Learn2Reg: Comprehensive Multi-Task Medical Image Registration Challenge, Dataset and Evaluation in the Era of Deep Learning.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Cross-term-compensated gradient waveform design for tensor-valued diffusion MRI.

Diffusion MRI uses magnetic field gradients to sensitize the signal to the random motion of spins. In addition to the prescribed gradient waveforms, background field gradients contribute to the diffusion weighting and thereby cause an error in the measured signal and consequent parameterization. The most prominent contribution to the error comes from so-called 'cross-terms.' In this work we present a novel gradient waveform design that enables diffusion encoding that cancels such cross-terms and yields a more accurate measurement. This is achieved by numerical optimization that maximizes encoding efficiency with a simultaneous constraint on the 'cross-term sensitivity' (c = 0). We found that the optimized cross-term-compensated waveforms were superior to previous cross-term-compensated designs for a wide range of waveform types that yield linear, planar, and spherical b-tensor encoding. The efficacy of the proposed design was also demonstrated in practical experiments using a clinical MRI system. The sensitivity to cross-terms was evaluated in a water phantom with a folded surface which provoked strong internal field gradients. In every comparison, the cross-term-compensated waveforms were robust to the effects of background gradients, whereas conventional designs were not. We also propose a method to measure background gradients from diffusion-weighted data, and show that cross-term-compensated waveforms produce parameters that are markedly less dependent on the background compared to non-compensated designs. Finally, we also used simulations to show that the proposed cross-term compensation was robust to background gradients in the interval 0 to 3 mT/m, whereas non-compensated designs were impacted in terms of a severe signal and parameter bias. In conclusion, we have proposed and demonstrated a waveform design that yields efficient cross-term compensation and facilitates accurate diffusion MRI in the presence of static background gradients regardless of their amplitude and direction. The optimization framework is compatible with arbitrary spin-echo sequence timing and RF events, b-tensor shapes, suppression of concomitant gradient effects and motion encoding, and is shared in open source.

Motion-compensated gradient waveforms for tensor-valued diffusion encoding by constrained numerical optimization.

PURPOSE: Diffusion-weighted MRI is sensitive to incoherent tissue motion, which may confound the measured signal and subsequent analysis. We propose a "motion-compensated" gradient waveform design for tensor-valued diffusion encoding that negates the effects bulk motion and incoherent motion in the ballistic regime. METHODS: Motion compensation was achieved by constraining the magnitude of gradient waveform moment vectors. The constraint was incorporated into a numerical optimization framework, along with existing constraints that account for b-tensor shape, hardware restrictions, and concomitant field gradients. We evaluated the efficacy of encoding and motion compensation in simulations, and we demonstrated the approach by linear and planar b-tensor encoding in a healthy heart in vivo. RESULTS: The optimization framework produced asymmetric motion-compensated waveforms that yielded b-tensors of arbitrary shape with improved efficiency compared with previous designs for tensor-valued encoding, and equivalent efficiency to previous designs for linear (conventional) encoding. Technical feasibility was demonstrated in the heart in vivo, showing vastly improved data quality when using motion compensation. The optimization framework is available online in open source. CONCLUSION: Our gradient waveform design is both more flexible and efficient than previous methods, facilitating tensor-valued diffusion encoding in tissues in which motion would otherwise confound the signal. The proposed design exploits asymmetric encoding times, a single refocusing pulse or multiple refocusing pulses, and integrates compensation for concomitant gradient effects throughout the imaging volume.

Tensor-valued diffusion encoding for diffusional variance decomposition (DIVIDE): Technical feasibility in clinical MRI systems.

Microstructure imaging techniques based on tensor-valued diffusion encoding have gained popularity within the MRI research community. Unlike conventional diffusion encoding-applied along a single direction in each shot-tensor-valued encoding employs diffusion encoding along multiple directions within a single preparation of the signal. The benefit is that such encoding may probe tissue features that are not accessible by conventional encoding. For example, diffusional variance decomposition (DIVIDE) takes advantage of tensor-valued encoding to probe microscopic diffusion anisotropy independent of orientation coherence. The drawback is that tensor-valued encoding generally requires gradient waveforms that are more demanding on hardware; it has therefore been used primarily in MRI systems with relatively high performance. The purpose of this work was to explore tensor-valued diffusion encoding on clinical MRI systems with varying performance to test its technical feasibility within the context of DIVIDE. We performed whole-brain imaging with linear and spherical b-tensor encoding at field strengths between 1.5 and 7 T, and at maximal gradient amplitudes between 45 and 80 mT/m. Asymmetric gradient waveforms were optimized numerically to yield b-values up to 2 ms/µm2. Technical feasibility was assessed in terms of the repeatability, SNR, and quality of DIVIDE parameter maps. Variable system performance resulted in echo times between 83 to 115 ms and total acquisition times of 6 to 9 minutes when using 80 signal samples and resolution 2×2×4 mm3. As expected, the repeatability, signal-to-noise ratio and parameter map quality depended on hardware performance. We conclude that tensor-valued encoding is feasible for a wide range of MRI systems-even at 1.5 T with maximal gradient waveform amplitudes of 33 mT/m-and baseline experimental design and quality parameters for all included configurations. This demonstrates that tissue features, beyond those accessible by conventional diffusion encoding, can be explored on a wide range of MRI systems.

Bayesian uncertainty quantification in linear models for diffusion MRI.

Diffusion MRI (dMRI) is a valuable tool in the assessment of tissue microstructure. By fitting a model to the dMRI signal it is possible to derive various quantitative features. Several of the most popular dMRI signal models are expansions in an appropriately chosen basis, where the coefficients are determined using some variation of least-squares. However, such approaches lack any notion of uncertainty, which could be valuable in e.g. group analyses. In this work, we use a probabilistic interpretation of linear least-squares methods to recast popular dMRI models as Bayesian ones. This makes it possible to quantify the uncertainty of any derived quantity. In particular, for quantities that are affine functions of the coefficients, the posterior distribution can be expressed in closed-form. We simulated measurements from single- and double-tensor models where the correct values of several quantities are known, to validate that the theoretically derived quantiles agree with those observed empirically. We included results from residual bootstrap for comparison and found good agreement. The validation employed several different models: Diffusion Tensor Imaging (DTI), Mean Apparent Propagator MRI (MAP-MRI) and Constrained Spherical Deconvolution (CSD). We also used in vivo data to visualize maps of quantitative features and corresponding uncertainties, and to show how our approach can be used in a group analysis to downweight subjects with high uncertainty. In summary, we convert successful linear models for dMRI signal estimation to probabilistic models, capable of accurate uncertainty quantification.

Constrained optimization of gradient waveforms for generalized diffusion encoding.

Diffusion MRI is a useful probe of tissue microstructure. The conventional diffusion encoding sequence, the single pulsed field gradient, has recently been challenged as more general gradient waveforms have been introduced. Out of these, we focus on q-space trajectory imaging, which generalizes the scalar b-value to a tensor valued entity. To take full advantage of its capabilities, it is imperative to respect the constraints imposed by the hardware, while at the same time maximizing the diffusion encoding strength. We provide a tool that achieves this by solving a constrained optimization problem that accommodates constraints on maximum gradient amplitude, slew rate, coil heating and positioning of radio frequency pulses. The method's efficacy and flexibility is demonstrated both experimentally and by comparison with previous work on optimization of isotropic diffusion sequences.

Dose-volume histogram prediction using density estimation.

Knowledge of what dose-volume histograms can be expected for a previously unseen patient could increase consistency and quality in radiotherapy treatment planning. We propose a machine learning method that uses previous treatment plans to predict such dose-volume histograms. The key to the approach is the framing of dose-volume histograms in a probabilistic setting.The training consists of estimating, from the patients in the training set, the joint probability distribution of some predictive features and the dose. The joint distribution immediately provides an estimate of the conditional probability of the dose given the values of the predictive features. The prediction consists of estimating, from the new patient, the distribution of the predictive features and marginalizing the conditional probability from the training over this. Integrating the resulting probability distribution for the dose yields an estimate of the dose-volume histogram.To illustrate how the proposed method relates to previously proposed methods, we use the signed distance to the target boundary as a single predictive feature. As a proof-of-concept, we predicted dose-volume histograms for the brainstems of 22 acoustic schwannoma patients treated with stereotactic radiosurgery, and for the lungs of 9 lung cancer patients treated with stereotactic body radiation therapy. Comparing with two previous attempts at dose-volume histogram prediction we find that, given the same input data, the predictions are similar.In summary, we propose a method for dose-volume histogram prediction that exploits the intrinsic probabilistic properties of dose-volume histograms. We argue that the proposed method makes up for some deficiencies in previously proposed methods, thereby potentially increasing ease of use, flexibility and ability to perform well with small amounts of training data.