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Magnetic resonance spectroscopy (MRS) thermometry offers a noninvasive, localized method for estimating temperature by leveraging the temperature-dependent chemical shift of water relative to a temperature-stable reference metabolite under suitable calibration. Consequentially, this technique has significant potential as a tool for postmortem MR examinations in forensic medicine and pathology. In these examinations, the deceased are examined at a wide range of body temperatures, and MRS thermometry may be used for the temperature adjustment of magnetic resonance imaging (MRI) protocols or for corrections in the analysis of MRI or MRS data. However, it is not yet clear to what extent postmortem changes may influence temperature estimation with MRS thermometry. In addition, N-acetylaspartate, which is commonly used as an in vivo reference metabolite, is known to decrease with increasing postmortem interval (PMI). This study shows that lactate, which is not only present in significant amounts postmortem but also has a temperature-stable chemical shift, can serve as a suitable reference metabolite for postmortem MRS thermometry. Using lactate, temperature estimation in postmortem brain tissue of severed sheep heads was accurate up to 60 h after death, with a mean absolute error of less than 0.5°C. For this purpose, published calibrations intended for in vivo measurements were used. Although postmortem decomposition resulted in severe metabolic changes, no consistent deviations were observed between measurements with an MR-compatible temperature probe and MRS thermometry with lactate as a reference metabolite. In addition, MRS thermometry was applied to 84 deceased who underwent a MR examination as part of the legal examination. MRS thermometry provided plausible results of brain temperature in comparison with rectal temperature. Even for deceased with a PMI well above 60 h, MRS thermometry still provided reliable readings. The results show a good suitability of MRS thermometry for postmortem examinations in forensic medicine., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

This study investigated differences in the concentration of gamma-aminobutyric acid (GABA) and the combination of glutamine and glutamate (as GLX) in the early visual cortex of patients with episodic migraine and the influence of transcranial direct current stimulation (tDCS) on GABA and GLX. In this single-blind, sham-controlled trial, we randomly assigned patients with episodic migraine to receive daily anodal tDCS or sham stimulation. In addition, we included healthy controls. We acquired proton MR spectroscopy data of the visual cortex with 3 Tesla MRI at baseline and from migraine patients directly after the stimulation period and 4 months later. In 22 migraineurs and 25 controls, the GABA and the GLX concentrations did not differ at baseline between the groups. tDCS resulted in reduced concentrations of GABA but not GLX or the migraine frequency directly after the stimulation period, but not 4 months later. The changes in the levels of GABA in the early visual cortex of patients with episodic migraine in the interictal period suggest an effect of tDCS that allowed for subsequent changes in the migraine frequency. However, we might have missed relevant variations in the concentrations of these neurotransmitters during the follow-up period, as changes in migraine frequency appeared after the first MRI and disappeared before the second., (© 2023 Wiley Periodicals LLC.)

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017)., (© 2023. Springer Nature Limited.)

Endogenous pain modulation in humans is frequently investigated with conditioned pain modulation (CPM). Deficient pain inhibition is a proposed mechanism that contributes to neuropathic pain (NP) after spinal cord injury (SCI). Recent studies have combined CPM testing and neuroimaging to reveal neural correlates of CPM efficiency in chronic pain. This study investigated differences in CPM efficiency in relation to resting-state functional connectivity (rsFC) between 12 SCI-NP subjects and 13 age- and sex-matched healthy controls (HC). Twelve and 11 SCI-NP subjects were included in psychophysical and rsFC analyses, respectively. All HC were included in the final analyses. Psychophysical readouts were analysed to determine CPM efficiency within and between cohorts. Group differences of rsFC, in relation to CPM efficiency, were explored with seed-to-voxel rsFC analyses with pain modulatory regions, e.g. ventrolateral periaqueductal gray (vlPAG) and amygdala. Overall, pain inhibition was not deficient in SCI-NP subjects and was greater in those with more intense NP. Greater pain inhibition was associated with weaker rsFC between the vlPAG and amygdala with the visual and frontal cortex, respectively, in SCI-NP subjects but with stronger rsFC in HC. Taken together, SCI-NP subjects present with intact pain inhibition, but can be differentiated from HC by an inverse relationship between CPM efficiency and intrinsic connectivity of supraspinal regions. Future studies with larger cohorts are necessary to consolidate the findings in this study., (© 2023. The Author(s).)

Object: Lower-field MR is reemerging as a viable, potentially cost-effective alternative to high-field MR, thanks to advances in hardware, sequence design, and reconstruction over the past decades. Evaluation of lower field strengths, however, is limited by the availability of lower-field systems on the market and their considerable procurement costs. In this work, we demonstrate a low-cost, temporary alternative to purchasing a dedicated lower-field MR system., Materials and Methods: By ramping down an existing clinical 3 T MRI system to 0.75 T, proton signals can be acquired using repurposed 13 C transmit/receive hardware and the multi-nuclei spectrometer interface. We describe the ramp-down procedure and necessary software and hardware changes to the system., Results: Apart from presenting system characterization results, we show in vivo examples of cardiac cine imaging, abdominal two- and three-point Dixon-type water/fat separation, water/fat-separated MR Fingerprinting, and point-resolved spectroscopy. In addition, the ramp-down approach allows unique comparisons of, e.g., gradient fidelity of the same MR system operated at different field strengths using the same receive chain, gradient coils, and amplifiers., Discussion: Ramping down an existing MR system may be seen as a viable alternative for lower-field MR research in groups that already own multi-nuclei hardware and can also serve as a testing platform for custom-made multi-nuclei transmit/receive coils., (© 2023. The Author(s).)

Purpose: To explore the use of conductive elastomer for MR signal detection and the utility of this approach for wearable detector arrays., Methods: An elastomer filled with silver microparticles was used to form stretchable radiofrequency coils for MR detection. Their electrical performance in terms of the Q unloaded and Q ratio was assessed in the relaxed state and under repeated strain up to 40%. In a phantom imaging study, the signal-to-noise ratio yield of conductive elastomer coils was compared with that of a reference copper coil. Four elastomer coils were integrated with a stretchable textile substrate to form a wearable array for knee imaging. The array was employed for multiple-angle and kinematic knee imaging in vivo., Results: The elastomer coils proved highly stretchable and mechanically robust. Upon repeated stretching by 20%, a medium-sized coil element settled at Q unloaded of 42 in the relaxed state and 32 at full strain, reflecting sample-noise dominance. The signal-to-noise ratio of elastomer coils was found to be 8% to 16% lower than that achieved with a conventional copper coil. Multiple-angle and kinematic knee imaging with the wearable array yielded high-quality results indicating robustness of detection performance against stretching and warping of the array., Conclusion: Conductive elastomer is a viable material for MR detection. Coils made from this material reconcile high stretchability and adequate electrical performance with ease of manufacturing. Conductive elastomer also offers inherent restoring forces and is readily washable and sanitizable, making it an excellent basis of wearable detector front ends., (© 2021 International Society for Magnetic Resonance in Medicine.)

Magnetic resonance imaging offers unique insights into three-dimensional foot bone motion. Thereby, adequate devices enabling defined loading and positioning of the foot are needed to profit from this noninvasive procedure. Tarsal bone positions of three healthy subjects were repeatedly measured in a pronated and a supinated foot excursion under bodyweight with a newly developed MR imaging procedure. The quantification of the transferred motion from the loading and positioning device to the calcaneus and an estimation of the required degrees to distinguish between tarsal joint rotations were used to evaluate the applicability of the procedure to investigate tarsal joint motion. It was found that 45-70% (75-95%) of the externally applied 15 deg foot pronation (supination) were transferred to the calcaneus. Furthermore, the talonavicular joint showed the largest amount of rotation up to 20 deg eversion-inversion and abadduction, followed by the subtalar joint showing nearly half of that motion. Considerably less motion was found between the cuboid and calcaneus (about 2-6 deg) and the cuboid nearly did not rotate relative to the navicular (on average 1 deg). The estimated necessary differences between tarsal joint movements to identify individual kinematic behavior were in the order of 2 deg (4 deg related to the talonavicular joint). Since the results were in agreement with the literature, it is concluded that the applicability of the presented procedure to investigate tarsal bone mechanics is warranted. The possibility to evaluate 3D tarsal joint motion in combination with bone morphology (e.g., joint curvature) may provide new insights in the still uncertain relationship between foot function and foot morphology. [DOI: 10.1115/1.2805400] Keywords: tarsal bones, kinematic analysis, magnetic resonance imaging

The descending pain modulatory system in humans is commonly investigated using conditioned pain modulation (CPM). Whilst variability in CPM efficiency, i.e., inhibition and facilitation, is normal in healthy subjects, exploring the inter-relationship between brain structure, resting-state functional connectivity (rsFC) and CPM readouts will provide greater insight into the underlying CPM efficiency seen in healthy individuals. Thus, this study combined CPM testing, voxel-based morphometry (VBM) and rsFC to identify the neural correlates of CPM in a cohort of healthy subjects (n =40), displaying pain inhibition (n = 29), facilitation (n = 10) and no CPM effect (n = 1). Clusters identified in the VBM analysis were implemented in the rsFC analysis alongside key constituents of the endogenous pain modulatory system. Greater pain inhibition was related to higher volume of left frontal cortices and stronger rsFC between the motor cortex and periaqueductal grey. Conversely, weaker pain inhibition was related to higher volume of the right frontal cortex - coupled with stronger rsFC to the primary somatosensory cortex, and rsFC between the amygdala and posterior insula. Overall, healthy subjects showed higher volume and stronger rsFC of brain regions involved with descending modulation, while the lateral and medial pain systems were related to greater pain inhibition and facilitation during CPM, respectively. These findings reveal structural alignments and functional interactions between supraspinal areas involved in CPM efficiency. Ultimately understanding these underlying variations and how they may become affected in chronic pain conditions, will advance a more targeted subgrouping in pain patients for future cross-sectional studies investigating endogenous pain modulation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Interoception, the perception of internal bodily states, is thought to be inextricably linked to affective qualities such as anxiety. Although interoception spans sensory to metacognitive processing, it is not clear whether anxiety is differentially related to these processing levels. Here we investigated this question in the domain of breathing, using computational modeling and high-field (7 T) fMRI to assess brain activity relating to dynamic changes in inspiratory resistance of varying predictability. Notably, the anterior insula was associated with both breathing-related prediction certainty and prediction errors, suggesting an important role in representing and updating models of the body. Individuals with low versus moderate anxiety traits showed differential anterior insula activity for prediction certainty. Multi-modal analyses of data from fMRI, computational assessments of breathing-related metacognition, and questionnaires demonstrated that anxiety-interoception links span all levels from perceptual sensitivity to metacognition, with strong effects seen at higher levels of interoceptive processes., Competing Interests: Declaration of interests F.V. has been invited to scientific meetings, consulted and/or served as speaker, and received compensation from Lundbeck, Servier, Recordati, Janssen, Otsuka, LivaNova, and Chiesi. None of these links are related to this work. The authors declare no other competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Occipital transcranial direct current stimulation (tDCS) is an effective and safe treatment for migraine attack prevention. Structural brain alterations have been found in migraineurs in regions related to pain modulation and perception, including occipital areas. However, whether these structural alterations can be dynamically modulated through tDCS treatment is understudied., Objective: To track longitudinally grey matter volume changes in occipital areas in episodic migraineurs during and up to five months after occipital tDCS treatment in a single-blind, and sham-controlled study., Methods: 24 episodic migraineurs were randomized to either receive verum or sham occipital tDCS treatment for 28 days. To investigate dynamic grey matter volume changes patients underwent structural MRI at baseline (prior to treatment), 1.5 months and 5.5 months (after completion of treatment). 31 healthy controls were scanned with the same MRI protocol. Morphometry measures assessed rate of changes over time and between groups by means of tensor-based morphometry., Results: Before treatment, migraineurs reported 5.6 monthly migraine days on average. A cross-sectional analysis revealed grey matter volume increases in the left lingual gyrus in migraineurs compared to controls. Four weeks of tDCS application led to a reduction of 1.9 migraine days/month and was paralleled by grey matter volume decreases in the left lingual gyrus in the treatment group; its extent overlapping with that seen at baseline., Conclusion: This study shows that migraineurs have increased grey matter volume in the lingual gyrus, which can be modified by tDCS. Tracking structural plasticity in migraineurs provides a potential neuroimaging biomarker for treatment monitoring., Trial Registration: ClinicalTrials.gov , NCT03237754 . Registered 03 August 2017 - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03237754 ., (© 2021. The Author(s).)

Neuropathic pain following spinal cord injury involves plastic changes along the whole neuroaxis. Current neuroimaging studies have identified grey matter volume (GMV) and resting-state functional connectivity changes of pain processing regions related to neuropathic pain intensity in spinal cord injury subjects. However, the relationship between the underlying neural processes and pain extent, a complementary characteristic of neuropathic pain, is unknown. We therefore aimed to reveal the neural markers of widespread neuropathic pain in spinal cord injury subjects and hypothesized that those with greater pain extent will show higher GMV and stronger connectivity within pain related regions. Thus, 29 chronic paraplegic subjects and 25 healthy controls underwent clinical and electrophysiological examinations combined with neuroimaging. Paraplegics were demarcated based on neuropathic pain and were thoroughly matched demographically. Our findings indicate that (a) spinal cord injury subjects with neuropathic pain display stronger connectivity between prefrontal cortices and regions involved with sensory integration and multimodal processing, (b) greater neuropathic pain extent, is associated with stronger connectivity between the posterior insular cortex and thalamic sub-regions which partake in the lateral pain system and (c) greater intensity of neuropathic pain is related to stronger connectivity of regions involved with multimodal integration and the affective-motivational component of pain. Overall, this study provides neuroimaging evidence that the pain phenotype of spinal cord injury subjects is related to the underlying function of their resting brain., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively., Objective: To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine., Materials and Methods: The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1 mA to 20 min) or sham tDCS (anodal-1 mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods., Results: Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n = 12), verum tDCS (n = 11) resulted in a lower number of migraine days (p = 0.010) across all follow-up periods. We found no significant change in total headache days (p = 0.165), anxiety (p = 0.884), or depression scores (p = 0.535). No serious adverse events occurred; minor side effects were similar in both groups., Conclusions: This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect., (© 2020 International Neuromodulation Society.)

Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology. After detailed clinical and neuropsychological characterization as well as a positron emission tomography (PET) scans with the tracer 11-[C]-Pittsburgh Compound B to estimate cerebral amyloid deposition, 14 subjects with mild cognitive impairment (MCI) (mean age 75.6 SD: 8.9) according to standard criteria and 21 cognitively healthy controls (HCS) (mean age 71.8 SD: 4.2) were assessed with EEG-fMRI. Thalamo-cortical alpha-fMRI signal coupling was only observed in HCS. Additional EEG-fMRI signal coupling differences between HCS and MCI were observed in parts of the default mode network, salience network, fronto-parietal network, and thalamus. Individuals with significant cerebral amyloid deposition (amyloid-positive MCI and HCS combined compared to amyloid-negative HCS) displayed abnormal EEG-fMRI signal coupling in visual, fronto-parietal regions but also in the parahippocampus, brain stem, and cerebellum. This finding was paralleled by stronger absolute fMRI signal in the parahippocampus and weaker absolute fMRI signal in the inferior frontal gyrus in amyloid-positive subjects. We conclude that the thalamocortical coupling in the alpha band in HCS more closely reflects previous findings observed in younger adults, while in MCI there is a clearly aberrant coupling in several networks dominated by an anticorrelation in the posterior cingulate cortex. While these findings may broadly indicate physiological changes in MCI, amyloid pathology was specifically associated with abnormal fMRI signal responses and disrupted coupling between brain oscillations and fMRI signal responses, which especially involve core regions of memory: the hippocampus, para-hippocampus, and lateral prefrontal cortex., Competing Interests: CH was employed by company Neurimmune AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Michels, Riese, Meyer, Kälin, Leh, Unschuld, Luechinger, Hock, O'Gorman, Kollias and Gietl.)

Background: Migraine is a primary headache disorder that can be classified into an episodic (EM) and a chronic form (CM). Network analysis within the graph-theoretical framework based on connectivity patterns provides an approach to observe large-scale structural integrity. We test the hypothesis that migraineurs are characterized by a segregated network., Methods: 19 healthy controls (HC), 17 EM patients and 12 CM patients were included. Cortical thickness and subcortical volumes were computed, and topology was analyzed using a graph theory analytical framework and network-based statistics. We further used support vector machines regression (SVR) to identify whether these network measures were able to predict clinical parameters., Results: Network based statistics revealed significantly lower interregional connectivity strength between anatomical compartments including the fronto-temporal, parietal and visual areas in EM and CM when compared to HC. Higher assortativity was seen in both patients' group, with higher modularity for CM and higher transitivity for EM compared to HC. For subcortical networks, higher assortativity and transitivity were observed for both patients' group with higher modularity for CM. SVR revealed that network measures could robustly predict clinical parameters for migraineurs., Conclusion: We found global network disruption for EM and CM indicated by highly segregated network in migraine patients compared to HC. Higher modularity but lower clustering coefficient in CM is suggestive of more segregation in this group compared to EM. The presence of a segregated network could be a sign of maladaptive reorganization of headache related brain circuits, leading to migraine attacks or secondary alterations to pain.

Remote neurodegenerative changes in supraspinal white matter (WM) can manifest after central lesions such as spinal cord injury (SCI). The majority of diffusion tensor imaging (DTI) studies use traditional metrics such as fractional anisotropy (FA) and mean diffusivity (MD) to investigate microstructural changes in cerebral WM after SCI. However, interpretation of FA readouts is often challenged by inherent limitations of the tensor model. Recent developments in novel diffusion markers, such as fiber density (FD), allows more accurate depictions of WM pathways and has shown more reliable quantification of WM alterations compared to FA in recent studies of neurological diseases. This study investigated if FD provides useful characterization of supraspinal WM integrity after SCI in addition to the traditional DTI readouts. FA, MD, and FD maps were derived from diffusion datasets of 20 patients with chronic SCI and compared with 19 healthy controls (HC). Group differences were investigated across whole brain WM using tract-based spatial statistics and averaged diffusion values of the corticospinal tract (CST) and thalamic radiation (TR) were extracted for comparisons between HC and SCI subgroups. We also related diffusion readouts of the CST and TR with clinical scores of sensorimotor function. To investigate which diffusion markers of the CST and TR delineate HC and patients with SCI a receiver operating characteristic (ROC) analysis was performed. Overall, patients with an SCI showed decreased FA of the TR and CST. ROC analysis differentiated HC and SCI based on diffusion markers of large WM tracts including FD of the TR. Furthermore, patients' motor function was positively correlated with greater microstructural integrity of the CST. While FD showed the strongest correlation, motor function was also associated with FA and MD of the CST. In summary, microstructural changes of supraspinal WM in patients with SCI can be detected using FD as a complementary marker to traditional DTI readouts and correlates with their clinical characteristics. Future DTI studies may benefit from utilizing this novel marker to investigate complex large WM tracts in patient cohorts with varying presentations of SCI or neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huynh, Staempfli, Luetolf, Luechinger, Curt, Kollias, Hubli and Michels.)

Purpose: The aim of this work was to provide parallel imaging capability for the human head in a gradient insert of 33-cm inner diameter within the related constraints of space, encoding ambiguity, and eddy current immunity., Methods: Eddy current behavior of the 8-channel transmit-receive array coil was investigated via heating and field deviation measurements. RF performance was evaluated using S-parameters, noise statistics, B 1 maps, and g-factor maps. In vivo images of a human head and knee were acquired with Cartesian readout and TE below 0.45 ms., Results: Under intense gradient use, the shield was heated up to 55°C and other coil structures to 40°C. After standard preemphasis calibration, eddy current-related field distortions caused by the developed RF coil were smaller than for a commercial receive-only coil. In the ambiguous regions of the gradient, B 1 + is 20 dB lower than in the center of the FOV. Coupling between elements is below -15 dB, and noise correlation is less than 0.31 when the coil is loaded with a head. Power efficiency was 0.52 ± 0.02 μT/√W, and the SD of the flip angle was below 10% in central slices of the brain. 2D, up to fourfold acceleration causes less than 30% noise amplification. The RF coil can be used during full gradient performance., Conclusion: Based on the described features, the presented coil enables parallel imaging in the high-performance gradient insert., (© 2020 International Society for Magnetic Resonance in Medicine.)

In modern magnetic resonance imaging, signal detection is performed by dense arrays of radiofrequency resonators. Tight-fitting arrays boost the sensitivity and speed of imaging. However, current devices are rigid and cage-like at the expense of patient comfort. They also constrain posture, limiting the examination of joints. For better ergonomics and versatility, detectors should be flexible, adapt to individual anatomy, and follow posture. Towards this goal, the present work proposes a novel design based on resonators formed by liquid metal in polymer tubes. Textile integration creates lightweight, elastic devices that are worn like pieces of clothing. A liquid-metal array tailored to the human knee is shown to deliver competitive image quality while self-adapting to individual anatomy and adding the ability to image flexion of the joint. Relative to other options for stretchable conductors, liquid metal in elastic tubes stands out by reconciling excellent electrical and mechanical properties with ease of manufacturing.