A perspective on muscle phenotyping in musculoskeletal research.

Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.

A sex-specific association of leukocyte telomere length with thigh muscle mass.

OBJECTIVES: Telomeres are DNA-protein complexes at the ends of linear chromosomes that protect against DNA degradation. Telomeres shorten during normal cell divisions and therefore, telomere length is an indicator of mitotic-cell age. In humans, telomere shortening is a potential biomarker for disease risk, progression and premature death. Physical activity has been associated with longer leukocyte telomere length (LTL) in some studies. In the current study the relationship between LTL, thigh muscle mass and adipose tissue distribution was explored. METHODS: We performed anthropometric measurements and magnetic resonance imaging (MRI) measurements of the thigh in 149 healthy subjects (77 male, 72 female). LTL was measured using qPCR. Additionally, the subjects answered a questionnaire concerning their training behaviour. RESULTS: In male subjects, LTL was significantly associated with thigh muscle mass, independent of age and body mass index (p=0.006). In addition, a slight association of LTL with weekly endurance units in the male group was found. These relations could not be observed in females. CONCLUSIONS: In conclusion, we observed a sex-specific association of LTL and thigh muscle mass in healthy males. The reason of this sex-specific association is currently unclear, but could be related to different training effects and/or hormonal pathways in men and women.

Distribution of subcutaneous and intermuscular fatty tissue of the mid-thigh measured by MRI-A putative indicator of serum adiponectin level and individual factors of cardio-metabolic risk.

Obesity and metabolic syndrome (MetS) are associated with hypoadiponectinemia. On the contrary, studies revealed correlations between the amount of subcutaneous adipose tissue (SAT) and higher serum adiponectin levels. Furthermore, independent association of intermuscular adipose tissue (IMAT) deposit in the thigh with cardiometabolic risk factors (including total blood cholesterol, low-density lipoprotein (LDL), and triglycerides), and decreased insulin sensitivity, as MetS components, are sufficiently described. The combined relationship of thigh IMAT and SAT with serum adiponectin, leptin levels, and cardiometabolic risk factors have not been investigated till date. Since both SAT and IMAT play a role in fat metabolism, we hypothesized that the distribution pattern of SAT and IMAT in the mid-thigh might be related to adiponectin, leptin levels, and serum lipid parameters. We performed adipose tissue quantification using magnetic resonance imaging (MRI) of the mid-thigh in 156 healthy volunteers (78 male/78 female). Laboratory measurements of lipid panel, serum adiponectin, and leptin levels were conducted. Total serum adiponectin level showed a significant correlation with the percentage of SAT of the total thigh adipose tissue (SAT/ (IMAT+SAT)) for the whole study population and in sex-specific analysis. Additionally, SAT/(IMAT+SAT) was negatively correlated with known cardiometabolic risk factors such as elevated total blood cholesterol, LDL, and triglycerides; but positively correlated with serum high-density lipoprotein. In multiple linear regression analysis, (SAT/(IMAT+SAT)) was the most strongly associated variable with adiponectin. Interestingly, leptin levels did not show a significant correlation with this ratio. Adipose tissue distribution in the mid-thigh is not only associated to serum adiponectin levels, independent of sex. This proposed quantitative parameter for adipose tissue distribution could be an indicator for individual factors of a person`s cardiometabolic risk and serve as additional non-invasive imaging marker to ensure the success of lifestyle interventions.

Detection and volume estimation of artificial hematomas in the subcutaneous fatty tissue: comparison of different MR sequences at 3.0 T.

In legal medicine, reliable localization and analysis of hematomas in subcutaneous fatty tissue is required for forensic reconstruction. Due to the absence of ionizing radiation, magnetic resonance imaging (MRI) is particularly suited to examining living persons with forensically relevant injuries. However, there is limited experience regarding MRI signal properties of hemorrhage in soft tissue. The aim of this study was to evaluate MR sequences with respect to their ability to show high contrast between hematomas and subcutaneous fatty tissue as well as to reliably determine the volume of artificial hematomas. Porcine tissue models were prepared by injecting blood into the subcutaneous fatty tissue to create artificial hematomas. MR images were acquired at 3T and four blinded observers conducted manual segmentation of the hematomas. To assess segmentability, the agreement of measured volume with the known volume of injected blood was statistically analyzed. A physically motivated normalization taking into account partial volume effect was applied to the data to ensure comparable results among differently sized hematomas. The inversion recovery sequence exhibited the best segmentability rate, whereas the T1T2w turbo spin echo sequence showed the most accurate results regarding volume estimation. Both sequences led to reproducible volume estimations. This study demonstrates that MRI is a promising forensic tool to assess and visualize even very small amounts of blood in soft tissue. The presented results enable the improvement of protocols for detection and volume determination of hemorrhage in forensically relevant cases and also provide fundamental knowledge for future in-vivo examinations.

Contrast of artificial subcutaneous hematomas in MRI over time.

In clinical forensic medicine, hematomas and other externally visible injuries build the basis for the reconstruction of events. However, dating of subcutaneous hematomas based on their external aspect is difficult. Magnetic resonance imaging (MRI) has proven its use in dating intracranial hemorrhage. Thus, the aim was to investigate if MRI can also be used for dating subcutaneous hematomas and to analyze an eventual influence of the hematoma shape. In 20 healthy volunteers (11 females, 9 males, aged 26.9 ± 3.8 years), 4 ml of autologous blood were injected subcutaneously in the thigh. The hematoma was scanned immediately after the injection, after 3 and 24 h and 3, 7, and 14 days using three sequences with different contrast. Data was analyzed by measuring signal intensities of the hematoma, the muscle, and the subcutaneous tissue over time, and the Michelson contrast coefficients between the tissues were calculated. In the analysis, hematoma shape was considered. Signal intensity of blood in the proton density-weighted sequence reached its maximum 3 h after the injection with a subsequent decrease, whereas the signal intensities of muscle and fatty tissue remained constant. The time course of the Michelson coefficient of blood versus muscle decreased exponentially with a change from hyperintensity to hypointensity at 116.9 h, depending on hematoma shape. In the other sequences, either variability was large or contrast coefficients stayed constant over time. The observed change of contrast of blood versus muscle permits a quick estimate of a hematoma's age. The consideration of the hematoma shape is expected to further enhance dating using MRI.

The impact of iterative reconstruction on image quality and radiation dose in thoracic and abdominal CT.

PURPOSE: To compare the image quality and radiation dose between iterative reconstruction (IR) and standard filtered back projection (FBP) in CT of the chest and abdomen. MATERIALS AND METHODS: Thoracic CT was performed in 50 patients (38 male, 12 female; mean age, 51 ± 23 yrs; range, 7-85 yrs) and abdominal CT was performed in 50 patients (36 male, 14 female; mean age, 62 ± 13 yrs; range, 20-85 yrs), using IR as well as FBP for image reconstruction. Image noise was quantitatively assessed measuring standard deviation of Hounsfield Units (HU) in defined regions of interest in subcutaneous tissue. Scan length and Computed Tomography Dose Index (CTDI) were documented. Scan length, image noise, and CTDI of both reconstruction techniques were compared by using paired tests according to the nature of variables (McNemar test or Student t test). Overall subjective image quality and subjective image noise were compared. RESULTS: There was no significant difference between the protocols in terms of mean scan length (p>0.05). Image noise was statistically significantly higher with IR, although the difference was clinically insignificant (13.3 ± 3.0 HU and 13.6 ± 3.0 HU for thoracic CT and 11.5 ± 3.1 HU and 11.7 ± 3.0 HU for abdominal CT, p<0.05). There was no significant difference in overall subjective image quality and subjective image noise. The radiation dose was significantly lower with IR. Volume-weighted CTDI decreased by 64% (6.2 ± 2.5 mGy versus 17.1 ± 9.5 mGy, p<0.001) for thoracic CT and by 58% (7.8 ± 4.6 mGy versus 18.5 ± 8.6 mGy, p<0.001) for abdominal CT. CONCLUSIONS: Our study shows that in thoracic and abdominal CT with IR, there is no clinically significant impact on image quality, yet a significant radiation dose reduction compared to FBP.