Recombination between heterologous human acrocentric chromosomes.

The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications1,2. Although the resolution of these regions in the first complete assembly of a human genome-the Telomere-to-Telomere Consortium's CHM13 assembly (T2T-CHM13)-provided a model of their homology3, it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago9.

A draft human pangenome reference.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

Dynamics and Coordination of a P2N2 Ligand - from Twisted Conformation to Chelation.

Based on their general spacial flexibility, their Lewis and Brønsted basicity, and ability to mimic second sphere effects the 1,5-diaza-3,7-diphosphacyclooctane ligand family and their complexes have regained substantial scientific interest. It was now possible to structurally analyze a recently reported member of this family with p-tolyl and t-butyl substituents on P and N, respectively, (P2 p-tolN2 tBu). Notably, the ligand crystallizes with a 'twisted' backbone. This compound is the very first of its kind to have been unambiguously characterized with regard to its chemical and molecular structure as being in this conformation. A temperature-dependent NMR study provides insight into the molecular dynamics of two isomers in solution, which are most likely also both twisted, as judged by the observed limited reactivity. Despite the in principle unfavorable conformation of the free ligand, it was successfully chelated to tungsten and molybdenum centers in mononuclear carbonyl complexes. The ligand, a derivative thereof and four new complexes were comprehensively characterized and analyzed in comparison. This includes single crystal XRD molecular structures of P2 p-tolN2 tBu and all four complexes. P2 p-tolN2 tBu, regardless of its twisted conformation, is able to coordinate to metal centers given that enough energy (heat) for a conformational change is provided.

Fracture sonography - Literature review and current recommendations.

PURPOSE: Over the course of more than two years, an expert group of 9 professional societies has created the S2e guidelines for fracture sonography. This publication summarizes the key points regarding the individual indications. MATERIALS AND METHODS: A systematic literature search was performed in PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews from 2000 to March 2021 with evaluation of the literature lists. Randomized controlled clinical trials, observational clinical trials, meta-analyses, and systematic reviews were included. Guidelines, conferences, reviews, case reports, and expert opinions were excluded. Evidence was graded using the SIGN grading system 1999-2012, and the SIGN tables were then presented to the expert group. These were used to develop specific recommendations for the use of fracture sonography. All recommendations were discussed in detail and finally unanimously agreed upon. RESULTS: Of the 520 primary literature sources found, 182 sources (146 clinical studies and 36 meta-analyses and systematic reviews) were evaluated after screening and content assessment. 21 indications that allow reasonable application of fracture sonography were identified. CONCLUSION: Ultrasound is a sensible, easy-to-use diagnostic method that is feasible for a large number of indications.

Fracture sonography-review of literature and current recommendations.

Over a span of more than two years, a collaborative expert group consisting of 9 professional societies has meticulously crafted the S2e guideline on fracture sonography. This publication encapsulates the essential insights pertaining to specific indications. A thorough and systematic literature search, covering the period from 2000 to March 2021, was conducted across PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews, complemented by an evaluation of bibliographies. Inclusion criteria encompassed randomized controlled clinical trials, observational clinical trials, meta-analyses, and systematic reviews, while guidelines, conferences, reviews, case reports, and expert opinions were excluded. The SIGN grading system (1999-2012) was applied to assess evidence, and resultant SIGN tables were presented to the expert group. Specific recommendations for the application of fracture sonography were then derived through unanimous consensus after detailed discussions. Out of the initial pool of 520 literature sources, a meticulous screening and content assessment process yielded 182 sources (146 clinical studies and 36 meta-analyses and systematic reviews) for evaluation. The comprehensive analysis identified twenty-one indications that substantiate the judicious use of fracture sonography. Ultrasound emerges as a pragmatic and user-friendly diagnostic method, showcasing feasibility across a diverse range of indications.

Earlier consolidation and improved knee function of medial open wedge high tibial osteotomy with autologous bone graft.

PURPOSE: Medial knee osteoarthritis can be treated with medial open wedge high tibial osteotomy (OWHTO). We sought to investigate osseous consolidation of the osteotomy with and without autologous bone grafts (ABG) to detect possible benefits of ABG in osseous healing and functional outcome. METHODS: In this prospective study, patients without graft transplantation were compared to those receiving ABG after medial OWHTO. They were followed up 6 weeks, 12 weeks, 6 months and 12 months postoperatively. Radiographic progress of consolidation, clinical scores, contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were assessed at each appointment. RESULTS: A total of 35 patients were enrolled, 20 without and 15 with graft transplantation. Radiologic evaluation showed a significantly earlier consolidation of the osteotomy gaps (p = 0.012) in patients with ABG, resulting in a significantly higher rate of consolidation 12 months after surgery (60% without bone graft vs. 100% with bone graft, p = 0.006). At 6 weeks as well as 6-month follow-up, a tendency of earlier consolidation with ABG was apparent, but not statistically significant (6 weeks: 50% vs. 80%, p = 0.089; 6 months: 30% vs. 60%, p = 0.097). CEUS and DCE-MRI showed physiological perfusion of the osteotomy gaps in both groups. A tendency to better function and less pain in patients with ABG was recognizable. CONCLUSION: In our study, autologous bone grafting evocated earlier osseous consolidation after medial OWHTO and showed a tendency to a better functional outcome.

Integration of NMR Spectroscopy in an Analytical Workflow to Evaluate the Effects of Oxidative Stress on Abituzumab: Beyond the Fingerprint of mAbs.

The assessment of the higher-order structure (HOS) by NMR is a powerful methodology to characterize the structural features of biologics. Forced oxidative stress studies are used to investigate the stability profile, to develop pharmaceutical formulations and analytical methods. Here, the effects of forced oxidative stress by H2O2 on the monoclonal antibody Abituzumab have been characterized by a multianalytical approach combining NMR spectroscopy, mass spectrometry, differential scanning calorimetry, surface plasmon resonance, computational tools, and bioassays. This integrated strategy has provided qualitative and semiquantitative characterization of the samples and information at residue level of the effects that oxidation has on the HOS of Abituzumab, correlating them to the loss of the biological activity.

Discovery of non-boronic acid Arginase 1 inhibitors through virtual screening and biophysical methods.

Inhibiting Arginase 1 (ARG1), a metalloenzyme that hydrolyzes l-arginine in the urea cycle, has been demonstrated as a promising therapeutic avenue in immuno-oncology through the restoration of suppressed immune response in several types of cancers. Most of the currently reported small molecule inhibitors are boronic acid based. Herein, we report the discovery of non-boronic acid ARG1 inhibitors through virtual screening. Biophysical and biochemical methods were used to experimentally profile the hits while X-ray crystallography confirmed a class of trisubstituted pyrrolidine derivatives as optimizable alternatives for the development of novel classes of immuno-oncology agents targeting this enzyme.

Autophagy compensates for defects in mitochondrial dynamics.

Compromising mitochondrial fusion or fission disrupts cellular homeostasis; however, the underlying mechanism(s) are not fully understood. The loss of C. elegans fzo-1MFN results in mitochondrial fragmentation, decreased mitochondrial membrane potential and the induction of the mitochondrial unfolded protein response (UPRmt). We performed a genome-wide RNAi screen for genes that when knocked-down suppress fzo-1MFN(lf)-induced UPRmt. Of the 299 genes identified, 143 encode negative regulators of autophagy, many of which have previously not been implicated in this cellular quality control mechanism. We present evidence that increased autophagic flux suppresses fzo-1MFN(lf)-induced UPRmt by increasing mitochondrial membrane potential rather than restoring mitochondrial morphology. Furthermore, we demonstrate that increased autophagic flux also suppresses UPRmt induction in response to a block in mitochondrial fission, but not in response to the loss of spg-7AFG3L2, which encodes a mitochondrial metalloprotease. Finally, we found that blocking mitochondrial fusion or fission leads to increased levels of certain types of triacylglycerols and that this is at least partially reverted by the induction of autophagy. We propose that the breakdown of these triacylglycerols through autophagy leads to elevated metabolic activity, thereby increasing mitochondrial membrane potential and restoring mitochondrial and cellular homeostasis.

ATP13A2-mediated endo-lysosomal polyamine export counters mitochondrial oxidative stress.

Recessive loss-of-function mutations in ATP13A2 (PARK9) are associated with a spectrum of neurodegenerative disorders, including Parkinson's disease (PD). We recently revealed that the late endo-lysosomal transporter ATP13A2 pumps polyamines like spermine into the cytosol, whereas ATP13A2 dysfunction causes lysosomal polyamine accumulation and rupture. Here, we investigate how ATP13A2 provides protection against mitochondrial toxins such as rotenone, an environmental PD risk factor. Rotenone promoted mitochondrial-generated superoxide (MitoROS), which was exacerbated by ATP13A2 deficiency in SH-SY5Y cells and patient-derived fibroblasts, disturbing mitochondrial functionality and inducing toxicity and cell death. Moreover, ATP13A2 knockdown induced an ATF4-CHOP-dependent stress response following rotenone exposure. MitoROS and ATF4-CHOP were blocked by MitoTEMPO, a mitochondrial antioxidant, suggesting that the impact of ATP13A2 on MitoROS may relate to the antioxidant properties of spermine. Pharmacological inhibition of intracellular polyamine synthesis with α-difluoromethylornithine (DFMO) also increased MitoROS and ATF4 when ATP13A2 was deficient. The polyamine transport activity of ATP13A2 was required for lowering rotenone/DFMO-induced MitoROS, whereas exogenous spermine quenched rotenone-induced MitoROS via ATP13A2. Interestingly, fluorescently labeled spermine uptake in the mitochondria dropped as a consequence of ATP13A2 transport deficiency. Our cellular observations were recapitulated in vivo, in a Caenorhabditis elegans strain deficient in the ATP13A2 ortholog catp-6 These animals exhibited a basal elevated MitoROS level, mitochondrial dysfunction, and enhanced stress response regulated by atfs-1, the C. elegans ortholog of ATF4, causing hypersensitivity to rotenone, which was reversible with MitoTEMPO. Together, our study reveals a conserved cell protective pathway that counters mitochondrial oxidative stress via ATP13A2-mediated lysosomal spermine export.

Contrast-enhanced ultrasound reveals perfusion differences between benign lipoma and semi-malignant atypical lipomatous tumors: A prospective clinical study.

PURPOSE: Soft tissue tumors (STT) are difficult to diagnose accurately, and distinguishing between benign and malignant tumors is challenging. Lipoma is the most common STT, while atypical lipomatous tumors (ALT) can dedifferentiate into malignant lipomatous tumors like grade 1 liposarcoma and require more radical therapy. This study aims to investigate the potential of contrast-enhanced ultrasound (CEUS) to differentiate between lipoma and ALT based on tumor perfusion. MATERIALS AND METHODS: We prospectively examined 52 patients who were scheduled for biopsy for suspected lipoma or ALT. The CEUS examination was performed using SonoVue as a contrast agent to quantify tumor perfusion using VueBox V7.1 software. Peak enhancement (PE), rise time (RT), wash-in perfusion index (WiPI), and wash-out rate (WoR) were used to assess contrast enhancement inside the STT. RESULTS: Among 50 tumors examined, 30 were lipomas, and 20 were ALTs. We found significant differences in perfusion between lipomas and ALTs (PE: 49.22 ± 45.75 a.u. vs. 165.67 ± 174.80; RT: 23.86 ± 20.47s vs. 10.72 ± 5.34 s; WiPI: 33.06 ± 29.94 dB vs. 107.21 ± 112.43 dB; WoR: 2.44 ± 3.70 dB/s vs. 12.75 ± 15.80 dB/s; p<.001). ROC analysis of PE resulted in a diagnostic accuracy of 74% for the detection of an ALT, and 77% for the detection of a lipoma. CONCLUSION: CEUS may enhance the differential diagnosis of benign lipomas and ALTs, with ALTs showing higher levels of perfusion. If larger prospective studies confirm these findings, CEUS could enhance diagnostic accuracy, guide surgical planning, and potentially reduce unnecessary treatments for patients presenting with ambiguous lipomatous tumors like lipoma or ALT.

Fine-Tuning Redox Properties of Heteroleptic Molybdenum Complexes through Ligand-Ligand-Cooperativity.

Heteroleptic molybdenum complexes bearing 1,5-diaza-3,7-diphosphacyclooctane (P2 N2 ) and non-innocent dithiolene ligands were synthesized and electrochemically characterized. The reduction potentials of the complexes were found to be fine-tuned by a synergistic effect identified by DFT calculations as ligand-ligand cooperativity via non-covalent interactions. This finding is supported by electrochemical studies combined with UV/Vis spectroscopy and temperature-dependent NMR spectroscopy. The observed behavior is reminiscent of enzymatic redox modulation using second ligand sphere effects.

NMR as powerful technology for noninvasively monitoring cell health and expansion during bioprocessing.

Over the last decades, the success of advanced cell therapies and the increasing production volumes of vaccines, proteins, or viral vectors have raised the need of robust cell-based manufacturing processes for ensuring product quality and satisfying good manufacturing practice requirements. The cultivation process of cells needs to be highly controlled for improved productivity, reduced variability, and optimized bioprocesses. Cell cultures can be easily monitored using different technologies, which could deliver direct or indirect assessment of the cells' viability. Among these techniques, nuclear magnetic resonance (NMR) spectroscopy is a powerful technology that permits the evaluation and the identification of key endogenous metabolites. NMR can provide information on the cell metabolic pathways, on the bioprocesses, and is also capable to quickly test for impurities. In this study, NMR was successfully used as a technology for monitoring cell viability and expansion in different supports for cell growth (including bioreactors), to predict the bioprocess output and for the early identification of key metabolites linked to cell starvation. This investigation will allow the timely control of culture conditions and favor the optimization of the bioprocesses.

Pre-diagnosis urine exosomal RNA (ExoDx EPI score) is associated with post-prostatectomy pathology outcome.

PURPOSE: ExoDx Prostate IntelliScore (EPI) is a non-invasive urine exosome RNA-based test for risk assessment of high-grade prostate cancer. We evaluated the association of pre-biopsy test results with post-radical prostatectomy (RP) outcomes to understand the potential utility of EPI to inform invasive treatment vs active surveillance (AS) decisions. METHODS: Urine samples were collected from 2066 men scheduled for initial biopsy with PSA between 2 and 10 ng/mL, no history of prostate cancer, and ≥ 50 years across multiple clinical studies. 310 men proceeded to RP, of which 111 patients had Gleason group grade 1 (GG1) at biopsy and would have been potential candidates for AS. We compared pre-biopsy urine scores with ERSPC and PCPT multivariate risk calculator scores for men with GG1 at biopsy to post-RP pathology. RESULTS: Urine EPI scores were significantly lower in men with GG1 at biopsy than in men with > GG1 (p = 0.04), while there were no differences in multivariate risk scores used in standard clinical practice (p > 0.05). Further, EPI scores were significantly lower in men with GG1 at biopsy who remained GG1 post-RP compared to men upgraded to ≥ GG3 post-RP (p < 0.001). In contrast, none of the multiparametric risk calculators showed significant differences (p > 0.05). Men with GG1 at biopsy and EPI score < 15.6 had zero rate of upgrading to ≥ GG3 post-RP compared to 16.0% for EPI scores ≥ 15.6. CONCLUSIONS: The EPI urine biomarker outperformed the multivariate risk calculators in a homogenous risk group of pre-biopsy men. The EPI score was associated with low-risk pathology post-RP, with potential implications on informing AS decisions. TRIAL REGISTRATION: NCT02702856, NCT03031418, NCT03235687, NCT04720599.

Delayed Fracture Healing.

Physiologic bone healing involves numerous parameters, such as microstability, fracture morphology, or tissue perfusion, to name just a few. Slight imbalances or a severe impairment of even one of these factors may, as the figurative weakest link in the chain, crucially or completely inhibit the regenerative potential of a fractured bone. This review revisits the physiology and pathophysiology of fracture healing and provides an insight into predispositions, subtypes, diagnostic tools, and therapeutic principles involved with delayed fracture healing and nonunions. Depending on the patients individual risk factors, nonunions may develop in a variety of subtypes, each of which may require a slightly or fundamentally different therapeutical approach. After a detailed analysis of these individual factors, additional diagnostic tools, such as magnetic resonance imaging (MRI), dynamic contrast-enhanced MRI, sonography, or contrast-enhanced ultrasonography, may be indicated to narrow down the most likely cause for the development of the nonunion and therefore help find and optimize the ideal treatment strategy.

Mapping developmental maturation of inner hair cell ribbon synapses in the apical mouse cochlea.

Ribbon synapses of cochlear inner hair cells (IHCs) undergo molecular assembly and extensive functional and structural maturation before hearing onset. Here, we characterized the nanostructure of IHC synapses from late prenatal mouse embryo stages (embryonic days 14-18) into adulthood [postnatal day (P)48] using electron microscopy and tomography as well as optical nanoscopy of apical turn organs of Corti. We find that synaptic ribbon precursors arrive at presynaptic active zones (AZs) after afferent contacts have been established. These ribbon precursors contain the proteins RIBEYE and piccolino, tether synaptic vesicles and their delivery likely involves active, microtubule-based transport pathways. Synaptic contacts undergo a maturational transformation from multiple small to one single, large AZ. This maturation is characterized by the fusion of ribbon precursors with membrane-anchored ribbons that also appear to fuse with each other. Such fusion events are most frequently encountered around P12 and hence, coincide with hearing onset in mice. Thus, these events likely underlie the morphological and functional maturation of the AZ. Moreover, the postsynaptic densities appear to undergo a similar refinement alongside presynaptic maturation. Blockwise addition of ribbon material by fusion as found during AZ maturation might represent a general mechanism for modulating ribbon size.

[Contrast-enhanced ultrasound in the diagnostics of non-unions]. / Kontrastmittelverstärkter Ultraschall in der Diagnostik von Pseudarthrosen.

Non-union represents a severe complication and a major socioeconomic challenge in orthopedics and trauma surgery. Timely and reliable diagnostics are obligatory to be able to carry out the treatment of non-unions in a patient-specific and efficient manner. Contrast-enhanced ultrasound (CEUS) is an important interface between clinical signs, imaging investigations and the results of the paraclinical diagnostics, e.g. C­reactive protein (CRP) and leukocyte count. It can display the microperfusion inside the non-union gap in real time and provide valuable information for exclusion of an infection or on the healing progress after revision surgery. An establishment of this diagnostic modality in routine orthopedic trauma surgery contributes to optimization of the treatment of non-unions.

Evidence-based uncertainty: do implant-related properties of titanium reduce the susceptibility to perioperative infections in clinical fracture management? A systematic review.

BACKGROUND: Implant-associated infections (IAI) remain a challenging complication in osteosynthesis. There is no consensus or clear evidence whether titanium offers a relevant clinical benefit over stainless steel. PURPOSE: In this systematic review, we sought to determine whether the implant properties of titanium reduce the susceptibility to IAI compared to stainless steel in fracture management. METHODS: A systematic literature search in German and English was performed using specific search terms and limits. Studies published between 1995 and 1st June 2020 in the Cochrane library, MEDLINE and Web of Science databases were included. Only clinical studies comparing titanium and stainless steel implants regarding the susceptibility to infections were selected for detailed review. RESULTS: Five studies out of 384 papers were identified and reviewed. From the studies meeting inclusion criteria one study was a systematic review, two studies were randomized controlled studies (RCT) and two studies were of retrospective comparative nature of level IV evidence. CONCLUSION: Our results show that currently, no proven advantage for titanium implants in respect to IAI can be seen in contemporary literature. Implants preserving periosteal blood-flow and minimising soft-tissue trauma show statistically significant benefits in reducing the incidence of IAI. Clinical studies providing reliable evidence regarding the influence of titanium implants on IAI and investigating the susceptibility of titanium to infection are necessary.

Participation in disease management programs and major adverse cardiac events in patients after acute myocardial infarction: a longitudinal study based on registry data.

BACKGROUND: Cardiovascular diseases are still the main cause of death in the western world. However, diminishing mortality rates of acute myocardial infarction (AMI) are motivating the need to investigate the process of secondary prevention after AMI. Besides cardiac rehabilitation, disease management programs (DMPs) are an important component of outpatient care after AMI in Germany. This study aims to analyze outcomes after AMI among those who participated in DMPs and cardiac rehabilitation (CR) in a region with overall increased cardiovascular morbidity and mortality. METHODS: Based on data from a regional myocardial infarction registry and a 2-year follow-up period, we assessed the occurrence of major adverse cardiac events (MACE) in relation to participation in CR and DMP, risk factors for complications and individual healths well as lifestyle characteristics. Multivariable Cox regression was performed to compare survival time between participants and non-participants until an adverse event occurred. RESULTS: Of 1094 observed patients post-AMI, 272 were enrolled in a DMP. An association between DMP participation and lower hazard rates for MACE compared to non-enrollees could not be proven in the crude model (hazard ratio = 0.93; 95% confidence interval = 0.65-1.33). When adjusted for possible confounding variables, these results remained virtually unchanged (1.03; 0.72-1.48). Furthermore, smokers and obese patients showed a distinctly lower chance of DMP enrollment. In contrast, those who participated in CR showed a lower risk for MACE in crude (0.52; 0.41-0.65) and adjusted analysis (0.56; 0.44-0.71). CONCLUSIONS: Participation in DMP was not associated with a lower risk of MACE, but participation in CR showed beneficial effects. Adjustment only slightly changed effect estimates in both cases, but it is still important to consider potential effects of additional confounding variables.

Posttraumatic Perfusion Analysis of Quadriceps, Patellar, and Achilles Tendon Regeneration With Dynamic Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Preliminary Results.

OBJECTIVES: The healing process of tendons after surgical treatment of tendon ruptures mainly depends on the perfusion of the tendon and its surrounding tissue. Dynamic contrast-enhanced ultrasound (DCE-US) and dynamic contrast-enhanced MRI (DCE-MRI) can provide additional information about the local microperfusion. In this pilot study, the feasibility of these techniques to assess the vascularization during tendon regeneration was evaluated. METHODS: Between 2013 and 2015, 23 patients with surgical treatment of traumatic rupture of quadriceps, patellar, and Achilles tendons were involved. All patients received clinical follow-up examinations at 6, 12, and at least 52 weeks postoperatively. Dynamic contrast-enhanced US and DCE-MRI examinations were performed 6 and 12 weeks postoperatively. Dynamic contrast-enhanced US perfusion was quantified by the parameters peak enhancement, wash-in area under the curve, rise time, and initial area under the curve. Correlations between these parameters were examined via the Spearman rank correlation. The clinical and functional outcomes were assessed via the Lysholm Knee Score and Knee and Osteoarthritis Outcome Score at 12 and 52 weeks postoperatively. RESULTS: Fourteen patients with quadriceps (n = 8), patellar (n = 4) and Achilles (n = 2) tendon ruptures with complete follow-up were available. The microperfusion could be successful assessed. We could detect a strong correlation of DCE-US (peak enhancement) parameters with DCE-MRI (initial area under the curve) parameters after 6 and 12 weeks. CONCLUSIONS: In this pilot study, DCE-US was able to visualize the microperfusion of healing tendons with a strong correlation with DCE-MRI. Our initial results are in favor of DCE-US as a potential quantitative imaging tool for evaluating the vascularization in tendon regeneration as a complementary method.