The study results of 'Isolated Organ Treatment with Catheter-Based Technology' are discussed in this work as my doctoral thesis research, which is focused on: (1) review of the nature of clinical problems: (2) potential solutions to reduce the risk of complications: and (3) a demonstration of the feasibility by in-vitro and in-vivo experiments.
One of the common underlying problems of intravenous delivery of diagnostic and therapeutic medical agents is that, once administered, they enter the systemic circulation of the body and could cause harmful effects, sometimes very serious, on organs not directly related to the disease. The complications, also known as "off-target toxicity", are especially common with chemotherapy drugs and radiographic contrast agents. The former can affect almost every organ in spite of location of targeted cancerous cells. For example, one of the most popular drugs for multiple sclerosis treatment is Tysabri (Natalizumab), which has been known, over the past years, to cause severe degenerative neurotoxicity. Another example is Raptiva (efalizumab), which has been popularly used for psoriasis treatment, yet it was recently withdrawn from the market due to fatal brain infections. Furthermore, there are direct effects on the quality of life after these treatments. The latter has an increased incidence due to the growing number of procedures and effects the kidneys due to the implicit nature of contrast media clearance. However, the mortality rate of patients developing this problem is significantly increased once renal dialysis is required to remedy the clinical problem.
My proposed concept to prevent off-target toxicities is to detect and remove them at the downstream site of the organ before they escape and enter the systemic circulation. Locally delivered agents to the targeted organ through the upstream (arterial side) enter the site through capillaries and eventually will re-converge at the downstream (venous side) of the organ. If it were possible to detect and remove the agents before they escape, we can significantly reduce the concentration of agents remaining in the systemic circulation, which would help to lower the risk of complication to patients.
To establish potential sensing strategies, various technical modalities were tested from optical and mechanical regimes. Among them, optical reflectance sensing was selected because: (1) it is relatively easy to be implemented for a prototype: (2) it can be miniaturized to be integrated with catheter-based technology: and (3) it is safe to use in the intravascular system.
A prototype of a reflectance sensing system integrated with a catheter was developed. To validate the principles of endovascular detection of contrast media, a set of in-vitro studies were performed. To assess the feasibility of in-vivo capability of detection and removal during angiography, in-vivo experiments were designed and performed using animal subjects.
The in-vitro study results showed the proportional relationship of HCT (Hematocrit) and reflectance intensity as well as the unique spectral variations were dependent on oxygen saturation level. A simple algorithm was also introduced to quantify HCT and oxygen saturation based on the reflectance spectra, which will facilitate the optical sensing system to monitor the hematological changes in addition to detecting contrast media. The in-vivo study results proved the applicability of endovascular sensing for contrast detection. The reflectance signal was successfully registered as contrast was injected and an average 59±11% of total injected contrast was removed from the animal subjects. Thus, the in-vivo study showed the feasibility of the active monitoring and removal of contrast agents. These two study results were successfully published in two peer-reviewed journals; Applied Optics (May 2009, Vol. 48, No. 13) and Journal of Invasive Cardiology (July 2009, Vol. 21, No. 7).
Throughout this work, the feasibility of isolated organ treatment to help to reduce the incidence of off-target complications was successfully demonstrated by means of an intravascular optical sensing system. My study results will help to develop guidelines for the further expansion and development of a new model of patient care with particular focus on optimizing patient safety during particular procedures and treatments.
