Tissue-Specific T2* Biomarkers in Patellar Tendinopathy by Subregional Quantification Using 3D Ultrashort Echo Time MRI

Background: Quantitative MRI of patellar tendinopathy (PT) can be challenging due to spatial variation of T2* relaxation times. Purpose: 1) To compare T2* quantification using a standard approach with analysis in specific tissue compartments of the patellar tendon. 2) To evaluate test–retest reliability of different methods for fitting ultrashort echo time (UTE)-relaxometry data. Study Type: Prospective. Subjects: Sixty-five athletes with PT. Field Strength/Sequence: 3D UTE scans covering the patellar tendon were acquired using a 3.0T scanner and a 16-channel surface coil. Assessment: Voxelwise median T2* was quantified with monoexponential, fractional-order, and biexponential fitting. We applied two methods for T2* analysis: first, a standard approach by analyzing all voxels covering the proximal patellar tendon. Second, within subregions of the patellar tendon, by using thresholds on biexponential fitting parameter percentage short T2* (0–30% for mostly long T2*, 30–60% for mixed T2*, and 60–100% for mostly short T2*). Statistical Tests: Average test–retest reliability was assessed in three athletes using coefficients-of-variation (CV) and coefficients-of-repeatability (CR). Results: With standard image analysis, we found a median [interquartile range, IQR] monoexponential T2* of 6.43 msec [4.32–8.55] and fractional order T2* 4.39 msec [3.06–5.78]. The percentage of short T2* components was 52.9% [35.5–69.6]. Subregional monoexponential T2* was 13.78 msec [12.11–16.46], 7.65 msec [6.49–8.61], and 3.05 msec [2.52–3.60] and fractional order T2* 11.82 msec [10.09–14.44], 5.14 msec [4.25–5.96], and 2.19 msec [1.82–2.64] for 0–30%, 30–60%, and 60–100% short T2*, respectively. Biexponential component short T2* was 1.693 msec [1.417–2.003] for tissue with mostly short T2* and long T2* of 15.79 msec [13.47–18.61] for mostly long T2*. The average CR (CV) was 2 msec (15%), 2 msec (19%) and 10% (22%) for monoexponential, fractional order and percentage short T2*, respectively. Data Conclusion: Patellar tendinopathy is characterized by regional variability in binding states of water. Quantitative multicompartment T2* analysis in PT can be facilitated using a voxel selection method based on using biexponential fitting parameters. Level of Evidence: 1. Technical Efficacy Stage: 1

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression

FcRn Overexpression in Transgenic Mice Results in Augmented APC Activity and Robust Immune Response with Increased Diversity of Induced Antibodies

Our previous studies have shown that overexpression of bovine FcRn (bFcRn) in transgenic (Tg) mice leads to an increase in the humoral immune response, characterized by larger numbers of Ag-specific B cells and other immune cells in secondary lymphoid organs and higher levels of circulating Ag-specific antibodies (Abs). To gain additional insights into the mechanisms underlying this increase in humoral immune response, we further characterized the bFcRn Tg mice. Our Western blot analysis showed strong expression of the bFcRn transgene in peritoneal macrophages and bone marrow derived dendritic cells; and a quantitative PCR analysis demonstrated that the expression ratios of the bFcRn to mFcRn were 2.6- and 10-fold in these cells, respectively. We also found that overexpression of bFcRn enhances the phagocytosis of Ag-IgG immune complexes (ICs) by both macrophages and dendritic cells and significantly improves Ag presentation by dendritic cells. Finally, we determined that immunized bFcRn mice produce a much greater diversity of Ag-specific IgM, whereas only the levels, but not the diversity, of IgG is increased by overexpression of bFcRn. We suggest that the increase in diversity of IgG in Tg mice is prevented by a selective bias towards immunodominant epitopes of ovalbumin, which was used in this study as a model antigen. These results are also in line with our previous reports describing a substantial increase in the levels of Ag-specific IgG in FcRn Tg mice immunized with Ags that are weakly immunogenic and, therefore, not affected by immunodominance