Search

Four-dimensional flow magnetic resonance imaging (4D flow MRI) provides volumetric and time-resolved visualization and quantification of blood flow. This review presents an overview of possible applications of 4D flow MRI for non-invasive assessment of abdominal hemodynamics. This review is based on the authors' experience and the current literature. A PubMed database literature research was performed in December 2019 focusing on abdominal applications of 4D flow MRI. We illustrated the review with exemplary figures and movies of clinical cases from our institution. 4D flow MRI offers the possibility of comprehensive assessment of abdominal blood flows in different vascular territories and organ systems. Results of recent studies indicate that 4D flow MRI improves understanding of altered hemodynamics in patients with abdominal disease and may be useful for monitoring therapeutic response. Future studies with larger cohorts aiming to integrate 4D flow MRI in the clinical routine setting are needed. · 4D flow MRI enables comprehensive visualization of the complex abdominal vasculature. · 4D flow MRI enables quantification of abdominal blood flow velocities and flow rates. · 4D flow MRI may enable deeper understanding of altered hemodynamics in abdominal disease. · Further validation studies are needed prior to broad distribution of abdominal 4D flow MRI.· Riedel C, Lenz A, Fischer L et al. Abdominal Applications of 4D Flow MRI. Fortschr Röntgenstr 2021; 193: 388 - 398. Die 4-dimensionale Fluss-Magnetresonanztomografie (4D-Fluss-MRT) erlaubt die zeitaufgelöste Darstellung und Quantifizierung des Blutflusses. Diese Übersichtsarbeit stellt die möglichen Anwendungen der 4D-Fluss-MRT zur nichtinvasiven Bildgebung der Hämodynamik im Abdomen zusammen. Diese Übersichtsarbeit basiert auf der Erfahrung der Autoren sowie einer aktuellen Literaturrecherche. Die Literaturrecherche wurde in der PubMed-Datenbank bezüglich abdomineller Anwendungen der 4D-Fluss-MRT im Dezember 2019 durchgeführt. Wir haben die Arbeit mit Abbildungen und Filmen klinischer Fälle aus unserer Institution illustriert. Die 4D-Fluss-MRT erlaubt die umfassende Beurteilung des abdominellen Blutflusses in verschiedenen Organsystemen und Gefäßterritorien. Die Ergebnisse neuerer Studien zeigen, dass die 4D-Fluss-MRT ein besseres Verständnis der veränderten Hämodynamik bei Patienten mit abdominellen Erkrankungen sowie die Überwachung des therapeutischen Ansprechens ermöglicht. Zukünftige Studien in größeren Kohorten sind nötig, um die 4D-Fluss-MRT in den klinischen Alltag zu integrieren. · Die 4D-Fluss-MRT ermöglicht eine umfassende Visualisierung der komplexen abdominellen Gefäßanatomie.. · Die 4D-Fluss-MRT ermöglicht die Quantifizierung der Geschwindigkeiten und der Flussraten in abdominellen Blutgefäßen.. · Die 4D-Fluss-MRT könnte zu einem besseren Verständnis der veränderten Hämodynamik bei unterschiedlichen abdominellen Erkrankungen beitragen.. · Weitere Studien zur Validierung der 4D-Fluss-MRT in der abdominellen Bildgebung sind vor der breiten Anwendung notwendig..

Background Aortic valve repair has become a treatment option for adults with symptomatic bicuspid (BAV) or unicuspid (UAV) aortic valve insufficiency. Our aim was to demonstrate the feasibility of 4D flow cardiovascular magnetic resonance (CMR) to assess the impact of aortic valve repair on changes in blood flow dynamics in patients with symptomatic BAV or UAV. Methods Twenty patients with adult congenital heart disease (median 35 years, range 18–64; 16 male) and symptomatic aortic valve regurgitation (15 BAV, 5 UAV) were prospectively studied. All patients underwent 4D flow CMR before and after aortic valve repair. Aortic valve regurgitant fraction and systolic peak velocity were estimated. The degree of helical and vortical flow was evaluated according to a 3-point scale. Relative flow displacement and wall shear stress (WSS) were quantified at predefined levels in the thoracic aorta. Results All patients underwent successful aortic valve repair with a significant reduction of aortic valve regurgitation (16.7 ± 9.8% to 6.4 ± 4.4%, p p = 0.014). Both helical flow (1.6 ± 0.6 vs. 0.9 ± 0.5, p p = 0.002) as well as both flow displacement (0.3 ± 0.1 vs. 0.25 ± 0.1, p = 0.031) and WSS (0.8 ± 0.2 N/m2 vs. 0.5 ± 0.2 N/m2, p Conclusions 4D flow CMR allows assessment of the impact of aortic valve repair on changes in blood flow dynamics in patients with bicuspid aortic valve disease.

Degradation at the modular head-neck interface in total hip arthroplasty (THA) is predominately expressed in the form of corrosion and fretting, potentially causing peri-prosthetic failure by adverse reactions to metal debris. This retrieval study aimed to quantify variations in stem taper surface topographies and to assess the influence on the formation of corrosion and/or fretting in titanium alloy stem tapers combined with metal and ceramic heads. Four hip stem designs (Alloclassic, CLS, Bicontact and SL-Plus) were characterized using high-resolution 3D microscopy, and corrosion and fretting were rated using the Goldberg scoring scheme. Quantification of the taper surface topographies revealed a high variability in surface characteristics between threaded stem tapers: Alloclassic and CLS tapers feature deeply threaded trapezoid-shaped profiles with thread heights over 65 µm. The sawtooth-shaped Bicontact and triangular SL-Plus taper are characterized by low thread heights below 14 µm. Significantly lower corrosion and fretting scores were observed in lightly threaded compared to deeply threaded tapers in ceramic head combinations. No significant differences in corrosion or fretting scores with thread height were found in pairings with metal heads. Understanding the relationship between stem taper surface topography and the formation of corrosion and fretting could help to improve the performance of modern THAs and lead to longer-lasting clinical results.

Denosumab is a potent osteoclast inhibitor targeted to prevent osteoporotic bone loss and thereby reduce fractures in the aging population. Recently, an elevated risk of rebound fractures following denosumab discontinuation was identified, unless patients were transitioned to an alternative antiresorptive medication. How denosumab affects the interaction of mechanosensitive osteocytes and bone quality remains unknown. We hypothesized that denosumab influences osteocyte function contributing to bone reorganization and increased fractures during discontinuation. Bone quality and osteocytes were assessed in archived iliac crest bone biopsies obtained from patients with high fracture occurrence from 2011 to 2016. Biopsies were obtained due to high fracture occurrence prior and during osteoporosis therapy from (i) patients with at least two semiannual subcutaneous injections of 60 mg denosumab, (ii) patients with rebound fractures during discontinuation, and (iii) patients of a treatment-naive group. In total, biopsies from 43 individuals were analyzed (mean age, 65.5 ± 12.1 years). Our results showed that during denosumab treatment, iliac cortical bone had a higher bone tissue hardness compared to treatment-naive bone (p = 0.0077) and a higher percentage of mineralized osteocyte lacunae (p = 0.0095). The density of empty osteocyte lacunae was higher with denosumab compared to treatment-naive (p = 0.014) and remained high in trabecular bone during discontinuation (p = 0.0071). We conclude that during denosumab treatment, increased bone hardness may contribute to improved fracture resistance. In biopsies from patients with high fracture occurrence, denosumab treatment reduced osteocyte viability, an effect that persisted during treatment discontinuation. High-resolution imaging of osteocyte viability indicates a role for osteocytes as a potential future mechanistic target to understand rebound bone loss and increased fractures with denosumab discontinuation.

Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naive patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.

Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth. Human femoral cortical bone was acquired from fetal (n = 1), infantile (n = 3), and 2- to 14-year-old cases (n = 4) at the mid-diaphysis. Bone quality was assessed in terms of bone structure, osteocyte characteristics, mineralization, and collagen orientation. The mechanical properties were investigated by measuring tensile deformation at multiple length scales via synchrotron X-ray diffraction. We find dramatic differences in mechanical resistance with age. Specifically, cortical bone in 2- to 14-year-old cases exhibits a 160% greater stiffness and 83% higher strength than fetal/infantile cases. The higher mechanical resistance of the 2- to 14-year-old cases is associated with advantageous bone quality, specifically higher bone volume fraction, better micronscale organization (woven versus lamellar), and higher mean mineralization compared with fetal/infantile cases. Our study reveals that bone quality is superior after remodeling/modeling processes convert the primary woven bone structure to lamellar bone. In this cohort of female children, the microstructural differences at the femoral diaphysis were apparent between the 1- to 2-year-old cases. Indeed, the lamellar bone in 2- to 14-year-old cases had a superior structural organization (collagen and osteocyte characteristics) and composition for resisting deformation and fracture than fetal/infantile bone. Mechanistically, the changes in bone quality during longitudinal bone growth lead to higher fracture resistance because collagen fibrils are better aligned to resist tensile forces, while elevated mean mineralization reinforces the collagen scaffold. Thus, our results reveal inherent weaknesses of the fetal/infantile skeleton signifying its inferior bone quality. These results have implications for pediatric fracture risk, as bone produced at ossification centers during children's longitudinal bone growth could display similarly weak points. © 2019 American Society for Bone and Mineral Research.

Within the mineralized bone, osteocytes form a multifunctional mechanosensitive network orchestrating bone remodelling. A preserved osteocyte population is a crucial determinant of bone quality. In human auditory ossicles, the early decrease in osteocyte numbers but maintained integrity remains an unexplained phenomenon that might serve for sound transmission from air to the labyrinth. Here we analysed the frequency, size and composition of osteocyte lacunae in the auditory ossicles of 22 individuals from early postnatal period to old age. Mineralization of the bone matrix was determined using backscattered electron imaging. No signs of bone remodelling were observed above the age of 1 year. We detected characteristics of early bone tissue aging, such as decrease in osteocytes, lower total lacunar density and lacunar area, as well as high matrix mineralization accompanied by distinct accumulation of micropetrotic lacunae and decreased indentation depths. The majority of these changes took place in the first months and years of life, while afterwards only minor reorganization was present. With osteocyte apoptosis potentially being a consequence of low mechanical stimuli, the early loss of osteocytes without initiation of bone remodelling indicates an adaptive response conserving the architecture of the auditory ossicles and ensuring stable sound transmission throughout life.

Strontium ranelate and fluoride salts are therapeutic options to reduce fracture risk in osteoporosis. Incorporation of these elements in the physiological hydroxyapatite matrix of bone is accompanied by changes in bone remodeling, composition, and structure. However, a direct comparison of the effectiveness of strontium and fluoride treatment in human cortical bone with a focus on the resulting mechanical properties remains to be established. Study groups are composed of undecalcified specimens from healthy controls, treatment-naïve osteoporosis cases, and strontium ranelate or fluoride-treated osteoporosis cases. Concentrations of both elements were determined using instrumental neutron activation analysis (INAA). Backscattered electron imaging was carried out to investigate the calcium content and the cortical microstructure. In comparison to osteoporotic patients, fluoride and strontium-treated patients have a lower cortical porosity indicating an improvement in bone microstructure. Mechanical properties were assessed via reference point indentation as a measure of bone's resistance to deformation. The strontium-incorporation led to significantly lower total indentation distance values compared to osteoporotic cases; controls have the highest resistance to indentation. In conclusion, osteoporosis treatment with strontium and fluoride showed positive effects on the microstructure and the mechanical characteristics of bone in comparison to treatment-naïve osteoporotic bone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 433-442, 2017.

Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.

Mucopolysaccharidosis-I (MPS-I) is a lysosomal storage disease (LSD) caused by inactivating mutations of IDUA, encoding the glycosaminoglycan-degrading enzyme α-l-iduronidase. Although MPS-I is associated with skeletal abnormalities, the impact of IDUA deficiency on bone remodeling is poorly defined. Here we report that Idua-deficient mice progressively develop a high bone mass phenotype with pathological lysosomal storage in cells of the osteoblast lineage. Histomorphometric quantification identified shortening of bone-forming units and reduced osteoclast numbers per bone surface. This phenotype was not transferable into wild-type mice by bone marrow transplantation (BMT). In contrast, the high bone mass phenotype of Idua-deficient mice was prevented by BMT from wild-type donors. At the cellular level, BMT did not only normalize defects of Idua-deficient osteoblasts and osteocytes but additionally caused increased osteoclastogenesis. Based on clinical observations in an individual with MPS-I, previously subjected to BMT and enzyme replacement therapy (ERT), we treated Idua-deficient mice accordingly and found that combining both treatments normalized all histomorphometric parameters of bone remodeling. Our results demonstrate that BMT and ERT profoundly affect skeletal remodeling of Idua-deficient mice, thereby suggesting that individuals with MPS-I should be monitored for their bone remodeling status, before and after treatment, to avoid long-term skeletal complications.