Bone Mineral Density Estimations From Routine Multidetector Computed Tomography: A Comparative Study of Contrast and Calibration Effects.

INTRODUCTION Phantom-based (synchronous and asynchronous) and phantomless (internal tissue calibration based) assessment of bone mineral density (BMD) in routine MDCT (multidetector computed tomography) examinations potentially allows for diagnosis of osteoporosis. Although recent studies investigated the effects of contrast-medium application on phantom-calibrated BMD measurements, it remains uncertain to what extent internal tissue-calibrated BMD measurements are also susceptible to contrast-medium associated density variation. The present study is the first to systemically evaluate BMD variations related to contrast application comparing different calibration techniques. PURPOSE To compare predicative performance of different calibration techniques for BMD measurements obtained from triphasic contrast-enhanced MDCT. MATERIALS AND METHODS Bone mineral density was measured on nonenhanced (NE), arterial (AR) and portal-venous (PV) contrast phase MDCT images of 46 patients using synchronous (SYNC) and asynchronous (ASYNC) phantom calibration as well as internal calibration (IC). Quantitative computed tomography (QCT) served as criterion standard. Density variations were analyzed for each contrast phase and calibration technique, and respective linear fitting was performed. RESULTS Both asynchronous calibration-derived BMD values (NE-ASYNC) and values estimated using IC (NE-IC) on NE MDCT images did reasonably well in predicting QCT BMD (root-mean-square deviation, 8.0% and 7.8%, respectively). Average NE-IC BMD was 2.7% lower when compared with QCT (P = 0.017), whereas no difference could be found for NE-ASYNC (P = 0.957). All average BMD estimates derived from contrast-enhanced scans differed significantly from QCT BMD (all P 6.0 mg/mL). All regression fits revealed a consistent linear dependency (R range, 0.861-0.963). Overall accuracy and goodness of fit tended to decrease from AR to PV contrast phase. Highest precision and best linear fit could be reached using a synchronously scanned phantom (root-mean-square deviation, 9.4% for AR and 14.4% for PV). Both ASYNC and IC estimations performed comparably accurate and precise. CONCLUSIONS Our data suggest that internal calibration driven BMD measurements derived from contrast-enhanced MDCT need the same amount of post hoc contrast-effect adjustment as measurements using phantom calibration. Adjustment using linear correction equations can correct for systematic bias of bone density variations related to contrast application, irrespective of the calibration technique used

Robust and parallel scalable iterative solutions for large-scale finite cell analyses

The finite cell method is a highly flexible discretization technique for numerical analysis on domains with complex geometries. By using a non-boundary conforming computational domain that can be easily meshed, automatized computations on a wide range of geometrical models can be performed. Application of the finite cell method, and other immersed methods, to large real-life and industrial problems is often limited due to the conditioning problems associated with these methods. These conditioning problems have caused researchers to resort to direct solution methods, which signifi- cantly limit the maximum size of solvable systems. Iterative solvers are better suited for large-scale computations than their direct counterparts due to their lower memory requirements and suitability for parallel computing. These benefits can, however, only be exploited when systems are properly conditioned. In this contribution we present an Additive-Schwarz type preconditioner that enables efficient and parallel scalable iterative solutions of large-scale multi-level hp-refined finite cell analyses.Comment: 32 pages, 17 figure

CNS demyelinating events in primary Sjogren's syndrome: A single-center case series on the clinical phenotype

ObjectiveThe study aimed to assess the prevalence, clinical characteristics, and therapeutic outcomes of the central nervous system (CNS) demyelinating disease in a large cohort of primary Sjogren's syndrome (pSS). MethodsThis is an explorative cross-sectional study of patients with pSS seen in the departments of rheumatology, otorhinolaryngology, or neurology of a tertiary university center between January 2015 and September 2021. ResultsIn a cohort of 194 pSS patients, 22 patients had a CNS manifestation. In this CNS group, 19 patients had a lesion pattern suggestive of demyelination. While there were no obvious differences in the patients' epidemiological disposition or rate of other extraglandular manifestations, the CNS group differed from the remaining patients with pSS by having less glandular manifestations but a higher seroprevalence for anti-SSA/Ro antibodies. Notably, patients with CNS manifestations were often diagnosed with multiple sclerosis (MS) and treated as such, although age and disease course were atypical of MS. Many first-line MS agents were ineffective in these MS look-alikes;however, the disease course was benign with B-cell-depleting agents. ConclusionNeurological symptoms of pSS are common and clinically manifest mainly as myelitis or optic neuritis. Notably, in the CNS, the pSS phenotype can overlap with MS. The prevailing disease is crucial since it has a major impact on the long-term clinical outcome and the choice of disease-modifying agents. Although our observations neither confirm pSS as a more appropriate diagnosis nor rule out simple comorbidity, physicians should consider pSS in the extended diagnostic workup of CNS autoimmune diseases

Multi-level hp-finite cell method for embedded interface problems with application in biomechanics

This work presents a numerical discretization technique for solving three-dimensional material interface problems involving complex geometry without conforming mesh generation. The finite cell method (FCM), which is a high-order fictitious domain approach, is used for the numerical approximation of the solution without a boundary-conforming mesh. Weak discontinuities at material interfaces are resolved by using separate FCM meshes for each material sub-domain, and weakly enforcing the interface conditions between the different meshes. Additionally, a recently developed hierarchical hp-refinement scheme is employed to locally refine the FCM meshes in order to resolve singularities and local solution features at the interfaces. Thereby, higher convergence rates are achievable for non-smooth problems. A series of numerical experiments with two- and three-dimensional benchmark problems is presented, showing that the proposed hp-refinement scheme in conjunction with the weak enforcement of the interface conditions leads to a significant improvement of the convergence rates, even in the presence of singularities. Finally, the proposed technique is applied to simulate a vertebra-implant model. The application showcases the method's potential as an accurate simulation tool for biomechanical problems involving complex geometry, and it demonstrates its flexibility in dealing with different types of geometric description

Combined Treatment With Pembrolizumab and Allogenic BK Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy A Case Report

Objective We report a combination of BK virus-specific T cells and pembrolizumab as a treatment option in progressive multifocal leukoencephalopathy (PML). Results A 57-year-old male patient diagnosed with PML presented a fast-progressing right hemiparesis, aphasia, and cognitive deficits. Brain MRI showed a severe leukoencephalopathy with diffusion restriction. The patient was treated with 10 doses of pembrolizumab (2 mg/kg body weight) in differing intervals and 2 partially human leukocyte antigen-matched allogenic BK virus-specific T cell transfusions after the fifth pembrolizumab treatment. Although pembrolizumab alone decreased the viral load but failed to control the virus, BK-specific T cell transfer further enhanced the decline of JC virus copies in the CSF. Moreover, the regression of leukoencephalopathy and disappearance of diffusion restriction in subsequent brain MRI were observed. The combined treatment resulted in a clinical stabilization with improvements of the cognitive and speech deficits. Discussion This case supports the hypothesis that pembrolizumab is more efficient in the presence of an appropriate number of functional antigen-specific T cells. Thus, the combined treatment of pembrolizumab and virus-specific T cells should be further evaluated as a treatment option for PML in future clinical trials

Level-Specific Volumetric BMD Threshold Values for the Prediction of Incident Vertebral Fractures Using Opportunistic QCT: A Case-Control Study

Purpose: To establish and evaluate the diagnostic accuracy of volumetric bone mineral density (vBMD) threshold values at different spinal levels, derived from opportunistic quantitative computed tomography (QCT), for the prediction of incident vertebral fractures (VF). Materials and Methods: In this case-control study, 35 incident VF cases (23 women, 12 men; mean age: 67 years) and 70 sex- and age-matched controls were included, based on routine multi detector CT (MDCT) scans of the thoracolumbar spine. Trabecular vBMD was measured from routine baseline CT scans of the thoracolumbar spine using an automated pipeline including vertebral segmentation, asynchronous calibration for HU-to-vBMD conversion, and correction of intravenous contrast medium (https://anduin.bonescreen.de). Threshold values at T1-L5 were calculated for the optimal operating point according to the Youden index and for fixed sensitivities (60 – 85%) in receiver operating characteristic (ROC) curves. Results: vBMD at each single level of the thoracolumbar spine was significantly associated with incident VFs (odds ratio per SD decrease [OR], 95% confidence interval [CI] at T1-T4: 3.28, 1.66–6.49; at T5-T8: 3.28, 1.72–6.26; at T9-T12: 3.37, 1.78–6.36; and at L1-L4: 3.98, 1.97–8.06), independent of adjustment for age, sex, and prevalent VF. AUC showed no significant difference between vertebral levels and was highest at the thoracolumbar junction (AUC = 0.75, 95%-CI = 0.63 - 0.85 for T11-L2). Optimal threshold values increased from lumbar (L1-L4: 52.0 mg/cm³) to upper thoracic spine (T1-T4: 69.3 mg/cm³). At T11-L2, T12-L3 and L1-L4, a threshold of 80.0 mg/cm³ showed sensitivities of 85 - 88%, and specificities of 41 - 49%. To achieve comparable sensitivity (85%) at more superior spinal levels, resulting thresholds were higher: 114.1 mg/cm³ (T1-T4), 92.0 mg/cm³ (T5-T8), 88.2 mg/cm³ (T9-T12). Conclusions: At all levels of the thoracolumbar spine, lower vBMD was associated with incident VFs in an elderly, predominantly oncologic patient population. Automated opportunistic osteoporosis screening of vBMD along the entire thoracolumbar spine allows for risk assessment of imminent VFs. We propose level-specific vBMD threshold at the thoracolumbar spine to identify individuals at high fracture risk

Denoising diffusion-based MR to CT image translation enables whole spine vertebral segmentation in 2D and 3D without manual annotations

Background: Automated segmentation of spinal MR images plays a vital role both scientifically and clinically. However, accurately delineating posterior spine structures presents challenges. Methods: This retrospective study, approved by the ethical committee, involved translating T1w and T2w MR image series into CT images in a total of n=263 pairs of CT/MR series. Landmark-based registration was performed to align image pairs. We compared 2D paired (Pix2Pix, denoising diffusion implicit models (DDIM) image mode, DDIM noise mode) and unpaired (contrastive unpaired translation, SynDiff) image-to-image translation using "peak signal to noise ratio" (PSNR) as quality measure. A publicly available segmentation network segmented the synthesized CT datasets, and Dice scores were evaluated on in-house test sets and the "MRSpineSeg Challenge" volumes. The 2D findings were extended to 3D Pix2Pix and DDIM. Results: 2D paired methods and SynDiff exhibited similar translation performance and Dice scores on paired data. DDIM image mode achieved the highest image quality. SynDiff, Pix2Pix, and DDIM image mode demonstrated similar Dice scores (0.77). For craniocaudal axis rotations, at least two landmarks per vertebra were required for registration. The 3D translation outperformed the 2D approach, resulting in improved Dice scores (0.80) and anatomically accurate segmentations in a higher resolution than the original MR image. Conclusion: Two landmarks per vertebra registration enabled paired image-to-image translation from MR to CT and outperformed all unpaired approaches. The 3D techniques provided anatomically correct segmentations, avoiding underprediction of small structures like the spinous process.Comment: 35 pages, 7 figures, Code and a model weights available https://doi.org/10.5281/zenodo.8221159 and https://doi.org/10.5281/zenodo.819869

Panoptica -- instance-wise evaluation of 3D semantic and instance segmentation maps

This paper introduces panoptica, a versatile and performance-optimized package designed for computing instance-wise segmentation quality metrics from 2D and 3D segmentation maps. panoptica addresses the limitations of existing metrics and provides a modular framework that complements the original intersection over union-based panoptic quality with other metrics, such as the distance metric Average Symmetric Surface Distance. The package is open-source, implemented in Python, and accompanied by comprehensive documentation and tutorials. panoptica employs a three-step metrics computation process to cover diverse use cases. The efficacy of panoptica is demonstrated on various real-world biomedical datasets, where an instance-wise evaluation is instrumental for an accurate representation of the underlying clinical task. Overall, we envision panoptica as a valuable tool facilitating in-depth evaluation of segmentation methods.Comment: 15 pages, 6 figures, 3 table

Associations Between Lumbar Vertebral Bone Marrow and Paraspinal Muscle Fat Compositions—An Investigation by Chemical Shift Encoding-Based Water-Fat MRI

Purpose: Advanced magnetic resonance imaging (MRI) methods enable non-invasive quantification of body fat situated in different compartments. At the level of the lumbar spine, the paraspinal musculature is the compartment spatially and functionally closely related to the vertebral column, and both vertebral bone marrow fat (BMF) and paraspinal musculature fat contents have independently shown to be altered in various metabolic and degenerative diseases. However, despite their close relationships, potential correlations between fat compositions of these compartments remain largely unclear.Materials and Methods: Thirty-nine female subjects (38.5% premenopausal women, 29.9 ± 7.1 years; 61.5% postmenopausal women, 63.2 ± 6.3 years) underwent MRI at 3T of the lumbar spine using axially- and sagittally-prescribed gradient echo sequences for chemical shift encoding-based water-fat separation. The erector spinae muscles and vertebral bodies of L1–L5 were segmented to determine the proton density fat fraction (PDFF) of the paraspinal and vertebral bone marrow compartments. Correlations were calculated between the PDFF of the paraspinal muscle and bone marrow compartments.Results: The average PDFF of the paraspinal muscle and bone marrow compartments were significantly lower in premenopausal women when compared to postmenopausal women (11.6 ± 2.9% vs. 24.6 ± 7.1% & 28.8 ± 8.3% vs. 47.2 ± 8.5%; p < 0.001 for both comparisons). In premenopausal women, no significant correlation was found between the PDFF of the erector spinae muscles and the PDFF of the bone marrow of lumbar vertebral bodies (p = 0.907). In contrast, a significant correlation was shown in postmenopausal women (r = 0.457, p = 0.025). Significance was preserved after inclusion of age and body mass index (BMI) as control variables (r = 0.472, p = 0.027).Conclusion: This study revealed significant correlations between the PDFF of paraspinal and vertebral bone marrow compartments in postmenopausal women. The PDFF of the paraspinal and vertebral bone marrow compartments and their correlations might potentially serve as biomarkers; however, future studies including more subjects are required to evaluate distinct clinical value and reliability. Future studies should also follow up our findings in patients suffering from metabolic and degenerative diseases to clarify how these correlations change in the course of such diseases