Clinical Imaging

Portable OCT system with handheld probe to visualize the normal and infectious middle ear.

 

Constructing portable systems, while a difficult task in and of itself, is only part of the equation. Operating in a clinical environment brings new opportunities for patient-relevant diagnostics, as well as added logistical challenges and expectations.

Our researchers experience working in a clinical environment and collaborate directly with physicians and healthcare providers to set up and carry out a wide range of imaging projects. Using the systems built in our lab, donning appropriate PPE if needed, researchers are in the outpatient clinic assisting with patient imaging or in the surgical ward imaging fresh ex vivo tissue samples from surgery. Both require working with hospital coordinators to find and consent subjects and often require early or long days to keep pace with clinical schedules.

When imaging samples in a lab environment, typically there is plenty of time to adjust sample positioning, recalibrate the system, or take multiple scans with different acquisition parameters. In a clinical setting, research is given at a maximum 2-5 minutes to complete imaging. Patient care comes first - surgery cannot be delayed if a system needs to reboot, nor can a patient visit in a primary care office extend beyond its allotted time to capture data. To ensure any potential issues are minimized, roughly an equal amount of time is spent developing these systems as is on streamlining these systems for clinical use. For analysis, collecting imaging data will be compared to the physician’s independent clinical impressions or histological validation, if available. Finding mutually satisfactory techniques to mark tissue without impacting pathologist’s analysis is no easy task! Similarly, ensuring sterility without impacting imaging capability when using a contact-based probe required significant testing.

It is an amazing privilege to be invited into these many clinical spaces – thanks to the many collaborating physicians and staff, and especially the patients/subjects, for taking part in research.

RECENT PUBLICATIONS:
  • Monroy, Guillermo L., Wenzhou Hong, Pawjai Khampang, Ryan G. Porter, Michael A. Novak, Darold R. Spillman, Ronit Barkalifa, Eric J. Chaney, Joseph E. Kerschner, and Stephen A. Boppart. "Direct analysis of pathogenic structures affixed to the tympanic membrane during chronic otitis media." Otolaryngology–Head and Neck Surgery 159, no. 1 (2018): 117-126.
  • Wang, J., Xu, Y., Mesa, K.J., South, F.A., Chaney, E.J., Spillman, D.R., Barkalifa, R., Marjanovic, M., Carney, P.S., Higham, A.M. and Liu, Z.G., 2018. Complementary use of polarization-sensitive and standard OCT metrics for enhanced intraoperative differentiation of breast cancer. Biomedical optics express, 9(12), pp.6519-6528.

OCT/ Raman imaging

Our portable OCT systems can detect the presence of fluid and biofilms behind the middle ear (structures and fluid), though it cannot discern what kind of bacteria or virus are present. A technique called Raman spectroscopy is one solution that can provide “fingerprint identification” of these pathogens. We are developing a combined Raman-OCT system to detect both middle ear fluid and biofilms as well as determine what type of pathogen caused the infection. This is crucial for physicians to know, as viral infections do not resolve with antibiotics. This will help physicians treat ear infections better and prevent the overuse of antibiotics.    

PUBLICATIONS:
  • Zhao Y, Monroy GL, You S, Shelton RL, Nolan RM, Tu H, Chaney EJ, Boppart SA. Rapid diagnosis and differentiation of microbial pathogens in otitis media with a combined Raman spectroscopy and low-coherence interferometry probe: toward in vivo implementation. J. Biomedical Optics, 21:107005. 2016.

Ear probes

Nearly everyone has directly experienced or knows someone that has had repeated issues with ear infections. Otitis media, the general clinical name for ear infections, are one of the most common reasons for kids to visit the doctor’s office. Our group has developed an imaging system and handheld imaging probe, based on optical coherence tomography, to visualize the contents of the middle ear noninvasively using infrared light no stronger than sunlight. This imaging system can detect the contents of the middle ear without relying on visualization of the eardrum surface, which is often blocked by earwax or a difficult-to-navigate ear canal. This helps physicians more accurately diagnose and ultimately treat ear infections.

PUBLICATIONS:
  • Monroy GL, Pande P, Nolan RM, Shelton RL, Porter RG, Novak MA, Spillman DR, Chaney EJ, McCormick DT, Boppart SA. Noninvasive in vivo optical coherence tomography tracking of chronic otitis media in pediatric subjects after surgical intervention. J Biomedical Optics, 22:121614. 2017.

Eardrum dynamics and mobility

Clinical diagnostic guidelines for otitis media, known as a middle ear infection, recommend the examination of eardrum mobility via pneumatic otoscopy. A pneumatic otoscope combines the standard otoscope with an insufflation bulb to generate variations in air pressure in the sealed ear canal. Nonetheless, pneumatic otoscopy is highly subjective and difficult to perform and interpret. We have developed the portable, handheld pneumatic LCI/OCT system that mimics a pneumatic otoscope but provides quantitative and in-depth visualization of the rapid eardrum dynamics. The pneumatic-driven stiffness and time lag were measured from subjects with otitis media and compared with standard diagnostic techniques. Furthermore, spatially and temporally varying eardrum dynamics were characterized using the high-speed pneumatic OCT system. Besides OCT, a novel video processing technique called motion magnification was employed to measure the eardrum mobility from a smartphone without the need to seal the ear canal.

Air pressure-driven movements of the eardrum were captured with a handheld probe-based OCT system. The pneumatic-driven stiffness and time lag were compared between the normal ear and the ear with a middle ear infection.  
PUBLICATIONS:
  • Shelton RL, Nolan RM, Monroy GM, Pande P, Novak MA, Porter RG, Boppart SA. Quantitative pneumatic otoscopy using a light-based ranging technique. Journal of the Association for Research in Otolaryngology, 18:555-568. 2017.
  • Won J, Monroy GL, Huang PC, Dsouza R, Hill MC, Novak MA, Porter RG, Chaney E, Barkarlifa R, Boppart SA. Pneumatic low-coherence interferometry otoscope to quantify tympanic membrane mobility and middle ear pressure. Biomed Opt Exp 9(2):397-409. 2018. 
  • Won J, Huang P-C, Boppart SA. Phase-based Eulerian motion magnification reveals eardrum mobility from pneumatic otoscopy without sealing the ear canal. 2:034004. 2020.

Detecting middle ear biofilms in vivo

Recent studies have shown that there is a correlation between recurrent and/or chronic otitis media and the presence of middle ear biofilm. With our portable, handheld OCT system for primary care imaging, bacterial biofilm was non-invasively observed from human subjects with chronic otitis media. The presence of middle ear biofilm visualized from OCT was microbiologically validated. In addition, the subjects with otitis media undergoing the surgical treatment (myringotomy and tympanostomy tube placement) were longitudinally and intraoperatively observed to assess the efficacy of the treatment based on the presence of middle ear fluid and biofilms. A novel analytical technique was also developed to enhance the detection sensitivity of OCT by quantifying nanometer-scale structural changes in the eardrum and biofilm. Furthermore, the presence of middle ear biofilms determined from OCT has also been correlated to acoustic measurements and showed the unique acoustic response of biofilms in the middle ear system.

OCT image of (A) a normal ear and (B) an ear with recurrent acute otitis media. A microbial infection-related structure is found to adhere to the eardrum and within the middle ear cavity in (B). Digital otoscopy images are inset in each panel. White dashed lines indicate the physical location on the eardrum where OCT scan was taken. Representative confocal laser scanning microscope (CLSM) images of fluorescence in situ hybridization (FISH)-tagged sample from the subject with recurrent otitis media. (C) Components identified with the universal bacteria probe, (D) H. influenzae, one of the primary bacteria strains in otitis media, (E) nuclei stain, and (F) overlay of the channels reveals the presence of bacteria dispersed throughout the sample.  

PUBLICATIONS:
  • Nguyen CT, Jung W, Kim J, Chaney EJ, Novak M, Stewart CN, Boppart SA. Non-invasive in vivo optical detection of biofilm in the human middle ear. Proceedings of the National Academy of Sciences, USA, 109:9529-9534. 2012.
  • Nguyen CT, Tu H, Chaney EJ, Stewart CN, Boppart SA.   Non-invasive optical interferometry for the assessment of biofilm growth in the middle ear.   Biomedical Optics Express, 1:1104-1116. 2010.
  • Monroy GL, Pande P, Nolan RM, Shelton RL, Porter RG, Novak MA, Spillman DR, Chaney EJ, McCormick DT, Boppart SA. Noninvasive in vivo optical coherence tomography tracking of chronic otitis media in pediatric subjects after surgical intervention. J Biomedical Optics, 22:121614. 2017.
  • Monroy GL, Hong W, Khampang P, Porter RG, Novak MA, Spillman DR, Barkalifa R, Chaney EJ, Kerschner JE, Boppart SA. Direct analysis of pathogenic structures affixed to the eardrum during chronic otitis media. Otolaryngology-Head and Neck Surgery, 159:117-126. 2018.
  • Dsouza R, Won J, Monroy GL, Hill MC, Porter RG, Novak MA, Boppart SA. In vivo detection of nanometer-scale structural changes of the human tympanic membrane in otitis media. Scientific Reports, 8:8777. 2018.
  • Won J, Monroy GL, Spillman DR Jr, Huang P-C, Hill MC, Novak MA, Porter RG, Chaney EJ, Barkalifa R, Boppart SA. Assessing the effect of middle ear effusions on wideband acoustic immittance using optical coherence tomography. Ear and Hearing, 41:811-824, 2020.