Self-powered, light-controlled, bioresorbable platforms for programmed drug delivery.

Degradable polymer matrices and porous scaffolds provide powerful mechanisms for passive, sustained release of drugs relevant to the treatment of a broad range of diseases and conditions. Growing interest is in active control of pharmacokinetics tailored to the needs of the patient via programmable engineering platforms that include power sources, delivery mechanisms, communication hardware, and associated electronics, most typically in forms that require surgical extraction after a period of use. Here we report a light-controlled, self-powered technology that bypasses key disadvantages of these systems, in an overall design that is bioresorbable. Programmability relies on the use of an external light source to illuminate an implanted, wavelength-sensitive phototransistor to trigger a short circuit in an electrochemical cell structure that includes a metal gate valve as its anode. Consequent electrochemical corrosion eliminates the gate, thereby opening an underlying reservoir to release a dose of drugs by passive diffusion into surrounding tissue. A wavelength-division multiplexing strategy allows release to be programmed from any one or any arbitrary combination of a collection of reservoirs built into an integrated device. Studies of various bioresorbable electrode materials define the key considerations and guide optimized choices in designs. In vivo demonstrations of programmed release of lidocaine adjacent the sciatic nerves in rat models illustrate the functionality in the context of pain management, an essential aspect of patient care that could benefit from the results presented here.

Modifying the trajectory of epicardial leads can substantially reduce MRI-induced RF heating in pediatric patients with a cardiac implantable electronic device at 1.5T.

PURPOSE: After epicardial cardiac implantable electronic devices are implanted in pediatric patients, they become ineligible to receive MRI exams due to an elevated risk of RF heating. We investigated whether simple modifications in the trajectories of epicardial leads could substantially and reliably reduce RF heating during MRI at 1.5 T, with benefits extending to abandoned leads. METHODS: Electromagnetic simulations were performed to assess RF heating of two common 35-cm epicardial lead trajectories exhibiting different degrees of coupling with MRI incident electric fields. Experiments in anthropomorphic phantoms implanted with commercial cardiac implantable electronic devices confirmed the findings. Both electromagnetic simulations and experimental measurements were performed using head-first and feet-first positioning and various landmarks. Transfer function approach was used to assess the performance of suggested modifications in realistic body models. RESULTS: Simulations (head-first, chest landmark) of a 35-cm epicardial lead with a trajectory where the excess length of the lead was looped and placed on the inferior surface of the heart showed an 87-fold reduction in the 0.1 g-averaged specific absorption rate compared with the lead where the excess length was looped on the anterior surface. Repeated experiments with a commercial epicardial device confirmed this. For fully implanted systems following low-specific absorption rate trajectories, there was a 16-fold reduction in the average temperature rise and a 28-fold reduction for abandoned leads. The transfer function method predicted a 7-fold reduction in the RF heating in 336 realistic scenarios. CONCLUSION: Surgical modification of epicardial lead trajectory can substantially reduce RF heating at 1.5 T, with benefits extending to abandoned leads.

Artifacts Can Be Deceiving: The Actual Location of Deep Brain Stimulation Electrodes Differs from the Artifact Seen on Magnetic Resonance Images.

INTRODUCTION: Deep brain stimulation (DBS) is a common treatment for a variety of neurological and psychiatric disorders. Recent studies have highlighted the role of neuroimaging in localizing the position of electrode contacts relative to target brain areas in order to optimize DBS programming. Among different imaging methods, postoperative magnetic resonance imaging (MRI) has been widely used for DBS electrode localization; however, the geometrical distortion induced by the lead limits its accuracy. In this work, we investigated to what degree the difference between the actual location of the lead's tip and the location of the tip estimated from the MRI artifact varies depending on the MRI sequence parameters such as acquisition plane and phase encoding direction, as well as the lead's extracranial configuration. Accordingly, an imaging technique to increase the accuracy of lead localization was devised and discussed. METHODS: We designed and constructed an anthropomorphic phantom with an implanted DBS system following 18 clinically relevant configurations. The phantom was scanned at a Siemens 1.5 Tesla Aera scanner using a T1MPRAGE sequence optimized for clinical use and a T1TSE sequence optimized for research purposes. We varied slice acquisition plane and phase encoding direction and calculated the distance between the caudal tip of the DBS lead MRI artifact and the actual tip of the lead, as estimated from MRI reference markers. RESULTS: Imaging parameters and lead configuration substantially altered the difference in the depth of the lead within its MRI artifact on the scale of several millimeters - with a difference as large as 4.99 mm. The actual tip of the DBS lead was found to be consistently more rostral than the tip estimated from the MR image artifact. The smallest difference between the tip of the DBS lead and the tip of the MRI artifact using the clinically relevant sequence (i.e., T1MPRAGE) was found with the sagittal acquisition plane and anterior-posterior phase encoding direction. DISCUSSION/CONCLUSION: The actual tip of an implanted DBS lead is located up to several millimeters rostral to the tip of the lead's artifact on postoperative MR images. This distance depends on the MRI sequence parameters and the DBS system's extracranial trajectory. MRI parameters may be altered to improve this localization.

Implants talk to each-other: RF heating changes when two DBS leads are present simultaneously during MRI.

Deep brain stimulation (DBS) has proven to be an effective treatment for Parkinson's disease and other brain disorders. The procedure often involves implanting two elongated leads aimed at specific brain nuclei in both the left and right hemispheres. However, evaluating the safety of MRI in patients with such implants has only been done on an individual lead basis, ignoring the possibility of crosstalk between the leads. This study evaluates the impact of crosstalk on power deposition at the lead tip through numerical simulation and phantom experiments. We used CT images to obtain patient-specific lead trajectories and compared the power deposition at the lead tip in cases with bilateral and unilateral DBS implants. Our results indicate that the RF power deposition at the lead tip can vary by up to 6-fold when two DBS leads are present together compared to when only one lead is present. Experimental measurements in a simplified case of two lead-only DBS systems confirmed the existence of crosstalk.Clinical Relevance-Our results indicate that RF heating of implanted leads during MRI can be affected by the presence of another lead in the body, which may increase or decrease the power deposition in the tissue depending on the position and configuration of the leads.

Rapid prediction of MRI-induced RF heating of active implantable medical devices using machine learning.

The interaction between an active implantable medical device and magnetic resonance imaging (MRI) radiofrequency (RF) fields can cause excessive tissue heating. Existing methods for predicting RF heating in the presence of an implant rely on either extensive phantom experiments or electromagnetic (EM) simulations with varying degrees of approximation of the MR environment, the patient, or the implant. On the contrary, fast MR thermometry techniques can provide a reliable real-time map of temperature rise in the tissue in the vicinity of conductive implants. In this proof-of-concept study, we examined whether a machine learning (ML) based model could predict the temperature increase in the tissue near the tip of an implanted lead after several minutes of RF exposure based on only a few seconds of experimentally measured temperature values. We performed phantom experiments with a commercial deep brain stimulation (DBS) system to train a fully connected feedforward neural network (NN) to predict temperature rise after ~3 minutes of scanning at a 3 T scanner using only data from the first 5 seconds. The NN effectively predicted ΔTmax-R2 = 0.99 for predictions in the test dataset. Our model also showed potential in predicting RF heating for other various scenarios, including a DBS system at a different field strength (1.5 T MRI, R2 = 0.87), different field polarization (1.2 T vertical MRI, R2 = 0.79), and an unseen implant (cardiac leads at 1.5 T MRI, R2 = 0.91). Our results indicate great potential for the application of ML in combination with fast MR thermometry techniques for rapid prediction of RF heating for implants in various MR environments.Clinical Relevance- Machine learning-based algorithms can potentially enable rapid prediction of MRI-induced RF heating in the presence of unknown AIMDs in various MR environments.

RF-induced heating of capped and uncapped abandoned epicardial leads during MRI at 1.5 T and 3 T.

There is a paucity of data regarding the safety of magnetic resonance imaging (MRI) in patients with abandoned epicardial leads. Few studies have reported temperature rises up to 76 °C during MRI at 1.5 T in gel phantoms implanted with epicardial leads; however, lead trajectories used in these experiments were not clinically relevant. This work reports patient-specific RF heating of both capped and uncapped abandoned epicardial lead configurations during MRI at both 1.5 T and 3 T field strengths. We found that leads routed along realistic, patient-derived trajectories generated substantially lower RF heating than the previously reported worst-case phantom experiments. We also found that MRI at the head imaging landmark leads to substantially lower RF heating compared to MRI at the chest or abdomen landmarks at both 1.5 T and 3 T. Our results suggest that patients with abandoned epicardial leads may safely undergo MRI for head imaging, but caution is warranted during chest and abdominal imaging.Clinical Relevance- Patients with abandoned epicardial leads may safely undergo MRI for head imaging, but caution is warranted during chest and abdominal imaging.

Age Matters: A Comparative Study of RF Heating of Epicardial and Endocardial Electronic Devices in Pediatric and Adult Phantoms during Cardiothoracic MRI.

This study focused on the potential risks of radiofrequency-induced heating of cardiac implantable electronic devices (CIEDs) in children and adults with epicardial and endocardial leads of varying lengths during cardiothoracic MRI scans. Infants and young children are the primary recipients of epicardial CIEDs, though the devices have not been approved as MR conditional by the FDA due to limited data, leading to pediatric hospitals either refusing the MRI service to most pediatric CIED patients or adopting a scan-all strategy based on results from adult studies. The study argues that risk-benefit decisions should be made on an individual basis. We used 120 clinically relevant epicardial and endocardial device configurations in adult and pediatric anthropomorphic phantoms to determine the temperature rise during RF exposure at 1.5 T. The results showed that there was significantly higher RF heating of epicardial leads than endocardial leads in the pediatric phantom, but not in the adult phantom. Additionally, body size and lead length significantly affected RF heating, with RF heating up to 12 °C observed in models based on younger children with short epicardial leads. The study provides evidence-based knowledge on RF-induced heating of CIEDs and highlights the importance of making individual risk-benefit decisions when assessing the potential risks of MRI scans in pediatric CIED patients.

A comparative study of MRI-induced RF heating in pediatric and adult populations with epicardial and endocardial implantable electronic devices.

Patients with congenital heart defects, inherited arrhythmia syndromes, and congenital disorders of cardiac conduction often receive a cardiac implantable electronic device (CIED). At least 75% of patients with CIEDs will need magnetic resonance imaging (MRI) during their lifetime. In 2011, the US Food and Drug Administration approved the first MR-conditional CIEDs for patients with endocardial systems, in which leads are passed through the vein and affixed to the endocardium. The majority of children, however, receive an epicardial CIED, where leads are directly sewn to the epicardium. Unfortunately, an epicardial CIED is a relative contraindication to MRI due to the unknown risk of RF heating. In this work, we performed anthropomorphic phantom experiments to investigate differences in RF heating between endocardial and epicardial leads in both pediatric and adult-sized phantoms, where adult endocardial CIED was the control. Clinical Relevance-This work provides a quantitative comparison of MRI RF heating of epicardial and endocardial leads in pediatric and adult populations.

True location of deep brain stimulation electrodes differs from what is seen on postoperative magnetic resonance images: An anthropomorphic phantom study.

Deep brain stimulation (DBS) is an established yet growing treatment for a range of neurological and psychiatric disorders. Over the last decade, numerous studies have underscored the effect of electrode placement on the clinical outcome of DBS. As a result, imaging is now extensively used for DBS electrode localization, even though the accuracy of different modalities in determining the true coordinates of DBS electrodes is less explored. Postoperative magnetic resonance imaging (MRI) is a gold standard method for DBS electrode localization, however, the geometrical distortion induced by the lead's artifact could limit the accuracy. In this work, we investigated to what degree the difference between the true location of the lead's tip and the location of the tip estimated from the MRI artifact varies depending on the MRI sequence parameters, acquisition plane, phase encoding direction, and the implant"s extracranial trajectory. Clinical Relevance- Results will help researchers and clinicians to estimate the true location of DBS leads and contacts from postoperative MRI scans.

The Position and Orientation of the Pulse Generator Affects MRI RF Heating of Epicardial Leads in Children.

Infants and children with congenital heart defects often receive a cardiac implantable electronic device (CIED). Because transvenous access to the heart is difficult in patients with small veins, the majority of young children receive epicardial CIEDs. Unfortunately, however, once an epicardial CIED is placed, patients are no longer eligible to receive magnetic resonance imaging (MRI) exams due to the unknown risk of MRI-induced radiofrequency (RF) heating of the device. Although many studies have assessed the role of device configuration in RF heating of endocardial CIEDs in adults, such case for epicardial devices in pediatric patients is relatively unexplored. In this study, we evaluated the variation in RF heating of an epicardial lead due to changes in the lateral position and orientation of the implantable pulse generator (IPG). We found that changing the orientation and position of the IPG resulted in a five-fold variation in the RF heating at the lead's tip. Maximum heating was observed when the IPG was moved to a left lateral abdominal position of patient, and minimum heating was observed when the IPG was positioned directly under the heart. Clinical Relevance- This study examines the role of device configuration on MRI-induced RF heating of an epicardial CIED in a pediatric phantom. Results could help pediatric cardiac surgeons to modify device implantation to reduce future risks of MRI in patients.

Patient-specific modeling of the volume of tissue activated (VTA) is associated with clinical outcome of DBS in patients with an obsessive-compulsive disorder.

Deep brain stimulation (DBS) promises to treat an increasing number of neurological and psychiatric disorders. DBS outcome is directly a factor of optimal targeting of the relevant brain structures. Computational models can help to interpret a patient's outcome by predicting the volume of tissue activated (VTA) around DBS electrode contacts. Here we report results of a preliminary study of DBS in two patients with obsessive-compulsive disorder and show that VTA predictions, which are based on patient-specific volume conductor models, correlate with clinical outcome. Our results suggest that patient specific VTA calculation can help inform device programing to maximize therapeutic effects and minimize side effects.Clinical Relevance- Patient-specific modeling of the volume of activated tissue can predict clinical outcomes and thus, can help to optimize DBS device programing to maximize therapeutic effects.

Effect of Biophysical Model Complexity on Predictions of Volume of Tissue Activated (VTA) during Deep Brain Stimulation.

Deep brain stimulation (DBS) has evolved to an important treatment for several drug-resistant neurological and psychiatric disorders, such as epilepsy, Parkinson's disease, essential tremor and dystonia. Despite general effectiveness of DBS, however, its mechanisms of action are not completely understood. Simulations are commonly used to predict the volume of tissue activated (VTA) around DBS electrodes, which in turn helps interpreting clinical outcomes and understand therapeutic mechanisms. Computational models are commonly used to visualize the extend of volume of activated tissue (VTA) for different stimulation schemes, which in turn helps interpreting and understanding the outcomes. The degree of model complexity, however, can affect the predicted VTA. In this work we investigate the effect of volume conductor model complexity on the predicted VTA, when the VTA is estimated from activation function field metrics. Our results can help clinicians to decide what level of model complexity is suitable for their specific need.