Prevention of taxane chemotherapy-induced nail changes and peripheral neuropathy by application of extremity cooling: a prospective single-centre study with intrapatient comparison.

PURPOSE: Common side effects of taxane chemotherapy are nail toxicity and peripheral neuropathy (CIPN) causing severe impact on the quality of life. Different methods of cryotherapy to prevent these side effects have been tested. We investigated the use of machine-controlled cooling of hands and feet to reduce nail toxicity and CIPN in patients receiving taxane chemotherapy. METHODS: Patients receiving Docetaxel (planned dose ≥ 300 mg/m2) or Paclitaxel (planned dose ≥ 720 mg/m2 - ) in the adjuvant or palliative setting of different cancers were included. The dominant hand and foot were cooled to approximately 10 °C using the Hilotherapy machine. The contralateral hand and foot were used as intrapatient comparison. The primary endpoint was the occurrence of any CIPN due to paclitaxel or nail toxicity due to Docetaxel. Both the intention to treat population (ITT) and the per protocol population (PPP) were analyzed. RESULTS: A total of 69 patients, 21 treated with Docetaxel and 48 with Paclitaxel, were included at our centre between 08/2020 and 08/2022. Nail toxicity due to Docetaxel was overall not significantly improved by cooling in the ITT or PPP but a significant benefit across visits was found for the ITT. CIPN due to Paclitaxel was numerically better in the ITT and significantly better in the PPP. A significant benefit of cooling on CIPN occurrence across visits was found for the ITT and the PPP. Cooling was very well tolerated. CONCLUSION: Cooling of hands and feet has a clinically meaningful impact on reducing occurrence of CIPN and nail toxicity on treatment with taxanes. Effects are more significant over time and are dose dependent. TRIAL REGISTRATION NUMBER: 2020-00381. Date of registration. 24th February 2020.

Magnetic Field Mapping and Correction for Moving OP-MEG.

BACKGROUND: Optically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data. OBJECTIVE: We model the spatial variation in the magnetic field and use the model to predict the movement artefact found in a dataset. METHODS: We demonstrate a method for modelling this field with a triaxial magnetometer, then show that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset. RESULTS: Using an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 27.8 ± 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows. CONCLUSION: The magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data. SIGNIFICANCE: Real-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement.

Mouth magnetoencephalography: A unique perspective on the human hippocampus.

Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependant task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus.

Pragmatic spatial sampling for wearable MEG arrays.

Several new technologies have emerged promising new Magnetoencephalography (MEG) systems in which the sensors can be placed close to the scalp. One such technology, Optically Pumped MEG (OP-MEG) allows for a scalp mounted system that provides measurements within millimetres of the scalp surface. A question that arises in developing on-scalp systems is: how many sensors are necessary to achieve adequate performance/spatial discrimination? There are many factors to consider in answering this question such as the signal to noise ratio (SNR), the locations and depths of the sources, density of spatial sampling, sensor gain errors (due to interference, subject movement, cross-talk, etc.) and, of course, the desired spatial discrimination. In this paper, we provide simulations which show the impact these factors have on designing sensor arrays for wearable MEG. While OP-MEG has the potential to provide high information content at dense spatial samplings, we find that adequate spatial discrimination of sources (< 1 cm) can be achieved with relatively few sensors (< 100) at coarse spatial samplings (~ 30 mm) at high SNR. After this point approximately 50 more sensors are required for every 1 mm improvement in spatial discrimination. Comparable discrimination for traditional cryogenic systems require more channels by these same metrics. We also show that sensor gain errors have the greatest impact on discrimination between deep sources at high SNR. Finally, we also examine the limitation that aliasing due to undersampling has on the effective SNR of on-scalp sensors.

Optically pumped magnetoencephalography in epilepsy.

We demonstrate the first use of Optically Pumped Magnetoencephalography (OP-MEG) in an epilepsy patient with unrestricted head movement. Current clinical MEG uses a traditional SQUID system, where sensors are cryogenically cooled and housed in a helmet in which the patient's head is fixed. Here, we use a different type of sensor (OPM), which operates at room temperature and can be placed directly on the patient's scalp, permitting free head movement. We performed OP-MEG recording in a patient with refractory focal epilepsy. OP-MEG-identified analogous interictal activity to scalp EEG, and source localized this activity to an appropriate brain region.

Author Correction: A tool for functional brain imaging with lifespan compliance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A tool for functional brain imaging with lifespan compliance.

The human brain undergoes significant functional and structural changes in the first decades of life, as the foundations for human cognition are laid down. However, non-invasive imaging techniques to investigate brain function throughout neurodevelopment are limited due to growth in head-size with age and substantial head movement in young participants. Experimental designs to probe brain function are also limited by the unnatural environment typical brain imaging systems impose. However, developments in quantum technology allowed fabrication of a new generation of wearable magnetoencephalography (MEG) technology with the potential to revolutionise electrophysiological measures of brain activity. Here we demonstrate a lifespan-compliant MEG system, showing recordings of high fidelity data in toddlers, young children, teenagers and adults. We show how this system can support new types of experimental paradigm involving naturalistic learning. This work reveals a new approach to functional imaging, providing a robust platform for investigation of neurodevelopment in health and disease.

Balanced, bi-planar magnetic field and field gradient coils for field compensation in wearable magnetoencephalography.

To allow wearable magnetoencephalography (MEG) recordings to be made on unconstrained subjects the spatially inhomogeneous remnant magnetic field inside the magnetically shielded room (MSR) must be nulled. Previously, a large bi-planar coil system which produces uniform fields and field gradients was used for this purpose. Its construction presented a significant challenge, six distinct coils were wound on two 1.6 × 1.6 m2 planes. Here, we exploit shared coil symmetries to produce coils simultaneously optimised to generate homogenous fields and gradients. We show nulling performance comparable to that of a six-coil system is achieved with this three-coil system, decreasing the strongest field component Bx by a factor of 53, and the strongest gradient dBx/dz by a factor of 7. To allow the coils to be used in environments with temporally-varying magnetic interference a dynamic nulling system was developed with a shielding factor of 40 dB at 0.01 Hz. Reducing the number of coils required and incorporating dynamic nulling should allow for greater take-up of this technology. Interactions of the coils with the high-permeability walls of the MSR were investigated using a method of images approach. Simulations show a degrading of field uniformity which was broadly consistent with measured values. These effects should be incorporated into future designs.

Imaging the human hippocampus with optically-pumped magnetoencephalography.

Optically-pumped (OP) magnetometers allow magnetoencephalography (MEG) to be performed while a participant's head is unconstrained. To fully leverage this new technology, and in particular its capacity for mobility, the activity of deep brain structures which facilitate explorative behaviours such as navigation, must be detectable using OP-MEG. One such crucial brain region is the hippocampus. Here we had three healthy adult participants perform a hippocampal-dependent task - the imagination of novel scene imagery - while being scanned using OP-MEG. A conjunction analysis across these three participants revealed a significant change in theta power in the medial temporal lobe. The peak of this activated cluster was located in the anterior hippocampus. We repeated the experiment with the same participants in a conventional SQUID-MEG scanner and found similar engagement of the medial temporal lobe, also with a peak in the anterior hippocampus. These OP-MEG findings indicate exciting new opportunities for investigating the neural correlates of a range of crucial cognitive functions in naturalistic contexts including spatial navigation, episodic memory and social interactions.

Wearable neuroimaging: Combining and contrasting magnetoencephalography and electroencephalography.

One of the most severe limitations of functional neuroimaging techniques, such as magnetoencephalography (MEG), is that participants must maintain a fixed head position during data acquisition. This imposes restrictions on the characteristics of the experimental cohorts that can be scanned and the experimental questions that can be addressed. For these reasons, the use of 'wearable' neuroimaging, in which participants can move freely during scanning, is attractive. The most successful example of wearable neuroimaging is electroencephalography (EEG), which employs lightweight and flexible instrumentation that makes it useable in almost any experimental setting. However, EEG has major technical limitations compared to MEG, and therefore the development of wearable MEG, or hybrid MEG/EEG systems, is a compelling prospect. In this paper, we combine and compare EEG and MEG measurements, the latter made using a new generation of optically-pumped magnetometers (OPMs). We show that these new second generation commercial OPMs, can be mounted on the scalp in an 'EEG-like' cap, enabling the acquisition of high fidelity electrophysiological measurements. We show that these sensors can be used in conjunction with conventional EEG electrodes, offering the potential for the development of hybrid MEG/EEG systems. We compare concurrently measured signals, showing that, whilst both modalities offer high quality data in stationary subjects, OPM-MEG measurements are less sensitive to artefacts produced when subjects move. Finally, we show using simulations that OPM-MEG offers a fundamentally better spatial specificity than EEG. The demonstrated technology holds the potential to revolutionise the utility of functional brain imaging, exploiting the flexibility of wearable systems to facilitate hitherto impractical experimental paradigms.

Data-driven model optimization for optically pumped magnetometer sensor arrays.

Optically pumped magnetometers (OPMs) have reached sensitivity levels that make them viable portable alternatives to traditional superconducting technology for magnetoencephalography (MEG). OPMs do not require cryogenic cooling and can therefore be placed directly on the scalp surface. Unlike cryogenic systems, based on a well-characterised fixed arrays essentially linear in applied flux, OPM devices, based on different physical principles, present new modelling challenges. Here, we outline an empirical Bayesian framework that can be used to compare between and optimise sensor arrays. We perturb the sensor geometry (via simulation) and with analytic model comparison methods estimate the true sensor geometry. The width of these perturbation curves allows us to compare different MEG systems. We test this technique using simulated and real data from SQUID and OPM recordings using head-casts and scanner-casts. Finally, we show that given knowledge of underlying brain anatomy, it is possible to estimate the true sensor geometry from the OPM data themselves using a model comparison framework. This implies that the requirement for accurate knowledge of the sensor positions and orientations a priori may be relaxed. As this procedure uses the cortical manifold as spatial support there is no co-registration procedure or reliance on scalp landmarks.

Towards OPM-MEG in a virtual reality environment.

Virtual reality (VR) provides an immersive environment in which a participant can experience a feeling of presence in a virtual world. Such environments generate strong emotional and physical responses and have been used for wide-ranging applications. The ability to collect functional neuroimaging data whilst a participant is immersed in VR would represent a step change for experimental paradigms; unfortunately, traditional brain imaging requires participants to remain still, limiting the scope of naturalistic interaction within VR. Recently however, a new type of magnetoencephalography (MEG) device has been developed, that employs scalp-mounted optically-pumped magnetometers (OPMs) to measure brain electrophysiology. Lightweight OPMs, coupled with precise control of the background magnetic field, enables participant movement during data acquisition. Here, we exploit this technology to acquire MEG data whilst a participant uses a virtual reality head-mounted display (VRHMD). We show that, despite increased magnetic interference from the VRHMD, we were able to measure modulation of alpha-band oscillations, and the visual evoked field. Moreover, in a VR experiment in which a participant had to move their head to look around a virtual wall and view a visual stimulus, we showed that the measured MEG signals map spatially in accordance with the known organisation of primary visual cortex. This technique could transform the type of neuroscientific experiment that can be undertaken using functional neuroimaging.

Optically pumped magnetometers: From quantum origins to multi-channel magnetoencephalography.

Optically Pumped Magnetometers (OPMs) have emerged as a viable and wearable alternative to cryogenic, superconducting MEG systems. This new generation of sensors has the advantage of not requiring cryogenic cooling and as a result can be flexibly placed on any part of the body. The purpose of this review is to provide a neuroscience audience with the theoretical background needed to understand the physical basis for the signal observed by OPMs. Those already familiar with the physics of MRI and NMR should note that OPMs share much of the same theory as the operation of OPMs rely on magnetic resonance. This review establishes the physical basis for the signal equation for OPMs. We re-derive the equations defining the bounds on OPM performance and highlight the important trade-offs between quantities such as bandwidth, sensor size and sensitivity. These equations lead to a direct upper bound on the gain change due to cross-talk for a multi-channel OPM system.

Cognitive neuroscience using wearable magnetometer arrays: Non-invasive assessment of language function.

Recent work has demonstrated that Optically Pumped Magnetometers (OPMs) can be utilised to create a wearable Magnetoencephalography (MEG) system that is motion robust. In this study, we use this system to map eloquent cortex using a clinically validated language lateralisation paradigm (covert verb generation: 120 trials, ∼10 min total duration) in healthy adults (n = 3). We show that it is possible to lateralise and localise language function on a case by case basis using this system. Specifically, we show that at a sensor and source level we can reliably detect a lateralising beta band (15-30 Hz) desynchronization in all subjects. This is the first study of human cognition using OPMs and not only highlights this technology's utility as tool for (developmental) cognitive neuroscience but also its potential to contribute to surgical planning via mapping of eloquent cortex, especially in young children.

A bi-planar coil system for nulling background magnetic fields in scalp mounted magnetoencephalography.

Small, commercially-available Optically Pumped Magnetometers (OPMs) can be used to construct a wearable Magnetoencephalography (MEG) system that allows large head movements to be made during recording. The small dynamic range of these sensors however means that movement in the residual static magnetic field found inside typical Magnetically Shielded Rooms (MSRs) can saturate the sensor outputs, rendering the data unusable. This problem can be ameliorated by using a set of electromagnetic coils to attenuate the spatially-varying remnant field. Here, an array of bi-planar coils, which produce an open and accessible scanning environment, was designed and constructed. The coils were designed using a harmonic minimisation method previously used for gradient coil design in Magnetic Resonance Imaging (MRI). Six coils were constructed to null Bx, By and Bz as well as the three dominant field gradients dBx/dz, dBy/dz and dBz/dz. The coils produce homogeneous (within ±5%) fields or field gradients over a volume of 40 × 40 × 40 cm3. This volume is sufficient to contain an array of OPMs, mounted in a 3D-printed scanner-cast, during basic and natural movements. Automated control of the coils using reference sensor measurements allows reduction of the largest component of the static field (Bx) from 21.8 ±â€¯0.2 nT to 0.47 ±â€¯0.08 nT. The largest gradient (dBx/dz) was reduced from 7.4 nT/m to 0.55 nT/m. High precision optical tracking allowed experiments involving controlled and measured head movements, which revealed that a rotation of the scanner-cast by ±34° and translation of ±9.7 cm of the OPMs in this field generated only a 1 nT magnetic field variation across the OPM array, when field nulling was applied. This variation could be further reduced to 0.04 nT by linear regression of field variations that were correlated with the measured motion parameters. To demonstrate the effectiveness of the bi-planar coil field cancellation system in a real MEG experiment, a novel measurement of retinotopy was investigated, where the stimulus remains fixed and head movements made by the subject shift the visual presentation to the lower left or right quadrants of the field of view. Left and right visual field stimulation produced the expected responses in the opposing hemisphere. This simple demonstration shows that the bi-planar coil system allows accurate OPM-MEG recordings to be made on an unrestrained subject.

Moving magnetoencephalography towards real-world applications with a wearable system.

Imaging human brain function with techniques such as magnetoencephalography typically requires a subject to perform tasks while their head remains still within a restrictive scanner. This artificial environment makes the technique inaccessible to many people, and limits the experimental questions that can be addressed. For example, it has been difficult to apply neuroimaging to investigation of the neural substrates of cognitive development in babies and children, or to study processes in adults that require unconstrained head movement (such as spatial navigation). Here we describe a magnetoencephalography system that can be worn like a helmet, allowing free and natural movement during scanning. This is possible owing to the integration of quantum sensors, which do not rely on superconducting technology, with a system for nulling background magnetic fields. We demonstrate human electrophysiological measurement at millisecond resolution while subjects make natural movements, including head nodding, stretching, drinking and playing a ball game. Our results compare well to those of the current state-of-the-art, even when subjects make large head movements. The system opens up new possibilities for scanning any subject or patient group, with myriad applications such as characterization of the neurodevelopmental connectome, imaging subjects moving naturally in a virtual environment and investigating the pathophysiology of movement disorders.

The SAKK cancer-specific geriatric assessment (C-SGA): a pilot study of a brief tool for clinical decision-making in older cancer patients.

BACKGROUND: Recommendations from international task forces on geriatric assessment emphasize the need for research including validation of cancer-specific geriatric assessment (C-SGA) tools in oncological settings. This study was to evaluate the feasibility of the SAKK Cancer-Specific Geriatric Assessment (C-SGA) in clinical practice. METHODS: A cross sectional study of cancer patients ≥65 years old (N = 51) with pathologically confirmed cancer presenting for initiation of chemotherapy treatment (07/01/2009-03/31/2011) at two oncology departments in Swiss canton hospitals: Kantonsspital Graubünden (KSGR N = 25), Kantonsspital St. Gallen (KSSG N = 26). Data was collected using three instruments, the SAKK C-SGA plus physician and patient evaluation forms. The SAKK C-SGA includes six measures covering five geriatric assessment domains (comorbidity, function, psychosocial, nutrition, cognition) using a mix of medical record abstraction (MRA) and patient interview. Five individual domains and one overall SAKK C-SGA score were calculated and dichotomized as below/above literature-based cut-offs. The SAKK C-SGA was evaluated by: patient and physician estimated time to complete, ease of completing, and difficult or unanswered questions. RESULTS: Time to complete the patient questionnaire was considered acceptable by almost all (≥96%) patients and physicians. Patients reported slightly shorter times to complete the questionnaire than physicians (17.33 ± 7.34 vs. 20.59 ± 6.53 minutes, p = 0.02). Both groups rated the patient questionnaire as easy/fairly easy to complete (91% vs. 84% respectively, p = 0.14) with few difficult or unanswered questions. The MRA took on average 8.32 ± 4.72 minutes to complete. Physicians (100%) considered time to complete MRA acceptable, 96% rated it as easy/fairly easy to complete. Individual study site populations differed on health-related characteristics (excellent/good physician-rated general health KSGR 71% vs. KSSG 32%, p = 0.007). The overall mean C-SGA score was 2.4 ± 1.12. Patients at KSGR had lower C-SGA scores (2.00 ± 1.19 vs. 2.81 ± 0.90, p = 0.009) and a smaller proportion (28% vs.65%, p = 0.008) was above the C-SGA cut-off score compared to KSSG. CONCLUSIONS: These results suggest the SAKK C-SGA is a feasible practical tool for use in clinical practice. It demonstrated discriminative ability based on objective geriatric assessment measures, but additional investigations on use for clinical decision-making are warranted. The SAKK C-SGA also provides important usable domain information for intervention to optimize outcomes in older cancer patients.

The frequency and distribution of minocycline induced hyperpigmentation in a rheumatoid arthritis population.

OBJECTIVE: Minocycline is particularly useful in patients with rheumatoid arthritis (RA) with previous major sepsis, where anti-tumor necrosis factor is relatively contraindicated. Pigmentation is a documented side effect, but predisposing factors in an RA population have not been established. We investigated minocycline induced pigmentation in a population with RA to determine whether skin type and eye color influence predisposition to this side effect. METHODS: Patients with RA attending a rheumatology unit who had received minocycline were contacted by telephone and some were also interviewed in the clinic. Those receiving therapy for more than 3 months were assessed. Hair color, eye color, tendency to burn in the sun, and dose and duration of therapy were documented. The frequency, type, and distribution of pigmentation were established. RESULTS: Of 37 patients identified, 10 were excluded because the duration of therapy was less than 3 months. Of the remaining 27 patients, 85% were female, with median age 64 years (range 44-88) and median disease duration 23.5 years (range 4-51). Eleven patients (41%) developed pigmentation after a median of 12 months. Four of the 11 stopped their minocycline due to pigmentation. Hair color, eye color, and tendency to burn in the sun did not predict patients who developed pigmentation. CONCLUSION: Pigmentation is a common side effect in patients receiving minocycline therapy for more than 3 months. Most patients do not stop therapy due to pigmentation. Those who stop are more likely to be female, less than 70 years of age, and have facial pigmentation.