A 97-Channel Read-Out ASIC for an Electrophysiological Mapping Catheter With an Optical Link.

Electrophysiological (EP) mapping catheters are medical equipment, which are widely used to diagnose and treat atrial fibrillation. The electrophysiology signals are sensed by the catheter's electrodes, for which a large electrode count becomes more and more essential because of the demand for a higher local resolution. A drawback of the large electrode count is the effort to pass through and to integrate the wires inside the catheter shaft. To overcome with this issue, this article describes the realization of an EP ASIC, which is placed close to the 97 electrodes and to perform an in-tip digitization. Thanks to an integrated optical link, only a single fiber is required to connect the catheter tip to an externally located electro-optical unit and thus shrinking the shaft volume to a minimum. The fiber is used to guide light from the electro-optical unit to the catheter tip and illuminate a blue LED, which is located close to the EP ASIC and acts as a photovoltaic cell. The EP ASIC is designed to use the LED as power source and a data transceiver while performing signal conditioning and digitization of the EP signals at the same time. The EP signals are captured with the ASIC's multi-channel read-out circuit consisting of 97 fully differential preamplifiers and additional filter stages. A switch network sequentially selects one single channel for further amplification and digitization of the EP signal. The read-out circuit is designed to process signals in the range of 500 µVpp to 20 mVpp with a bandwidth of 5 Hz to 100 Hz.

A chip-based C-band ODNP platform.

In this paper, we present a chip-based C-band ODNP platform centered around an NMR-on-a-chip transceiver and a printed microwave (MW) Alderman-Grant (AG) coil with a broadband tunable frequency range of 528MHz. The printable ODNP probe is optimized for a high input-power-to-magnetic-field conversion-efficiency, achieving a measured ODNP enhancement factor of -151 at microwave power levels of 33.3dBm corresponding to 2.1W. NMR measurements with and without microwave irradiation verify the functionality and the state-of-the-art performance of the proposed ODNP platform. The wide tuning range of the system allows for indirect measurements of the EPR signal of the DNP agent by sweeping the microwave excitation frequency and recording the resulting NMR signal. This feature can, e.g., be used to detect line broadening of the DNP agent. Moreover, we demonstrate experimentally that the wide tuning range of the new ODNP platform can be used to perform multi-tone microwave excitation for further signal enhancement: Using a 10mM TEMPOL solution, we improved the enhancement by a factor of two.

Comparison of Pre- and Postoperative Motor-proprioceptive Abilities in Patients with Gonarthrosis. / Vergleich prä- und postoperativer motorisch-propriozeptiver Fähigkeiten von Patienten mit Gonarthrose.

Both surgeons and patients want to achieve a high level of satisfaction and the best possible functional results within a short time after knee TEP surgery. By using a tool that digitally records various measurement parameters of balance and motor function preoperatively and postoperatively on a mobile basis and with little time expenditure, progressive results can be compared. Individual factors can thus be determined and these can influence the progress in regeneration and training progress perioperatively.In a prospective study, 100 patients before and 66 patients after installation of a cement-retained knee TEP were evaluated for the following parameters: balance, maximum strength, and power. All measurements were performed with the KMP measurement platform from MotoSana. The second measurements were performed in each case after a standardised follow-up treatment.It was shown that there are significant relationships between personal factors such as age, height, body weight and with baseline values and performance measures: maximum strength and power. Furthermore, it was shown that postoperative improvement could be achieved for the most part around balance support. All patients who previously had to hold on with one hand or both hands no longer needed support after surgery to maintain the single-leg stance for the specified time of 15 s. For a more detailed analysis of the balance parameters, the samples were adjusted and only the patients who did not hold on for support pre- and postoperatively were counted. In patients with low and medium initial stance, the sway area increased at the second measurement session, and in patients with large sway areas, it decreased, and the stance became more stable. In the area of maximum strength and power, patients with high baseline values still had higher values after AHB compared with the other patients, but lower values compared with their own baseline values.Patients who already had very good motor skills before surgery were able to achieve a greater increase in motor skills compared to the weaker group. However, all patients failed to reach their preoperative baseline values after completion of the AHB. Deficits in balance were still detectable in all groups. By using the presented force plate, measurement-based coordinated rehabilitation procedures are possible during and after completion of the AHB. Rehabilitation with individualised improvement of balance and motor function could be expected to prevent dissatisfaction after knee arthroplasty, e.g. due to muscular imbalance in femoropatellar pain syndromes.

Development of Low-Magnetic Susceptibility Microcoils via 5-Axis Machining for Analysis of Biological and Environmental Samples.

In environmental research, it is critical to understand how toxins impact invertebrate eggs and egg banks, which, due to their tiny size, are very challenging to study by conventional nuclear magnetic resonance (NMR) spectroscopy. Microcoil technology has been extensively utilized to enhance the mass-sensitivity of NMR. In a previous study, 5-axis computer numerical control (CNC) micromilling (shown to be a viable alternative to traditional microcoil production methods) was used to create a prototype copper slotted-tube resonator (STR). Despite the excellent limit of detection (LOD) of the resonator, the quality of the line shape was very poor due to the magnetic susceptibility of the copper resonator itself. This is best solved using magnetic susceptibility-matched materials. In this study, approaches are investigated that improve the susceptibility while retaining the versatility of coil milling. One method involves machining STRs from various copper/aluminum alloys, while the other involves machining ones from an aluminum 2011 alloy and electroplating them with copper. In all cases, combining copper and aluminum to produce resonators resulted in improved line shape and SNR compared to pure copper resonators due to their reduced magnetic susceptibility. However, the copper-plated aluminum resonators showed optimal performance from the devices tested. The enhanced LOD of these STRs allowed for the first 1H-13C heteronuclear multiple quantum coherence (HMQC) of a single intact 13C-labeled Daphnia magna egg (∼4 µg total biomass). This is a key step toward future screening programs that aim to elucidate the toxic processes in aquatic eggs.

Early Complication Analysis of Dynamic Intraligamentary Stabilization versus Anterior Cruciate Ligament Reconstruction.

PURPOSE: Both dynamic intraligamentary stabilization (DIS) and reconstruction (RECO) are common treatment methods for anterior cruciate ligament (ACL) rupture. We report short term outcomes after DIS (Ligamys, Mathys, Bettlach, Switzerland) and RECO using semitendinosus tendon. We compared postoperative complications, deficits of range-of-motion (ROM), and revision rates between the two treatment options. METHODS: A total of 690 patients (437 male, 253 female), after either DIS or RECO, were included. Of these, 147 patients (21%) received DIS and 543 (79%) underwent RECO. Follow-up examination focused on clinical examination, complications and revision rates. Anteroposterior instability and ROM deficits were analyzed in order to evaluate our policy of early intervention for all cases of ROM restrictions. RESULTS: Relevant ROM restrictions occurred at a significantly higher rate after DIS than after RECO (4.8% vs. 1.3%; p = 0.008). Flexion was more restricted after DIS than RECO (110° vs. 124°, p < 0.001). Extension deficits also occurred more frequently after DIS compared to RECO (49.7% vs. 24.5%; p < 0.001). Total revision surgery rate was 9.1%, with patients after DIS being significantly more frequently affected (20.4% vs. 6.1%; p < 0.001). CONCLUSIONS: Our findings indicate a significantly higher risk for ROM restriction after DIS compared to RECO, resulting in a significantly higher revision rate.

A Portable Chip-Based NMR Relaxometry System With Arbitrary Phase Control for Point-of-Care Blood Analysis.

In this article, we present a portable NMR relaxometry system optimized for the point-of-care analysis of body liquids such as blood. The presented system is centered on an NMR-on-a-chip transceiver ASIC, a reference frequency generator with arbitrary phase control, and a custom-designed miniaturized NMR magnet with a field strength of 0.29 T and a total weight of 330 g. The NMR-ASIC co-integrates a low-IF receiver, a power amplifier, and a PLL-based frequency synthesizer on a total chip area of 1100 × 900 µm 2. The arbitrary reference frequency generator enables the use of conventional CPMG and inversion sequences, as well as modified water-suppression sequences. Moreover, it is used to implement an automatic frequency lock to correct temperature-induced magnetic field drifts. Proof-of-concept measurements on NMR phantoms and human blood samples show an excellent concentration sensitivity of v[Formula: see text] = 2.2 mM/[Formula: see text]. This very good performance renders the presented system an ideal candidate for the future NMR-based point-of-care detection of biomarkers such as the blood glucose concentration.

A portable NMR platform with arbitrary phase control and temperature compensation.

In this paper, we present a custom-designed nuclear magnetic resonance (NMR) platform based on a broadband complementary metal-oxide-semiconductor (CMOS) NMR-on-a-chip transceiver and a synchronous reference signal generator, which features arbitrary phase control of the excitation pulse in combination with phase-coherent detection at a non-zero intermediate frequency (IF). Moreover, the presented direct digital synthesis (DDS)-based frequency generator enables a digital temperature compensation scheme similar to classical field locking without the need for additional hardware. NMR spectroscopy and relaxometry measurements verify the functionality of the proposed frequency reference and temperature compensation scheme as well as the overall state-of-the-art performance of the presented system.

A 96-Channel Electrophysiology Catheter with Integrated Read-Out ASIC and Optical Link.

This paper describes a realization of an electrophysiology (EP) catheter with 96 electrodes which requires no electrical wiring to the outside by relying on an optical link for both power supply and data communication. The catheter tip is constructed from a liquid crystal polymer (LCP) material. It features 96 gold electrodes, which are uniformly arranged along an expandable basket. An integrated ASIC amplifies, filters and digitizes the EP signals and establishes communication to a data processing unit outside the patient's body. The optical interface consists of a conventional multi-mode fiber and a single blue LED inside the catheter. The external unit used to generate optical power, establish communication and perform data post-processing comprises a laser module, optics, and electrical components. The catheter is designed to capture EP signals in the range of 600 µVpp to 20 mVpp in a frequency range between 8 Hz and 120 Hz.

Time-Resolved Scanning Ion Conductance Microscopy for Three-Dimensional Tracking of Nanoscale Cell Surface Dynamics.

Nanocharacterization plays a vital role in understanding the complex nanoscale organization of cells and organelles. Understanding cellular function requires high-resolution information about how the cellular structures evolve over time. A number of techniques exist to resolve static nanoscale structure of cells in great detail (super-resolution optical microscopy, EM, AFM). However, time-resolved imaging techniques tend to either have a lower resolution, are limited to small areas, or cause damage to the cells, thereby preventing long-term time-lapse studies. Scanning probe microscopy methods such as atomic force microscopy (AFM) combine high-resolution imaging with the ability to image living cells in physiological conditions. The mechanical contact between the tip and the sample, however, deforms the cell surface, disturbs the native state, and prohibits long-term time-lapse imaging. Here, we develop a scanning ion conductance microscope (SICM) for high-speed and long-term nanoscale imaging of eukaryotic cells. By utilizing advances in nanopositioning, nanopore fabrication, microelectronics, and controls engineering, we developed a microscopy method that can resolve spatiotemporally diverse three-dimensional (3D) processes on the cell membrane at sub-5-nm axial resolution. We tracked dynamic changes in live cell morphology with nanometer details and temporal ranges of subsecond to days, imaging diverse processes ranging from endocytosis, micropinocytosis, and mitosis to bacterial infection and cell differentiation in cancer cells. This technique enables a detailed look at membrane events and may offer insights into cell-cell interactions for infection, immunology, and cancer research.

NMR magnets for portable applications using 3D printed materials.

In this paper, we introduce 3D printing as a possibility for realizing lightweight, yet high-precision NMR magnets. Using a commercially available filament containing steel particles allows for the realization of critical components of NMR magnets such as pole pieces and even the flux-conducting yoke. In contrast to shimming structures made of iron, 3D printed structures made of the lightweight filament allow for a robust and inexpensive way of realizing high-performance NMR magnets for future portable NMR applications. We demonstrate the versatility and achievable high performance of the proposed solution with two different H-shaped NMR magnets. In the first magnet, the 3D-printed filament is used to realize the yoke that guides the magnetic flux inside the magnet, providing the potential for a substantial weight reduction compared to a conventional iron yoke. In the second magnet, we use the 3D-printed material to realize arbitrarily shaped passive shim structures. Numerical size and shape optimizations using non-uniform rational basis splines (NURBS) have been applied to obtain the optimal geometry. The two manufactured magnets achieve measured NMR spectral line widths of 54 ppm and 250 ppm, respectively. Our results clearly demonstrate the efficiency and versatility of the proposed design and optimization approach.

Progress in miniaturization and low-field nuclear magnetic resonance.

In this paper, we review the latest developments in miniaturization of NMR systems with an emphasis on low-field NMR. We briefly cover the topics of magnet and coil miniaturization, elaborating on the advantages and disadvantages of miniaturized coils for different applications. The main part of the article is dedicated to progress in NMR electronics. Here, we touch upon software-defined radios as an emerging gadget for NMR before we provide a detailed discussion of NMR-on-a-chip transceivers as the ultimate solution in terms of miniaturization of NMR electronics. In addition to discussing the miniaturization capabilities of the NMR-on-a-chip approach, we also investigate the potential use of NMR-on-a-chip devices for an improved NMR system performance. Here, we also discuss the possibility of combining the NMR-on-a-chip approach with EPR-on-a-chip spectrometers to form compact DNP-on-a-chip systems that can provide a significant sensitivity boost, especially for low-field NMR systems.

When the MOUSE leaves the house.

Change is inherent to time being transient. With the NMR-MOUSE (MObile Universal Surface Explorer) having matured into an established NMR tool for nondestructive testing of materials, this forward-looking retrospective assesses the challenges the NMR-MOUSE faced when deployed outside a protected laboratory and how its performance quality can be maintained and improved when operated under adverse conditions in foreign environments. This work is dedicated to my dear colleague and friend Geoffrey Bodenhausen on the occasion of his crossing an honorable timeline in appreciation of his ever-continuing success of fueling the dynamics of magnetic resonance.

Rapid-scan electron paramagnetic resonance using an EPR-on-a-Chip sensor.

Electron paramagnetic resonance (EPR) spectroscopy is the method of choice to investigate and quantify paramagnetic species in many scientific fields, including materials science and the life sciences. Common EPR spectrometers use electromagnets and microwave (MW) resonators, limiting their application to dedicated lab environments. Here, novel aspects of voltage-controlled oscillator (VCO)-based EPR-on-a-Chip (EPRoC) detectors are discussed, which have recently gained interest in the EPR community. More specifically, it is demonstrated that with a VCO-based EPRoC detector, the amplitude-sensitive mode of detection can be used to perform very fast rapid-scan EPR experiments with a comparatively simple experimental setup to improve sensitivity compared to the continuous-wave regime. In place of a MW resonator, VCO-based EPRoC detectors use an array of injection-locked VCOs, each incorporating a miniaturized planar coil as a combined microwave source and detector. A striking advantage of the VCO-based approach is the possibility of replacing the conventionally used magnetic field sweeps with frequency sweeps with very high agility and near-constant sensitivity. Here, proof-of-concept rapid-scan EPR (RS-EPRoC) experiments are performed by sweeping the frequency of the EPRoC VCO array with up to 400 THz s-1, corresponding to a field sweep rate of 14 kT s-1. The resulting time-domain RS-EPRoC signals of a micrometer-scale BDPA sample can be transformed into the corresponding absorption EPR signals with high precision. Considering currently available technology, the frequency sweep range may be extended to 320 MHz, indicating that RS-EPRoC shows great promise for future sensitivity enhancements in the rapid-scan regime.

On the modeling of amplitude-sensitive electron spin resonance (ESR) detection using voltage-controlled oscillator (VCO)-based ESR-on-a-chip detectors.

In this paper, we present an in-depth analysis of a voltage-controlled oscillator (VCO)-based sensing method for electron spin resonance (ESR) spectroscopy, which greatly simplifies the experimental setup compared to conventional detection schemes. In contrast to our previous oscillator-based ESR detectors, where the ESR signal was encoded in the oscillation frequency, in the amplitude-sensitive method, the ESR signal is sensed as a change of the oscillation amplitude of the VCO. Therefore, using VCO architecture with a built-in amplitude demodulation scheme, the experimental setup reduces to a single permanent magnet in combination with a few inexpensive electronic components. We present a theoretical analysis of the achievable limit of detection, which uses perturbation-theory-based VCO modeling for the signal and applies a stochastic averaging approach to obtain a closed-form expression for the noise floor. Additionally, the paper also introduces a numerical model suitable for simulating oscillator-based ESR experiments in a conventional circuit simulator environment. This model can be used to optimize sensor performance early on in the design phase. Finally, all presented models are verified against measured results from a prototype VCO operating at 14 GHz inside a 0.5 T magnetic field.

Digital Measurement of Individual Motor and Proprioceptive Skills in Patients with Osteoarthritis of the Knee Prior to Total Knee Replacement. / Präoperative digitale Messung individueller motorischer und propriozeptiver Fähigkeiten bei Gonarthrosepatienten.

PURPOSE: In spite of consistent improvement in operative methods for total knee arthroplasty, individual motor deficits may lead to a lower outcome. The preoperative classification in individual motoric capacity may get more significance for the future. Complementary to established questionnaires and clinical tests, this pilot study should demonstrate that it is possible to generate a preoperative motor score using a force platform measurement (KMP). Compared to questionnaires the new score represents digital values suitable for everyday clinical use. METHODS: In total 63 Patients were randomized selected on the day before a bicondylar total knee replacement. A mobile force platform KMP (Motosana) measured the parameter maximum force, power and balance. Fluctuation area was measured in mm² and fluctuation path in mm. One leg standing without holding, transient help or permanent holding at armrests were registered. The force (Newton) was measured while a modified cross lift exercise and power (Watt) by performing five squads. RESULTS: Based on comprehensive statistical consolidated data of maximum force, power and balance it was possible to create a new motor score "Knie Fit 1.0". Depending on interindividual performance patients were divided into those with higher or lower results. Regarding to their individual motor proprioceptive capacity we could also graduate patients into 4 different groups for force/power and balance. In total 17 of 63 patients offered a complex motor deficit, but on the other hand 17 different patients showed superior results in all categories. CONCLUSION: It is possible to measure the motor capacity of patients using the mobile force platform (KMP) in everyday clinical practice. Based on this data a new motor score "KnieFit 1.0" was generated and groups of patients with different insufficiencies were created. Further follow-up studies should proof and compare the pre- and postoperative outcome in this field. With "KnieFit 1.0" it may be possible to create an individual perioperative rehabilitation program for compensation of detected deficits.

Prospective pilot study to identify psychological factors influencing peri-operative pain in total knee arthroplasty (TKA).

PURPOSE: Up to 20% of total knee arthroplasty (TKA) patients remain dissatisfied, with chronic pain as the most frequently named cause. A pilot study was conducted to assess the progression of peri-operative pain intensity and the parallel development of different psychological factors and coping strategies, as well as correlations indicating potential inter-relationships. METHODS: Pain, psychological impairment [FESV BE], and coping strategies [FESV BW] were assessed before and after TKA [days - 5 to 31]. Patients were stratified according to the presence or absence of peri-operative pain improvement [decreasing pain: Group 1 [69%; n = 36]; persisting pain: group 2 [31%; n = 16]]. Group 2 was additionally tested with the Toronto Alexithymia Scale [TAS] and Screening for Somatoform Disorders [SOMS]. RESULTS: Pain intensity in group 1 decreased from significantly higher pre-operative levels to significantly lower values at 31 days post-operatively, whereas group 2 did not show significant changes. Concurrently, the psychological impairment parameter anxiety (AN) significantly decreased and the pain coping parameter relaxation significantly increased in group 1, but not in group 2. Whereas pre-operative pain was positively and significantly correlated with AN throughout time in group 2, it was negatively correlated with relaxation at day 29 in group 1. Concerning TAS and SOMS, considerable percentages of the participants in group 2 (37.5% and 68.75%, respectively) showed values > 50% of those in normal controls. CONCLUSIONS: Parallel (or anti-parallel) and partially correlated developments of pain improvement and parameters of psychological impairment or coping strategies after TKA suggest a pre-operative screening with tools like the FESV BE and BW or TAS and SOMS questionnaires in order to classify individuals for peri-operative mental training.

A Signal Acquisition Setup for Ultrashort Echo Time Imaging Operating in Parallel on Unmodified Clinical MRI Scanners Achieving an Acquisition Delay of [Formula: see text].

Ultrashort echo time imaging on clinical systems is still limited by the rather long radio frequency switching times achievable with standard front end concepts. In this contribution, an independent parallel receive-only system is interfaced to an unmodified clinical MRI system, enabling imaging of species with ultrashort relaxation times, such as bone, tendon, teeth, or lung tissue. Synchronization of the system is achieved by an electronically decoupled one-way trigger line, a clock reference signal, and RF pulse tracking, thus ensuring minimal interference with the host system. With the proposed system, an acquisition delay of [Formula: see text] is experimentally demonstrated.

A CMOS NMR needle for probing brain physiology with high spatial and temporal resolution.

Magnetic resonance imaging and spectroscopy are versatile methods for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that combines an ultra-sensitive 300 µm NMR coil with a complete NMR transceiver, enabling in vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz.

Comparison of prospective head motion correction with NMR field probes and an optical tracking system.

PURPOSE: The aim of this study was to compare prospective head motion correction and motion tracking abilities of two tracking systems: Active NMR field probes and a Moiré phase tracking camera system using an optical marker. METHODS: Both tracking systems were used simultaneously on human subjects. The prospective head motion correction was compared in an MP2RAGE and a gradient echo sequence. In addition, the motion tracking trajectories for three subjects were compared against each other and their correlation and deviations were analyzed. RESULTS: With both tracking systems motion artifacts were visibly reduced. The precision of the field probe system was on the order of 50 µm for translations and 0.03° for rotations while the camera's was approximately 5 µm and 0.007°. The comparison of the measured trajectories showed close correlation and an average absolute deviation below 500 µm and 0.5°. CONCLUSION: This study presents the first in vivo comparison between NMR field probes and Moiré phase tracking. For the gradient echo images, the field probes had a similar motion correction performance as the optical tracking system. For the MP2RAGE measurement, however, the camera yielded better results. Still, both tracking systems substantially decreased image artifacts in the presence of subject motion. Thus, the motion tracking modality should be chosen according to the specific requirements of the experiment while considering the desired image resolution, refresh rate, and head coil constraints.

An EM Simulation-Based Design Flow for Custom-Built MR Coils Incorporating Signal and Noise.

Developing custom-built MR coils is a cumbersome task, in which an a priori prediction of the coils' SNR performance, their sensitivity pattern, and their depth of penetration helps to greatly speed up the design process by reducing the required hardware manufacturing iterations. The simulation-based design flow presented in this paper takes the entire MR imaging process into account. That is, it includes all geometric and material properties of the coil and the phantom, the thermal noise as well as the target MR sequences. The proposed simulation-driven design flow is validated using a manufactured prototype coil, whose performance was optimized regarding its SNR performance, based on the presented design flow, by comparing the coil's measured performance against the simulated results. In these experiments, the mean and the standard deviation of the relative error between the simulated and measured coil sensitivity pattern were found to be and . Moreover, the peak deviation between the simulated and measured voxel SNR was found to be less than 4%, indicating that simulations are in good accordance with the measured results, validating the proposed software-based design approach.