Design Considerations to Facilitate Clinical Radiological Evaluation of Implantable Biomedical Structures

Abstract

Clinical effectiveness of implantable medical devices would be improved with in situ monitoring to ensure device positioning, determine subsequent damage, measure biodegradation, and follow healing. While standard clinical imaging protocols are appropriate for diagnosing disease and injury, these protocols have not been vetted for imaging devices. This study investigated how radiologists use clinical imaging to detect the location and integrity of implanted devices and whether embedding nanoparticle contrast agents into devices can improve assessment. To mimic the variety of devices available, phantoms from hydrophobic polymer films and hydrophilic gels were constructed, with and without computed tomography (CT)-visible TaO x and magnetic resonance imaging (MRI)-visible Fe 3 O 4 nanoparticles. Some phantoms were purposely damaged by nick or transection. Phantoms were implanted in vitro into tissue and imaged with clinical CT, MRI, and ultrasound. In a blinded study, radiologists independently evaluated whether phantoms were present, assessed the type, and diagnosed whether phantoms were damaged or intact. Radiologists identified the location of phantoms 80% of the time. However, without incorporated nanoparticles, radiologists correctly assessed damage in only 54% of cases. With an incorporated imaging agent, the percentage jumped to 86%. The imaging technique which was most useful to radiologists varied with the properties of phantoms. With benefits and drawbacks to all three imaging modalities, future implanted devices should be engineered for visibility in the modality which best fits the treated tissue, the implanted device's physical location, and the type of required information. Imaging protocols should also be tailored to best exploit the properties of the imaging agents.

Methacrylate‐Modified Gold Nanoparticles Enable Noninvasive Monitoring of Photocrosslinked Hydrogel Scaffolds

“…[ 63 ] Of particular note, 50 m m TaO x NPs were reported to provide sufficient signal/noise within tissue phantoms for clinical CT imaging. [ 64 ] On the other hand, another study reported in vivo micro‐CT imaging of 3D‐printed gelMA + Au scaffolds comprising 0.16 m m Au NPs, [ 38 ] but did not report X‐ray attenuation in Hounsfield units (HU) making interpretation difficult. Therefore, the relatively low concentration of Au NPs required for sufficient CT imaging contrast and monitoring degradation of the scaffolds in this in vitro study is encouraging but must be further investigated in vivo.…”

“…MRI is able to provide sufficient contrast for imaging and monitoring degradation in hydrogel or polymeric scaffolds at lower NP concentrations, e.g., %0.4-10 mM (%0.01-0.2 wt%) Fe 3 O 4 NPs. [25][26][27]64] However, MRI is limited by low spatial and temporal resolution. [13] Optical imaging (e.g., fluorescence) has been more widely used to image and monitor scaffolds with even lower concentrations (μM) of fluorophores or NPs, [19][20][21][22][23][24] but is not suitable for deep tissue imaging due to the limited depth of light penetration(<1 cm).…”

Incorporating Radiopacity into Implantable Polymeric Biomedical Devices for Clinical Radiological Monitoring

“…[4] However, for applications that require diagnosing implant damage, without concurrent interrogation of soft tissue status, the high clinical throughput, low-cost and favorable signal-to-noise ratio from surrounding tissue make CT beneficial for in situ monitoring. [3] To utilize CT for monitoring polymeric biomedical devices, radiopacity must be introduced.…”

Radiopaque Implantable Biomaterials for Nerve Repair

“…To enable longitudinal non-invasive radiological monitoring of polymeric PNI devices, contrast must be introduced into the polymer matrix. The use of nanoparticulate contrast agents incorporated into polymeric devices has been shown to significantly increase radiologists’ ability to non-invasively identify implant location and damage, using computed tomography (CT) imaging and magnetic resonance imaging (MRI) [8,9]. While both techniques are widely used in the clinic, CT is a readily available and cost-effective imaging modality, that can generate high-resolution 3D images with no limitation on tissue depth [10].…”

“…While TaO x nanoparticle contrast agents have been demonstrated to significantly improve radiopacity of synthetic polymers [8], little is known about their interaction with nerve tissue or during the complex process of nerve regeneration. Repair of PNI is highly coordinated, relying on glial cells to first bridge the injury and then guide regenerating neurons across the site.…”