NIDA Boosts Research and Development of Medical Devices for Substance use Disorder via the NIH Blueprint MedTech Initiative.

Background: Deaths from drug overdose have reached a crisis level, with more than 100,000 reported from April 2020 to April 2021. Novel approaches to address it are urgently needed. Objectives: National Institute on Drug Abuse (NIDA) is leading novel comprehensive efforts to develop safe and effective products that address the needs of the citizens affected by SUD. NIDA aims to support research and development of medical devices intended to monitor, diagnose, or treat substance use disorders. Results: NIDA participates in Blueprint MedTech program is part of the large NIH Blueprint for Neurological Research Initiative. It supports the research and development of new medical devices through product optimization, pre-clinical testing, and human subject studies, including clinical trials. The program is structured in two main components - Blueprint MedTech Incubator and Blueprint MedTech Translator. It offers free to the researcher services that are typically unavailable in academic environment - business expertise facilities and staffing to successfully develop minimum viable devices, pre-clinical bench testing, clinical studies, planning and executing in manufacturing, as well as regulatory expertise. Conclusions: Through Blueprint MedTech, NIDA provides innovators with expanded resources to ensure the success of the research.

Parallel transmission to reduce absorbed power around deep brain stimulation devices in MRI: Impact of number and arrangement of transmit channels.

PURPOSE: To assess the mean and variance performance of parallel transmission (pTx) coils for reduction of the absorbed power around electrodes (APAE) in patients implanted with deep brain stimulation (DBS) devices. METHODS: We simulated 4 pTx coils (8 and 16 channels, head and body coils) and a birdcage body coil. We characterized the RF safety risk using the APAE, which is the integral of the deposited power (in Watts) in a small cylindrical volume of brain tissue surrounding the electrode tips. We assessed the APAE mean and variance by simulation of 5 realistic DBS patient models that include the full DBS implant length, extracranial loops, and implanted pulse generator. RESULTS: PTx coils with 8 (16) channels were able to reduce the APAE by >18× (>169×) compared to the birdcage coil in average for all patient models, at no cost in term of flip angle uniformity or global specific absorption rate (SAR). Moreover, local pTx coils performed significantly better than body arrays. CONCLUSION: PTx is a possible solution to the problem of RF heating of DBS patients when performing MRI, but the large interpatient variability of the APAE indicates that patient-specific safety monitoring may be needed.

Reducing RF-induced Heating near Implanted Leads through High-Dielectric Capacitive Bleeding of Current (CBLOC).

Patients with implanted medical devices such as deep brain stimulation or spinal cord stimulation are often unable to receive magnetic resonance imaging (MRI). This is because once the device is within the radiofrequency (RF) field of the MRI scanner, electrically conductive leads act as antenna, amplifying the RF energy deposition in the tissue and causing possible excessive tissue heating. Here we propose a novel concept in lead design in which 40cm lead wires are coated with a ~1.2mm layer of high dielectric constant material (155 < ε r < 250) embedded in a weakly conductive insulation (σ = 20S/m). The technique called High-Dielectric Capacitive Bleeding of Current, or CBLOC, works by forming a distributed capacitance along the lengths of the lead, efficiently dissipating RF energy before it reaches the exposed tip. Measurements during RF exposure at 64 MHz and 123 MHz demonstrated that CBLOC leads generated 20-fold less heating at 1.5 T, and 40-fold less heating at 3 T compared to control leads. Numerical simulations of RF exposure at 297 MHz (7T) predicted a 15-fold reduction in specific absorption rate (SAR) of RF energy around the tip of CBLOC leads compared to control leads.

Numerical and Experimental Analysis of Radiofrequency-Induced Heating Versus Lead Conductivity During EEG-MRI at 3 T.

This study investigates radiofrequency (RF)-induced heating in a head model with a 256-channel electroencephalogram (EEG) cap during magnetic resonance imaging (MRI). Nine computational models were implemented each with different EEG lead electrical conductivity, ranging from 1 to 5.8 × 107 S/m. The peak values of specific absorption rate (SAR) averaged over different volumes were calculated for each lead conductivity. Experimental measurements were also performed at 3-T MRI with a Gracilaria Lichenoides (GL) phantom with and without a low-conductive EEG lead cap ("InkNet"). The simulation results showed that SAR was a nonlinear function of the EEG lead conductivity. The experimental results were in line with the numerical simulations. Specifically, there was a ΔT of 1.7 °C in the GL phantom without leads compared to ΔT of 1.8 °C calculated with the simulations. Additionally, there was a ΔT of 1.5 °C in the GL phantom with the InkNet compared to a ΔT of 1.7 °C in the simulations with a cap of similar conductivity. The results showed that SAR is affected by specific location, number of electrodes, and the volume of tissue considered. As such, SAR averaged over the whole head, or even SAR averaged over volumes of 1 or 0.1 g, may conceal significant heating effects and local analysis of RF heating (in terms of peak SAR and temperature) is needed.

The 'virtual DBS population': five realistic computational models of deep brain stimulation patients for electromagnetic MR safety studies.

We design, develop, and disseminate a 'virtual population' of five realistic computational models of deep brain stimulation (DBS) patients for electromagnetic (EM) analysis. We found five DBS patients in our institution' research patient database who received high quality post-DBS surgery computer tomography (CT) examinations of the head and neck. Three patients have a single implanted pulse generator (IPG) and the two others have two IPGs (one for each lead). Moreover, one patient has two abandoned leads on each side of the head. For each patient, we combined the head and neck volumes into a 'virtual CT', from which we extracted the full-length DBS path including the IPG, extension cables, and leads. We corrected topology errors in this path, such as self-intersections, using a previously published optimization procedure. We segmented the virtual CT volume into bones, internal air, and soft tissue classes and created two-manifold, watertight surface meshes of these distributions. In addition, we added a segmented model of the brain (grey matter, white matter, eyes and cerebrospinal fluid) to one of the model (nickname Freddie) that was derived from a T1-weighted MR image obtained prior to the DBS implantation. We simulated the EM fields and specific absorption rate (SAR) induced at 3 Tesla by a quadrature birdcage body coil in each of the five patient models using a co-simulation strategy. We found that inter-subject peak SAR variability across models was independent of the target averaging mass and equal to ~45%. In our simulations of the full brain segmentation and six simplified versions of the Freddie model, the error associated with incorrect dielectric property assignment around the DBS electrodes was greater than the error associated with modeling the whole model as a single tissue class. Our DBS patient models are freely available on our lab website (Webpage of the Martinos Center Phantom Resource 2018 https://phantoms.martinos.org/Main_Page).

Changes in the specific absorption rate (SAR) of radiofrequency energy in patients with retained cardiac leads during MRI at 1.5T and 3T.

PURPOSE: To evaluate the local specific absorption rate (SAR) and heating around retained cardiac leads during MRI at 64 MHz (1.5T) and 127 MHz (3T) as a function of RF coil type and imaging landmark. METHODS: Numerical models of retained cardiac leads were built from CT and X-ray images of 6 patients with retained cardiac leads. Electromagnetic simulations and bio-heat modeling were performed with MRI RF body and head coils tuned to 64 MHz and 127 MHz and positioned at 9 different imaging landmarks covering an area from the head to the lower limbs. RESULTS: For all patients and at both 1.5T and 3T, local transmit head coils produced negligible temperature rise ( Δ T < 0.1 ° C ) for ‖ ‖ B 1 + ‖ ‖ ≤ 3 µ T . For body imaging with quadrature-driven coils at 1.5T, Δ T during a 10-min scan remained < 3°C at all imaging landmarks for ‖ ‖ B 1 + ‖ ‖ ≤ 3 µ T and <6°C for ‖ ‖ B 1 + ‖ ‖ ≤ 4 µ T . For body imaging at 3T, Δ T during a 10-min scan remained < 6°C at all imaging landmarks for ‖ ‖ B 1 + ‖ ‖ ≤ 2 µ T . For shorter pulse sequences up to 2 min, Δ T remained < 6°C for ‖ ‖ B 1 + ‖ ‖ ≤ 3 µ T . CONCLUSION: For the models based on 6 patients studied, simulations suggest that MRI could be performed safely using a local head coil at both 1.5T and 3T, and with a body coil at 1.5T with pulses that produced ‖ ‖ B 1 + ‖ ‖ ≤ 4 µ T . MRI at 3T could be performed safely in these patients using pulses with ‖ ‖ B 1 + ‖ ‖ ≤ 2 µ T .

RF-induced heating in tissue near bilateral DBS implants during MRI at 1.5 T and 3T: The role of surgical lead management.

Access to MRI is limited for patients with deep brain stimulation (DBS) implants due to safety hazards, including radiofrequency (RF) heating of tissue surrounding the leads. Computational models provide an exquisite tool to explore the multi-variate problem of RF heating and help better understand the interaction of electromagnetic fields and biological tissues. This paper presents a computational approach to assess RF-induced heating, in terms of specific absorption rate (SAR) in the tissue, around the tip of bilateral DBS leads during MRI at 64MHz/1.5 T and 127 MHz/3T. Patient-specific realistic lead models were constructed from post-operative CT images of nine patients operated for sub-thalamic nucleus DBS. Finite element method was applied to calculate the SAR at the tip of left and right DBS contact electrodes. Both transmit head coils and transmit body coils were analyzed. We found a substantial difference between the SAR and temperature rise at the tip of right and left DBS leads, with the lead contralateral to the implanted pulse generator (IPG) exhibiting up to 7 times higher SAR in simulations, and up to 10 times higher temperature rise during measurements. The orientation of incident electric field with respect to lead trajectories was explored and a metric to predict local SAR amplification was introduced. Modification of the lead trajectory was shown to substantially reduce the heating in phantom experiments using both conductive wires and commercially available DBS leads. Finally, the surgical feasibility of implementing the modified trajectories was demonstrated in a patient operated for bilateral DBS.

Effect Of Incident Field Magnitude And Phase Distribution On Rfinduced Heating Due To Hip Implants.

We investigated how the distribution of magnitude and phase of incident electric field affects RFinduced heating near a hip implant. The results showed that varying the incident electric field, for example due to different phantom shape or different landmark position, for two-or three-dimensional implants can result in up to 50% variation of estimated RF-induced temperature rise. To avoid systematic errors in predicting the RF-induced heating, varied distributions of the incident electric field should be applied.

Radio-Frequency Safety Assessment of Stents in Blood Vessels During Magnetic Resonance Imaging.

Purpose: The purpose of this study was to investigate the need for high-resolution detailed anatomical modeling to correctly estimate radio-frequency (RF) safety during magnetic resonance imaging (MRI). RF-induced heating near metallic implanted devices depends on the electric field tangential to the device (Etan ). Etan and specific absorption rate (SAR) were analyzed in blood vessels of an anatomical model to understand if a standard gel phantom accurately represents the potential heating in tissues due to passive vascular implants such as stents. Methods: A numerical model of an RF birdcage body coil and an anatomically realistic virtual patient with a native spatial resolution of 1 mm3 were used to simulate the in vivo electric field at 64 MHz (1.5 T MRI system). Maximum values of SAR inside the blood vessels were calculated and compared with peaks in a numerical model of the ASTM gel phantom to see if the results from the simplified and homogeneous gel phantom were comparable to the results from the anatomical model. Etan values were also calculated in selected stent trajectories inside blood vessels and compared with the ASTM result. Results: Peak SAR values in blood vessels were up to ten times higher than those found in the ASTM standard gel phantom. Peaks were found in clinically significant anatomical locations, where stents are implanted as per intended use. Furthermore, Etan results showed that volume-averaged SAR values might not be sufficient to assess RF safety. Conclusion: Computational modeling with a high-resolution anatomical model indicated higher values of the incident electric field compared to the standard testing approach. Further investigation will help develop a robust safety testing method which reflects clinically realistic conditions.

Retrospective analysis of RF heating measurements of passive medical implants.

PURPOSE: The test reports for the RF-induced heating of metallic devices of hundreds of medical implants have been provided to the U.S. Food and Drug Administration as a part of premarket submissions. The main purpose of this study is to perform a retrospective analysis of the RF-induced heating data provided in the reports to analyze the trends and correlate them with implant geometric characteristics. METHODS: The ASTM-based RF heating test reports from 86 premarket U.S. Food and Drug Administration submissions were reviewed by three U.S. Food and Drug Administration reviewers. From each test report, the dimensions and RF-induced heating values for a given whole-body (WB) specific absorption rate (SAR) and local background (LB) SAR were extracted and analyzed. The data from 56 stents were analyzed as a subset to further understand heating trends and length dependence. RESULTS: For a given WB SAR, the LB/WB SAR ratio varied significantly across the test labs, from 2.3 to 11.3. There was an increasing trend on the temperature change per LB SAR with device length. The maximum heating for stents occurred at lengths of approximately 100 mm at 3 T, and beyond 150 mm at 1.5 T. CONCLUSIONS: Differences in the LB/WB SAR ratios across testing labs and various MRI scanners could lead to inconsistent WB SAR labeling. Magnetic resonance (MR) conditional labeling based on WB SAR should be derived from a conservative estimate of global LB/WB ratios.

Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies.

We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a 'virtual CT' image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg-1 (full model, helicoidal conductors) to 43.6 kW kg-1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg-1 (full model, straight conductors) to 73.8 kW kg-1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9.5% and 27.6%.

A Study on the Feasibility of the Deep Brain Stimulation (DBS) Electrode Localization Based on Scalp Electric Potential Recordings.

Deep Brain Stimulation (DBS) is an effective therapy for patients disabling motor symptoms from Parkinson's disease, essential tremor, and other motor disorders. Precise, individualized placement of DBS electrodes is a key contributor to clinical outcomes following surgery. Electroencephalography (EEG) is widely used to identify the sources of intracerebral signals from the potential on the scalp. EEG is portable, non-invasive, low-cost, and it could be easily integrated into the intraoperative or ambulatory environment for localization of either the DBS electrode or evoked potentials triggered by stimulation itself. In this work, we studied with numerical simulations the principle of extracting the DBS electrical pulse from the patient's EEG - which normally constitutes an artifact - and localizing the source of the artifact (i.e., the DBS electrodes) using EEG localization methods. A high-resolution electromagnetic head model was used to simulate the EEG potential at the scalp generated by the DBS pulse artifact. The potential distribution on the scalp was then sampled at the 256 electrode locations of a high-density EEG Net. The electric potential was modeled by a dipole source created by a given pair of active DBS electrodes. The dynamic Statistical Parametric Maps (dSPM) algorithm was used to solve the EEG inverse problem, and it allowed localization of the position of the stimulus dipole in three DBS electrode bipolar configurations with a maximum error of 1.5 cm. To assess the accuracy of the computational model, the results of the simulation were compared with the electric artifact amplitudes over 16 EEG electrodes measured in five patients. EEG artifacts measured in patients confirmed that simulated data are commensurate to patients' data (0 ± 6.6 µV). While we acknowledge that further work is necessary to achieve a higher accuracy needed for surgical navigation, the results presented in this study are proposed as the first step toward a validated computational framework that could be used for non-invasive localization not only of the DBS system but also brain rhythms triggered by stimulation at both proximal and distal sites in the human central nervous system.

A numerical investigation on the effect of RF coil feed variability on global and local electromagnetic field exposure in human body models at 64 MHz.

PURPOSE: This study aims to investigate how the positions of the feeding sources of the transmit radiofrequency (RF) coil, field orientation direction with respect to the patient, and patient dimensions affect the global and local electromagnetic exposure in human body models. METHODS: Three RF coil models were implemented, namely a specific two-source (S2) feed and two multisource feed configurations: generic 32-source (G32) and hybrid 16-source (H16). Thirty-two feeding conditions were studied for the S2, whereas two were studied for the G32 and H16. The study was performed using five human body models. Additionally, for two of the body models, the case of a partially implanted lead was evaluated. RESULTS: The results showed an overall variation due to coil feeding conditions of the whole-body specific absorption rate (SAR) of less than 20%, but deviations up to 98% of the magnitude of the electric field tangential to a possible lead path. For the analysis with the partially implanted lead, a variation of local SAR at the tip of the lead of up to 60% was observed with respect to feed position and field orientation direction. CONCLUSION: The results of this study suggest that specific information about feed position and field orientation direction must be considered for an accurate evaluation of patient exposure. Magn Reson Med 79:1135-1144, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Investigating the effect of coil model losses on computational electromagnetic exposure of an ASTM phantom at 64 MHz MRI.

The goal of this work is to investigate the effect of coil losses on the electromagnetic field generated in an ASTM phantom by a birdcage coil. The study was based on different numerical implementations of an RF body coil at 64 MHz, using the same 3D EM and RF circuit co-simulation procedure. The coil quality factor was evaluated with respect to losses due to power feed mismatch and to resistive losses of the coil components. The results of the study showed that the magnetic field at the coil iso-center, normalized to the square root of the whole body specific absorption rate, depends on the coil quality factor.

Feasibility of using linearly polarized rotating birdcage transmitters and close-fitting receive arrays in MRI to reduce SAR in the vicinity of deep brain simulation implants.

PURPOSE: MRI of patients with deep brain stimulation (DBS) implants is strictly limited due to safety concerns, including high levels of local specific absorption rate (SAR) of radiofrequency (RF) fields near the implant and related RF-induced heating. This study demonstrates the feasibility of using a rotating linearly polarized birdcage transmitter and a 32-channel close-fit receive array to significantly reduce local SAR in MRI of DBS patients. METHODS: Electromagnetic simulations and phantom experiments were performed with generic DBS lead geometries and implantation paths. The technique was based on mechanically rotating a linear birdcage transmitter to align its zero electric-field region with the implant while using a close-fit receive array to significantly increase signal to noise ratio of the images. RESULTS: It was found that the zero electric-field region of the transmitter is thick enough at 1.5 Tesla to encompass DBS lead trajectories with wire segments that were up to 30 degrees out of plane, as well as leads with looped segments. Moreover, SAR reduction was not sensitive to tissue properties, and insertion of a close-fit 32-channel receive array did not degrade the SAR reduction performance. CONCLUSION: The ensemble of rotating linear birdcage and 32-channel close-fit receive array introduces a promising technology for future improvement of imaging in patients with DBS implants. Magn Reson Med 77:1701-1712, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Local SAR near deep brain stimulation (DBS) electrodes at 64 and 127 MHz: A simulation study of the effect of extracranial loops.

PURPOSE: MRI may cause brain tissue around deep brain stimulation (DBS) electrodes to become excessively hot, causing lesions. The presence of extracranial loops in the DBS lead trajectory has been shown to affect the specific absorption rate (SAR) of the radiofrequency energy at the electrode tip, but experimental studies have reported controversial results. The goal of this study was to perform a systematic numerical study to provide a better understanding of the effects of extracranial loops in DBS leads on the local SAR during MRI at 64 and 127 MHz. METHODS: A total of 160 numerical simulations were performed on patient-derived data, in which relevant factors including lead length and trajectory, loop location and topology, and frequency of MRI radiofrequency (RF) transmitter were assessed. RESULTS: Overall, the presence of extracranial loops reduced the local SAR in the tissue around the DBS tip compared with straight trajectories with the same length. SAR reduction was significantly larger at 127 MHz compared with 64 MHz. SAR reduction was significantly more sensitive to variable loop parameters (eg, topology and location) at 127 MHz compared with 64 MHz. CONCLUSION: Lead management strategies could exist that significantly reduce the risks of 3 Tesla (T) MRI for DBS patients. Magn Reson Med 78:1558-1565, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Improvement of Electromagnetic Field Distributions Using High Dielectric Constant (HDC) Materials for CTL-Spine MRI: Numerical Simulations and Experiments.

This study investigates the use of pads with high dielectric constant (HDC) materials to alter electromagnetic field distributions in patients during magnetic resonance imaging (MRI). The study was performed with numerical simulations and phantom measurements. An initial proof-of-concept and validation was performed using a phantom at 64 MHz, showing increases of up to 10% in electromagnetic field when using distilled water as the high dielectric material. Additionally, numerical simulations with computational models of human anatomy were performed at 128 MHz. Results of these simulations using barium titanate (BaTiO3) beads showed a 61% increase of [Formula: see text] with a quadrature driven RF coil and a 64% increase with a dual-transmit array. The presence of the HDC material also allowed for a decrease of SAR up to twofold (e.g., peak 10 g-averaged SAR from 54 to 22 W/kg with a quadrature driven RF coil and from 27 to 22 W/kg with a dual-transmit array using CaTiO3 powder at 128 MHz). The results of this study show that the use of HDC pads at 128 MHz for MRI spine applications could result in improved magnetic fields within the region of interest, while decreasing SAR outside the region.

RF Safety Evaluation of a Breast Tissue Expander Device for MRI: Numerical Simulation and Experiment.

This study describes the MRI-related radio frequency (RF) safety evaluation of breast tissue expander devices to establish safety criteria. Numerical simulations and experimental measurements were performed at 64 MHz with a gel phantom containing a breast expander. Additionally, computational modeling was performed (64 and 128 MHz) with an adult female model, containing a virtually implanted breast tissue expander device for four imaging landmark positions. The presence of the breast tissue expander device led to significant alterations in specific absorption rate (SAR) and|B1+|distributions. The main source of SAR alterations with the use of the breast expander device was the saline-filled pouch of the expander. Conversely, the variation of RF magnetic field (B1+) was mainly caused by the metallic port. The measured values of electric field magnitude did not increase significantly due to the introduction of the expander device. The maximum 1g- or 10g-averaged SAR values in tissues near the implant were lower than those expected in other regions of the patient body with normalization of both|B1+|equal to 2 µT at the coil isocenter and whole body averaged SAR equal to 4W/kg.

Construction and modeling of a reconfigurable MRI coil for lowering SAR in patients with deep brain stimulation implants.

Post-operative MRI of patients with deep brain simulation (DBS) implants is useful to assess complications and diagnose comorbidities, however more than one third of medical centers do not perform MRIs on this patient population due to stringent safety restrictions and liability risks. A new system of reconfigurable magnetic resonance imaging head coil composed of a rotatable linearly-polarized birdcage transmitter and a close-fitting 32-channel receive array is presented for low-SAR imaging of patients with DBS implants. The novel system works by generating a region with low electric field magnitude and steering it to coincide with the DBS lead trajectory. We demonstrate that the new coil system substantially reduces the SAR amplification around DBS electrodes compared to commercially available circularly polarized coils in a cohort of 9 patient-derived realistic DBS lead trajectories. We also show that the optimal coil configuration can be reliably identified from the image artifact on B1+ field maps. Our preliminary results suggest that such a system may provide a viable solution for high-resolution imaging of DBS patients in the future. More data is needed to quantify safety limits and recommend imaging protocols before the novel coil system can be used on patients with DBS implants.

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices.

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making.