T2-weighted MRI, an integrated part of multi-parametric MRI for prostate cancer diagnostics, is indispensable for qualitative evaluation of prostate anomalies. For quantitative assessment, however, normalization is necessary for comparison within and between patients. In this study, we developed and validated a fully automated object recognition method for multi-reference tissue normalization. The performance of the method was superior to existing fully automated normalization strategies, and the resulting pseudo T2 values were close to true T2 values from literature. The developed multi-reference tissue normalization method may thus improve the reproducibility and diagnostic performance of T2-weighted image features in future quantitative applications.
Figure 1 gives an overview of the proposed method, which was trained (N=40), tested (N=20) and validated (N=20) using the images and prostate segmentations from the PROMISE12 grand challenge multi-center / multi-vendor dataset (N=80).3 Briefly, two separate aggregate channel features (ACF) object detectors 4 were trained to detect rectangular regions-of-interest containing fat and muscle, respectively, in the 2D T2-weighted MR slices. Fat and muscle regions-of-interest were then obtained as the largest connected bright and dark structures in the detected rectangle, respectively, using Otsu thresholding, 5 and fat and muscle intensity values (Ifat and Imuscle, respectively) were calculated. Subsequently, the 3D image intensities I(x,y,z) were normalized to pseudo T2 values pT2(x,y,z) by linearly scaling Ifat and Imuscle to their respective T2 values at 3T from literature (T2fat = 121 ms and T2muscle = 40 ms), 6 using $$$pT2(x,y,z) = (T2^{fat} – T2^{muscle}) / (I^{fat} – I^{muscle}) * (I(x,y,z) – I^{muscle}) + T2^{muscle}$$$.
The training and test datasets were used to train the object detectors and to find the pre- and post-processing settings that resulted in the best performance, defined as the lowest between-patient standard deviation of mean prostate intensities in the test set. The trained detectors and optimal parameter settings were subsequently applied to the validation set. The performance of the proposed method (autoref) was measured as the mean histogram intersection of each patient with all other patients in the validation set (prostate only). Paired t-tests were used to assess differences between the proposed method, the original dataset (orig), and three other automated normalization methods: histogram stretching (stretch), z-score normalization (z-score), and histogram equalization (equal).7 The resulting pseudo T2 values of prostate tissue were compared to T2 values found in literature.6 The algorithm was implemented in MATLAB 2017b (The Mathworks, Nattick, MA).
The proposed image normalization method successfully reduced the non-biological between-patient variation in T2-weighted intensities, which could facilitate the extraction and application of meaningful intensity-based features for quantitative assessment of prostate cancer, e.g. in a radiomics setting.8 Stoilescu et al. found that multi-reference tissue normalization of T2-weighted prostate images indeed significantly improves the diagnostic accuracy, but their method was based on manually delineated regions-of-interest so far.2 The ACF detector used in this work is a classical machine learning approach that accurately detected fat and muscle regions, despite the small training dataset.
An advantage of our method to e.g. z-score normalization is that the image intensities could be correctly mapped to literature T2 values. These pseudo T2 values could be an interesting alternative to quantitative T2 mapping given the limited scan time in clinical practice.9 Unfortunately, quantitative T2 maps were not available for direct comparison in this work. Whether our normalization method can improve the reproducibility and diagnostic performance of T2-weighted image features extracted from prostate cancer regions-of-interest remains part of future research.
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