Retinal functional imaging

Blood oxygenation levels and flow dynamics in the retina can provide critical insight into early pathologic changes, as well as prove to be an important tool during critical care. Venous oxygen saturation is related to the local oxygen metabolism while arterial oxygen saturation is connected to the patient respiratory function.

Noninvasive measurements of oxygen saturation and flow in the retina are desirable for many different clinical applications; for example, early changes in auto-regulation and blood flow in the retina have been linked to the onset of diabetic retinopathy (DR). Various studies have suggested that detection and treatment of diabetic retinopathy and diabetic macular edema can significantly reduce the risk of visual loss. Lack of oxygenation and the resultant abnormal angiogenesis leads to loss of retinal tissue and resulting vision impairment. Although mechanisms for retinal damage in the late stages of detectable DR have been described, early changes, which lead to the onset of disease, are not well recognized. We are developing instrumentation and algorithms aimed at measuring oxygen saturation and flow rate in the superficial vasculature of the retina.

More about our approach in these publications

  • Xuan Liu, Jessica C. Ramella-Roman, Jin Kang, “Robust spectral-domain optical coherence tomography speckle model and its cross-correlation coefficient analysis,” JOSA A 30, 1, 51–59 (2013)
  • Xuan Liu, Yong Huang, Jessica C. Ramella-Roman, Scott A. Mathews, and Jin U. Kang, “Quantitative transverse flow measurement using optical coherence tomography speckle decorrelation analysis,” Opt. Lett. 38, 805-807 (2013)
  • L. Luu, P. A. Roman, Scott A. Mathews, J.C. Ramella-Roman, “Microfluidics based phantoms of superficial vascular network,” Biomedical Optics Express, 3(6), 1350-1364, (2012)
  • P. Lemaillet and J.C. Ramella-Roman, “An eye phantom for measurement of retinal oxygenation,” J. of Biomedical Optics, 14, 064008, (2009)
  • J.C. Ramella-Roman, S.A. Mathews, H. Kandimalla, A. Nabili, D.D. Duncan, S.A. D’Anna, S.M. Shah, Q.Q. Nguyen, “Measurement of oxygen saturation in the retina with a spectroscopic sensitive multi aperture camera,” Optics Express, 16, 6170-6182, (2008)

Support

We gratefully acknowledge the support of the following agencies during this research effort:
  • NIH/NEI
  • The Coulter Foundation

Non linear imaging of the retina

Second Harmonic and two photon microscopy of the eye can give novel insight into retinal disease. We are developing novel tools based on non-linear microscopy to image the eye and other environments.

More about our approach in these publications

  • Xuan Liu, Jessica C. Ramella-Roman, Jin Kang, “Robust spectral-domain optical coherence tomography speckle model and its cross-correlation coefficient analysis,” JOSA A 30, 1, 51–59 (2013)
  • Xuan Liu, Yong Huang, Jessica C. Ramella-Roman, Scott A. Mathews, and Jin U. Kang, “Quantitative transverse flow measurement using optical coherence tomography speckle decorrelation analysis,” Opt. Lett. 38, 805-807 (2013)
  • L. Luu, P. A. Roman, Scott A. Mathews, J.C. Ramella-Roman, “Microfluidics based phantoms of superficial vascular network,” Biomedical Optics Express, 3(6), 1350-1364, (2012)
  • P. Lemaillet and J.C. Ramella-Roman, “An eye phantom for measurement of retinal oxygenation,” J. of Biomedical Optics, 14, 064008, (2009)
  • J.C. Ramella-Roman, S.A. Mathews, H. Kandimalla, A. Nabili, D.D. Duncan, S.A. D’Anna, S.M. Shah, Q.Q. Nguyen, “Measurement of oxygen saturation in the retina with a spectroscopic sensitive multi aperture camera,” Optics Express, 16, 6170-6182, (2008)

Support

We gratefully acknowledge the support of the following agencies during this research effort:
  • NIH/NEI

Pre term labor

MPreterm birth (PTB) presents a serious medical heath concern throughout the world. There is a high incidence of PTB in both developed and developing countries ranging from 11%-15%, respectively. The incidence of PTB has not shown any significant decrease in the past decade, although research into the causes and treatments has been ongoing. Medical advances have provided more sophisticated methods to treat pre-term babies but the long-term outcome for the child is riddled with numerous long-term health issues. PTB is the number one cause of infant mortality and results in neurological, hearing, learning and a variety of other disorders. Although the exact cause of PTB remains unknown, studies have shown there may be numerous precursors to PTB including infections, genetic predisposition, nutrition and various other morbidities which all lead to a premature disorganization in the cervical collagen resulting in the weakening of the structure designed to keep the fetus in utero. The ability to predict at risk pregnancies to initiate medical interventions is paramount. We have developed a PReterm IMaging System (PRIM) based on principled of Mueller Matrix polarimetry, the system is sensitive to collagen architecture and content and is curren in clinical testing.

More about our approach in these publications

  • Susan Stoff, Joseph Chue-Sang, Nola A. Holness, Amir Gandjbakhche, Viktor Chernomordik, Jessica Ramella-Roman, “Cervical collagen imaging for determining preterm labor risks using a colposcope with full mueller matrix capability,” (SPIE, Bellingham, WA 2015) Proc. SPIE 9689, Photonic Therapeutics and Diagnostics XII, 968947 (February 29, 2016); doi:10.1117/12.2213387
  • J. Chue-Sang, Y. Bai, S. Stoff, D. Straton, S. Ramaswamy, J. C. Ramella-Roman, “Use of a combined polarization-sensitive optical coherence tomography system and Mueller matrix imaging polarimetry for the polarimetric characterization of excised biological tissue,” J. Biomed. Opt. 21(7) 071109 doi: 10.1117/1.JBO.21.7.071109, (2016)

Modeling of light transport in biological media

Models of light transport in biological media are useful tools in bio-photonics research. Monte Carlo programs are based on a technique proposed first by Metropolis and Ulam. The main idea is the use of a stochastic approach to model a physical phenomenon. In the biomedical field, Monte Carlo programs have been used to model laser tissue interactions, fluorescence, and many other phenomena.

In Standard Monte Carlo, the user is interested only in the distribution of absorbed, transmitted or reflected photons; in the polarized Monte Carlo, other parameters must be tracked. We have created three different ways to build polarized Monte Carlo programs for light propagation in biological media that are available for download here. The computational analysis is combined with experimental validation with the development of Stokes Vector Polarimeters, Mueller Matrix Polarimeters, Imaging Polarimeters, and PS-OCT for the study of polarized light transport in biological media.

More about our approach in these publications

  • B. Boulbry, J.C. Ramella-Roman, T.A. Germer, “Self-consistent calibration of a spectroellipsometer using a Fresnel rhomb as a reference sample,” Applied Optics, 46, 8533-8541, (2007)
  • J.C. Ramella-Roman, S.A. Prahl , S.L. Jacques, “Three Monte Carlo programs of polarized light transport into scattering media: part I,” Optics Express, 13, 4420-4438, (2005)
  • J.C. Ramella-Roman, S.A. Prahl, S.L. Jacques, “Three Monte Carlo programs of polarized light transport into scattering media: part II,” Optics Express, 13, 10392-10405, (2005)
  • J.C. Ramella-Roman, A. Nayak, S.A. Prahl, “Spectroscopic sensitive polarimeter for biomedical applications,” J. Biomed. Opt. 16, 047001, doi:10.1117/1.3561907 (2011)

Structural and functional imaging of skin

Skin breakdown is a prevalent and costly medical condition worldwide, with the etiologic and healing processes being complex and multifactorial. Quantitative assessment of wound healing is challenging due to the subjective measurement of wound size and related characteristics. We are conducting research in two main types of injuries pressure induced trauma (pressure ulcers) and burn trauma.

Clinicians' recommendations on wheelchair pressure reliefs in the context of the high prevalence of pressure ulcers that occur in people with spinal cord injury is not supported by strong experimental evidence. Some data indicates that altered tissue perfusion and oxygenation occurring under pressure loads, such as during sitting, induce various pathophysiologic changes that may lead to pressure ulcers. Pressure causes a cascade of responses, including initial tissue hypoxia, which leads to ischemia, vascular leakage, tissue acidification, compensatory angiogenesis, thrombosis, and hyperemia, all of which may lead to tissue damage. We have developed an advanced skin sensor that allows measurement of oxygenation in addition to perfusion, and can be safely used during sitting. The overriding goal of this work is to develop the evidence base for clinical recommendations on pressure reliefs.

Burn injuries are among the most devastating of all traumatic injuries and a major global public health concern. Burns are the fourth most common type of trauma worldwide and the most vulnerable groups for burn injuries are children, women and the elderly. For those who survive the burn injury, there is the added burden of a permanent disability and economic hardship for the patient and the family. Up to 91% of individuals surviving burn injury will develop hypertrophic scars with reduced function and serious issues with body dysmorphic disorders and social reintegration. Unfortunately, to this date, scar formation is a poorly understood process and the efficacy of interventional procedures such as compression therapy, massage therapy, or corticosteroids, have shown inconclusive scientific and clinical evidence. We are studying the process of wound healing and scar formation with the ultimate goal of validating these therapeutic techniques and providing quantifiable metrics to assist clinicians in the diagnosis and treatment of scar formation.

More about our approach in these publications

  • Taryn E. Travis, Pejhman Ghassemi, Jessica C. Ramella-Roman, Nicholas J. Prindeze, Dereck W. Paul, Lauren T. Moffatt, Marion H. Jordan, Jeffrey W. Shupp, "A Multi-Modal Assessment of Melanin and Melanocyte Activity in Abnormally Pigmented Hypertrophic Scar," The Journal of burn care & rehabilitation (Accepted 2014)
  • Pejhman Ghassemi, Taryn E. Travis, Lauren T. Moffatt, Jeffrey W. Shupp, and Jessica C. Ramella-Roman, "A polarized multispectral imaging system for quantitative assessment of hypertrophic scars," (submitted June 13 2014)
  • Taryn E Travis, Matthew Mino, Lauren Moffatt, Neil Mauskar, Pejhman Ghassemi, Jessica Ramella-Roman, Marion H Jordan, Jeffrey W. Shupp, “Biphasic Presence of Fibrocytes in a Porcine Hypertrophic Scar Model,” Journal of Burn Care & Rehabilitation, 34:2, (2013)
  • J.W. Shupp, L.T. Moffatt, T.A. Nguyen, J.C. Ramella-Roman, R. Hammamieh, R.J. Leto, D.Y. Jo, P.R. Randad, M. Jett, J.C. Jeng, and M.H. Jordan “Examination of Local and Systemic In vivo Responses to Electrical Injury Using an Electrical Burn Delivery System,” Journal of Burn Care & Research, 33 – 1 (2012)
  • Nguyen, Thu T. A.; Ramella-Roman, Jessica C.; Moffatt, Lauren T.; Ortiz, Rachel T.; Jordan, Marion H.; Shupp, Jeffrey W., “Novel Application of a Spatial Frequency Domain Imaging System to Determine Signature Spectral Differences Between Infected and Noninfected Burn Wounds,” Journal of Burn Care & Research, 34 - 1 44–50 (2013) (2012 Burke/Yannas Bioengineering Award)
  • T.A. Nguyen, J.W. Shupp, L.T. Moffatt, M.H. Jordan, J.C. Jeng, E. Leto, and J.C. Ramella-Roman “Assessment the viability of electrical injury using Spatial Frequency Domain Imaging in an in vivo electrical injury model,” IEEE J. of Selected Topics in Quantum Electronics 10.1109/JSTQE.2011.2179525 (2011)
  • Support

    We gratefully acknowledge the support of the following agencies during this research effort:
    • NIH/NIBIB
    • NIDER