Two-dimensional (2D) ultrasound imaging is commonly used for diagnosis in a variety of medical fields. However, there are several drawbacks of conventional 2D-ultrasound imaging. These include prostate or transducer movement that produces sets of different images that are difficult to interpret. Also during patient's reexamination correspondence between sets of images before reexamination and after is difficult to establish. This can be described as a problem of correlation between two sets of images: the first created before distortion or examination, the second one after. We propose a method to register 2D ultrasound volumes based on external markers introduced in the prostate. The metal balls are inserted in the prostate at three distinct locations in the prostate. These appear as bright dots in the ultrasound field, serve as reference points, are then outlined through a user-interactive program from two sets of images. Then, the computer program rotates and translates till they match respectively, and displays the mapped points with their corresponding location. Based on this idea we developed an image-guided system for PDT that require high-precision placement of implants. In the planning stage, the system performs an automatic acquisition of 2D transrectal ultrasound images that will ultimately be used to construct the treatment plan. At the time of the therapy, new sets of ultrasound images are acquired and a match is established between the virtual world and the patient's real world with the aid of manually introduced markers and image matching algorithms.
Photodynamic therapy (PDT) is an emerging minimally invasive treatment that can be employed in many human diseases including prostate cancer. This treatment of human prostate cancer depends on the localization of a drug (photosensitizer) into the prostate. The photosensitizer is activated by high- energy laser light and the active drug destroys cancerous tissue. The success of PDT depends on precise placement of light diffusers in the prostate. Since the prostate is irregular in shape, with different dimensions, a transurethral light delivery that is circular in distribution cannot be used in most cases of carcinoma of the prostate. Sources of light and their spatial distribution must be tailored to each individual patient. More uniform, therapeutic light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. For this reason, we are developing a computer program that can calculate the distribution of energy depending on the number of light sources placed in the prostate, their position in the gland, the dimension of the prostate, and the attenuation coefficient. A patient's three-dimensional prostate model is built based on ultrasound images. Then the program is being designated to predict the best set of parameters and position of light diffusers in space, displays them in graphical form or in numerical form. The program is amenable for interfacing with robotic treatment systems.
We have been investigating the potential applicability of photodynamic therapy for the treatment of benign and malignant disease of the prostate. Both transurethral and transperineal approaches to the delivery of light to the tin ethyl etiopurpurin sensitized canine prostate have been studied. Pharmacologic studies were performed and suggested that delaying light treatment for 7 days after drug administration would maximize the desired effect on the targeted prostatic tissue while minimizing the damage to surrounding bladder and rectum. A total of 12 dogs were treated with transurethral light alone (n=6) or the combination of transurethral light and transperineal light one week after tin ethyl etiopurpurin administration. (Previous studies have shown that light alone has no effect on prostate size or histology.) Animals were euthanized 48 hours and 3 weeks after completion of treatment (drug, 1mg/kg day 0, light [400mw/750sec]day 7). Tissue response was determined by gross and microscopic examination. Additionally, pre- and post- treatment transrectal ultrasounds were compared to assess changes in prostate volume and tissue echogenicity. The combination of transurethral and transperineal light results in extensive destruction of glandular epithelium with minimal damage to surrounding structures. Prostate volumes decreased by an average of 52%. Untreated areas were found to lie greater than 0.5 cm from the light diffuser. These studies have encouraged us to continue to investigate this modality as a technique for total ablation of prostatic glandular epithelium.
A series of experiments was undertaken to determine the uptake of the photosensitizer tin ethyl etiopurpurin in the canine prostate. At increasing time intervals after intravenous injection, tissue photosensitizer levels were determined for the prostate, urinary bladder and other selected sites. Tissue effects resulting from either transurethral or transperineal delivery of light to the prostate after tin ethyl etiopurpurin-photosensitization were then assessed by light microscopy. Both resulted in hemorrhagic necrosis of the target prostatic tissue. Photodynamic therapy of the prostate using tin ethyl etiopurpurin as photosensitizer for the treatment of both benign prostatic enlargement and adenocarcinoma is worth of further investigation.
Experiments were undertaken to determine whether 5-aminoleuvinic acid in combination with light could be used as an adjunct to intestinal bladder augmentation with the aim of removing intestinal mucosa with subsequent re-epithelialization of the treated segment with urothelium. Histopathologic studies of so-treated intestinal segments used in bladder augmentation demonstrate the feasibility of this approach.
A series of experiments was undertaken to determine the effects of the combination of light and the tissue photosensitizer, tin etiopurpurin, on the canine prostate. Mongrel dogs were injected intravenously with 1.0 mg/kg of photosensitizer twenty-four hours prior to light delivery. Laser light, 660 nm, was administered either transurethrally or interstitially and tissue effects were assessed by histopathologic examination. Both techniques of light delivery resulted in hemorrhagic necrosis of the surrounding tissue. Photodynamic therapy may offer a novel approach to the treatment of both benign and malignant diseases of the prostate.
Lasers have traditionally been the preferred light source for activation of the photosensitizing agents used in photodynamic therapy (PDT). Their monochromaticity, high power, and the ability to efficiently couple that power into optical fibers have dictated their use. Dye lasers, metal vapor lasers, or ion gas lasers have been used in the past as the excitation source for PDT, largely because they provided the only available alternatives. These laser systems are very large and complex, and are very expensive to operate. The introduction of high power visible red laser diodes have provided a cost effective alternative to existing lasers for use in PDT. This paper will describe the features of a prototype preclinical red laser diode source for photodynamic therapy, and will present the results of an animal study conducted with this device. The study, using the photosensitizer SnET2, compared the efficacy of PDT performed with the diode laser system with the results obtained from a traditional dye laser system. Future plans for a clinical version of the system will also be discussed.
Lasers have traditionally been the preferred light source for activation of the photosensitizing agents used in photodynamic therapy (PDT). Their monochromaticity, high power, and the ability to couple that high power into optical fibers have dictated their use. There are however, many potential applications for PDT which do not require fiberoptic light delivery, and thus, need not incur the high cost associated with the use of laser systems. Treatment of skin cancer, cervical cancer, and cancers in the oral cavity could be effectively treated with alternative light sources, which would greatly reduce the cost of treatment. This paper will describe the features of a preclinical light emitting diode (LED) based source for photodynamic therapy, designed and built by PDT Systems. The results of an animal study, using the photosensitizer SnET2 activated at 660 nm, which compared the efficacy of PDT performed with a dye laser system with that of the LED system will be presented. Future plans for a clinical version of the LED system will also be discussed.
Over the last decade considerable interest has developed in the use of exogenously administered chromophores in combination with visible light for the treatment of human tumors. Whether cells are killed directly, or indirectly as a result of disruption of the tissue, microvasculature is unknown. The authors have developed methods to assess in short term culture the effects of PDT on precision cut tissue slices. The use of these tissue slices provide an important link between in vivo studies and in vitro isolated cultured cells for the following reasons: 1) slices contain all of the normal cells in their proper in vivo architectural arrangement; 2) since slices can be obtained relatively easily and in a very short period of time (a few minutes), animals can be treated with compounds in vivo, the tissue can be removed, sliced and mechanistic studies performed in vitro (without the several hours delay required to produce cultured cells); 3) in vitro comparisons between species, including human, can be readily made; and 4) mechanisms of PDT-induced cell killing can be studied in the absence of a functioning vascular system. Using this in vivo drug/in vitro light system, the results presented will detail the findings using normal rat liver and a transplantable rat tumor model.
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