RUF Project: Introduction

Advanced screening techniques over the past decade have led to an increase in the percentage of patients diagnosed with organ confined prostate cancer. Prostate brachytherapy has emerged as one of the principal treatment modalities available for those patients. Numerous studies have demonstrated the efficacy and safety of transperineal prostate brachytherapy in the therapy of prostate cancer. The success of brachytherapy chiefly depends on our ability to intra-operatively tailor the radiation dose to the patient's individual anatomy, i.e. to adequately “cover” the prostate with sufficient radiation while still avoiding excessive radiation to surrounding organs (rectum, urethra, and bladder), thereby curing the cancer and avoiding unnecessary side effects at the same time. The failure of the former could cause early recurrence, while that of the latter results in adverse side effects like rectal ulceration, incontinence, and impotence.

The ability to perform intra-operative dosimetry may change the standard of care in brachytherapy by allowing the physician to achieve technically excellent brachytherapy implants, resulting in improved disease control and quality of life for a large and steadily growing group of patients. Unfortunately, such level of precision is not always achievable even by the most experienced of physicians. Owing to a plethora of technical problems (including deformation and dislocation of the prostate, needle bending under tissue forces, and seeds sliding within the needle tract after the needle is removed) the implanted seeds usually do not end up exactly in their intended positions. Thus many implants fail or cause severe side effects owing to faulty seed placement, yet this cannot be identified or corrected in the operating room today. While this problem has been known to brachytherapists, current technology does not allow for reliable localization of the implanted sources, thereby prohibiting the prediction and modification of seed distribution intra-operatively.

In contemporary practice, ultrasound is used to observe the prostate during the procedure, but seeds cannot readily be seen on the ultrasound image once they have been deployed. X-rays are used to visualize the seeds, though only for a gross qualitative estimate. No C-arm based quantitative dose measurements systems are available inside the OR. Intra-operative dose calculations based on CT or MRI are impractical for obvious reasons. Since over two-thirds of the practitioners have C-arms available, it would be an ideal solution to combine quantitative measurements from C-arm fluoroscopy and ultrasound.

The achievement of these goals does not fall under the expertise of any one department or discipline. Therefore, there is an outstanding need for multidisciplinary academicians who master the technological aspects while are trained in clinical medical physics aspects of the field. The objective of this research is to design, develop, and evaluate ex-vivo a method for intra-operative localization of the implanted seeds in relation to the prostate, to allow for in-situ dosimetric optimization and exit dosimetry.

Specific Research Aims: We propose to develop a method for the fusion of ultrasound (which can view the prostate but not the seeds) with X-ray fluoroscopy (which is capable of viewing the seeds but not the prostate). In particular, we will:

[1]Registration of Ultrasound to Fluoroscopy (RUF): Develop methods for reconstruction of seed implants from X-ray fluoroscopy and spatially register them to the prostate anatomy identified in TRUS

[2]System Integration: Integrate the above methods in a software package and link it with the FDA-approved CMS Interplant® prostate brachytherapy system to enable in-situ dosimetry calculation

[3]Experimental Validation: Evaluate the performance of the RUF system on phantoms, pre-recorded patient data and finally on clinical trials.

In Aim-1, we will first mount our specially designed X-ray fiducial system (FTRAC) on a precisely manufactured carrier with respect to TRUS stepper, and then apply the FTRAC for tracking the C-arm. The preliminary tracking algorithm has shown adequate accuracy and robustness, and it would be further perfected to do away with the complex task of accurate segmentation. This, along with segmented seed information, will be fed to the algorithm we have developed (MARSHAL) that will reconstruct the 3D locations of implanted seeds from three (or more) X-ray images. Though the present version of MARSHAL is very robust on pres-segmented seeds, it needs to be extended to include hidden and spuriously segmented seeds in C-arm images. Moreover, here too, the problem of sensitivity to segmentation will be addressed. The reconstructed implant configuration will be projected into ultrasound space where it can be superimposed on the prostate boundary.

In Aim-2, we will integrate the above algorithmic components as a standalone computer software. This system will communicate with the FDA-approved Interplant® (CMS, St. Louis, MO) prostate brachytherapy planning system that provides dosimetric analysis and proposes appropriate changes in the remainder of the treatment plan. This process will be repeated to obtain dosimetric update for every batch of needles (say a row of needles), and at the end of the procedure to obtain exit dose. Thus intra-operative dosimetry will be realized.

In Aim-3, we will perform pre-clinical laboratory testing to validate the accuracy, consistency, and robustness of ultrasound-fluoroscopy registration and seed implant reconstruction. In particular, we will first conduct workspace and accuracy analysis on images of appropriately fabricated prostate phantoms, and then on pre-recorded brachytherapy cases of real patients.