Portable systems

Our portable systems are custom-built and designed to work in a range of clinical scenarios and imaging configurations. The systems are in use from the outpatient clinic to the surgical suite, and with handheld probes (both standoff and contact for in-situ imaging) and catheters for in vivo imaging, and upright and inverted microscope designs for ex vivo samples.

These systems have been developed over many years by many contributors and would not be possible without their combined efforts. Students, Postdocs, Lab and research Staff, UIUC Machine shop and UIUC 3D printing facilities, local steel manufacturers and powder coaters for cart hardware, component vendors, and collaborators, the list is long. Our clinical partners in addition to our group and those listed above have similarly contributed invaluable access, time, and input to the design and use of these systems.

Building these systems doesn’t come without challenges and tradeoffs. Miniaturizing the optical systems used for these systems while retaining SNR and imaging performance is tricky and takes significant engineering effort. These portable optical systems have to remain stable over months of heavy clinical use, compared to the non-portable systems that typically would sit on a floating optical table. Similarly, these systems must be robust when transported from our lab to the imaging site, sometimes frequently (several times per week).

  • Monroy, Guillermo L., Jungeun Won, Darold R. Spillman Jr, Roshan Dsouza, and Stephen A. Boppart. "Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements." Journal of biomedical optics 22, no. 12 (2017): 121715.
  • Erickson-Bhatt, Sarah J., Ryan M. Nolan, Nathan D. Shemonski, Steven G. Adie, Jeffrey Putney, Donald Darga, Daniel T. McCormick et al. "Real-time imaging of the resection bed using a handheld probe to reduce incidence of microscopic positive margins in cancer surgery." Cancer research 75, no. 18 (2015): 3706-3712.
  • Sun, Y., You, S., Tu, H., Spillman, D.R., Chaney, E.J., Marjanovic, M., Li, J., Barkalifa, R., Wang, J., Higham, A.M. and Luckey, N.N., 2018. Intraoperative visualization of the tumor microenvironment and quantification of extracellular vesicles by label-free nonlinear imaging. Science advances4(12), p.eaau5603.
  • Monroy, Guillermo L., Paritosh Pande, Ryan M. Nolan, Ryan L. Shelton, Ryan G. Porter, Michael A. Novak, Darold R. Spillman, Eric J. Chaney, Daniel T. McCormick, and Stephen A. Boppart. "Noninvasive in vivo optical coherence tomography tracking of chronic otitis media in pediatric subjects after surgical intervention." Journal of biomedical optics 22, no. 12 (2017): 121614.
  • Dsouza, Roshan, Jungeun Won, Guillermo L. Monroy, Darold R. Spillman, and Stephen A. Boppart. "Economical and compact briefcase spectral-domain optical coherence tomography system for primary care and point-of-care applications." Journal of biomedical optics 23, no. 9 (2018): 096003.

AI driven solutions for fluid diagnosis

Using our extensive library of imaging data and years of experience in ear diagnostic imaging, a machine-learning platform was developed that can automatically detect the signs of infection in the middle ear. When an OCT image of the ear is taken using one of our portable systems, the software takes approximately 20 seconds to automatically evaluate the data and identify middle ear fluid or biofilms behind the eardrum, or, if the ear appears normal. With further development, this platform can enable any user to have the diagnostic ability of an expert physician. Armed with precise knowledge of the infection in this patient, physicians can prescribe the ideal treatment for each patient. 

  • Monroy GL, Won J, Dsouza R, Pande P, Hill MC, Porter RG, Novak MA, Spillman DR, Boppart SA. Automated classification platform for the identification of otitis media using optical coherence tomography. Nature Digital Medicine, 2:22. 2019.

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.

  • 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.  
  • 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.

Intraoperative label-free multimodal nonlinear optical imaging

The majority of the current intraoperative optical imaging techniques involve labeling which perturbs the tissue microenvironment and alters the optical signatures of various biochemical processes. In contrast, multiple nonlinear optical imaging (NLOI) modalities have been demonstrated to have the ability to visualize microstructures and provide molecular and functional information. With the development and demonstration of our lab-based simultaneous label-free autofluorescence and multi-harmonics (SLAM) microscope,  continuous efforts have been made to adapt this multimodal NLOI platform to a portable system for intraoperative cancer imaging. Previously we have demonstrated one version of our intraoperative label-free NLOI system in human breast cancer surgeries. Correlations with the histology results have shown that this intraoperative NLOI platform has the potential to provide diagnostic information at point-of-procedure without destroying the biological tissue integrity. With our recent upgrades on the imaging system, we were able to provide optical assessment of needle biopsies taken from live animal patients during veterinary surgeries. We are working towards further improvement of the intraoperative label-free NLOI system to enable real-time screening of needle biopsies and surgical specimens for cancer diagnosis at point-of-procedure. 

Label-free multimodal NLOI results (left) along with corresponding histology images (right) from human breast tissue specimens diagnosed as (A) invasive ductal carcinoma (IDC), with the red dashed arrow showing an overall orientation of collagen alignment, (B-C) ductal carcinoma in situ (DCIS), showing adipocytes (red dashed arrows), blood vessel (red solid arrow in B), and mammary duct (red solid arrow in C), and (D) healthy breast tissue from a breast reduction surgery. Scale bars represent 100 µm. Channel pseudo-colors: THG, magenta; 3PF, cyan; SHG, green; 2PF, yellow.

  • Sun, Y., You, S., Tu, H., Spillman, D. R., Chaney, E. J. Marjanovic, M. Li, J., Barkalifa, R., Wang, J., Higham, A. M., Luckey, N. N., Cradock, K. A., Liu, Z. G., & Boppart, S. A. “Intraoperative visualization of the tumor microenvironment and of extracellular vesicles by label-free nonlinear imaging,” Science Advances, vol. 4, no. 12, eaau5603, 2018.
  • Yang, L., Park, J., Marjanovic, M., Chaney, E. J., Spillman, D. R., Phillips, H. & Boppart, S. A. "Intraoperative label-free multimodal nonlinear optical imaging for point-of-procedure cancer diagnostics." IEEE JSTQE, submitted. 

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.  

  • 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.