-Echo Magnetic Resonance Imaging, Magnetic Resonance in Medicine 53:1347–1354 (2005).