Experimental and virtual testing of bone-implant systems equipped with the AO Fracture Monitor with regard to interfragmentary movement.

Introduction: The management of fractured bones is a key domain within orthopedic trauma surgery, with the prevention of delayed healing and non-unions forming a core challenge. This study evaluates the efficacy of the AO Fracture Monitor in conjunction with biomechanical simulations to better understand the local mechanics of fracture gaps, which is crucial for comprehending mechanotransduction, a key factor in bone healing. Through a series of experiments and corresponding simulations, the study tests four hypotheses to determine the relationship between physical measurements and the predictive power of biomechanical models. Methods: Employing the AO Fracture Monitor and Digital Image Correlation techniques, the study demonstrates a significant correlation between the surface strain of implants and interfragmentary movements. This provides a foundation for utilizing one-dimensional AO Fracture Monitor measurements to predict three-dimensional fracture behavior, thereby linking mechanical loading with fracture gap dynamics. Moreover, the research establishes that finite element simulations of bone-implant systems can be effectively validated using experimental data, underpinning the accuracy of simulations in replicating physical behaviors. Results and Discussion: The findings endorse the combined use of monitoring technologies and simulations to infer the local mechanical conditions at the fracture site, offering a potential leap in personalized therapy for bone healing. Clinically, this approach can enhance treatment outcomes by refining the assessment precision in trauma trials, fostering the early detection of healing disturbances, and guiding improvements in future implant design. Ultimately, this study paves the way for more sophisticated patient monitoring and tailored interventions, promising to elevate the standard of care in orthopedic trauma surgery.

Photodynamic Eradication of Pseudomonas aeruginosa with Ru-Photosensitizers Encapsulated in Enzyme Degradable Nanocarriers.

The development of new approaches for the treatment of the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa was targeted by enhancing the effect of local antimicrobial photodynamic therapy (aPDT) using poly(ethylene glycol)-block-poly(lactic acid) (PEG114-block-PLAx) nanocarriers that were loaded with a ruthenium-based photosensitizer (PS). The action of tris(1,10-phenanthroline) ruthenium (II) bis(hexafluorophosphate) (RuPhen3) encapsulated in PEG114-block-PLAx micelles and vesicles was shown to result in an appreciable aPDT inactivation efficiency against planktonic Pseudomonas aeruginosa. In particular, the encapsulation of the PS, its release, and the efficiency of singlet oxygen (1O2) generation upon irradiation with blue light were studied spectroscopically. The antimicrobial effect was analyzed with two strains of Pseudomonas aeruginosa. Compared with PS-loaded micelles, formulations of the PS-loaded vesicles showed 10 times enhanced activity with a strong photodynamic inactivation effect of at least a 4.7 log reduction against both a Pseudomonas aeruginosa lab strain and a clinical isolate collected from the lung of a cystic fibrosis (CF) patient. This work lays the foundation for the targeted eradication of Pseudomonas aeruginosa using aPDT in various medical application areas.

In vitro regulation of fibroblast growth factor 23 by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D synthesized by osteocyte-like MC3T3-E1 cells.

Fibroblast growth factor 23 (FGF23) is produced and secreted by osteocytes and is essential for maintaining phosphate homeostasis. One of the main regulators of FGF23, 1,25-dihydroxyvitamin D (1,25(OH)2D3), is primarily synthesized in the kidney from 25-hydroxyvitamin D (25(OH)D) by 1α-hydroxylase (encoded by CYP27B1). Hitherto, it is unclear whether osteocytes can convert 25(OH)D and thereby allow for 1,25(OH)2D3 to induce FGF23 production and secretion locally. Here, we differentiated MC3T3-E1 cells toward osteocyte-like cells expressing and secreting FGF23. Treatment with 10-6 M 25(OH)D resulted in conversion of 25(OH)D to 150 pmol/L 1,25(OH)2D3 and increased FGF23 expression and secretion, but the converted amount of 1,25(OH)2D3 was insufficient to trigger an FGF23 response, so the effect on FGF23 was most likely directly caused by 25(OH)D. Interestingly, combining phosphate with 25(OH)D resulted in a synergistic increase in FGF23 expression and secretion, likely due to activation of additional signaling pathways by phosphate. Blockage of the vitamin D receptor (VDR) only partially abolished the effects of 25(OH)D or 25(OH)D combined with phosphate on Fgf23, while completely inhibiting the upregulation of cytochrome P450 family 24 subfamily A member 1 (Cyp24a1), encoding for 24-hydroxylase. RNA sequencing and in silico analyses showed that this could potentially be mediated by the nuclear receptors Retinoic Acid Receptor ß (RARB) and Estrogen Receptor 2 (ESR2). Taken together, we demonstrate that osteocytes are able to convert 25(OH)D to 1,25(OH)2D3, but this is insufficient for FGF23 activation, implicating a direct effect of 25(OH)D in the regulation of FGF23, which occurs at least partially independent from its cognate VDR. Moreover, phosphate and 25(OH)D synergistically increase expression and secretion of FGF23, which warrants investigating consequences in patients receiving a combination of vitamin D analogues and phosphate supplements. These observations help us to further understand the complex relations between phosphate, vitamin D, and FGF23.

Lipid Signatures and Inter-Cellular Heterogeneity of Naïve and Lipopolysaccharide-Stimulated Human Microglia-like Cells.

Microglia are non-neuronal cells, which reside in the central nervous system and are known to play an important role in health and disease. We investigated the lipidomic phenotypes of human naïve and stimulated microglia-like cells by atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI). With lateral resolutions between 5 and 1.5 µm pixel size, we were able to chart lipid compositions of individual cells, enabling differentiation of cell lines and stimulation conditions. This allowed us to reveal local lipid heterogeneities in naïve and lipopolysaccharide (LPS)-stimulated cells. We were able to identify individual cells with elevated triglyceride (TG) levels and could show that the number of these TG-enriched cells increased with LPS stimulation as a hallmark for a proinflammatory phenotype. Additionally, the observed local abundance alterations of specific phosphatidylinositols (PIs) indicate a cell specific regulation of the PI metabolism.

Molecular Highway Patrol for Ribosome Collisions.

During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions.

Simulation-based prediction of bone healing and treatment recommendations for lower leg fractures: Effects of motion, weight-bearing and fibular mechanics.

Despite recent experimental and clinical progress in the treatment of tibial and fibular fractures, in clinical practice rates of delayed bone healing and non-union remain high. The aim of this study was to simulate and compare different mechanical conditions after lower leg fractures to assess the effects of postoperative motion, weight-bearing restrictions and fibular mechanics on the strain distribution and the clinical course. Based on the computed tomography (CT) data set of a real clinical case with a distal diaphyseal tibial fracture, a proximal and a distal fibular fracture, finite element simulations were run. Early postoperative motion data, recorded via an inertial measuring unit system and pressure insoles were recorded and processed to study strain. The simulations were used to compute interfragmentary strain and the von Mises stress distribution of the intramedullary nail for different treatments of the fibula, as well as several walking velocities (1.0 km/h; 1.5 km/h; 2.0 km/h) and levels of weight-bearing restriction. The simulation of the real treatment was compared to the clinical course. The results show that a high postoperative walking speed was associated with higher loads in the fracture zone. In addition, a larger number of areas in the fracture gap with forces that exceeded beneficial mechanical properties longer was observed. Moreover, the simulations showed that surgical treatment of the distal fibular fracture had an impact on the healing course, whereas the proximal fibular fracture barely mattered. Weight-bearing restrictions were beneficial in reducing excessive mechanical conditions, while it is known that it is difficult for patients to adhere to partial weight-bearing recommendations. In conclusion, it is likely that motion, weight bearing and fibular mechanics influence the biomechanical milieu in the fracture gap. Simulations may improve decisions on the choice and location of surgical implants, as well as give recommendations for loading in the postoperative course of the individual patient.

A sub-ppbv-level Acetone and Ethanol Quantum Cascade Laser Based Photoacoustic Sensor - Characterization and Multi-Component Spectra Recording in Synthetic Breath.

Trace gas analysis in breath is challenging due to the vast number of different components. We present a highly sensitive quantum cascade laser based photoacoustic setup for breath analysis. Scanning the range between 8263 and 8270 nm with a spectral resolution of 48 pm, we are able to quantify acetone and ethanol within a typical breath matrix containing water and CO2. We photoacoustically acquired spectra within this region of mid-infra-red light and prove that those spectra do not suffer from non-spectral interferences. The purely additive behavior of a breath sample spectrum was verified by comparing it with the independently acquired single component spectra using Pearson and Spearman correlation coefficients. A previously presented simulation approach is improved and an error attribution study is presented. With a 3σ detection limit of 6.5 ppbv in terms of ethanol and 250 pptv regarding acetone, our system is among the best performing presented so far.

Determining Lennard-Jones Parameters Using Multiscale Target Data through Presampling-Enhanced, Surrogate-Assisted Global Optimization.

Force field-based models are a Newtonian mechanics approximation of reality and are inherently noisy. Coupling models from different molecular scale domains (including single, gas-phase molecules up to multimolecule, condensed phase ensembles) is difficult, which is also the case for finding solutions that transfer well between the scales. In this contribution, we introduce a surrogate-assisted algorithm to optimize Lennard-Jones parameters for target data from different scale domains to overcome the difficulties named above. Specifically, our approach combines a surrogate-assisted global evolutionary optimization method with a presampling phase that takes advantage of one scale domain being less computationally expensive to evaluate. The algorithm's components were evaluated individually, elucidating their individual merits. Our findings show that the process of parametrizing force fields can significantly benefit from both the presampling method, which alleviates the need to have a good initial guess for the parameters, and the surrogate model, which improves efficiency.

Synthesis and preclinical evaluation of novel 99mTc-labeled PSMA ligands for radioguided surgery of prostate cancer.

BACKGROUND: Radioguided surgery (RGS) has recently emerged as a valuable new tool in the management of recurrent prostate cancer (PCa). After preoperative injection of a 99mTc-labeled prostate-specific membrane antigen (PSMA) inhibitor, radioguided intraoperative identification and resection of lesions is facilitated by means of suitable γ-probes. First clinical experiences show the feasibility of RGS and suggest superiority over conventional lymph node dissection in recurrent PCa. However, commonly used [99mTc]Tc-PSMA-I&S exhibits slow whole-body clearance, thus hampering optimal tumor-to-background ratios (TBR) during surgery. We therefore aimed to develop novel 99mTc-labeled, PSMA-targeted radioligands with optimized pharmacokinetic profile to increase TBR at the time of surgery. METHODS: Three 99mTc-labeled N4-PSMA ligands were preclinically evaluated and compared to [99mTc]Tc-PSMA-I&S. PSMA affinity (IC50) and internalization were determined on LNCaP cells. Lipophilicity was assessed by means of the distribution coefficient logD7.4 and an ultrafiltration method was used to determine binding to human plasma proteins. Biodistribution studies and static µSPECT/CT-imaging were performed at 6 h p.i. on LNCaP tumor-bearing CB17-SCID mice. RESULTS: The novel N4-PSMA tracers were readily labeled with [99mTc]TcO4- with RCP > 95%. Comparable and high PSMA affinity was observed for all [99mTc]Tc-N4-PSMA-ligands. The ligands showed variable binding to human plasma and medium to low lipophilicity (logD7.4 - 2.6 to - 3.4), both consistently decreased compared to [99mTc]Tc-PSMA-I&S. Biodistribution studies revealed comparable tumor uptake among all [99mTc]Tc-N4-PSMA-ligands and [99mTc]Tc-PSMA-I&S, while clearance from most organs was superior for the novel tracers. Accordingly, increased TBR were achieved. [99mTc]Tc-N4-PSMA-12 showed higher TBR than [99mTc]Tc-PSMA-I&S for blood and all evaluated tissue. In addition, a procedure suitable for routine clinical production of [99mTc]Tc-N4-PSMA-12 was established. Labeling with 553 ± 187 MBq was achieved with RCP of 98.5 ± 0.6% (n = 10). CONCLUSION: High tumor accumulation and favorable clearance from blood and non-target tissue make [99mTc]Tc-N4-PSMA-12 an attractive tracer for RGS, possibly superior to currently established [99mTc]Tc-PSMA-I&S. Its GMP-production according to a method presented here and first clinical investigations with this novel radioligand is highly recommended.

Influence of image contrasts and reconstruction methods on the classification of multiple sclerosis-like lesions in simulated sodium magnetic resonance imaging.

PURPOSE: To evaluate the classifiability of small multiple sclerosis (MS)-like lesions in simulated sodium (23 Na) MRI for different 23 Na MRI contrasts and reconstruction methods. METHODS: 23 Na MRI and 23 Na inversion recovery (IR) MRI of a phantom and simulated brain with and without lesions of different volumes (V = 1.3-38.2 nominal voxels) were simulated 100 times by adding Gaussian noise matching the SNR of real 3T measurements. Each simulation was reconstructed with four different reconstruction methods (Gridding without and with Hamming filter, Compressed sensing (CS) reconstruction without and with anatomical 1 H prior information). Based on the mean signals within the lesion volumes of simulations with and without lesions, receiver operating characteristics (ROC) were determined and the area under the curve (AUC) was calculated to assess the classifiability for each lesion volume. RESULTS: Lesions show higher classifiability in 23 Na MRI than in 23 Na IR MRI. For typical parameters and SNR of a 3T scan, the voxel normed minimal classifiable lesion volume (AUC > 0.9) is 2.8 voxels for 23 Na MRI and 19 voxels for 23 Na IR MRI, respectively. In terms of classifiability, Gridding with Hamming filter and CS without anatomical 1 H prior outperform CS reconstruction with anatomical 1 H prior. CONCLUSION: Reliability of lesion classifiability strongly depends on the lesion volume and the 23 Na MRI contrast. Additional incorporation of 1 H prior information in the CS reconstruction was not beneficial for the classification of small MS-like lesions in 23 Na MRI.

Understanding and Managing Direct Operating Room Supply Costs in Cardiac Surgery.

BACKGROUND: Value-based bundles require surgeons to understand their costs. Current approaches to cost reporting are confusing and difficult to reproduce. Using the Epic surgical receipt function, we describe an intuitive and systematic approach for evaluating financial data within the operating room. METHODS: We conducted a retrospective review of all congenital cardiac procedures performed at a single academic medical center between January 1, 2020, and January 1, 2021. Direct operating room supply costs were obtained using the Epic surgical receipt function. Costs were analyzed on the basis of contribution to total annual cost and variability in case cost. Implications for strategies identified within congenital cardiac surgery were then evaluated in adult cardiac surgery. RESULTS: Five procedures representing 71 patients accounted for more than 50% of the total direct operating room supply costs (left ventricular assist device, Norwood procedure, pulmonary valve replacement, right ventricle-to-pulmonary artery shunt, and aortic arch augmentation). Disposable vascular clips, suture brand preference, and surgical patch materials accounted for 3.7%, 6.6%, and 26.5% of annual direct operating room supply costs, respectively. Improvements to these categories would represent 12% to 14% ($250 000) in annual savings without an anticipated effect on outcomes. Across adult and congenital cardiac surgery, 95% of all name-brand suture use was tied to preference cards. An opt-in vs default approach to name-brand polypropylene suture could save more than $250 000 annually. CONCLUSIONS: The surgical receipt represents a reliable and intuitive way for reporting surgical costs. Systematically analyzing costs and their impact on outcomes will help surgeons improve the value of care they provide.

Assessing muscle-specific potassium concentrations in human lower leg using potassium magnetic resonance imaging.

Noninvasively assessing tissue potassium concentrations (TPCs) using potassium magnetic resonance imaging (39 K MRI) could give valuable information on physiological processes connected to various pathologies. However, because of inherently low 39 K MR image resolution and strong signal blurring, a reliable measurement of the TPC is challenging. The aim of this work was to investigate the feasibility of a muscle-specific TPC determination with a focus on the influence of a varying residual quadrupolar interaction in human lower leg muscles. The quantification accuracy of a muscle-specific TPC determination was first assessed using simulated 39 K MRI data. In vivo 39 K and corresponding sodium (23 Na) MRI data of healthy lower leg muscles (n = 14, seven females) were acquired on a 7-T MR system using a double-resonant 23 Na/39 K birdcage Tx/Rx RF coil. Additional 1 H MR images were acquired on a 3-T MR system and used for tissue segmentation. Quantification of TPC was performed after a region-based partial volume correction (PVC) using five external reference phantoms. Simulations not only underlined the importance of PVC for correctly assessing muscle-specific TPC values, but also revealed the strong impact of a varying residual quadrupolar interaction between different muscle regions on the measured TPC. Using 39 K T2 * decay curves, we found significantly higher residual quadrupolar interaction in tibialis anterior muscle (TA; ωq = 194 ± 28 Hz) compared with gastrocnemius muscle (medial/lateral head, GM/GL; ωq = 151 ± 25 Hz) and soleus muscle (SOL; ωq = 102 ± 32 Hz). If considered in the PVC, TPC in individual muscles was similar (TPC = 98 ± 11/96 ± 14/99 ± 8/100 ± 12 mM in GM/GL/SOL/TA). Comparison with tissue sodium concentrations suggested that residual quadrupolar interactions might also influence the 23 Na MRI signal of lower leg muscles. A TPC determination of individual lower leg muscles is feasible and can therefore be applied in future studies. Considering a varying residual quadrupolar interaction for PVC of 39 K MRI data is essential to reliably assess potassium concentrations in individual muscles.

Methylglyoxal - an advanced glycation end products (AGEs) precursor - Inhibits differentiation of human MSC-derived osteoblasts in vitro independently of receptor for AGEs (RAGE).

A major precursor of advanced glycation end-products (AGEs) - methylglyoxal (MG) - is a reactive carbonyl metabolite that originates from glycolytic pathways. MG formation and accumulation has been implicated in the pathogenesis of diabetes and age-related chronic musculoskeletal disorders. Human bone marrow-derived stromal cells (BMSCs) are multipotent cells that have the potential to differentiate into cells of mesenchymal origin including osteoblasts, but the role of MG on their differentiation is unclear. We therefore evaluated the effect of MG on proliferation and differentiation of BMSC-derived osteoblasts. Cells were treated with different concentrations of MG (600, 800 and 1000 µM). Cell viability was assessed using a Cell Counting Kit-8 assay. Alkaline phosphatase (ALP) activity and calcium deposition assays were performed to evaluate osteoblast differentiation and mineralization. Gene expression was measured using qRT-PCR, whereas AGE specific receptor (RAGE) and collagen 1 were examined by immunocytochemistry and Western blotting. RAGE knockdown was performed by transducing RAGE specific short hairpin RNAs (shRNAs) using lentivirus. During osteogenic differentiation, MG treatment resulted in reduction of cell viability (27.7 %), ALP activity (45.5 %) and mineralization (82.3 %) compared to untreated cells. MG significantly decreased expression of genes involved in osteogenic differentiation - RUNX2 (2.8 fold), ALPL (3.2 fold), MG detoxification through glyoxalase - GLO1 (3 fold) and collagen metabolism - COL1A1 (4.9 fold), COL1A2 (6.8 fold), LOX (5.4 fold) and PLOD1 (1.7 fold). MG significantly reduced expression of collagen 1 (53.3 %) and RAGE (43.1 %) at protein levels. Co-treatment with a MG scavenger - aminoguanidine - prevented all negative effects of MG. RAGE-specific knockdown during MG treatment did not reverse the effects on cell viability, osteogenic differentiation or collagen metabolism. In conclusion, MG treatment can negatively influence the collagen metabolism and differentiation of BMSCs-derived osteoblasts through a RAGE independent mechanism.

Quantitative 7T sodium magnetic resonance imaging of the human brain using a 32-channel phased-array head coil: Application to patients with secondary progressive multiple sclerosis.

Apparent tissue sodium concentrations (aTSCs) determined by 23 Na brain magnetic resonance imaging (MRI) have the potential to serve as a biomarker in pathologies such as multiple sclerosis (MS). However, the quantification is hindered by the intrinsically low signal-to-noise ratio of 23 Na MRI. The purpose of this study was to improve the accuracy and reliability of quantitative 23 Na brain MRI by implementing a dedicated postprocessing pipeline and to evaluate the applicability of the developed approach for the examination of MS patients. 23 Na brain MRI measurements of 13 healthy volunteers and 17 patients with secondary progressive multiple sclerosis (SPMS) were performed at 7 T using a dual-tuned 23 Na/1 H birdcage coil with a receive-only 32-channel phased array. The aTSC values were determined for normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in healthy subjects and SPMS patients. Signal intensities were normalized using the mean cerebrospinal fluid (CSF) sodium concentration determined in 37 separate patients receiving a spinal tap for routine diagnostic purposes. Five volunteers underwent MRI examinations three times in a row to assess repeatability. Coefficients of variation (CoVs) were used to quantify the repeatability of the proposed method. aTSC values were compared regarding brain regions and subject cohort using the paired-samples Wilcoxon rank-sum test. Laboratory CSF sodium concentration did not differ significantly between patients without and with MS (p = 0.42). The proposed quantification workflow for 23 Na MRI was highly repeatable with CoVs averaged over all five volunteers of 1.9% ± 0.9% for NAWM and 2.2% ± 1.6% for NAGM. Average NAWM aTSC was significantly higher in patients with SPMS compared with the control group (p = 0.009). Average NAGM aTSC did not differ significantly between healthy volunteers and MS patients (p = 0.98). The proposed postprocessing pipeline shows high repeatability and the results can serve as a baseline for further studies establishing 23 Na brain MRI as a biomarker in diseases such as MS.

Motion-corrected 23 Na MRI of the human brain using interleaved 1 H 3D navigator images.

PURPOSE: To evaluate the feasibility of motion correction for sodium (23 Na) MRI based on interleaved acquired 3D proton (1 H) navigator images. METHODS: A 3D radial density-adapted sequence for interleaved 23 Na/1 H MRI was implemented on a 7 Tesla whole-body MRI system. The 1 H data obtained during the 23 Na acquisition were used to reconstruct 140 navigator image volumes with a nominal spatial resolution of (2.5 mm)3 and a temporal resolution of 6 s. The motion information received from co-registration was then used to correct the 23 Na image dataset, which also had a nominal spatial resolution of (2.5 mm)3 . The approach was evaluated on six healthy volunteers, whose motion during the scans had different intensities and characteristics. RESULTS: Interleaved acquisition of two nuclei did not show any relevant influence on image quality (SNR of 13.0 for interleaved versus 13.2 for standard 23 Na MRI and 176.4 for interleaved versus 178.0 for standard 1 H MRI). The applied motion correction increased the consistency between two consecutive scans for all examined volunteers and improved the image quality for all kinds of motion. The SD of the differences ranged between 2.30% and 6.96% for the uncorrected and between 2.13% and 2.67% for the corrected images. CONCLUSION: The feasibility of interleaved acquired 1 H navigator images to be used for retrospective motion correction of 23 Na images was successfully demonstrated. The approach neither affected the 23 Na image quality nor elongated the scan time and can therefore be an important tool to improve the accuracy of quantitative 23 Na MRI.

An Algorithmic Approach to Compute the Effect of Non-Radiative Relaxation Processes in Photoacoustic Spectroscopy.

Successful transfer of photoacoustic gas sensors from laboratory to real-life applications requires knowledge about potential cross-sensitivities towards environmental and gas matrix changes. Multi-dimensional calibration in case of cross-sensitivities can become very complex or even unfeasible. To address this challenge, we present a novel algorithm to compute the collision based non-radiative efficiency and phase lag of energy relaxation on a molecular level (CoNRad) for photoacoustic signal calculation. This algorithmic approach allows to calculate the entire relaxation cascade of arbitrarily complex systems, yielding a theoretical photoacoustic signal. In this work the influence of varying bulk compositions, i.e. nitrogen (N2), oxygen (O2) and water (H2O) on the photoacoustic signal during methane (CH4) detection is demonstrated. The applicability of the algorithm to other photoacoustic setups is shown exemplary by applying it to the relaxational system investigated in [1]. Hayden et al. examined the effect of water on photoacoustic carbon monoxide (CO) detection.

Open Reduction and Screw Fixation of a Diastatic Bipartite Hallux Sesamoid in Turf Toe Injury: A Case Report.

We present a case of a 25-year-old male professional soccer player who complained of severe pain over the first metatarsal head after opponent contact during a soccer game. Clinical findings showed swelling and tenderness. Initial radiographs showed a diastasis of a bipartite medial sesamoid between the fragments as compared to radiographs taken 4 years earlier of the same foot. A computed tomography scan was performed objectifying the widened interval and also showing an angulation of the proximal fragment. Open reduction and screw fixation were performed, leading to adequate positioning of the 2 bipartite fragments. The patient showed good clinical recovery and returned to the same performance level. Turf toe injury with diastasis of a medial bipartite sesamoid can be treated successfully with this operative technique.Levels of Evidence: Level V: Case report.

Hybrid B1+ -shimming and gradient adaptions for improved pseudo-continuous arterial spin labeling at 7 Tesla.

PURPOSE: To improve pseudo-continuous arterial spin labeling (pcASL) at 7T by exploiting a hybrid homogeneity- and efficiency-optimized B1+ -shim with adapted gradient strength as well as background suppression. METHODS: The following three experiments were performed at 7T, each employing five volunteers: (1) A hybrid (ie, homogeneity-efficiency optimized) B1+ -shim was introduced and evaluated for variable-rate selective excitation pcASL labeling. Therefore, B1+ -maps in the V3 segment and time-of-flight images were acquired to identify the feeding arteries. For validation, a gradient-echo sequence was applied in circular polarized (CP) mode and with the hybrid B1+ -shim. Additionally, the gray matter (temporal) signal-to-noise ratio (tSNR) in pcASL perfusion images was evaluated. (2) Bloch simulations for the pcASL labeling were conducted and validated experimentally, with a focus on the slice-selective gradients. (3) Background suppression was added to the B1+ -shimmed, gradient-adapted 7T sequence and this was then compared to a matched sequence at 3T. RESULTS: The B1+ -shim improved the signal within the labeling plane (23.6%) and the SNR/tSNR increased (+11%/+11%) compared to its value in CP mode; however, the increase was not significant. In accordance with the simulations, the adapted gradients increased the tSNR (35%) and SNR (45%) significantly. Background suppression further improved the perfusion images at 7T, and this protocol performed as well as a resolution-matched protocol at 3T. CONCLUSION: The combination of the proposed hybrid B1+ -phase-shim with the adapted slice-selective gradients and background suppression shows great potential for improved pcASL labeling under suboptimal B1+ conditions at 7T.

Direct imaging of white matter ultrashort T2∗ components at 7 Tesla.

PURPOSE: To demonstrate direct imaging of the white matter ultrashort T2∗ components at 7 Tesla using inversion recovery (IR)-enhanced ultrashort echo time (UTE) MRI. To investigate its characteristics, potentials and limitations, and to establish a clinical protocol. MATERIAL AND METHODS: The IR UTE technique suppresses long T2∗ signals within white matter by using adiabatic inversion in combination with dual-echo difference imaging. Artifacts arising at 7 T from long T2∗ scalp fat components were reduced by frequency shifting the IR pulse such that those frequencies were inverted likewise. For 8 healthy volunteers, the T2∗ relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed. RESULTS: A frequency shift of -1.2 ppm of the IR pulse (i.e. towards the fat frequency) provided a good suppression of artifacts. With this, an ultrashort compartment of (68 ± 6) % with a T2∗ time of (147 ± 58) µs was quantified with a chemical shift of (-3.6 ± 0.5) ppm from water. Within healthy volunteers' white matter, a stable ultrashort T2∗ fraction contrast was calculated. For the MS patients, a significant fraction reduction in the identified lesions as well as in the normal-appearing white matter was observed. CONCLUSIONS: The quantification results indicate that the observed ultrashort components arise primarily from myelin tissue. Direct IR UTE imaging of the white matter ultrashort T2∗ components is thus feasible at 7 T with high quantitative inter-subject repeatability and good detection of signal loss in MS.

Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies.

Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, this review first highlights the current state of the art of curative or preventive aPDT applications with relevant clinical trials. In addition, the most recent developments in photochemistry and photophysics as well as advanced carrier systems in the context of aPDT are provided, with a focus on the latest generations of efficient and versatile PSs and the progress towards hybrid-multicomponent systems. In particular, deeper insight into combinatory aPDT approaches is afforded, involving non-radiative or other light-based modalities. Selected aPDT perspectives are outlined, pointing out new strategies to target and treat microorganisms. Finally, the review works out the evolution of the conceptually simple PDT methodology towards a much more sophisticated, integrated, and innovative technology as an important element of potent antimicrobial strategies.