Detecting Cardiac Allograft Transplant Rejection
This essay is the seventh in the series Drexel students write about Drexel innovations
Detecting Cardiac Allograft Transplant Rejection
by Steven Doll and Amanda O’Malley
The immune system is a primary form of defense against foreign bodies for multi-cellular organisms. The immune systems of vertebrates in particular are by far the most intricate, consisting of several layers of defense against pathogens. Vertebrate immune systems feature a function known as acquired immunity. “Immunology”, by George Pinchuck, states that “The acquired immunity is highly specific, i.e., the system discriminates between various antigens, responding with a unique reaction to every particular antigen” (2). An antigen is usually a protein embedded in a cell’s surface (or viral capsule) that can be bound by a certain antibody. Antibodies that are bound to a pathogen in this manner signal to other cells of the immune system that said pathogen is foreign to the body. This triggers a cascade of events that results in a specific response to the recognized antigen (Immunology 6).
The article “Rejection: Organ Transplantation”, electronically published by the University of Iowa Hospitals and Clinics, indicates that after an organ transplant has been completed, there is a risk of the host’s immune system recognizing and tagging the cells of the transplanted organ as foreign. When this happens, the transplanted organ is attacked by the cells of the immune system. Immunosuppressive drugs reduce the tendency of the immune system to target and attack a transplanted organ. In addition to using immunosuppressive medications, regular biopsies must be performed, in which a small sample of the tissue of the donated organ is removed and examined for signs of rejection.
Dr. Chang Chang and Dr. Eisen J. Howard of Drexel University suggest a new method of identifying organ transplant rejection that can be used in place of biopsies in their patent application titled “Biomarker for cardiac transplant rejection”. During organ rejection, sites of fibrosis form in which tissues damaged by the host’s immune system are being repaired. Such damaged tissue contains increased levels of the chemical messenger serotonin. Such increased levels of serotonin can be detected through the use of Raman spectroscopy, due to its chemical composition. The method applies Raman spectroscopy to cardiac allograft rejection in an attempt to provide a new and safer way to screen for organ rejection that is can to be used in place of biopsies (Chang).
According the thesis “Detection of Cardiac Allograft Rejection using Raman Spectroscopy”, by Yoon-Gi Chung, “Raman spectroscopy is a powerful technique to obtain molecularly specific information nondestructively” (2). Raman spectroscopy makes use of Raman scattering, which is the inelastic scattering of photons when incident light strikes a target (see figure 1). Most light that strikes a target scatters elastically, with a small proportion being scattered inelastically (Chung 2). “Introduction to Raman spectroscopy”, a guide published by Thermo Fisher Scientific, states that, “When a sample is irradiated with an intense monochromatic light source (usually a laser), most of the radiation is scattered by the sample at the same wavelength as that of the incoming laser radiation in a process known as Rayleigh scattering. However, a small proportion of the incoming light – approximately one photon out of a million – is scattered at a wavelength that is shifted from the original laser wavelength”. Incident light excites the molecules of a target and increases the magnitude of their dipole moments. The excited molecule scatters photons as it loses energy. Raman spectroscopy is concerned with the frequencies of the wavelengths produced by photons scattered inelastically (Introduction to Raman Spectroscopy 3).
The chemical nature of serotonin, specifically the rings paramount to its structure, allows for its concentration to be measured through Raman spectroscopy (Chang). A molecule excited by incident light will scatter photons inelastically with wavelengths of a particular frequency. Some of these wavelengths posses more energy than that of the incident light (known as an anti-Stokes Raman shift), and some less (known as a Stokes Raman shift). The wavelengths produced by photons scattered inelastically are collected and used to produce Raman spectra consisting of Stokes and Anti-Stokes Raman shift peaks for a molecule of interest (Introduction to Raman Spectroscopy 5). Raman peaks may be used to determine the concentration of a target molecule such as serotonin. When a Raman peak of serotonin in a transplanted organ is compared to the Raman peak generated by performing this process on a normal tissue, organ rejection can be detected (Chang).
The article “Applications of Raman and Surface-enhanced Raman Scattering Spectroscopy in Medicine”, by Igor Nabiev et al, examines a few of the uses of Raman Spectroscopy in modern medicine as of 1994. Raman spectroscopy has been used in the diagnosis of cancer, particularly gynecological cancer. Raman Spectroscopy has been able to “…(a) locate the tumour with an accuracy of less than a few hundred micro-metres (b) detect gynecological cancer at an early stage and (c) probe a gynecological tract directly using an endoscope” (Nabiev et al 14). Raman spectroscopy has also proven useful in diagnosing atherosclerosis, as Raman spectra can be collected for the various hydrocarbon molecules present in the bloodstream, such as cholesterol (Nabiev et al 14). Yet another use for Raman spectroscopy in medicine is the detection of cataracts in the eyes. “The ocular lens is a good object to investigate non-destructively by mean of laser Raman spectroscopy…Since lens proteins are tightly packed, especially in the nucleus centre, a good Raman spectrum can be obtained from the lens proteins in the lens in situ” (Nabiev et al 15). Alterations in the protein composition of the ocular lens can be measured through Raman spectroscopy, making it a viable method for cataract diagnosis.
This method developed by Dr. Chang Chang and Dr. Eisen J. Howard defines innovation; it finds a new use for Raman spectroscopy, which was discovered nearly a century ago. Raman spectroscopy has already had its uses in medicine, and perhaps this new application of the technique will be practiced. Innovations such as this novel means of detecting organ transplant rejection move biomedical technology forward and improve upon our quality of life.
Chang, Chang, and Howard J. Eisen. Biomarker for Cardiac Transplant Rejection. Drexel University and Philadelphia Health & Education Corporation, D/b/a Drexel University College of Medicine, assignee. Patent 12/080285. 25 Dec. 2008. Print.
Chung, Yoon-GI. Detection of Cardial Allograft Rejection Using Raman Spectroscopy. Thesis. Drexel University, 2007. Philadelphia: Drexel University, 2007. Print.
Introduction to Raman Spectroscopy. Thermo Fisher Scientific Inc., 2003, 2008. PDF.
Nabiev, Igor, et al. "Applications of Raman and Surface-Enhanced Raman Scattering Spectroscopy in Medicine." Journal of Raman Spectroscopy 25 (1994): 13-23. Wiley Online Library. Web. 9 Mar. 2011. <http://onlinelibrary.wiley.com/doi/10.1002/jrs.1250250104/pdf>.
Pinchuk, George. "Overview of Immunity and the Immune System." Immunonlogy. United States of America: McGraw Hill Comanies, 2002. 1-12. Print.
"Surgery: Organ Transplant: Rejection: Surgery: UI Health Topics: Surgery: UI Health Topics." UI Health Care Home. University of Iowa Hospitals & Clinics, 7 Aug. 2006. Web. 15 Mar. 2011. <http://www.uihealthcare.com/topics/medicaldepartments/surgery/rejection/index.html>.
 Incident light is light that is directed at a surface so that such light strikes the surface.