Abstract
Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients’ biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.
Highlights
The success of cardiac transplantation depends foremost on the immune response to the new implant[1]
Prolonged tissue damage, which could be a result of immune attack, injury or toxins etc. may result in deposition of extracellular matrix components at the site of damage, leading to a condition termed as fibrosis[5,6,7]
Use of ratios instead of absolute values ensures that these metric definitions are independent of variability in instrumentation and sample preparation steps. We evaluated these metrics in terms of their ability to separate the classes by using minimum error in identification of class and the area under the curve (AUC) for the Receiver Operating Characteristic (ROC)
Summary
The success of cardiac transplantation depends foremost on the immune response to the new implant[1]. Grade of acute cellular rejection, as defined by the revised ISHLT (International Society for Heart & Lung Transplantation) heart biopsy grading scale[4] is determined by the presence of infiltrate and associated myocyte damage. Grade 0 signifies no rejection while grade 2 (mild rejection), 3 (moderate rejection) and 4 (severe rejection) requires assessing the number of foci of infiltrate and associated myocardium damage. May result in deposition of extracellular matrix components at the site of damage, leading to a condition termed as fibrosis[5,6,7]. Such an observation of fibrosis is important in assessing myocardium damage in case of allograft rejection. For a detailed description of histopathology associated with cardiac allograph rejection, the readers are directed to available literature[3,4,5]
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