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- Nielson, Carrie M., et al.
(författare)
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Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 31:12, s. 2085-2097
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (β=0.22, p=1.9×10-8) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (β=0.09, p=1.2×10-10) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4×10-4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β=0.12, FDR p=1.7×10-3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence.
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2. |
- DeSouza, Nandita M., et al.
(författare)
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Standardised lesion segmentation for imaging biomarker quantitation : a consensus recommendation from ESR and EORTC
- 2022
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Ingår i: Insights into Imaging. - : Springer. - 1869-4101. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Lesion/tissue segmentation on digital medical images enables biomarker extraction, image-guided therapy delivery, treatment response measurement, and training/validation for developing artificial intelligence algorithms and workflows. To ensure data reproducibility, criteria for standardised segmentation are critical but currently unavailable. Methods A modified Delphi process initiated by the European Imaging Biomarker Alliance (EIBALL) of the European Society of Radiology (ESR) and the European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group was undertaken. Three multidisciplinary task forces addressed modality and image acquisition, segmentation methodology itself, and standards and logistics. Devised survey questions were fed via a facilitator to expert participants. The 58 respondents to Round 1 were invited to participate in Rounds 2-4. Subsequent rounds were informed by responses of previous rounds. Results/conclusions Items with >= 75% consensus are considered a recommendation. These include system performance certification, thresholds for image signal-to-noise, contrast-to-noise and tumour-to-background ratios, spatial resolution, and artefact levels. Direct, iterative, and machine or deep learning reconstruction methods, use of a mixture of CE marked and verified research tools were agreed and use of specified reference standards and validation processes considered essential. Operator training and refreshment were considered mandatory for clinical trials and clinical research. Items with a 60-74% agreement require reporting (site-specific accreditation for clinical research, minimal pixel number within lesion segmented, use of post-reconstruction algorithms, operator training refreshment for clinical practice). Items with <= 60% agreement are outside current recommendations for segmentation (frequency of system performance tests, use of only CE-marked tools, board certification of operators, frequency of operator refresher training). Recommendations by anatomical area are also specified.
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4. |
- Fournier, Laure, et al.
(författare)
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Incorporating radiomics into clinical trials : expert consensus endorsed by the European Society of Radiology on considerations for data-driven compared to biologically driven quantitative biomarkers
- 2021
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Ingår i: European Radiology. - : SPRINGER. - 0938-7994 .- 1432-1084. ; 31:8, s. 6001-6012
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Tidskriftsartikel (refereegranskat)abstract
- Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials.
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5. |
- Aliukonyte, Ieva, et al.
(författare)
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Unlocking the potential of photon counting detector CT for paediatric imaging: a pictorial essay
- 2024
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Ingår i: BJR OPEN. - : BRITISH INST RADIOLOGY. - 2513-9878. ; 6:1
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Forskningsöversikt (refereegranskat)abstract
- Recent advancements in CT technology have introduced a revolutionary innovation to practice known as the Photon-Counting detector (PCD) CT imaging. The pivotal hardware enhancement of the PCD-CT scanner lies in its detectors, which consist of smaller pixels than standard detectors and allow direct conversion of individual X-rays to electrical signals. As a result, CT images are reconstructed at higher spatial resolution (as low as 0.2 mm) and reduced overall noise, at no expense of an increased radiation dose. These features are crucial for paediatric imaging, especially for infants and young children, where anatomical structures are notably smaller than in adults and in whom keeping dose as low as possible is especially relevant. Since January 2022, our hospital has had the opportunity to work with PCD-CT technology for paediatric imaging. This pictorial review will showcase clinical examples of PCD-CT imaging in children. The aim of this pictorial review is to outline the potential paediatric applications of PCD-CT across different anatomical regions, as well as to discuss the benefits in utilizing PCD-CT in comparison to conventional standard energy integrating detector CT.
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6. |
- Booij, Ronald, et al.
(författare)
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Assessment of visibility of bone structures in the wrist using normal and half of the radiation dose with photon-counting detector CT
- 2023
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Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 159
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To quantitatively and qualitatively assess the visibility of bone structures in the wrist on photon-counting detector computed tomography (PCD-CT) images compared to state-of-the-art energy-integrating de-tector CT (EID-CT).Method: Four human cadaveric wrist specimens were scanned with EID-CT and PCD-CT at identical CTDIvolof 12.2 mGy and with 6.1 mGy (half dose PCD-CT). Axial images were reconstructed using the thinnest possible slice thickness, i.e. 0.4 mm on EID-CT and 0.2 mm on PCD-CT, with the largest image matrix size possible using reconstruction kernels optimized for bone (EID-CT: Ur68, PCD-CT: Br92). Quantitative evaluation was performed to determine contrast-noise ratio (CNR) of bone/ fat, cortical and trabecular sharpness. An observer study using visual grading characteristics (VGC) analysis was performed by six observers to assess the visibility of nutrient canals, trabecular architecture, cortical bone and the general image quality.Results: At equal dose, images obtained with PCD-CT had 39 +/- 6 % lower CNR (p = 0.001), 71 +/- 57 % higher trabecular sharpness in the radius (p = 0.02) and 42 +/- 8 % (p < 0.05) sharper cortical edges than those obtained with EID-CT. This was confirmed by VGC analysis showing a superior visibility of nutrient canals, trabeculae and cortical bone area under the curve (AUC) > 0.89) for PCD-CT, even at half dose.Conclusions: Despite a lower CNR and increased noise, the trabecular and cortical sharpness were twofold higher with PCD-CT. Visual grading analysis demonstrated superior visibility of cortical bone, trabeculae, nutrient canals and an overall improved image quality with PCD-CT over EID-CT. At half dose, PCD-CT also yielded superior image quality, both in quantitative measures and as evaluated by radiologists.
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7. |
- Emin, Sevgi, et al.
(författare)
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Imaging-based assessment of fatty acid composition in human bone marrow adipose tissue at 7 T : Method comparison and in vivo feasibility
- 2023
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 90:1, s. 240-249
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To demonstrate the feasibility and accuracy of chemical shift–encoded imaging of the fatty acid composition (FAC) of human bone marrow adipose tissue at 7 T, and to determine suitable image-acquisition parameters using simulations. Methods: The noise performance of FAC estimation was investigated using simulations with a range of inter-echo time, and accuracy was assessed using a phantom experiment. Furthermore, one knee of 8 knee-healthy subjects (ages 35–54 years) was imaged, and the fractions of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) were mapped. Values were compared between reconstruction methods, and between anatomical regions. Results: Based on simulations, ΔTE = 0.6 ms was chosen. The phantom experiment demonstrated high accuracy of especially SFA using a constrained reconstruction model (slope = 1.1, average bias = −0.2%). The lowest accuracy was seen for PUFA using a free model (slope = 2.0, average bias = 9.0%). For in vivo images, the constrained model resulted in lower intersubject variation compared with the free model (e.g., in the femoral shaft, the SFA percent-point range was within 1.0% [vs. 3.0%]). Furthermore, significant regional FAC differences were detected. For example, using the constrained approach, the femoral SFA in the medial condyle was lower compared with the shaft (median [range]: 27.9% [27.1%, 28.4%] vs. 32.5% [31.8%, 32.8%]). Conclusion: Bone marrow adipose tissue FAC quantification using chemical-shift encoding is feasible at 7 T. Both the noise performance and accuracy of the technique are superior using a constrained signal model.
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8. |
- Mourad, Charbel, et al.
(författare)
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Chances and challenges of photon-counting CT in musculoskeletal imaging
- 2024
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Ingår i: Skeletal Radiology. - : SPRINGER. - 0364-2348 .- 1432-2161.
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Forskningsöversikt (refereegranskat)abstract
- In musculoskeletal imaging, CT is used in a wide range of indications, either alone or in a synergistic approach with MRI. While MRI is the preferred modality for the assessment of soft tissues and bone marrow, CT excels in the imaging of high-contrast structures, such as mineralized tissue. Additionally, the introduction of dual-energy CT in clinical practice two decades ago opened the door for spectral imaging applications. Recently, the advent of photon-counting detectors (PCDs) has further advanced the potential of CT, at least in theory. Compared to conventional energy-integrating detectors (EIDs), PCDs provide superior spatial resolution, reduced noise, and intrinsic spectral imaging capabilities. This review briefly describes the technical advantages of PCDs. For each technical feature, the corresponding applications in musculoskeletal imaging will be discussed, including high-spatial resolution imaging for the assessment of bone and crystal deposits, low-dose applications such as whole-body CT, as well as spectral imaging applications including the characterization of crystal deposits and imaging of metal hardware. Finally, we will highlight the potential of PCD-CT in emerging applications, underscoring the need for further preclinical and clinical validation to unleash its full clinical potential.
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9. |
- Plagou, Athena, et al.
(författare)
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Recommendations of the ESSR Arthritis Subcommittee on Ultrasonography in Inflammatory Joint Disease
- 2016
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Ingår i: Seminars in Musculoskeletal Radiology. - : Georg Thieme Verlag KG. - 1089-7860 .- 1098-898X. ; 20:5, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- This article presents the recommendations of the European Society of Musculoskeletal Radiology Arthritis Subcommittee. on the use of ultrasonography (US) in rheumatic disease, focused on the examination of joints in the adult population. The recommended examination technique and protocols used in a radiologic work-up are discussed. The main US features that can lead to a final diagnosis in the most common rheumatic diseases are addressed. The differential diagnosis that should be considered at image interpretation is presented. The role of US in interventional procedures and clinically important recent developments is also discussed.
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10. |
- Rio, Ebonie Kendra, et al.
(författare)
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ICON PART-T 2019-International Scientific Tendinopathy Symposium Consensus : recommended standards for reporting participant characteristics in tendinopathy research (PART-T)
- 2020
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 54:11, s. 627-630
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to establish consensus for reporting recommendations relating to participant characteristics in tendon research. A scoping literature review of tendinopathy studies (Achilles, patellar, hamstring, gluteal and elbow) was followed by an online survey and face-to-face consensus meeting with expert healthcare professionals (HCPs) at the International Scientific Tendon Symposium, Groningen 2018. We reviewed 263 papers to form statements for consensus and invited 30 HCPs from different disciplines and geographical locations; 28 completed the survey and 15 attended the meeting. There was consensus that the following data should be reported for cases and controls: sex, age, standing height, body mass, history of tendinopathy, whether imaging was used to confirm pathology, loading tests, pain location, symptom duration and severity, level of disability, comorbidities, physical activity level, recruitment source and strategies, and medication use history. Standardised reporting of participant characteristics aims to benefit patients and clinicians by guiding researchers in the conduct of their studies. We provide free resources to facilitate researchers adopting our recommendations.
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12. |
- Sudol-Szopinska, Iwona, et al.
(författare)
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Recommendations of the ESSR Arthritis Subcommittee for the Use of Magnetic Resonance Imaging in Musculoskeletal Rheumatic Diseases
- 2015
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Ingår i: Seminars in Musculoskeletal Radiology. - : Georg Thieme Verlag KG. - 1089-7860 .- 1098-898X. ; 19:4, s. 396-411
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Tidskriftsartikel (refereegranskat)abstract
- This article presents the recommendations of the European Society of Muscloskeletal Radiology Arthritis Subcommittee regarding the standards of the use of MRI in the diagnosis of musculoskeletal rheumatic diseases. The recommendations discuss (1) the role of MRI in current classification criteria of musculoskeletal rheumatic diseases (including early diagnosis of inflammation, disease follow-up, and identification of disease complications); (2) the impact of MRI on the diagnosis of axial and peripheral spondyloarthritis, rheumatoid arthritis, and juvenile spondyloarthritis; (3) MRI protocols for the axial and peripheral joints; (4) MRI interpretation and reporting for axial and peripheral joints; and finally, (5) methods for assessing MR images including quantitative, semiquantitative, and dynamic contrast-enhanced MRI studies.
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13. |
- van der Voet, Jan A., et al.
(författare)
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Factors associated with longitudinal change of meniscal extrusion in overweight women without clinical signs of osteoarthritis
- 2021
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:11, s. 5175-5184
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To identify variables associated with longitudinal change in meniscal extrusion, which might be used as possible targets for knee osteoarthritis (KOA) prevention. METHODS: In a high-risk population of middle-aged overweight women, meniscal extrusion was assessed with magnetic resonance imaging (1.5 T, coronal proton density, in-plane resolution 0.5 mm2, Sante DICOM Editor) at baseline and after 30 months. Outcomes were the absolute change in medial and lateral extrusion (mm) and relative change in extrusion (%). Based upon literature, 11 factors were hypothesized to be associated with longitudinal change. Generalized estimating equations were used to model the effect on meniscal change (P <0.05). RESULTS: In total, 677 knees of 343 women were available for analysis, with a mean age of 55.7 years (+/-3.2) and a mean BMI of 32.3 kg/m2 (+/-4.2). The greatest change in meniscal extrusion appeared medially with incident meniscal tear (4.4%; absolute 0.9 mm (95% CI: 0.3, 1.5; P =0.004); relative 14.5% (4.4, 24.7; 0.005)). Varus malalignment was associated with an increase of medial extrusion of 0.6 mm (37.6%; 0.1, 1.0; 0.009). A 5 kg/m2 higher baseline BMI was associated with absolute and relative increase of medial extrusion of 0.2 mm and 2.96% (0.1, 0.3; <0.001 and 1.3, 4.8; 0.002). Less explicit but significant changes in extrusion appeared with longitudinal change in BMI. CONCLUSION: Meniscal tears, varus malalignment and BMI were significantly associated with change in meniscal extrusion in middle-aged overweight women, providing viable therapeutic targets to prevent or reduce extrusion and thereby decelerate KOA development.
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14. |
- Vicenzino, Bill, et al.
(författare)
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ICON 2019-International Scientific Tendinopathy Symposium Consensus : There are nine core health-related domains for tendinopathy (CORE DOMAINS): Delphi study of healthcare professionals and patients
- 2020
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Ingår i: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 54:8, s. 444-451
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe absence of any agreed-upon tendon health-related domains hampers advances in clinical tendinopathy research. This void means that researchers report a very wide range of outcome measures inconsistently. As a result, substantial synthesis/meta-analysis of tendon research findings is almost futile despite researchers publishing busily. We aimed to determine options for, and then define, core health-related domains for tendinopathy.MethodsWe conducted a Delphi study of healthcare professionals (HCP) and patients in a three-stage process. In stage 1, we extracted candidate domains from clinical trial reports and developed an online survey. Survey items took the form: 'The 'candidate domain' is important enough to be included as a core health-related domain of tendinopathy'; response options were: agree, disagree, or unsure. In stage 2, we administered the online survey and reported the findings. Stage 3 consisted of discussions of the findings of the survey at the ICON (International Scientific Tendinopathy Symposium Consensus) meeting. We set 70% participant agreement as the level required for a domain to be considered 'core'; similarly, 70% agreement was required for a domain to be relegated to 'not core' (see Results next).ResultsTwenty-eight HCP (92% of whom had >10 years of tendinopathy experience, 71% consulted >10 cases per month) and 32 patients completed the online survey. Fifteen HCP and two patients attended the consensus meeting. Of an original set of 24 candidate domains, the ICON group deemed nine domains to be core. These were: (1) patient rating of condition, (2) participation in life activities (day to day, work, sport), (3) pain on activity/loading, (4) function, (5) psychological factors, (6) physical function capacity, (7) disability, (8) quality of life and (9) pain over a specified time. Two of these (2, 6) were an amalgamation of five candidate domains. We agreed that seven other candidate domains were not core domains: range of motion, pain on clinician applied test, clinical examination, palpation, drop out, sensory modality pain and pain without other specification. We were undecided on the other five candidate domains of physical activity, structure, medication use, adverse effects and economic impact.ConclusionNine core domains for tendon research should guide reporting of outcomes in clinical trials. Further research should determine the best outcome measures for each specific tendinopathy (ie, core outcome sets).
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15. |
- Woisetschläger, Mischa, et al.
(författare)
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Improved visualization of the bone-implant interface and osseointegration in ex vivo acetabular cup implants using photon-counting detector CT
- 2023
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Ingår i: EUROPEAN RADIOLOGY EXPERIMENTAL. - : SPRINGERNATURE. - 2509-9280. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSuccessful osseointegration of joint replacement implants is required for long-term implant survival. Accurate assessment of osseointegration could enable clinical discrimination of failed implants from other sources of pain avoiding unnecessary surgeries. Photon-counting detector computed tomography (PCD-CT) provides improvements in image resolution compared to conventional energy-integrating detector CT (EID-CT), possibly allowing better visualization of bone-implant-interfaces and osseointegration. The aim of this study was to assess the quality of visualization of bone-implant-interfaces and osseointegration in acetabular cup implants, using PCD-CT compared with EID-CT.MethodsTwo acetabular implants (one cemented, one uncemented) retrieved during revision surgery were scanned using PCD-CT and EID-CT at equal radiation dose. Images were reconstructed using different reconstruction kernels and iterative strengths. Delineation of the bone-implant and bone-cement-interface as an indicator of osseointegration was scored subjectively for image quality by four radiologists on a Likert scale and assessed quantitatively.ResultsDelineation of bone-implant and bone-cement-interfaces was better with PCD-CT compared with EID-CT (p <= 0.030). The highest ratings were given for PCD-CT at sharper kernels for the cemented cup (PCD-CT, median 5, interquartile range 4.25-5.00 versus EID-CT, 3, 2.00-3.75, p < 0.001) and the uncemented cup (5, 4.00-5.00 versus 2, 2-2, respectively, p < 0.001). The bone-implant-interface was 35-42% sharper and the bone-cement-interface was 28-43% sharper with PCD-CT compared with EID-CT, depending on the reconstruction kernel.ConclusionsPCD-CT might enable a more accurate assessment of osseointegration of orthopedic joint replacement implants.
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16. |
- Zhang, Fan, et al.
(författare)
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The association between meniscal body extrusion and the development/enlargement of bone marrow lesions on knee MRI in overweight and obese women
- 2020
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 1:3-4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the association between meniscal body extrusion and bone marrow lesion (BML) development/enlargement in overweight and obese women at high risk of knee osteoarthritis (OA). Design: We used baseline and 30 months follow-up data of the PROOF study, Netherlands, comprising overweight or obese women aged 50–60 years, free of clinical knee OA. All subjects (n = 395) completed a questionnaire on knee complaints and physical activity, underwent physical examination, radiography, and repeated 1.5 T MRI of both knees. Using the mid-coronal MRI slice, one observer measured tibial plateau width and meniscal body extrusion of both menisci in both knees. BMLs and meniscal damage were read using the semi-quantitative MOAKS scoring system by another observer. The association between BML development and meniscal extrusion was primarily analyzed with a random-effects logistic regression model adjusted for age, body weight, body height, physical activity, meniscus damage, knee alignment, and tibia width. In addition, we used a fixed-effect regression model for evaluation of knee-specific factors. Results: In our primary model, there was about 24% increased risk of BML incidence/enlargement per 1 mm extrusion (95% confidence interval [CI] 0.99, 1.57) for medial compartments and 69% risk increase (95% confidence interval [CI] 1.27, 2.25) for the lateral compartments. Results from the fixed-effects regression model were similar, strengthening the validity of the findings. Conclusions: Meniscal body extrusion is an important factor influencing BML development/enlargement, and thus may be a potential treatment target in knee OA development.
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