Xin Ge1,2, Xueying Huang2, Aijun Wang2, Kai Zhu2, Xiaocheng Wei3, Min Li4, Ying Shen1,2, Wenxiao Liu1,2, Peng Yong1,2, Ruirui Lv1,2, Xuhong Yang1,2, and Xiaodong Wang2
1Ningxia Medical University, Yinchuan, China, 2General Hospital of Ningxia Medical University, Yinchuan, China, 3GE Healthcare, MR Research, Beijing, China, Beijing, China, 4GE Healthcare, MR Enhancement Application, Beijing, China, Beijing, China
Synopsis
This
work sought to investigate the performance of synthetic MRI, ASL and DWI in
differentiating LGGs from HGGs as compared
to conventional MRI. It was concluded that the T1 and PD from synthetic MRI can be used as novel quantitative imaging
biomarkers for grading gliomas. Combining
T1, PD, CBF and ADC may explore as an effective strategy to improve the ability
for discriminating gliomas grade, and outperformed conventional approaches.
Introduction
Gliomas are the most common primary intracranial tumors of
neuroepithelial origin, which are classified by the WHO into four grades according
to pathological appearance1. State-of-the-art gliomas treatment
including surgery and concurrent chemoradiation2. The ability of
discriminating low-grade gliomas (LGGs) from high-grade gliomas (HGGs) is
essential for appropriate diagnosis and treatment, especially when it is in an
unresectable state. At present, the diagnosis of gliomas mainly depends on
histopathology, and the tumor tissue needs to be obtained by biopsy or surgical
excision, which is not only invasive, but also subject to sampling bias and it
may not be representative of the intra-tumoral heterogeneity3. As an image-based conventional
MR glioma grading system, Visually-AcceSAble-Rembrandt-Images (VASARI) is
widely adopted and is often used in articles
that include tumor morphology description4, 5. Meanwhile, contrast-free MRI techniques, including ASL and DWI, have also
been intensely investigated6. In recent years, proposed synthetic
MRI using the magnetic resonance image compilation (MAGiC) has emerged, which
can simultaneously quantify tissues’ synthetic relaxometry (T1, T2) and PD, as
well as a variety of weighted images within a clinically acceptable scan time7,
8. In addition, each individual MR method has its unique virtues and
drawbacks which could yield complementary information, thus combining different
modalities has been suggested to increase prediction accuracy9. Thus, the purpose of this study was to investigate and compare the
diagnostic performance of synthetic MRI, ASL and DWI and their combination for
the diagnosis and grading of glioma, aiming to find a quantitative and
contrast-free alternative to conventional MRI.Material and Methods
From August 2020 to July 2021, a total of 72 gliomas
patients (40 men and 32 women; mean age, 45.06 ± 17.15 years; age range, 4-72
years) were confirmed by biopsy or surgical pathology enrolled in the study. All
patients underwent MR exams with a 3.0T whole-body scanner (Signa Architect, GE,
USA) with a 48-channel phased-array head coil. The scan sequences included
synthetic MRI, ASL, DWI and contrast-enhanced T1FLAIR (T1FLAIR+C). Synthetic
relaxometry (T1, T2) and PD maps, were generated from the raw data produced by MAGIC
sequence using a vendor-provided program (MAGiC, v. 100.1.1). The detailed
parameters for imaging sequences are shown in Table 1. For synthetic MRI, three
ROIs (25-35mm2) were manually drawn on the largest area of the solid
portion lesion. The ROIs were then mapped to the CBF and ADC images. Finally,
the mean values of ROIs for each parameter were calculated. For the purposes of
this study, the two relevant VASARI features (enhancement quality, EQ;
proportion enhancing, PE) were used to describe the conventional
contrast-enhanced MRI features of gliomas. These variables were visually
estimated by 2 observers and then divided into categories and scoring according
to the VASARI guide. (http://wiki. cancer imaging archive.
net/display/Public/VASARI+Research+Project). The Student’s t-test, Mann-Whitney
U-test or Fisher’s exact test was used to compare the parameters between LGGs
and HGGs. Receiver operating characteristic (ROC) curves (AUC) were also
evaluated to assess the diagnostic value of parameters for discrimination.Results
Representative images are illustrated in Figure 1 and 2. The differences
of T1, T2, PD, CBF, ADC, EQ and PE between LGGs and HGGs are summarized in
Table 2. There are significant differences in T1, PD, CBF, ADC, EQ and PE values
between the LGGs and HGGs group (all P<0.001). Table 3 shows the AUC, Sen,
Spe, PPV and NPV for the determined cut-off values. ROC analysis showed that
ADC presented the largest AUC of 0.905 for identifying LGGs, followed by T1
(AUC=0.861), PD (AUC=0.855) and CBF (AUC=0.784). Combination of four parameters
(T1+PD+CBF+ADC) have the highest AUC (0.993) among all combined parameters.
DeLong test indicates T1+PD+CBF+ADC is significantly higher than CBF+ADC
(P=0.0158), as well as EQ+PE (P=0.0016). However, there is no
significant difference (P=0.2078) observed between CBF+ADC and EQ+PE.Discussion
The results revealed that
lower T1, PD, CBF, EQ and PE as well as higher ADC in LGGs than HGGs,
furthermore, quantitative multi-parameters of T1+PD+CBF+ADC improved the
differentiation performance. The synthetic relaxometry represent the inherent
properties of matter and the ADC show microstructural differences at the
cellular level, if necessary, the CBF could bring hemodynamic information which
may thereby improve the situation of enhanced T1 (EQ and PE) just reflects a
disrupted BBB and reduce visual information characteristics of subjectivity.These advanced protocols would
have an omni-directional and omni-depth role in assessing the tumor biological
characteristics, thereby reducing the dependence of diagnosis on subjective
factors. Of note, as none of synthetic relaxometry, ASL or DWI rely on
exogenous contrast or tracers, would be beneficial for pregnant patients and
those with gadolinium contrast agent allergy or decreased renal function10,11.The
number of patients included in this study is limited, particularly that of
LGGs, a study with larger cohorts is still needed for further clinical
validation.Conclusion
We have demonstrated that relaxometry parameters
derived from synthetic MRI contributed to the discrimination of LGGs from HGGs.
Proposed contrast-free approach combining T1, PD, CBF and ADC showed a strong
discriminative power, and outperformed conventional approaches.Acknowledgements
No acknowledgement found.References
1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health
Organization Classification of Tumors of the Central Nervous System: a summary.
Acta Neuropathol 2016;131:803-20.
2. Thust SC, Heiland S, Falini A,
et al. Glioma imaging in Europe: A
survey of 220 centres and recommendations for best clinical practice. Eur
Radiol 2018;28:3306-17.
3. Xiao H, Chen Z, Lou X, et al.
Astrocytic tumour grading: a comparative study of three-dimensional
pseudocontinuous arterial spin labelling, dynamic susceptibility
contrast-enhanced perfusion-weighted imaging, and diffusion-weighted imaging.
Eur Radiol 2015;25:3423-30.
4. Su CQ, Lu SS, Zhou MD, et al.
Combined texture analysis of diffusion-weighted imaging with conventional MRI
for non-invasive assessment of IDH1 mutation in anaplastic gliomas. Clin
Radiol. 2019 Feb;74:154-60.
5. Su CQ, Lu SS, Han QY, et al. Intergrating conventional MRI, texture
analysis of dynamic contrast-enhanced MRI, and susceptibility weighted imaging
for glioma grading. Acta Radiol. 2019 Jun;60:777-87.
6. Kang X, Xi Y, Liu T, et al.
Grading of Glioma: combined diagnostic value of amide proton transfer weighted,
arterial spin labeling and diffusion weighted magnetic resonance imaging. Bmc
Med Imaging 2020;20:50.
7. Tanenbaum LN, Tsiouris AJ,
Johnson AN, et al. Synthetic MRI for Clinical Neuroimaging: Results of the
Magnetic Resonance Image Compilation (MAGiC) Prospective, Multicenter,
Multireader Trial. Am J Neuroradiol 2017;38:1103-10.
8. Warntjes JBM, Leinhard OD, West J, et al. Rapid magnetic
resonance quantification on the brain: Optimization for clinical usage. Magn
Reson Med 2008;60:320-9.
9. Heiss WD, Raab P, Lanfermann H. Multimodality assessment
of brain tumors and tumor recurrence. J Nucl Med. 2011;52:1585 –1600.
10. Gao W, Zhang S, Guo J, et al. Investigation of Synthetic Relaxometry and Diffusion Measures in the
Differentiation of Benign and Malignant Breast Lesions as Compared to BI‐RADS.
J Magn Reson Imaging 2021;53:1118-27.
11. Kang
KM, Choi SH, Hwang M, et al. T1 Shortening in the Globus
Pallidus after Multiple Administrations of Gadobutrol: Assessment with a
Multidynamic Multiecho Sequence. Radiology 2018;287:258-66.