Wirelessly interfacing sensor-equipped implants and MR scanners for improved safety and imaging.

PURPOSE: To investigate a novel reduced RF heating method for imaging in the presence of active implanted medical devices (AIMDs) which employs a sensor-equipped implant that provides wireless feedback. METHODS: The implant, consisting of a generator case and a lead, measures RF-induced E $$ E $$ -fields at the implant tip using a simple sensor in the generator case and transmits these values wirelessly to the MR scanner. Based on the sensor signal alone, parallel transmission (pTx) excitation vectors were calculated to suppress tip heating and maintain image quality. A sensor-based imaging metric was introduced to assess the image quality. The methodology was studied at 7T in testbed experiments, and at a 3T scanner in an ASTM phantom containing AIMDs instrumented with six realistic deep brain stimulation (DBS) lead configurations adapted from patients. RESULTS: The implant successfully measured RF-induced E $$ E $$ -fields (Pearson correlation coefficient squared [R2 ] = 0.93) and temperature rises (R2 = 0.95) at the implant tip. The implant acquired the relevant data needed to calculate the pTx excitation vectors and transmitted them wirelessly to the MR scanner within a single shot RF sequence (<60 ms). Temperature rises for six realistic DBS lead configurations were reduced to 0.03-0.14 K for heating suppression modes compared to 0.52-3.33 K for the worst-case heating, while imaging quality remained comparable (five of six lead imaging scores were ≥0.80/1.00) to conventional circular polarization (CP) images. CONCLUSION: Implants with sensors that can communicate with an MR scanner can substantially improve safety for patients in a fast and automated manner, easing the current burden for MR personnel.

Failure Reason of PI Test Samples of Neural Implants.

Samples that were meant to simulate the behavior of neural implants were put into Ringer's solution, and the occurring damage was assessed. The samples consist of an interdigitated gold-structure and two contact pads embedded between two Polyimide layers, resulting in free-floating structures. The two parts of the interdigitated structure have no electric contacts and are submerged in the solution during the experiment. The samples were held at temperatures of 37 and 57 ∘C in order to undergo an accelerated lifetime test and to compare the results. During the course of the experiment, a voltage was applied and measured over a resistance of 1 kOhm over time. Arduinos were used as measuring devices. As the intact samples are insulating, a sudden rise in voltage indicates a sample failure due to liquid leaking in between the two polyimide layers. Once a short-circuit occurred and a sample broke down, the samples were taken out of the vial and examined under a microscope. In virtually all cases, delamination was observable, with variation in the extent of the delaminated area. A comparison between measured voltages after failure and damage did not show a correlation between voltage and area affected by delamination. However, at a temperature of 37 ∘C, voltage remained constant most of the time after delamination, and a pin-hole lead to a lower measured voltage and strong fluctuations. Visually, no difference in damage between the 37 and the 57 ∘C samples was observed, although fluctuations of measured voltage occurred in numerous samples at a higher temperature. This difference hints at differences in the reasons for failure and thus limited applicability of accelerated lifetime tests.

Implanting mechanics of PEG/DEX coated flexible neural probe: impacts of fabricating methods.

Resorbable coatings are processed on flexible implants to facilitate penetrations. However, impacts of fabricating methods on implantation damage of coated probes are unclear. Herein, photosensitive polyimide (PSPI) based flexible neural implants are fabricated through clean-room technology. Polyethyleneglycol (PEG) - dexamethasone (DEX) coatings are processed through an improved micro moulding protocol in micro channels, fabricated by computer-numerical-controlled (CNC) micro milling, laser machining, and deep reactive ion etching (DRIE), respectively. An in vitro testing system is developed, using maximum insertion force [Formula: see text] and mean region-of-interest strain [Formula: see text] to accurately evaluate effects of the three fabricating methods on implantation damage at different insertion speed. Rat cerebrum, agarose gel, and silicone rubber are used as brain phantoms for tests. Results show that lower insertion speed, and micro channels fabricated by CNC micro milling or DRIE can minimize implantation damage. The decrease of insertion speed from 2.0 mm/s to 0.5 mm/s reduces [Formula: see text] by 76.2% ~85.1% and [Formula: see text] by 11.6% ~14.7%, respectively. Compared with laser machining, CNC micro milling and DRIE ensure dimensional accuracy of the PEG/DEX coating, reducing [Formula: see text] by 20.2% ~51.4% and [Formula: see text] by 8.0% ~11.6%, respectively. Compared with biological rat cerebrum, [Formula: see text] reduces by 5.8% ~25.1% in agarose gel phantom and increases by 7.7% ~21.0% in silicone rubber phantom, respectively. This study improves processing methods of polymer coatings and reveals mechanical difference between current used abiotic brain phantoms and biological brain tissues. Implantation tests establish quantitative relationship among insertion speed, fabricating methods, and implantation damage.

Biochemically Controlled Release of Dexamethasone Covalently Bound to PEDOT.

PEDOT (Poly(3,4-ethylenedioxythiophene)) is one of the most promising electrode materials for biomedical applications like neural recording and stimulation, thanks to its enhanced biocompatibility and electronic properties. Drug delivery by PEDOT is typically achieved by incorporating drugs as dopants during the electrodeposition procedure and a subsequent release can be promoted by applying a cathodic trigger that reduces PEDOT while enabling the drug to diffuse. This approach has several disadvantages including, for instance, the release of contaminants mainly due to PEDOT decomposition during electrochemical release. Herein we describe a new strategy based on the formation of a chemical linkage between the drug and the conductive polymer. In particular, dexamethasone was successfully integrated into a new electropolymerized PEDOT-Dex composite, leading to a self-adjusting drug release system based on a biochemically hydrolysable bond between dexamethasone and PEDOT.

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters.

OBJECTIVE: The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. METHODS: We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. RESULTS: We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. CONCLUSIONS: Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10-10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation.

Energy harvesting from cerebrospinal fluid pressure fluctuations for self-powered neural implants.

In this paper, a novel method to generate electrical energy by converting available mechanical energy from pressure fluctuations of the cerebrospinal fluid within lateral ventricles of the brain is presented. The generated electrical power can be supplied to the neural implants and either eliminate their battery need or extend the battery lifespan. A diaphragm type harvester comprised of piezoelectric material is utilized to convert the pressure fluctuations to electrical energy. The pressure fluctuations cause the diaphragm to bend, and the strained piezoelectric materials generate electricity. In the framework of this study, an energy harvesting structure having a diameter of 2.5 mm was designed and fabricated using microfabrication techniques. A 1:1 model of lateral ventricles was 3D-printed from raw MRI images to characterize the harvester. Experimental results show that a maximum power of 0.62 nW can be generated from the harvester under similar physical conditions in lateral ventricles which corresponds to energy density of 12.6 nW/cm2. Considering the available area within the lateral ventricles and the size of harvesters that can be built using microfabrication techniques it is possible to amplify to power up to 26 nW. As such, the idea of generating electrical energy by making use of pressure fluctuations within brain is demonstrated in this work via the 3D-printed model system.

Long term performance of porous platinum coated neural electrodes.

Over the last several years, there has been a growing interest in neural implants for the study and diagnostics of neurological disorders as well as for the symptomatic treatment of central nervous system related diseases. One of the major challenges is the trade-off between small electrode sizes for high selectivity between single neurons and large electrode-tissue interface areas for excellent stimulation and recording properties. This paper presents an approach of increasing the real surface area of the electrodes by creating a surface microstructure. Two major novelties let this work stand out from existing approaches which mainly make use of porous coatings such as platinum black or iridium oxide, or Poly(3,4-ethylenedioxythiophene) (PEDOT). Roughening is carried out by a dry etching process on the silicon electrode core before being coated by a sputtered platinum layer, eliminating complicated deposition processes as for the materials described above. The technology is compatible with any commonly used coating material. In addition, the surface roughening is compatible with high aspect ratio penetrating electrode arrays such as the well-established Utah electrode array, whose unique geometry presents a challenge in the surface modification of active electrode sites. The dry etching process is well characterized and yields a high controllability of pore size and depth. This paper confirms the superior electrochemical properties including impedance, charge injection capacity, and charge storage capacity of surface engineered electrode arrays compared to conventional arrays over a period of 12 weeks. Furthermore, mechanical stability of the modified electrodes was tested by implantation in the brain of a recently deceased rat. In conclusion, the larger interface surface of the electrodes does not only decrease the impedance which should lead to enhanced Signal to noise ratio (SNR) for recording purposes, but also yields higher charge injection capacities, which improve the stimulation characteristics of the implants.

Autonomous control for mechanically stable navigation of microscale implants in brain tissue to record neural activity.

Emerging neural prosthetics require precise positional tuning and stable interfaces with single neurons for optimal function over a lifetime. In this study, we report an autonomous control to precisely navigate microscale electrodes in soft, viscoelastic brain tissue without visual feedback. The autonomous control optimizes signal-to-noise ratio (SNR) of single neuronal recordings in viscoelastic brain tissue while maintaining quasi-static mechanical stress conditions to improve stability of the implant-tissue interface. Force-displacement curves from microelectrodes in in vivo rodent experiments are used to estimate viscoelastic parameters of the brain. Using a combination of computational models and experiments, we determined an optimal movement for the microelectrodes with bidirectional displacements of 3:2 ratio between forward and backward displacements and a inter-movement interval of 40 s for minimizing mechanical stress in the surrounding brain tissue. A regulator with the above optimal bidirectional motion for the microelectrodes in in vivo experiments resulted in significant reduction in the number of microelectrode movements (0.23 movements/min) and longer periods of stable SNR (53 % of the time) compared to a regulator using a conventional linear, unidirectional microelectrode movement (with 1.48 movements/min and stable SNR 23 % of the time).

Implantable photonic nano-modulators open perspectives for advanced optical interfaces with deep brain areas.

An emerging trend at the forefront of optical neural interfaces leverages the optical properties of photonic nanostructures to modulate light delivery and collection patterns in deep brain regions. This perspective article surveys the early works that have spearheaded this promising strategy, and discusses its promise towards the establishment of a class of augmented nano-neurophotonic probes.

Electrically Controlled Vasodilator Delivery from PEDOT/Silica Nanoparticle Modulates Vessel Diameter in Mouse Brain.

Vascular damage and reduced tissue perfusion are expected to majorly contribute to the loss of neurons or neural signals around implanted electrodes. However, there are limited methods of controlling the vascular dynamics in tissues surrounding these implants. This work utilizes conducting polymer poly(ethylenedioxythiophene) and sulfonated silica nanoparticle composite (PEDOT/SNP) to load and release a vasodilator, sodium nitroprusside, to controllably dilate the vasculature around carbon fiber electrodes (CFEs) implanted in the mouse cortex. The vasodilator release is triggered via electrical stimulation and the amount of release increases with increasing electrical pulses. The vascular dynamics are monitored in real-time using two-photon microscopy, with changes in vessel diameters quantified before, during, and after the release of the vasodilator into the tissues. This work observes significant increases in vessel diameters when the vasodilator is electrically triggered to release, and differential effects of the drug release on vessels of different sizes. In conclusion, the use of nanoparticle reservoirs in conducting polymer-based drug delivery platforms enables the controlled delivery of vasodilator into the implant environment, effectively altering the local vascular dynamics on demand. With further optimization, this technology could be a powerful tool to improve the neural electrode-tissue interface and study neurovascular coupling.

Neuroscience and Society: Supporting and Unsettling Public Engagement.

Advancing neuroscience is one of many topics that pose a challenge often called "the alignment problem"-the challenge, that is, of assuring that science policy is responsive to and in some sense squares with the public's values. This issue of the Hastings Center Report launches a series of scholarly essays and articles on the ethical and social issues raised by this vast body of medical research and bench science. The series, which will run under the banner "Neuroscience and Society," is supported by the Dana Foundation and seeks to promote deliberative public engagement, broadly understood, about neuroscience. As a social goal, deliberative public engagement is both ubiquitous and elusive-called for everywhere yet difficult to undertake at a national level on a complex scientific topic. To be meaningful, deliberative public engagement must occur in many locations in a society and be carried forward by many actors. Scholarly writing might contribute in several ways.

Towards biologically plausible phosphene simulation for the differentiable optimization of visual cortical prostheses.

Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or 'phosphenes') has limited resolution, and a great portion of the field's research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator's suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.

Commonly Overlooked Factors in Biocompatibility Studies of Neural Implants.

Biocompatibility of cutting-edge neural implants, surgical tools and techniques, and therapeutic technologies is a challenging concept that can be easily misjudged. For example, neural interfaces are routinely gauged on how effectively they determine active neurons near their recording sites. Tissue integration and toxicity of neural interfaces are frequently assessed histologically in animal models to determine tissue morphological and cellular changes in response to surgical implantation and chronic presence. A disconnect between histological and efficacious biocompatibility exists, however, as neuronal numbers frequently observed near electrodes do not match recorded neuronal spiking activity. The downstream effects of the myriad surgical and experimental factors involved in such studies are rarely examined when deciding whether a technology or surgical process is biocompatible. Such surgical factors as anesthesia, temperature excursions, bleed incidence, mechanical forces generated, and metabolic conditions are known to have strong systemic and thus local cellular and extracellular consequences. Many tissue markers are extremely sensitive to the physiological state of cells and tissues, thus significantly impacting histological accuracy. This review aims to shed light on commonly overlooked factors that can have a strong impact on the assessment of neural biocompatibility and to address the mismatch between results stemming from functional and histological methods.

Sulfobetaine-based ultrathin coatings as effective antifouling layers for implantable neuroprosthetic devices.

Foreign body response (FBR), inflammation, and fibrotic encapsulation of neural implants remain major problems affecting the impedance of the electrode-tissue interface and altering the device performance. Adhesion of proteins and cells (e.g., pro-inflammatory macrophages, and fibroblasts) triggers the FBR cascade and can be diminished by applying antifouling coatings onto the implanted devices. In this paper, we report the deposition and characterization of a thin (±6 nm) sulfobetaine-based coating onto microfabricated platinum electrodes and cochlear implant (CI) electrode arrays. We found that this coating has stable cell and protein-repellent properties, for at least 31 days in vitro, not affected by electrical stimulation protocols. Additionally, its effect on the electrochemical properties relevant to stimulation (i.e., impedance, charge injection capacity) was negligible. When applied to clinical CI electrode arrays, the film was successful at inhibiting fibroblast adhesion on both the silicone packaging and the platinum/iridium electrodes. In vitro, in fibroblast cultures, coated CI electrode arrays maintained impedance values up to five times lower compared to non-coated devices. Our studies demonstrate that such thin sulfobetaine containing layers are stable and prevent protein and cell adhesion in vitro and are compatible for use on CI electrode arrays. Future in vivo studies should be conducted to investigate its ability to mitigate biofouling, fibrosis, and the resulting impedance changes upon long-term implantation in vivo.

Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes.

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models. In vivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2 µA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over 8 months at a markedly low charge injection of 0.25 nC/phase. Quantified histological analyses show that chronic ICMS by StimNETs induces no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially selective neuromodulation at low currents, which lessens risk of tissue damage or exacerbation of off-target side effects.

Robotic multi-probe single-actuator inchworm neural microdrive.

A wide range of techniques in neuroscience involve placing individual probes at precise locations in the brain. However, large-scale measurement and manipulation of the brain using such methods have been severely limited by the inability to miniaturize systems for probe positioning. Here, we present a fundamentally new, remote-controlled micropositioning approach composed of novel phase-change material-filled resistive heater micro-grippers arranged in an inchworm motor configuration. The microscopic dimensions, stability, gentle gripping action, individual electronic control, and high packing density of the grippers allow micrometer-precision independent positioning of many arbitrarily shaped probes using a single piezo actuator. This multi-probe single-actuator design significantly reduces the size and weight and allows for potential automation of microdrives. We demonstrate accurate placement of multiple electrodes into the rat hippocampus in vivo in acute and chronic preparations. Our robotic microdrive technology should therefore enable the scaling up of many types of multi-probe applications in neuroscience and other fields.

Neuroenhancements in the Military: A Mixed-Method Pilot Study on Attitudes of Staff Officers to Ethics and Rules.

Utilising science and technology to maximize human performance is often an essential feature of military activity. This can often be focused on mission success rather than just the welfare of the individuals involved. This tension has the potential to threaten the autonomy of soldiers and military physicians around the taking or administering of enhancement neurotechnologies (e.g., pills, neural implants, and neuroprostheses). The Hybrid Framework was proposed by academic researchers working in the U.S. context and comprises "rules" for military neuroenhancement (e.g., ensuring transparency and maintaining dignity of the warfighter). Integrating traditional bioethical perspectives with the unique requirements of the military environment, it has been referenced by military/government agencies tasked with writing official ethical frameworks. Our two-part investigation explored the ethical dimensions of military neuroenhancements with military officers - those most likely to be making decisions in this area in the future. In three workshops, structured around the Hybrid Framework, we explored what they thought about the ethical issues of enhancement neurotechnologies. From these findings, we conducted a survey (N = 332) to probe the extent of rule endorsement. Results show high levels of endorsement for a warfighter's decision-making autonomy, but lower support for the view that enhanced warfighters would pose a danger to society after service. By examining the endorsement of concrete decision-making guidelines, we provide an overview of how military officers might, in practice, resolve tensions between competing values or higher-level principles. Our results suggest that the military context demands a recontextualisation of the relationship between military and civilian ethics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12152-022-09490-2.

DyNeuMo Mk-1: Design and pilot validation of an investigational motion-adaptive neurostimulator with integrated chronotherapy.

There is growing interest in using adaptive neuromodulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the 'Picostim DyNeuMo Mk-1' (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient's movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.

Emerging Materials and Technologies with Applications in Flexible Neural Implants: A Comprehensive Review of Current Issues with Neural Devices.

Neuroscience is an essential field of investigation that reveals the identity of human beings, with a comprehensive understanding of advanced mental activities, through the study of neurobiological structures and functions. Fully understanding the neurotransmission system that allows for connectivity among neuronal circuits has paved the way for the development of treatments for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and depression. The field of flexible implants has attracted increasing interest mainly to overcome the mechanical mismatch between rigid electrode materials and soft neural tissues, enabling precise measurements of neural signals from conformal contact. Here, the current issues of flexible neural implants (chronic device failure, non-bioresorbable electronics, low-density electrode arrays, among others are summarized) by presenting material candidates and designs to address each challenge. Furthermore, the latest investigations associated with the aforementioned issues are also introduced, including suggestions for ideal neural implants. In terms of the future direction of these advances, designing flexible devices would provide new opportunities for the study of brain-machine interfaces or brain-computer interfaces as part of locomotion through brain signals, and for the treatment of neurodegenerative diseases.

Functionalized carbon nanotube microfibers for chronic neural implants.

BACKGROUND: Much progress has been made at the interface between neural tissue and electrodes for neurophysiology. However, there continues to be a need for novel materials that integrate well with the nervous system and facilitate neural recordings with longer-term sustainability and stability. Such materials have the potential to improve clinical approaches and provide important tools for basic neuroscience research. NEW METHOD: In this paper, we explore the use of dry-spun untreated or functionalized carbon nanotube fibers as implantable electrodes for neural recordings from insects over extended time periods. RESULTS: Measurements of fly eyes responding to light flashes illustrate the suitability of these materials for recording both the low- and high-frequency components of neural signals. Repeated recordings show good sustainability, especially with functionalized carbon nanotube fibers. In particular, recordings from the optic lobes of Madagascar hissing cockroaches last for at least 8 weeks. COMPARISON WITH EXISTING METHOD(S): Electrophysiological research continues to rely heavily on metal electrodes that are good for short-lived preparations but less suitable for longer-term recordings, as scar tissue formation and cytotoxicity tend to cause a gradual reduction in signals. CONCLUSIONS: Functionalized carbon nanotubes are a promising novel material that can be used to obtain long-term or repeated stable recordings, which are necessary for longitudinal studies, or to maintain other neural tissue interfaces such as those in insect-machine hybrid robots. The introduced insect preparation can also be used for the relatively rapid and cost-efficient testing of novel electrode materials.