Surface markers for image-guided interstitial photodynamic therapy

Presently, there is no universally effective treatment for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). In many cases, these tumors fail to respond or recur subsequent to standard therapies (radiation, chemotherapy, or surgery). Recent clinical studies suggest that interstitial photodynamic therapy (I-PDT) is a promising palliative treatment for these patients. Photodynamic therapy (PDT) involves the injection of a photosensitizing drug (photosensitizer, PS) followed by PS activation by a therapeutic light dose. The interaction between the light and the PS produces highly reactive, cytotoxic oxygen species which ultimately leads to cell death.;In I-PDT, an array of laser light sources is inserted into the target tumor volume via catheter embedded fiber optics. These light sources are used to provide a prescribed light dose to the clinical target volume (CTV). Due to the complex anatomy of the head and neck, careful planning of fiber insertions is required for I-PDT of LA-HNSCC. Previous work has verified that image based, pre-treatment computer simulations can assist in planning and monitoring I-PDT. These simulations can be used to determine the number and location of laser fibers, which would result in the delivery of an effective light dose to the CTV. However, in treating LA-HNSCC, the remaining challenge is to implement the treatment plan.;The locations of the catheters and therefore optical fibers often differ from the treatment plan due to manual placement. While high resolution computed tomography (CT) and/or magnetic resonance imaging (MRI) are used for the I-PDT pretreatment planning, ultrasound (US) is the preferred method for the insertion of the catheters during the therapy. The inherent difference between the imaging modalities is one reason for discrepancies in catheter location. The catheters' positions may also differ from the plan as a result of the mechanical force imposed on the tumor due to tissue deformation, the variation in patient position between the imaging suite and the operating room, and the skills of the operating surgeons as they prefer free-hand insertion of catheters into the tumor. Any deviation from the treatment plan has the potential to result in either over- or under- treatment of the target tumor volume. Additionally, discrepancies in fiber position can limit the ability to monitor I-PDT treatment, in near real time.;One objective of the work disclosed in this thesis was to develop means of assessing discrepancies in fiber locations, in near real time, and to evaluate the effect of these fiber discrepancies on the resulting light dose within the CTV. This work also focused on investigating the potential benefit of using reference CT surface markers and a flexible adhesive grid to guide and improve the insertion of treatment fibers. The overall hypothesis is that through the use of the CT markers and the grid, any difference in fiber location could be reduced to the order of millimeters. Additionally, by monitoring discrepancies in fiber placement in near real time, the pre-treatment computer simulations could be updated to assess I-PDT efficacy and to adjust the treatment plan such that the prescribed light dose is administered to the CTV.;Phantoms were constructed using hard silicone geometries embedded in ballistic gel to mimic the mechanical and physical properties of tumors in soft tissue. The phantoms were imaged with CT. The CT scans were reconstructed to create computerized (CAD based), three-dimensional (3D) geometries using an image visualization and analysis software package (Simpleware, Exeter, UK). These 3D models were imported into a Finite Element Analysis (FEA) software (COMSOL 4.4, Comsol AB Stockholm, Sweden) where our previously verified image-based I-PDT treatment planning algorithm was employed to compute plans for fiber location and light doses. Insertion of catheters into the phantoms was performed utilizing a flexible grid and CT surface markers. Additional CT scans of the phantoms were taken post catheter insertion. These scans were used to measure the differences between the planned and actual catheter locations, and to construct a new simulation for computing the light dose based on definite catheter/fiber locations. The above procedure was implemented for five different phantoms. The resulting percent difference between the planned and the actual depth of insertion for all fibers did not exceed 22%, with the exception of one catheter which had an approximate 52% difference. Additionally, the catheters were placed within 8 mm of the planned locations. The new light dose differed from the original plan by less than 18%.;In this study, an improved method for guiding the insertion of the catheters/fibers into the CTV was developed. (Abstract shortened by UMI.).