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 Fe₃O₄ 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.

Keywords: clinical imaging; contrast agent; implantable device; nanoparticles.

Figure 1.

Phantoms of medical devices were constructed from gels and films incorporating nanoparticles. (a-b) PLGA films were wrapped around tissue to create (a) intact films and (b) damaged films. (c) Intact agarose gels before implantation. From left to right: no nanoparticles, 10 mM TaO_x, 25 mM TaO_x, 50 mM TaO_x, 100 mM TaO_x, 0.1 mM Fe₃O₄, 1 mM Fe₃O₄. (d-e) Intact or damaged TaO_x phantoms, viewed as 3D reconstructions of CT scans: (d) gels were implanted intact, cut or gouged and (e) films were intact or notched. (f) Signal/noise ratios were calculated for each concentration of nanoparticles in films and gels. A signal/noise ratio above 10 in the nanoparticle’s preferred imaging modality, was observed to be enough contrast. This was seen in (g) CT imaging of TaO_x dilutions in gels (top) and films (bottom) and (h) MRI imaging of Fe₃O₄ dilutions in gels (top) and films (bottom). (a-c) Scale is in mm.

Figure 2.

Phantoms were evaluated with clinical imaging techniques after implantation in lamb shanks. (a) A schematic of implantation. Typical cross-sections are shown after imaging with (b) CT, (c) MRI and (d-i) ultrasound. (b) Gels and films with TaO_x nanoparticles were more easily seen in CT; insets are transverse views of a gel (cut) and film. (c) Phantoms with Fe₃O₄ nanoparticles appeared dark in MRI; insets showing transverse views of a gel (gouged) and film. Images in (b-c) are of the same lamb shank; white arrowheads: phantoms without nanoparticles, blue arrowheads: phantoms with Fe₃O₄, orange arrowheads: phantoms with TaO_x. (d-i) Ultrasound images were taken at each phantom location: (d) intact film with Fe3O4, (e) damaged film with no nanoparticles, (f) damaged film with TaO_x, (g) intact gel with no nanoparticles, (h) damaged (cut) gel with TaO_x, and (i) damaged (gouged) gel with Fe₃O₄. Arrows mark the location of phantoms. Scale bars in (d-i): 5 mm.

Figure 3.

The type of implanted phantom impacted the ability of radiologists to correctly identify key features. (a) Once implanted, the presence of gels was harder for radiologists to assess, compared to films. The high level of shams marked incorrectly, indicated that the surgical approach was often mistaken for an implanted phantom. (b) When assessing implanted phantoms, films were more often identified correctly than gels. (c) Damage was harder to assess for films than gels, mostly likely due to the subtle mode of damage. However, the mode of damage also played a role in radiologists’ ability to determine if gels were damaged as well. (d) Gels with a gouge were always identified correctly, compared to those with a cut, which averaged only 79% correct.

Figure 4.

Radiological assessment of phantoms in a realistic model of nerve damage. (a) Films were sutured to the lamb sciatic nerve, acting as nerve wraps and were imaged with (b-c) ultrasound, (d) CT and (e) MRI. Ultrasound was able to detect films with (b) TaO_x nanoparticles and (c) Fe₃O₄ nanoparticles. (d) CT imaging was only able to detect the film with TaO_x nanoparticles, while (e) MRI imaging showed the Fe₃O₄ nanoparticle film most clearly (top: coronal view, bottom: sagittal). Arrows identify the implants. Scale bar (b-c): 5 mm.