John G. Strang

Tissue elasticity properties as biomarkers for prostate cancer

In this paper we evaluate tissue elasticity as a longstanding but qualitative biomarker for prostate cancer and sonoelastography as an emerging imaging tool for providing qualitative and quantitative measurements of prostate tissue stiffness. A Kelvin-Voigt Fractional Derivative (KVFD) viscoelastic model was used to characterize mechanical stress relaxation data measured from human prostate tissue samples. Mechanical testing results revealed that the viscosity parameter for cancerous prostate tissue is greater than that derived from normal tissue by a factor of approximately 2.4. It was also determined that a significant difference exists between normal and cancerous prostate tissue stiffness (p < 0.01) yielding an average elastic contrast that increases from 2.1 at 0.1 Hz to 2.5 at 150 Hz. Qualitative sonoelastographic results show promise for cancer detection in prostate and may prove to be an effective adjunct imaging technique for biopsy guidance. Elasticity images obtained with quantitative sonoelastography agree with mechanical testing and histological results. Overall, results indicate tissue elasticity is a promising biomarker for prostate cancer.

Quantitative characterization of viscoelastic properties of human prostate correlated with histology.

Quantification of mechanical properties of human prostate tissue is important for developing sonoelastography for prostate cancer detection. In this study, we characterized the frequency-dependent complex Youngs modulus of normal and cancerous prostate tissues in vitro by using stress relaxation testing and viscoelastic tissue modeling methods. After radical prostatectomy, small cylindrical tissue samples were acquired in the posterior region of each prostate. A total of 17 samples from eight human prostates were obtained and tested. Stress relaxation tests on prostate samples produced repeatable results that fit a viscoelastic Kelvin-Voigt fractional derivative (KVFD) model (r(2)>0.97). For normal (n = 8) and cancerous (n = 9) prostate samples, the average magnitudes of the complex Youngs moduli (|E*|) were 15.9 +/- 5.9 kPa and 40.4 +/- 15.7 kPa at 150 Hz, respectively, giving an elastic contrast of 2.6:1. Nine two-sample t-tests indicated that there are significant differences between stiffness of normal and cancerous prostate tissues in the same gland (p < 0.01). This study contributes to the current limited knowledge on the viscoelastic properties of the human prostate, and the inherent elastic contrast produced by cancer.

Three-dimensional registration and fusion of ultrasound and MRI using major vessels as fiducial markers

This paper describes fusion of three-dimensional (3-D) ultrasound (US) and magnetic resonance imaging (MRI) data sets, without the assistance of external fiducial markers or external position sensors. Fusion of these two modalities combines real-time 3-D ultrasound scans of soft tissue with the larger anatomical framework from MRI. The complementary information available from multiple imaging modalities warrants the development of robust fusion capabilities. We describe the data acquisition, specialized algorithms, and results for 3-D fused data from phantom studies and in vivo studies of the normal human vasculature and musculoskeletal systems.

US Elastography of Breast and Prostate Lesions

Elastography is a technique that maps relative tissue stiffness. Ultrasonographic (US) elastography (sonoelastography) is a novel modality that is the subject of active research for clinical applications, primarily breast and prostate lesion imaging. Breast and prostate tumors generally have biomechanical properties different from those of normal tissues: Tumors are usually stiffer. This phenomenon is responsible for tissue contrast on elastograms. For the prostate gland and breast, the main image acquisition techniques are vibration sonoelastography and compression sonoelastography. The sonoelastographic appearances of several common breast lesions, including fibroadenomas, simple and complex cysts, ductal carcinomas, malignant lymph nodes, and hematomas, are reviewed. In addition, the US elastographic appearances of the normal prostate gland, prostate carcinomas, and benign prostate hyperplasia are illustrated. Potential pitfalls in the interpretation of elastograms, including false-positive and false-negative images, are illustrated. These imaging findings are derived from ongoing research because sonoelastography is not yet accepted for routine clinical use.

In vivo motion and force measurement of surgical needle intervention during prostate brachytherapy

In this paper, we present needle insertion forces and motion trajectories measured during actual brachytherapy needle insertion while implanting radioactive seeds in the prostate glands of 20 different patients. The needle motion was captured using ultrasound images and a 6 degree-of-freedom electromagnetic-based position sensor. Needle velocity was computed from the position information and the corresponding time stamps. From in vivo data we found the maximum needle insertion forces to be about 15.6 and 8.9N for 17gauge (1.47mm) and 18gauge (1.27mm) needles, respectively. Part of this difference in insertion forces is due to the needle size difference (17G and 18G) and the other part is due to the difference in tissue properties that are specific to the individual patient. Some transverse forces were observed, which are attributed to several factors such as tissue heterogeneity, organ movement, human factors in surgery, and the interaction between the template and the needle. However, theses insertion forces are significantly responsible for needle deviation from the desired trajectory and target movement. Therefore, a proper selection of needle and modulated velocity (translational and rotational) may reduce the tissue deformation and target movement by reducing insertion forces and thereby improve the seed delivery accuracy. The knowledge gleaned from this study promises to be useful for not only designing mechanical/robotic systems but also developing a predictive deformation model of the prostate and real-time adaptive controlling of the needle.

Intraoperative optimized inverse planning for prostate brachytherapy: early experience

PURPOSE To demonstrate the feasibility of an intraoperative inverse planning technique with advanced optimization for prostate seed implantation. METHODS AND MATERIALS We have implemented a method for optimized inverse planning of prostate seed implantation in the operating room (OR), based on the genetic algorithm (GA) driven Prostate Implant Planning Engine for Radiotherapy (PIPER). An integrated treatment planning system was deployed, which includes real-time ultrasound image acquisition, treatment volume segmentation, GA optimization, real-time decision making and sensitivity analysis, isodose and DVH evaluation, and virtual reality navigation and surgical guidance. Ten consecutive patients previously scheduled for implantation were included in the series. RESULTS The feasibility of the technique was established by careful monitoring of each step in the OR and comparison with conventional preplanned implants. The median elapsed time for complete image capture, segmentation, GA optimization, and plan evaluation was 4, 10, 2.2, and 2 min, respectively. The dosimetric quality of the OR-based plan was shown to be equivalent to the corresponding preplan. CONCLUSION An intraoperative optimized inverse planning technique was developed for prostate brachytherapy. The feasibility of the method was demonstrated through an early clinical experience.

Robot-Assisted prostate brachytherapy

In contemporary brachytherapy procedures, needle placement at the desired target is challenging due to a variety of reasons. A robot-assisted brachytherapy system can improve the needle placement and seed delivery resulting in enhanced patient care. In this paper we present a 16 DOF (degrees-of-freedom) robotic system (9DOF positioning module and 7 DOF surgery module) developed and fabricated for prostate brachytherapy. Techniques to reduce needle deflection and target movement have been incorporated after verifying with extensive experiments. Provisions for needle motion and force feedback have been included into the system for improving the robot control and seed delivery. Preliminary experimental results reveal that the prototype system is quite accurate (sub-millimeter) in placing brachytherapy needles.

Effects of Velocity Modulation during Surgical Needle Insertion

Precise interstitial intervention is essential for many medical diagnostic and therapeutic procedures. But accurate insertion and placement of surgical needle in soft tissue is quite challenging. The understanding of the interaction between surgical needle and soft tissue is very important to develop new devices and systems to achieve better accuracy and to deliver quality treatment. In this paper we present the effects of velocity (linear, rotational, and oscillatory) modulation on needle force and target deflection. We have experimentally verified our hypothesis that needle insertion with continuous rotation reduces target movement and needle force significantly. We have observed little changes in force and target deflection in rotational oscillation (at least at lower frequency) of the needle

Real-time sonoelastography of hepatic thermal lesions in a swine model

Sonoelastography has been developed as an ultrasound-based elasticity imaging technique. In this technique, external vibration is induced into the target tissue. In general, tissue stiffness is inversely proportional to the amplitude of tissue vibration. Imaging tissue vibration will provide the elasticity distribution in the target region. This study investigated the feasibility of using real-time sonoelastography to detect and estimate the volume of thermal lesions in porcine livers in vivo. A total of 32 thermal lesions with volumes ranging from 0.2to5.3cm3 were created using radiofrequency ablation (RFA) or high-intensity focused ultrasound (HIFU) technique. Lesions were imaged using sonoelastography and coregistered B-mode ultrasound. Volumes were reconstructed from a sequence of two-dimensional scans. The comparison of sonoelastographic measurements and pathology findings showed good correlation with respect to the area of the lesions (r2=0.8823 for RFA lesions, r2=0.9543 for HIFU lesions). In addition, good correspondence was found between three-dimensional sonoelastography and gross pathology (3.6% underestimate), demonstrating the feasibility of sonoelastography for volume estimation of thermal lesions. These results support that sonoelastography outperforms conventional B-mode ultrasound and could potentially be used for assessment of thermal therapies.

AUTOMATED TREATMENT PLANNING ENGINE FOR PROSTATE SEED IMPLANT BRACHYTHERAPY

PURPOSE To develop a computer-intelligent planning engine for automated treatment planning and optimization of ultrasound- and template-guided prostate seed implants. METHODS AND MATERIALS The genetic algorithm was modified to reflect the 2D nature of the implantation template. A multi-objective decision scheme was used to rank competing solutions, taking into account dose uniformity and conformity to the planning target volume (PTV), dose-sparing of the urethra and the rectum, and the sensitivity of the resulting dosimetry to seed misplacement. Optimized treatment plans were evaluated using selected dosimetric quantifiers, dose-volume histogram (DVH), and sensitivity analysis based on simulated seed placement errors. These dosimetric planning components were integrated into the Prostate Implant Planning Engine for Radiotherapy (PIPER). RESULTS PIPER has been used to produce a variety of plans for prostate seed implants. In general, maximization of the minimum peripheral dose (mPD) for given implanted total source strength tended to produce peripherally weighted seed patterns. Minimization of the urethral dose further reduced the loading in the central region of the PTV. Isodose conformity to the PTV was achieved when the set of objectives did not reflect seed positioning uncertainties; the corresponding optimal plan generally required fewer seeds and higher source strength per seed compared to the manual planning experience. When seed placement uncertainties were introduced into the set of treatment planning objectives, the optimal plan tended to reach a compromise between the preplanned outcome and the likelihood of retaining the preferred outcome after implantation. The reduction in the volatility of such seed configurations optimized under uncertainty was verified by sensitivity studies. CONCLUSION An automated treatment planning engine incorporating real-time sensitivity analysis was found to be a useful tool in dosimetric planning for prostate brachytherapy.