A novel 3-D segmentation algorithm for anatomic liver and tumor volume calculations for liver cancer treatment planning

Three-Dimensional (3-D) imaging is vital in computer-assisted surgical planning including minimal invasive surgery, targeted drug delivery, and tumor resection. Selective Internal Radiation Therapy (SIRT) is a liver directed radiation therapy for the treatment of liver cancer. Accurate calculation of anatomical liver and tumor volumes are essential for the determination of the tumor to normal liver ratio and for the calculation of the dose of Y-90 microspheres that will result in high concentration of the radiation in the tumor region as compared to nearby healthy tissue. Present manual techniques for segmentation of the liver from Computed Tomography (CT) tend to be tedious and greatly dependent on the skill of the technician/doctor performing the task. ^ This dissertation presents the development and implementation of a fully integrated algorithm for 3-D liver and tumor segmentation from tri-phase CT that yield highly accurate estimations of the respective volumes of the liver and tumor(s). The algorithm as designed requires minimal human intervention without compromising the accuracy of the segmentation results. Embedded within this algorithm is an effective method for extracting blood vessels that feed the tumor(s) in order to plan effectively the appropriate treatment. ^ Segmentation of the liver led to an accuracy in excess of 95% in estimating liver volumes in 20 datasets in comparison to the manual gold standard volumes. In a similar comparison, tumor segmentation exhibited an accuracy of 86% in estimating tumor(s) volume(s). Qualitative results of the blood vessel segmentation algorithm demonstrated the effectiveness of the algorithm in extracting and rendering the vasculature structure of the liver. Results of the parallel computing process, using a single workstation, showed a 78% gain. Also, statistical analysis carried out to determine if the manual initialization has any impact on the accuracy showed user initialization independence in the results. ^ The dissertation thus provides a complete 3-D solution towards liver cancer treatment planning with the opportunity to extract, visualize and quantify the needed statistics for liver cancer treatment. Since SIRT requires highly accurate calculation of the liver and tumor volumes, this new method provides an effective and computationally efficient process required of such challenging clinical requirements.^

Microspheres for liver radiomicrospheres therapy and planning

Liver cancer accounts for nearly 10% of all cancers in the US. Intrahepatic Arterial Radiomicrosphere Therapy (RMT), also known as Selective Internal Radiation Treatment (SIRT), is one of the evolving treatment modalities. Successful patient clinical outcomes require suitable treatment planning followed by delivery of the microspheres for therapy. The production and in vitro evaluation of various polymers (PGCD, CHS and CHSg) microspheres for a RMT and RMT planning are described. Microparticles with a 30±10 µm size distribution were prepared by emulsion method. The in vitro half-life of the particles was determined in PBS buffer and porcine plasma and their potential application (treatment or treatment planning) established. Further, the fast degrading microspheres (≤ 48 hours in vitro half-life) were labeled with 68Ga and/or 99mTc as they are suitable for the imaging component of treatment planning, which is the primary emphasis of this dissertation. Labeling kinetics demonstrated that 68Ga-PGCD, 68Ga-CHSg and 68Ga-NOTA-CHSg can be labeled with more than 95% yield in 15 minutes; 99mTc-PGCD and 99mTc-CHSg can also be labeled with high yield within 15-30 minutes. In vitro stability after four hours was more than 90% in saline and PBS buffer for all of them. Experiments in reconstituted hemoglobin lysate were also performed. Two successful imaging (RMT planning) agents were found: 99mTc-CHSg and 68Ga-NOTA-CHSg. For the 99mTc-PGCD a successful perfusion image was obtained after 10 minutes, however the in vivo degradation was very fast (half-life), releasing the 99mTc from the lungs. Slow degrading CHS microparticles (> 21 days half-life) were modified with p-SCN-b-DOTA and labeled with 90 Y for production of 90Y-DOTA-CHS. Radiochemical purity was evaluated in vitro and in vivo showing more than 90% stability after 72 and 24 hours respectively. All agents were compared to their respective gold standards (99mTc-MAA for 68Ga-NOTA-CHSg and 99m Tc-CHSg; 90Y-SirTEX for 90Y-DOTA-CHS) showing superior in vivo stability. RMT and RMT planning agents (Therapy, PET and SPECT imaging) were designed and successfully evaluated in vitro and in vivo.

Microspheres for Liver Radiomicrospheres Therapy and Planning

Liver cancer accounts for nearly 10% of all cancers in the US. Intrahepatic Arterial Radiomicrosphere Therapy (RMT), also known as Selective Internal Radiation Treatment (SIRT), is one of the evolving treatment modalities. Successful patient clinical outcomes require suitable treatment planning followed by delivery of the microspheres for therapy. The production and in vitro evaluation of various polymers (PGCD, CHS and CHSg) microspheres for a RMT and RMT planning are described. Microparticles with a 30±10 µm size distribution were prepared by emulsion method. The in vitro half-life of the particles was determined in PBS buffer and porcine plasma and their potential application (treatment or treatment planning) established. Further, the fast degrading microspheres (≤ 48 hours in vitro half-life) were labeled with 68Ga and/or 99mTc as they are suitable for the imaging component of treatment planning, which is the primary emphasis of this dissertation. Labeling kinetics demonstrated that 68Ga-PGCD, 68Ga-CHSg and 68Ga-NOTA-CHSg can be labeled with more than 95% yield in 15 minutes; 99mTc-PGCD and 99mTc-CHSg can also be labeled with high yield within 15-30 minutes. In vitro stability after four hours was more than 90% in saline and PBS buffer for all of them. Experiments in reconstituted hemoglobin lysate were also performed. Two successful imaging (RMT planning) agents were found: 99mTc-CHSg and 68Ga-NOTA-CHSg. For the 99mTc-PGCD a successful perfusion image was obtained after 10 minutes, however the in vivo degradation was very fast (half-life), releasing the 99mTc from the lungs. Slow degrading CHS microparticles (> 21 days half-life) were modified with p-SCN-b-DOTA and labeled with 90Y for production of 90Y-DOTA-CHS. Radiochemical purity was evaluated in vitro and in vivo showing more than 90% stability after 72 and 24 hours respectively. All agents were compared to their respective gold standards (99mTc-MAA for 68Ga-NOTA-CHSg and 99mTc-CHSg; 90Y-SirTEX for 90Y-DOTA-CHS) showing superior in vivo stability. RMT and RMT planning agents (Therapy, PET and SPECT imaging) were designed and successfully evaluated in vitro and in vivo.