Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.06.28.544314

Clinical super-resolution computed tomography of bone microstructure: application in musculoskeletal and dental imaging

Abstract

ObjectivesClinical cone-beam computed tomography (CBCT) devices are limited to imaging features of half a millimeter in size. Hence, they do not allow clinical quantification of bone microstructure, which plays an important role in osteoarthritis, osteoporosis and fracture risk. For maxillofacial imaging, changes in small mineralized structures are important for dental, periodontal and ossicular chain diagnostics as well as treatment planning. Deep learning (DL)-based super-resolution (SR) models could allow for better evaluation of these microstructural details. In this study, we demonstrate a widely applicable method for increasing the spatial resolution of clinical CT images using DL, which only requires training on a limited set of data that are easy to acquire in a laboratory setting from e.g. cadaver knees. Our models are assessed rigorously for technical image quality, ability to predict bone microstructure, as well as clinical image quality of the knee, wrist, ankle and dentomaxillofacial region. Materials and methodsKnee tissue blocks from five cadavers and six total knee replacement patients as well as 14 extracted teeth from eight patients were scanned using micro-computed tomography. The images were used as training data for the developed DL-based SR technique, inspired by previous studies on single-image SR. The technique was benchmarked with an ex vivo test set, consisting of 52 small osteochondral samples imaged with clinical and laboratory CT scanners, to quantify bone morphometric parameters. A commercially available quality assurance phantom was imaged with a clinical CT device, and the technical image quality was quantified with a modulation transfer function. To visually assess the clinical image quality, CBCT studies from wrist, knee, ankle, and maxillofacial region were enhanced with SR and contrasted to interpolated images. A dental radiologist and dental surgeon reviewed maxillofacial CBCT studies of nine patients and corresponding SR predictions. ResultsThe SR models yielded a higher Pearson correlation to bone morphological parameters on the ex vivo test set compared to the use of a conventional image processing pipeline. The phantom analysis confirmed a higher spatial resolution on the images enhanced by the SR approach. A statistically significant increase of spatial resolution was seen in the third, fourth, and fifth line pair patterns. However, the predicted grayscale values of line pair patterns exceeded those of uniform areas. Musculoskeletal CBCT images showed more details on SR predictions compared to interpolation. Averaging predictions on orthogonal planes improved visual quality on perpendicular planes but could smear the details for morphometric analysis. SR in dental imaging allowed to visualize smaller mineralized structures in the maxillofacial region, however, some artifacts were observed near the crown of the teeth. The readers assessed mediocre overall scores in all categories for both CBCT and SR. Although not statistically significant, the dental radiologist slightly preferred the original CBCT images. The dental surgeon scored one of the SR models slightly higher compared to CBCT. The interrater variability {kappa} was mostly low to fair. The source code (https://doi.org/10.5281/zenodo.8041943) and pretrained SR networks (https://doi.org/10.17632/4xvx4p9tzv.1) are publicly available. ConclusionsUtilizing experimental laboratory imaging modalities in model training could allow pushing the spatial resolution limit beyond state-of-the-art clinical musculoskeletal and dental CBCT imaging. Implications of SR include higher patient throughput, more precise diagnostics, and disease interventions at an earlier state. However, the grayscale distribution of the images is modified, and the predictions are limited to depicting the mineralized structures rather than estimating density or tissue composition. Finally, while the musculoskeletal images showed promising results, a larger maxillofacial dataset would be recommended for training SR models in dental applications.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rytky, S. J. O., Tiulpin, A., Finnilä, M. A. J., Karhula, S. S., Sipola, A., Kurttila, V., Valkealahti, M., Lehenkari, P., Joukainen, A., Kröger, H., Korhonen, R. K., Saarakkala, S., Niinimäki, J.. 2023-06-30. Clinical super-resolution computed tomography of bone microstructure: application in musculoskeletal and dental imaging. https://doi.org/10.1101/2023.06.28.544314

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

spatialMET: an open and scalable framework for spatial metabolomics analysis

Mass spectrometry imaging (MSI) enables spatially resolved metabolomics in intact tissue sections, but analysis remains challenging at scale. Existing MSI workflows often require users to combine multiple software tools, while others rely on proprietary vendor software that limits interoperability and reproducibility. To address these challenges, we developed spatialMET, an open-source framework that provides an end-to-end workflow for MSI analysis. spatialMET provides a unified platform for preprocessing, spatial domain detection, and visualization. Downstream analyses include differential abundance testing, spatial autocorrelation and gradient analysis, dimensionality reduction, and correlation network analysis. Spatial domain detection uses hcdist, a C-based hierarchical clustering implementation that substantially reduces runtime and memory use relative to existing R-based approaches. spatialMET can be run through an interactive R Shiny application or as a standalone command-line workflow for larger datasets or high-performance computing environments. Applied to mouse small cell lung cancer MALDI-MSI data containing 284,673 pixels, spatialMET identified tumor-associated, stromal, and adjacent lung spatial domains that aligned with matched histology. Differential abundance analysis identified 117 m/z features that differed between tumor and stromal regions, while spatial autocorrelation analyses revealed spatially structured abundance patterns. Applying spatialMET to mouse lung adenocarcinoma data from an entire lung lobe containing 338,477 pixels further demonstrated scalability and captured spatial heterogeneity across tumor and surrounding lung tissue. In summary, spatialMET provides a scalable, open-source framework for end-to-end spatial metabolomics analysis, and it is distributed as a Docker container for reproducible deployment. Source code and installation instructions are available at https://github.com/biodatalab/spatialMET.

bioinformatics↗

Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

bioinformatics↗

An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry.

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single cell RNA sequencing data. We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes. A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work. Application of the proposed framework to single cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data. Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype and phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.

bioinformatics↗