Simulation, phantom validation, and clinical evaluation of fast pH-weighted molecular imaging using amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) in glioma at 3 T

Robert J Harris; Timothy F Cloughesy; Linda M Liau; Phioanh L Nghiemphu; Albert Lai; Whitney B Pope; Benjamin M Ellingson

doi:10.1002/nbm.3611

Simulation, phantom validation, and clinical evaluation of fast pH-weighted molecular imaging using amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) in glioma at 3 T

NMR Biomed. 2016 Nov;29(11):1563-1576. doi: 10.1002/nbm.3611. Epub 2016 Sep 15.

Authors

Robert J Harris^{1

2

3}, Timothy F Cloughesy⁴, Linda M Liau^{5

6}, Phioanh L Nghiemphu⁴, Albert Lai^{4

5}, Whitney B Pope², Benjamin M Ellingson^{7

8

9

10

11

12}

Affiliations

¹ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
² Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
³ Department of Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁴ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁵ UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁶ Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁷ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. bellingson@mednet.ucla.edu.
⁸ Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. bellingson@mednet.ucla.edu.
⁹ Department of Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. bellingson@mednet.ucla.edu.
¹⁰ UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. bellingson@mednet.ucla.edu.
¹¹ Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, California, USA. bellingson@mednet.ucla.edu.
¹² Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. bellingson@mednet.ucla.edu.

PMID: 27717216
DOI: 10.1002/nbm.3611

Abstract

Acidity within the extracellular milieu is a hallmark of cancer. There is a current need for fast, high spatial resolution pH imaging techniques for clinical evaluation of cancers, including gliomas. Chemical exchange saturation transfer (CEST) MRI targeting fast-exchanging amine protons can be used to obtain high-resolution pH-weighted images, but conventional CEST acquisition strategies are slow. There is also a need for more accurate MR simulations to better understand the effects of amine CEST pulse sequence parameters on pH-weighted image contrast. In the current study we present a simulation of amine CEST contrast specific for a newly developed CEST echoplanar imaging (EPI) pulse sequence. The accuracy of the simulations was validated by comparing the exchange rates and Z-spectrum under a variety of conditions using physical phantoms of glutamine with different pH values. The effects of saturation pulse shapes, pulse durations, pulse train lengths, repetition times, and relaxation rates of bulk water and exchangeable amine protons on the CEST signal were explored for normal-appearing white matter (NAWM), glioma, and cerebrospinal fluid. Last, 18 patients with WHO II-IV gliomas were evaluated. Results showed that the Z-spectrum was highly dependent on saturation pulse shape, repetition time, saturation amplitude, magnetic field strength, and T₂ within bulk water; however, the Z-spectrum was only minimally influenced by saturation pulse duration and the specific relaxation rates of amine protons. Results suggest that a Gaussian saturation pulse train consisting of 3 × 100 ms pulses using the minimum allowable repetition time is optimal for achieving over 90% available contrast across all tissues. Results also demonstrate that high saturation pulse amplitude and scanner field strength (>3 T) are necessary for adequate endogenous pH-weighted amine CEST contrast. pH-weighted amine CEST contrast increased with increasing tumor grade, with glioblastoma showing significantly higher contrast compared with WHO II or III gliomas.

Keywords: Bloch-McConnell; CEST; EPI; amino acid; glioma; pH; pH-weighted MRI; simulation.

Publication types

Evaluation Study
Validation Study

MeSH terms

Algorithms
Amines / chemistry
Amines / metabolism
Amino Acids / chemistry
Amino Acids / metabolism*
Biomarkers, Tumor / chemistry
Biomarkers, Tumor / metabolism*
Brain Neoplasms / chemistry
Brain Neoplasms / diagnostic imaging
Brain Neoplasms / metabolism*
Computer Simulation
Echo-Planar Imaging / instrumentation
Echo-Planar Imaging / methods*
Glioma / chemistry
Glioma / diagnostic imaging
Glioma / metabolism*
Humans
Hydrogen-Ion Concentration*
Image Enhancement / methods
Image Interpretation, Computer-Assisted / methods
Magnetic Resonance Spectroscopy / methods
Models, Biological
Molecular Imaging / methods*
Phantoms, Imaging
Reproducibility of Results
Sensitivity and Specificity
Signal Processing, Computer-Assisted

Substances

Amines
Amino Acids
Biomarkers, Tumor