Mutual Information Neural Estimation for Unsupervised Multi-Modal Registration of Brain Images.

Many applications in image-guided surgery and therapy require fast and reliable non-linear, multi-modal image registration. Recently proposed unsupervised deep learning-based registration methods have demonstrated superior per-formance compared to iterative methods in just a fraction of the time. Most of the learning-based methods have focused on mono-modal image registration. The extension to multi-modal registration depends on the use of an appropriate similarity function, such as the mutual information (MI). We propose guiding the training of a deep learning-based registration method with MI estimation between an image-pair in an end-to-end trainable network. Our results show that a small, 2-layer network produces competitive results in both mono- and multi-modal registration, with sub-second run-times. Comparisons to both iterative and deep learning-based methods show that our MI-based method produces topologically and qualitatively superior results with an extremely low rate of non-diffeomorphic transformations. Real-time clinical application will benefit from a better visual matching of anatomical structures and less registration failures/outliers.

Pelvic tilt from supine to standing in patients with symptomatic acetabular retroversion of the hip.

AIMS: Acetabular retroversion is a recognized cause of hip impingement and can be influenced by pelvic tilt (PT), which changes in different functional positions. Positional changes in PT have not previously been studied in patients with acetabular retroversion. METHODS: Supine and standing anteroposterior (AP) pelvic radiographs were retrospectively analyzed in 69 patients treated for symptomatic acetabular retroversion. Measurements were made for acetabular index (AI), lateral centre-edge angle (LCEA), crossover index, ischial spine sign, and posterior wall sign. The change in the angle of PT was measured both by the sacro-femoral-pubic (SFP) angle and the pubic symphysis to sacroiliac (PS-SI) index. RESULTS: In the supine position, the mean PT (by SFP) was 1.05° (SD 3.77°), which changed on standing to a PT of 8.64° (SD 5.34°). A significant increase in posterior PT from supine to standing of 7.59° (SD 4.5°; SFP angle) and 5.89° (SD 3.33°; PS-SI index) was calculated (p < 0.001). There was a good correlation in PT change between measurements using SFP angle and PS-SI index (0.901 in the preoperative group and 0.815 in the postoperative group). Signs of retroversion were significantly reduced in standing radiographs compared to supine: crossover index (0.16 (SD 0.16) vs 0.38 (SD 0.15); p < 0.001), crossover sign (19/28 hips vs 28/28 hips; p < 0.001), ischial spine sign (10/28 hips vs 26/28 hips; p < 0.001), and posterior wall sign (12/28 hips vs 24/28 hips; p < 0.001). CONCLUSION: Posterior PT increased from supine to standing in patients with symptomatic acetabular retroversion. The features of acetabular retroversion were less evident on standing radiographs. The low PT angle in the supine position is a factor in the increased appearance of acetabular retroversion. Patients presenting with symptoms of hip impingement should be assessed by supine and standing pelvic radiographs to highlight signs of acetabular retroversion, and to assist with optimizing acetabular correction at the time of surgery. Cite this article: Bone Joint J 2022;104-B(7):786-791.

Elucidating distinct clinico-radiologic signatures in the borderland between neuromyelitis optica and multiple sclerosis.

BACKGROUND: Separating antibody-negative neuromyelitis optica spectrum disorders (NMOSD) from multiple sclerosis (MS) in borderline cases is extremely challenging due to lack of biomarkers. Elucidating different pathologies within the likely heterogenous antibody-negative NMOSD/MS overlap syndrome is, therefore, a major unmet need which would help avoid disability from inappropriate treatment. OBJECTIVE: In this study we aimed to identify distinct subgroups within the antibody-negative NMOSD/MS overlap syndrome. METHODS: Twenty-five relapsing antibody-negative patients with NMOSD features underwent a prospective brain and spinal cord MRI. Subgroups were identified by an unsupervised algorithm based on pre-selected NMOSD/MS discriminators. RESULTS: Four subgroups were identified. Patients from Group 1 termed "MS-like" (n = 6) often had central vein sign and cortical lesions (83% and 67%, respectively). All patients from Group 2 ("spinal MS-like", 8) had short-segment myelitis and no MS-like brain lesions. Group 3 ("classic NMO-like", 6) had high percentage of bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM, 80% and 60%, respectively) and normal brain appearance (100%). Group 4 ("NMO-like with brain involvement", 5) typically had a history of NMOSD-like brain lesions and LETM. When compared with other groups, Group 4 had significantly decreased fractional anisotropy in non-lesioned tracts (0.46 vs. 0.49, p = 0.003) and decreased thalamus volume (0.84 vs. 0.98, p = 0.04). CONCLUSIONS: NMOSD/MS cohort contains distinct subgroups likely corresponding to different pathologies and requiring tailored treatment. We propose that non-conventional MRI might help optimise diagnosis in these challenging patients.

Significant differences in rates of aseptic loosening between two variations of a popular total knee arthroplasty design.

PURPOSE: The NexGen Legacy Posterior Stabilised (LPS) prosthesis (Zimmer Biomet, Warsaw, IN, USA) has augmentable and non-augmentable tibial baseplate options. We have noted an anecdotal increase in the number of cases requiring early revision for aseptic loosening since adopting the non-augmentable option. The purpose of this study was to ascertain our rates of aseptic tibial loosening for the two implant types within five years of implantation and to investigate the causes for any difference observed. METHODS: A database search was performed for all patients who underwent primary total knee arthroplasty (TKA) using the NexGen LPS between 2009 and 2015. Kaplan-Meier curves were plotted to assess for differences in revision rates between cohorts. We collected and compared data on gender, age, body mass index, component alignment and cement mantle quality as these were factors thought to affect the likelihood of aseptic loosening. RESULTS: Two thousand one hundred seventy-two TKAs were included with five year follow-up. There were 759 augmentable knees of which 14 were revised and 1413 non-augmentable knees of which 48 were revised. The overall revision rate at five years was 1.84% in the augmentable cohort and 3.4% in the non-augmentable cohort. The revision rate for aseptic loosening was 0.26% in the augmentable group and 1.42% in the non-augmentable group (p = 0.0241). CONCLUSIONS: We have identified increased rates of aseptic loosening in non-augmentable components. This highlights the effect that minor implant changes can have on outcomes. We recommend that clinicians remain alert to implant changes and publish their own results when important trends are observed.

Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Quantitative susceptibility mapping by inversion of a perturbation field model: correlation with brain iron in normal aging.

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or "QSIP." The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.

A retrospective review of the Dall-Miles plate for periprosthetic femoral fractures: twenty-seven cases and a review of the literature.

A retrospective review of the use of the Dall-Miles plate for periprothetic femoral fractures was performed at our institution. Twenty-seven fractures around a hip replacement were fixed using a Dall-Miles plate within 34 months. The mean age at operation was 74 (33-90) years. Twenty fractures were Vancouver B1, two B2, and five type C. Mean follow-up was 11 (2-41) months. Two fractured plates required revision and two fixations loosened, developing varus malunion. One malunion was related to deep infection. All four events occurred within six months of fixation. Two individuals were deceased within 3 months of surgery. Similar complications were evident in nine series published between 1990 and 2012. Increased incidence of periprosthetic femoral fractures is anticipated in a population with significant co-morbidities. Cortical strut allograft, iliac autograft and orthobiological supplementation remain options where non-union is anticipated.

MRF-based deformable registration and ventilation estimation of lung CT.

Deformable image registration is an important tool in medical image analysis. In the case of lung computed tomography (CT) registration there are three major challenges: large motion of small features, sliding motions between organs, and changing image contrast due to compression. Recently, Markov random field (MRF)-based discrete optimization strategies have been proposed to overcome problems involved with continuous optimization for registration, in particular its susceptibility to local minima. However, to date the simplifications made to obtain tractable computational complexity reduced the registration accuracy. We address these challenges and preserve the potentially higher quality of discrete approaches with three novel contributions. First, we use an image-derived minimum spanning tree as a simplified graph structure, which copes well with the complex sliding motion and allows us to find the global optimum very efficiently. Second, a stochastic sampling approach for the similarity cost between images is introduced within a symmetric, diffeomorphic B-spline transformation model with diffusion regularization. The complexity is reduced by orders of magnitude and enables the minimization of much larger label spaces. In addition to the geometric transform labels, hyper-labels are introduced, which represent local intensity variations in this task, and allow for the direct estimation of lung ventilation. We validate the improvements in accuracy and performance on exhale-inhale CT volume pairs using a large number of expert landmarks.

Towards realtime multimodal fusion for image-guided interventions using self-similarities.

Image-guided interventions often rely on deformable multimodal registration to align pre-treatment and intra-operative scans. There are a number of requirements for automated image registration for this task, such as a robust similarity metric for scans of different modalities with different noise distributions and contrast, an efficient optimisation of the cost function to enable fast registration for this time-sensitive application, and an insensitive choice of registration parameters to avoid delays in practical clinical use. In this work, we build upon the concept of structural image representation for multi-modal similarity. Discriminative descriptors are densely extracted for the multi-modal scans based on the "self-similarity context". An efficient quantised representation is derived that enables very fast computation of point-wise distances between descriptors. A symmetric multi-scale discrete optimisation with diffusion reguIarisation is used to find smooth transformations. The method is evaluated for the registration of 3D ultrasound and MRI brain scans for neurosurgery and demonstrates a significantly reduced registration error (on average 2.1 mm) compared to commonly used similarity metrics and computation times of less than 30 seconds per 3D registration.

The impact of heterogeneity and uncertainty on prediction of response to therapy using dynamic MRI data.

A comprehensive framework for predicting response to therapy on the basis of heterogeneity in dceMRI parameter maps is presented. A motion-correction method for dceMRI sequences is extended to incorporate uncertainties in the pharmacokinetic parameter maps using a variational Bayes framework. Simple measures of heterogeneity (with and without uncertainty) in parameter maps for colorectal cancer tumours imaged before therapy are computed, and tested for their ability to distinguish between responders and non-responders to therapy. The statistical analysis demonstrates the importance of using the spatial distribution of parameters, and their uncertainties, when computing heterogeneity measures and using them to predict response on the basis of the pre-therapy scan. The results also demonstrate the benefits of using the ratio of Ktrans with the bolus arrival time as a biomarker.

Edge- and detail-preserving sparse image representations for deformable registration of chest MRI and CT volumes.

Deformable medical image registration requires the optimisation of a function with a large number of degrees of freedom. Commonly-used approaches to reduce the computational complexity, such as uniform B-splines and Gaussian image pyramids, introduce translation-invariant homogeneous smoothing, and may lead to less accurate registration in particular for motion fields with discontinuities. This paper introduces the concept of sparse image representation based on supervoxels, which are edge-preserving and therefore enable accurate modelling of sliding organ motions frequently seen in respiratory and cardiac scans. Previous shortcomings of using supervoxels in motion estimation, in particular inconsistent clustering in ambiguous regions, are overcome by employing multiple layers of supervoxels. Furthermore, we propose a new similarity criterion based on a binary shape representation of supervoxels, which improves the accuracy of single-modal registration and enables multimodal registration. We validate our findings based on the registration of two challenging clinical applications of volumetric deformable registration: motion estimation between inhale and exhale phase of CT scans for radiotherapy planning, and deformable multi-modal registration of diagnostic MRI and CT chest scans. The experiments demonstrate state-of-the-art registration accuracy, and require no additional anatomical knowledge with greatly reduced computational complexity.

Target identification for stereotactic thalamotomy using diffusion tractography.

BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery.

Motion correction and parameter estimation in dceMRI sequences: application to colorectal cancer.

We present a novel Bayesian framework for non-rigid motion correction and pharmacokinetic parameter estimation in dceMRI sequences which incorporates a physiological image formation model into the similarity measure used for motion correction. The similarity measure is based on the maximization of the joint posterior probability of the transformations which need to be applied to each image in the dataset to bring all images into alignment, and the physiological parameters which best explain the data. The deformation framework used to deform each image is based on the diffeomorphic logDemons algorithm. We then use this method to co-register images from simulated and real dceMRI datasets and show that the method leads to an improvement in the estimation of physiological parameters as well as improved alignment of the images.