Walter Zhao1,2, Zheyuan Hu1, Anahita Fathi Kazerooni3,4, Gregor Körzdörfer5, Matthias Nittka5, Christos Davatzikos3,4, Satish E. Viswanath1, Xiaofeng Wang6, Chaitra Badve7, and Dan Ma1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 2Medical Scientist Training Program, Case Western Reserve University, Cleveland, OH, United States, 3Center for Biomedical Image Computing and Analysis, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 4Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 5Siemens Healthineers, Erlangen, Germany, 6Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States, 7Department of Radiology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, United States
Synopsis
MR fingerprinting (MRF) is a rapid, quantitative imaging
approach with significant potential for use in clinical studies, including
radiomic applications. Due to its quantitative nature, robustness to system
imperfections, and requiring fewer image preprocessing steps, we believe MRF
radiomics is uniquely positioned to offer improved reproducibility and
generalizability compared to conventional MRI. Here we report reproducibility
results of MRF T1 and T2 radiomic features in the healthy human brain, and
introduce a novel physics-informed quantization approach for improved
reproducibility of quantitative image texture features.
Introduction
MR fingerprinting (MRF) is a rapid quantitative imaging technique with
superior repeatability and reproducibility compared to conventional MRI1–3
and thus significant potential for use in large-scale clinical studies.
Previous MRF reproducibility studies have been limited to relaxometry. Because
MRF is inherently quantitative, robust to system
imperfections4, and does not
require significant image
preprocessing , we hypothesize that MRF will
contribute to more reproducible
image analysis and outcome prediction5,6 . This study is a first attempt at
comprehensively evaluating the reproducibility of MRF T1 and T2 radiomic
features in the healthy human brain. In addition, we propose and evaluate the utility of a
novel, physics-informed (PI) quantization approach for more reproducible
texture feature calculation of quantitative images.Methods
Study design, imaging protocol, and preprocessing
Conventional MRI and prototype MRF data from three healthy volunteers
were obtained using five distinct 3T MAGNETOM Vida scanners (Siemens
Healthcare, Erlangen, Germany). Each volunteer underwent five scans on each
scanner, for a total of 25 scans. Examinations included whole-head 3D T1-weighted
MPRAGE (0.94x0.94x0.9 mm3) and 2D FISP MRF7,8
(1.0x1.0x5.0 mm3, 13
slices) acquisitions. T1w images were segmented using an atlas-based approach9
and registered to MRF T1 and T2 maps, after which 14 brain regions were
identified for analysis.
Quantization approaches for radiomic analysis
Three-dimensional radiomic features were extracted using in-house
MATLAB (MathWorks, Natick, MA, USA) software benchmarked to Image Biomarker
Standardization Initiative (IBSI) guidelines10. Twenty-five
intensity and 74 texture features were extracted for each experimental setting
and image type (T1, T2, and T1w).
Because of its weighted contrast, T1w texture features were only
calculated using conventional fixed bin count quantization: the range of
intensities in an ROI are divided into a pre-defined number of equally spaced
bins, then intensities are mapped to their corresponding bin (Figure 1). To
analyze the effect of preprocessing on texture feature reproducibility from T1w images, radiomic features were also calculated after intensity normalization (min-max
or z-score) or after resolution matching to MRF.
The proposed physics-informed (PI) approach (Figure
1) performs quantization using a universally fixed intensity range, bin width,
and bin count, and takes advantage of the quantitative nature of MRF: voxel
intensities are a direct measure of tissue properties. Thus, an absolute range
of MRF measurement values can be identified from a standard reference (for
maximum T1 and T2, NMR relaxometry of pure water). A fixed bin width can also
be defined using the dictionary step size. Given a fixed range and bin width, a
fixed bin count is then defined. Importantly, the intensity range, bin width,
and bin count are then universally applied to all images, independent of
individual ROI information and without requiring intensity normalization or
outlier removal. MRF texture features were calculated using physics-informed
(PI) quantization (Figure 1) and fixed bin count quantization.
Statistical analysis
Feature reproducibility was measured via coefficient
of variation (CV), the ratio of standard deviation to mean, for T1w images and T1 and T2 maps over each volunteer’s
25 scans. The following CV ranges were defined: excellent (CV < 5%), good
(5% <= CV < 10%), moderate (10% <= CV < 20%), and poor (CV >=
20%).Results
MRF intensity features demonstrate superior
reproducibility compared to T1w
A comprehensive heatmap of T1, T2, and T1w intensity feature
reproducibility is shown in Figure 2. Overall, more T1 (44.9%) and T2 (34.3%)
intensity features demonstrated excellent reproducibility compared to T1w (4.9%).
Physics-informed quantization offers tissue-specific
physiologic interpretation of and more reproducible MRF radiomic features
Compared to conventional quantization, PI quantization preserves the
physiological meaning of quantitative data like between GM and WM regions
(Figure 3). PI quantization also allows for greater standardization of radiomic
findings and offers reduced sensitivity to sources of study variability such as
segmentation errors and measurement outliers (Figure 3).
T1 and T2 texture feature reproducibility in temporal WM following PI
and conventional quantization (32 bins) was compared to T1w via thermometer
plots with bars representing the proportion of features in each CV range
(Figure 4). For all texture families, T1 PI quantization had the greatest
proportion of features with excellent reproducibility compared to T1 or T1w conventional
quantization.
The effect of varying bin count,
intensity normalization, and matching spatial resolution on T1w texture
reproducibility was assessed (Figure 5). No appreciable improvement in
reproducibility was seen after any operations.Discussion
This study comprehensively
evaluated the reproducibility of MRF radiomics in the healthy human brain: we report superior reproducibility of MRF
intensity and texture features compared to conventional MRI. We also introduce
a physics-informed (PI) approach to quantitative image quantization that offers
several advantages including robustness to outliers and segmentation, reduced
sensitivity to preprocessing variation, and preservation of physiological
meaning of data. These advantages improve reproducibility of MRF T1
and T2 texture features compared to conventional MRI, even after varying bin count, intensity
normalization, and resolution matching.
Besides MRF, PI quantization is
applicable to any quantitative imaging technique including other quantitative MRI
methods or computed tomography (CT). This method thus has considerable
application in improving replicability and generalizability of radiomics and
machine learning findings.Conclusion
We report superior reproducibility
of MRF radiomic features compared to conventional MRI and demonstrate the
significant advantages of our proposed physics-informed radiomics quantization
approach.Acknowledgements
This work was supported in part by Siemens Healthineers as well as NIH grants R01 NS109439, R21 EB026764, T32 GM007250, and TL1 TR000441.References
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