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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. Ted Kennedy 1932-2009. 3.

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slide1

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

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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

glioma tx radiation

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

tx efficacy vs differential dx

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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?
diffusion weighted mri apparent diffusion coefficient

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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).
diffusion weighted mri apparent diffusion coefficient1

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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

apparent diffusion coefficient sulci density maps

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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

apparent diffusion coefficient

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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.
apparent diffusion coefficient uncertainty with different dw techniques

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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.
adc how to quantify uncertainty

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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
adc how to quantify uncertainty1

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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

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ADC: How to Quantify Uncertainty?

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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).
slide15

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ADC – Longitudinal Monitoring

Radial Diffusion vs. Echo Planar

Echo Planar

Radial Diffusion

magnetic resonance spectroscopy

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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

magnetic resonance spectroscopy1

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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.
magnetic resonance spectroscopy2

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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.
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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.
acknowledgement

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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

echo planar adjustment propeller

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
radial diffusion
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).
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