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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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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


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


Glioma tx radiation


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


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


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


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


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


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


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


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


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.



ADC: How to Quantify Uncertainty?


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).


ADC – Longitudinal Monitoring

Radial Diffusion vs. Echo Planar

Echo Planar

Radial Diffusion

Magnetic resonance spectroscopy


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







Magnetic resonance spectroscopy1


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


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.


Difficulties in Glioma Diagnosis/Monitoring:

ADCs, MRS and the Role of Uncertainty


  • 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.




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


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).