Noise Reduction to Compute Tissue Mineral Density and Trabecular Bone Volume Fraction from Low Resolution QCT

We propose a 3D neural network with specific loss functions for quantitative computed tomography (QCT) noise reduction to compute micro-structural parameters such as tissue mineral density (TMD) and bone volume ratio (BV/TV) with significantly higher accuracy than using no or standard noise reduction filters. The vertebra-phantom study contained high resolution peripheral and clinical CT scans with simulated in vivo CT noise and nine repetitions of three different tube currents (100, 250 and 360 mAs). Five-fold cross validation was performed on 20466 purely spongy pairs of noisy and ground-truth patches. Comparison of training and test errors revealed high robustness against over-fitting. While not showing effects for the assessment of BMD and voxel-wise densities, the filter improved thoroughly the computation of TMD and BV/TV with respect to the unfiltered data. Root-mean-square and accuracy errors of low resolution TMD and BV/TV decreased to less than 17% of the initial values. Furthermore filtered low resolution scans revealed still more TMD- and BV/TV-relevant information than high resolution CT scans, either unfiltered or filtered with two state-of-the-art standard denoising methods. The proposed architecture is threshold and rotational invariant, applicable on a wide range of image resolutions at once, and likely serves for an accurate computation of further micro-structural parameters. Furthermore, it is less prone for over-fitting than neural networks that compute structural parameters directly. In conclusion, the method is potentially important for the diagnosis of osteoporosis and other bone diseases since it allows to assess relevant 3D micro-structural information from standard low exposure CT protocols such as 100 mAs and 120 kVp.

Generative Modelling of 3D in-silico Spongiosa with Controllable Micro-Structural Parameters

Research in vertebral bone micro-structure generally requires costly procedures to obtain physical scans of real bone with a specific pathology under study, since no methods are available yet to generate realistic bone structures in-silico. Here we propose to apply recent advances in generative adversarial networks (GANs) to develop such a method. We adapted style-transfer techniques, which have been largely used in other contexts, in order to transfer style between image pairs while preserving its informational content. In a first step, we trained a volumetric generative model in a progressive manner using a Wasserstein objective and gradient penalty (PWGAN-GP) to create patches of realistic bone structure in-silico. The training set contained 7660 purely spongeous bone samples from twelve human vertebrae (T12 or L1) with isotropic resolution of 164um and scanned with a high resolution peripheral quantitative CT (Scanco XCT). After training, we generated new samples with tailored micro-structure properties by optimizing a vector z in the learned latent space. To solve this optimization problem, we formulated a differentiable goal function that leads to valid samples while compromising the appearance (content) with target 3D properties (style). Properties of the learned latent space effectively matched the data distribution. Furthermore, we were able to simulate the resulting bone structure after deterioration or treatment effects of osteoporosis therapies based only on expected changes of micro-structural parameters. Our method allows to generate a virtually infinite number of patches of realistic bone micro-structure, and thereby likely serves for the development of bone-biomarkers and to simulate bone therapies in advance.