Equation of State of Ultracold Fermions in the 2D BEC-BCS Crossover Region.

We report the experimental measurement of the equation of state of a two-dimensional Fermi gas with attractive s-wave interactions throughout the crossover from a weakly coupled Fermi gas to a Bose gas of tightly bound dimers as the interaction strength is varied. We demonstrate that interactions lead to a renormalization of the density of the Fermi gas by several orders of magnitude. We compare our data near the ground state and at finite temperature with predictions for both fermions and bosons from quantum Monte Carlo simulations and Luttinger-Ward theory. Our results serve as input for investigations of close-to-equilibrium dynamics and transport in the two-dimensional system.

Observation of Pair Condensation in the Quasi-2D BEC-BCS Crossover.

The condensation of fermion pairs lies at the heart of superfluidity. However, for strongly correlated systems with reduced dimensionality the mechanisms of pairing and condensation are still not fully understood. In our experiment we use ultracold atoms as a generic model system to study the phase transition from a normal to a condensed phase in a strongly interacting quasi-two-dimensional Fermi gas. Using a novel method, we obtain the in situ pair momentum distribution of the strongly interacting system and observe the emergence of a low-momentum condensate at low temperatures. By tuning temperature and interaction strength, we map out the phase diagram of the quasi-2D BEC-BCS crossover.

Observation of the Berezinskii-Kosterlitz-Thouless Phase Transition in an Ultracold Fermi Gas.

We experimentally investigate the first-order correlation function of a trapped Fermi gas in the two-dimensional BEC-BCS crossover. We observe a transition to a low-temperature superfluid phase with algebraically decaying correlations. We show that the spatial coherence of the entire trapped system can be characterized by a single temperature-dependent exponent. We find the exponent at the transition to be constant over a wide range of interaction strengths across the crossover. This suggests that the phase transitions in both the bosonic regime and the strongly interacting crossover regime are of Berezinskii-Kosterlitz-Thouless type and lie within the same universality class. On the bosonic side of the crossover, our data are well described by the quantum Monte Carlo calculations for a Bose gas. In contrast, in the strongly interacting regime, we observe a superfluid phase which is significantly influenced by the fermionic nature of the constituent particles.

Bone and cartilage demonstrate changes localized to bone marrow edema-like lesions within osteoarthritic knees.

OBJECTIVE: Our objective is to understand the biological and mechanical pathways linking cartilage, bone, and marrow changes in the progression of osteoarthritis (OA). The aim of the present study was to evaluate bone structure and composition within bone marrow edema-like lesion (BMEL) regions associated with knee OA. METHODS: Tibial plateau specimens (n = 18) were collected from 10 subjects with knee OA during total knee arthroplasty (TKA). Magnetic resonance (MR) imaging was used to identify BMEL and quantify metrics of cartilage composition. Micro-computed tomography (µCT) and high-resolution peripheral quantitative computed tomography (HR-pQCT) were used to quantify density and microstructure of the subchondral trabecular bone. Fourier transform infrared (FTIR) spectroscopy was used to quantify tissue composition. RESULTS: Trabecular bone within BMEL was higher in volume fraction, with more and thicker trabeculae that were more plate-like in structure compared to unaffected regions. BMEL trabecular tissue composition had decreased phosphate and carbonate content. Marrow infiltration by a fibrous collagen network and evidence of increased bone remodeling were present. Structural and compositional changes were specifically localized to regions underlying cartilage degradation. CONCLUSION: These results support the paradigm of focal interactions among bone, marrow, and cartilage in the progression of knee OA. Quantitative evaluation of tissue changes and interactions may aid in the understanding of disease pathophysiology and provide imaging markers for disease progression.

Radiosensitisation by olaparib through focused ultrasound delivery in a diffuse midline glioma model.

BACKGROUND AND PURPOSE: Diffuse midline glioma H3K27-altered (DMG) is an aggressive, inoperable, predominantly paediatric brain tumour. Treatment strategies are limited, resulting in a median survival of only 11 months. Currently, radiotherapy (RT), often combined with temozolomide, is considered the standard of care but remains palliative, highlighting the urgency for new therapies. Radiosensitisation by olaparib, an inhibitor of PARP1 and subsequently PAR-synthesis, is a promising treatment option. We assessed whether PARP1 inhibition enhances radiosensitivity in vitro and in vivo following focused ultrasound mediated blood-brain barrier opening (FUS-BBBO). METHODS: Effects of PARP1 inhibition were evaluated in vitro using viability, clonogenic, and neurosphere assays. In vivo olaparib extravasation and pharmacokinetic profiling following FUS-BBBO was measured by LC-MS/MS. Survival benefit of FUS-BBBO combined with olaparib and RT was assessed using a patient-derived xenograft (PDX) DMG mouse model. RESULTS: Treatment with olaparib in combination with radiation delayed tumour cell proliferation in vitro through the reduction of PAR. Prolonged exposure of low olaparib concentration was more efficient in delaying cell growth than short exposure of high concentration. FUS-BBBO increased olaparib bioavailability in the pons by 5.36-fold without observable adverse effects. A Cmax of 54.09 µM in blood and 1.39 µM in the pontine region was achieved following administration of 100 mg/kg olaparib. Although RT combined with FUS-BBBO mediated olaparib extravasation delayed local tumour growth, survival benefits were not observed in an in vivo DMG PDX model. CONCLUSIONS: Olaparib effectively radiosensitises DMG cells in vitro and reduces primary tumour growth in vivo when combined with RT. Further studies are needed to investigate the therapeutic benefit of olaparib in suitable preclinical PDX models.

Simultaneous T1 measurements and proton resonance frequency shift based thermometry using variable flip angles.

A method is presented which allows precise temperature and longitudinal (T(1)) relaxation time measurements with high spatial and temporal resolution. This is achieved by combining dynamic variable flip angle based T(1) relaxation mapping with proton resonance frequency shift based thermometry. Herein, dynamic T(1) mapping is either used as a complementary measure of temperature or for the detection of T(1) contrast agent release. For the first application, the temperature evolution during a high-intensity focused ultrasound tissue ablation experiment was measured in both, porcine fat and muscle, simultaneously. In this application, temperature accuracies of 2.5 K for T(1)-based thermometry in fat and 1.2 K for proton resonance frequency shift-based thermometry in muscle were observed. The second application relates to MR-guidance of high-intensity focused ultrasound-induced local drug delivery by means of thermo-sensitive liposomes labeled with a T(1) contrast agent (Gd-HPDO3A). When the measured temperature exceeded the phase transition temperature of the liposomes, T(1) was observed to decrease with a good temporal and spatial correlation due to the release of Gd-HPDO3A. The presented results demonstrate the feasibility of the proposed method for two important applications in MR-guided noninvasive therapy. It offers a high temporal resolution when compared with interleaved Look-Locker based T(1) mapping techniques and thus represents an interesting candidate for simultaneous real-time monitoring of T(1) and temperature changes.

Spin-lattice relaxation rates and water content of freeze-dried articular cartilage.

OBJECTIVE: Nuclear magnetic resonance (NMR) spin-lattice relaxation rates were measured in bovine and porcine articular cartilage as a function of water content. METHODS: Water content was varied by freeze-drying samples for short periods of time (up to 15 min). The samples were weighed at all stages of drying so that water content could be quantified. Spin-lattice relaxation rates were measured using magnetic resonance imaging (MRI). RESULTS: Linear correlations were observed between relaxation rate and two measures of inverse water content: (1) solid-to-water ratio (ρ), expressed as a ratio of the mass of the solid component of the cartilage (m(s)) and the mass of water at each freeze-drying time point (m(w)), and (2) a ratio of the total mass of the fully-hydrated cartilage and m(w) (1/w). These correlations did not appear significantly different for the bovine and porcine data. However, fitting the data to a piecewise-linear model revealed differences between these two species. We interpret the first two segments of the piecewise model as the depletion of different water phases but conjecture that the third segment is partially caused by changes in relaxation rates as a result of a reduction in macromolecular mobilities. CONCLUSIONS: Whilst we can produce linear correlations which broadly describe the dependence of the measured spin-lattice relaxation rate on (inverse) water content, the linear model seems to obscure a more complicated relationship which potentially provides us with more information about the structure of articular cartilage and its extracellular water.

Towards optimized MR thermometry of the human heart at 3T.

Catheter ablation using radio frequency (RF) has been used increasingly for the treatment of cardiac arrhythmias and may be combined with proton resonance frequency shift (PRFS) -based MR thermometry to determine the therapy endpoint. We evaluated the suitability of two different MR thermometry sequences (TFE and TFE-EPI) and three blood suppression techniques. Experiments were performed without heating, using an optimized imaging protocol including navigator respiratory compensation, cardiac triggering, and image processing for the compensation of motion and susceptibility artefacts. Blood suppression performance and its effect on temperature stability were evaluated in the ventricular septum of eight healthy volunteers using multislice double inversion recovery (MDIR), motion sensitized driven equilibrium (MSDE), and inflow saturation by saturation slabs (IS). It was shown that blood suppression during MR thermometry improves the contrast-to-noise ratio (CNR), the robustness of the applied motion correction algorithm as well as the temperature stability. A gradient echo sequence accelerated by an EPI readout and parallel imaging (SENSE) and using inflow saturation blood suppression was shown to achieve the best results. Temperature stabilities of 2 °C or better in the ventricular septum with a spatial resolution of 3.5 × 3.5 × 8mm(3) and a temporal resolution corresponding to the heart rate of the volunteer, were observed. Our results indicate that blood suppression improves the temperature stability when performing cardiac MR thermometry. The proposed MR thermometry protocol, which optimizes temperature stability in the ventricular septum, represents a step towards PRFS-based MR thermometry of the heart at 3 T.

Fermionization of two distinguishable fermions.

We study a system of two distinguishable fermions in a 1D harmonic potential. This system has the exceptional property that there is an analytic solution for arbitrary values of the interparticle interaction. We tune the interaction strength and compare the measured properties of the system to the theoretical prediction. For diverging interaction strength, the energy and square modulus of the wave function for two distinguishable particles are the same as for a system of two noninteracting identical fermions. This is referred to as fermionization. We have observed this phenomenon by directly comparing two distinguishable fermions with diverging interaction strength with two identical fermions in the same potential. We observe good agreement between experiment and theory. By adding more particles our system can be used as a quantum simulator for more complex systems where no theoretical solution is available.

Impact of preoperative antibiotic use in preventing complications of cochlear implantation surgery.

OBJECTIVE: To examine the impact of preoperative antibiotic prophylaxis on the occurrence of postoperative complications. MATERIALS AND METHODS: Data of 491 patients undergoing cochlear implantation were included in a non-randomized retrospective comparative cohort study. Demographic data, cochlear implant and surgical details, use of preoperative antibiotics and occurrence of postoperative complications were analyzed using a binary logistic regression model. RESULTS: There were 317 patients (64.56%) who did not receive preoperative antibiotic prophylaxis and 174 (35.44%) patients who received preoperative antibiotic prophylaxis with ceftriaxone. The overall rate of complications requiring surgical treatment was 2.85%. Younger patient age was identified as a positive predictive factor for administering preoperative antibiotic prophylaxis (p<0.001, OR 1.05 CI 95% 1.0124-1.0826). No difference in complication rate was observed between the two groups. No correlation between sex, age, manufacturer, surgeon and postoperative complications were noted (p=0.45). CONCLUSION: There is insufficient evidence to inform decision making regarding preoperative intravenous ceftriaxone use for prevention of infection after cochlear implantation surgery, with data failing to show that administration of preoperative antibiotics leads to a decrease in complication rate. Considering a very low overall complication rate, with few complications related to infection, routine use of preoperative antibiotic prophylaxis should be analyzed further.

Two-color synchrotron X-ray spectroscopy based on transverse resonance island buckets.

We report on a novel multi-color method of X-ray spectroscopy at a Synchrotron radiation source that uses two simultaneously filled electron orbits in an electron storage ring to generate multiple soft or tender X-ray beams of different wavelength. To establish the second orbit, we use nonlinear beam dynamics in the so called TRIBs-transverse resonance island buckets-mode of the BESSY II storage ring, where a second electron orbit winds around the regular one leading to transversely separated source points. X-ray beams of multiple colors are generated by imaging the individual source points via different pathways through a monochromator. The particular colors can be varied by changing the traversal electron beam positions through storage-ring parameters and/or via the monochromator dispersion. As a proof of principle, X-ray absorption spectroscopy is performed on thin Fe films in transmission as well as a scanning transmission measurement on a Fe3GeTe2 sample of inhomogeneous thickness normalizing resonant signals with the pre-edge intensity. Using the extraordinary pointing fidelity of successive X-ray macro-pulses arriving at MHz repetition rates, a detection of tiny contrasts in diluted systems, contrast enhancement in X-ray microscopy as well as fast dynamics studies come into reach.

Quantitative investigation of dose accumulation errors from intra-fraction motion in MRgRT for prostate cancer.

Accurate spatial dose delivery in radiotherapy is frequently complicated due to changes in the patient's internal anatomy during and in-between therapy segments. The recent introduction of hybrid MRI radiotherapy systems allows unequaled soft-tissue visualization during radiation delivery and can be used for dose reconstruction to quantify the impact of motion. To this end, knowledge of anatomical deformations obtained from continuous monitoring during treatment has to be combined with information on the spatio-temporal dose delivery to perform motion-compensated dose accumulation (MCDA). Here, the influence of the choice of deformable image registration algorithm, dose warping strategy, and magnetic resonance image resolution and signal-to-noise-ratio on the resulting MCDA is investigated. For a quantitative investigation, four 4D MRI-datasets representing typical patient observed motion patterns are generated using finite element modeling and serve as a gold standard. Energy delivery is simulated intra-fractionally in the deformed image space and, subsequently, MCDA-processed. Finally, the results are substantiated by comparing MCDA strategies on clinically acquired patient data. It is shown that MCDA is needed for correct quantitative dose reconstruction. For prostate treatments, using the energy per mass transfer dose warping strategy has the largest influence on decreasing dose estimation errors.

Deep correction of breathing-related artifacts in real-time MR-thermometry.

Real-time MR-imaging has been clinically adapted for monitoring thermal therapies since it can provide on-the-fly temperature maps simultaneously with anatomical information. However, proton resonance frequency based thermometry of moving targets remains challenging since temperature artifacts are induced by the respiratory as well as physiological motion. If left uncorrected, these artifacts lead to severe errors in temperature estimates and impair therapy guidance. In this study, we evaluated deep learning for on-line correction of motion related errors in abdominal MR-thermometry. For this, a convolutional neural network (CNN) was designed to learn the apparent temperature perturbation from images acquired during a preparative learning stage prior to hyperthermia. The input of the designed CNN is the most recent magnitude image and no surrogate of motion is needed. During the subsequent hyperthermia procedure, the recent magnitude image is used as an input for the CNN-model in order to generate an on-line correction for the current temperature map. The method's artifact suppression performance was evaluated on 12 free breathing volunteers and was found robust and artifact-free in all examined cases. Furthermore, thermometric precision and accuracy was assessed for in vivo ablation using high intensity focused ultrasound. All calculations involved at the different stages of the proposed workflow were designed to be compatible with the clinical time constraints of a therapeutic procedure.

Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data.

BACKGROUND: We analysed 5-year treatment with agalsidase alfa enzyme replacement therapy in patients with Fabry's disease who were enrolled in the Fabry Outcome Survey observational database (FOS). METHODS: Baseline and 5-year data were available for up to 181 adults (126 men) in FOS. Serial data for cardiac mass and function, renal function, pain, and quality of life were assessed. Safety and sensitivity analyses were done in patients with baseline and at least one relevant follow-up measurement during the 5 years (n=555 and n=475, respectively). FINDINGS: In patients with baseline cardiac hypertrophy, treatment resulted in a sustained reduction in left ventricular mass (LVM) index after 5 years (from 71.4 [SD 22.5] g/m(2.7) to 64.1 [18.7] g/m(2.7), p=0.0111) and a significant increase in midwall fractional shortening (MFS) from 14.3% (2.3) to 16.0% (3.8) after 3 years (p=0.02). In patients without baseline hypertrophy, LVM index and MFS remained stable. Mean yearly fall in estimated glomerular filtration rate versus baseline after 5 years of enzyme replacement therapy was -3.17 mL/min per 1.73 m(2) for men and -0.89 mL/min per 1.73 m(2) for women. Average pain, measured by Brief Pain Inventory score, improved significantly, from 3.7 (2.3) at baseline to 2.5 (2.4) after 5 years (p=0.0023). Quality of life, measured by deviation scores from normal EuroQol values, improved significantly, from -0.24 (0.3) at baseline to -0.17 (0.3) after 5 years (p=0.0483). Findings were confirmed by sensitivity analysis. No unexpected safety concerns were identified. INTERPRETATION: By comparison with historical natural history data for patients with Fabry's disease who were not treated with enzyme replacement therapy, long-term treatment with agalsidase alfa leads to substantial and sustained clinical benefits. FUNDING: Shire Human Genetic Therapies AB.

Correlation of pre-operative computed tomography, intra-operative findings and surgical outcomes in revision tympanomastoidectomy.

OBJECTIVE: To correlate pre-operative computed tomography findings, intra-operative details and surgical outcomes with cholesteatoma recurrence in revision tympanomastoidectomy. METHODS: This retrospective, non-randomised, single-institution cohort study included 42 patients who underwent pre-operative computed tomography imaging and revision surgery for recurrent chronic otitis media. Twelve disease localisations noted during revision surgery were correlated with pre-operative temporal bone computed tomography scans. A matched pair analysis was performed on patients with similar intra-operative findings, but without pre-operative computed tomography scans. RESULTS: Pre-operative computed tomography identified 25 out of 31 cholesteatoma recurrences. Computed tomography findings correlated with: recurrent cholesteatoma when attic opacification and ossicular chain involvement were present; and revision surgery type. Sinodural angle disease, posterior canal wall erosion and dehiscent dura were identified as predictors of canal wall down tympanomastoidectomy. Patients with pre-operative computed tomography scans had a higher rate of cholesteatoma recurrence, younger age at diagnosis of recurrent disease, more revision surgical procedures and less time between previous and revision surgical procedures (all p < 0.05). CONCLUSION: Pre-operative imaging and intra-operative findings have important clinical implications in revision surgery for chronic otitis media. Performing pre-operative computed tomography increases diagnosis accuracy and reduces the time required to diagnose recurrent disease.

Patch-based field-of-view matching in multi-modal images for electroporation-based ablations.

Various multi-modal imaging sensors are currently involved at different steps of an interventional therapeutic work-flow. Cone beam computed tomography (CBCT), computed tomography (CT) or Magnetic Resonance (MR) images thereby provides complementary functional and/or structural information of the targeted region and organs at risk. Merging this information relies on a correct spatial alignment of the observed anatomy between the acquired images. This can be achieved by the means of multi-modal deformable image registration (DIR), demonstrated to be capable of estimating dense and elastic deformations between images acquired by multiple imaging devices. However, due to the typically different field-of-view (FOV) sampled across the various imaging modalities, such algorithms may severely fail in finding a satisfactory solution. In the current study we propose a new fast method to align the FOV in multi-modal 3D medical images. To this end, a patch-based approach is introduced and combined with a state-of-the-art multi-modal image similarity metric in order to cope with multi-modal medical images. The occurrence of estimated patch shifts is computed for each spatial direction and the shift value with maximum occurrence is selected and used to adjust the image field-of-view. The performance of the proposed method - in terms of both registration accuracy and computational needs - is analyzed in the practical case of on-line irreversible electroporation procedures. In total, 30 pairs of pre-/per-operative IRE images are considered to illustrate the efficiency of our algorithm. We show that a regional registration approach using voxel patches provides a good structural compromise between the voxel-wise and "global shifts" approaches. The method was thereby beneficial for CT to CBCT and MRI to CBCT registration tasks, especially when highly different image FOVs are involved. Besides, the benefit of the method for CT to CBCT and MRI to CBCT image registration is analyzed, including the impact of artifacts generated by percutaneous needle insertions. Additionally, the computational needs using commodity hardware are demonstrated to be compatible with clinical constraints in the practical case of on-line procedures. The proposed patch-based workflow thus represents an attractive asset for DIR at different stages of an interventional procedure.

Anatomically-adaptive multi-modal image registration for image-guided external-beam radiotherapy.

Image-guided radiotherapy (IGRT) allows observation of the location and shape of the tumor and organs-at-risk (OAR) over the course of a radiation cancer treatment. Such information may in turn be used for reducing geometric uncertainties during therapeutic planning, dose delivery and response assessment. However, given the multiple imaging modalities and/or contrasts potentially included within the imaging protocol over the course of the treatment, the current manual approach to determining tissue displacement may become time-consuming and error prone. In this context, variational multi-modal deformable image registration (DIR) algorithms allow automatic estimation of tumor and OAR deformations across the acquired images. In addition, they require short computational times and a low number of input parameters, which is particularly beneficial for online adaptive applications, which require on-the-fly adaptions with the patient on the treatment table. However, the majority of such DIR algorithms assume that all structures across the entire field-of-view (FOV) undergo a similar deformation pattern. Given that various anatomical structures may behave considerably different, this may lead to the estimation of anatomically implausible deformations at some locations, thus limiting their validity. Therefore, in this paper we propose an anatomically-adaptive variational multi-modal DIR algorithm, which employs a regionalized registration model in accordance with the local underlying anatomy. The algorithm was compared against two existing methods which employ global assumptions on the estimated deformations patterns. Compared to the existing approaches, the proposed method has demonstrated an improved anatomical plausibility of the estimated deformations over the entire FOV as well as displaying overall higher accuracy. Moreover, despite the more complex registration model, the proposed approach is very fast and thus suitable for online scenarios. Therefore, future adaptive IGRT workflows may benefit from an anatomically-adaptive registration model for precise contour propagation and dose accumulation, in areas showcasing considerable variations in anatomical properties.

Generation of intense and coherent sub-femtosecond X-ray pulses in electron storage rings.

Temporally short X-ray pulses are an indispensable tool for the study of electron transitions close to the Fermi energy and structural changes in molecules undergoing chemical reactions which take place on a time-scale of hundreds of femtoseconds. The time resolution of experiments at 3rd generation light sources which produce intense synchrotron radiation is limited fundamentally by the electron-bunch length in the range of tens of picoseconds. Here we propose a new scheme for the generation of intense and coherent sub-femtoseconds soft X-ray pulses in storage rings by applying the Echo-Enabled Harmonic Generation (EEHG) method. Many issues for obtaining the EEHG structure such as two modulators and a radiator are solved by a paradigm shift in an achromatic storage ring cell. Numerical demonstration of the feasibility of the scheme for the BESSY II beam parameters is presented.

Online correction of respiratory-induced field disturbances for continuous MR-thermometry in the breast.

MR-thermometry allows monitoring of the local temperature evolution during minimally invasive interventional therapies. However, for the particular case of MR-thermometry in the human breast, magnetic field variations induced by the respiratory cycle lead to phase fluctuations requiring a suitable correction strategy to prevent thermometry errors. For this purpose a look-up-table-based multibaseline approach as well as a model-based correction algorithm were applied to MR-thermometry to correct for the periodic magnetic field changes. The proposed correction method is compatible with a variety of sensors monitoring the current respiratory state. The ability to remove phase artefacts during MR-thermometry of the human breast was demonstrated experimentally in five healthy volunteers during 3 min of free-breathing using pencil-beam navigators for respiratory control. An increase of 170-530% in temperature precision was observed for the look-up-table-based approach, whereas a further improvement by 16-36% could be achieved by applying the extended model-based correction.

A 74-year-old man with an enlarging pleural-based mass that was not a mesothelioma.

Soft tissue sarcomas of the chest wall, also known as primary malignant mesenchymal tumors, may be mistaken for a malignant mesothelioma because of their histologic similarities. Reports of primary pleural sarcomas are exceedingly uncommon. We present an unusual case of a primary pleural sarcoma with unique clinical and histological features not previously seen in any other subtype of pulmonary sarcoma.