Determining optimal eluter design by modeling physical dose enhancement in brachytherapy.

PURPOSE: In situ drug release concurrent with radiation therapy has been proposed to enhance the therapeutic ratio of permanent prostate brachytherapy. Both brachytherapy sources and brachytherapy spacers have been proposed as potential eluters to release compounds, such as nanoparticles or chemotherapeutic agents. The relative effectiveness of the approaches has not been compared yet. This work models the physical dose enhancement of implantable eluters in conjunction with brachytherapy to determine which delivery mechanism provides greatest opportunity to enhance the therapeutic ratio. MATERIALS AND METHODS: The combined effect of implanted eluters and radioactive sources were modeled in a manner that allowed the comparison of the relative effectiveness of different types of implantable eluters over a range of parameters. Prostate geometry, source, and spacer positions were extracted from treatment plans used for 125 I permanent prostate implants. Compound concentrations were calculated using steady-state solution to the diffusion equation including an elimination term characterized by the diffusion-elimination modulus (ϕb ). Does enhancement was assumed to be dependent on compound concentration up to a saturation concentration (csat ). Equivalent uniform dose (EUD) was used as an objective to determine the optimal configuration of eluters for a range of diffusion-elimination moduli, concentrations, and number of eluters. The compound delivery vehicle that produced the greatest enhanced dose was tallied for points in parameter space mentioned to determine the conditions under whether there are situations where one approach is preferable to the other. RESULTS: The enhanced effect of implanted eluters was calculated for prostate volumes from 14 to 45 cm3 , ϕb from 0.01 to 4 mm-1 , csat from 0.05 to 7.5 times the steady-state compound concentration released from the surface of the eluter. The number of used eluters (ne ) was simulated from 10 to 60 eluters. For the region of (csat , Φ)-space that results in a large fraction of the gland being maximally sensitized, compound eluting spacers or sources produce equal increase in EUD. In the majority of the remaining (csat , Φ)-space, eluting spacers result in a greater EUD than sources even where sources often produce greater maximal physical dose enhancement. Placing eluting implants in planned locations throughout the prostate results in even greater enhancement than using only source or spacer locations. CONCLUSIONS: Eluting brachytherapy spacers offer an opportunity to increase EUD during the routine brachytherapy process. Incorporating additional needle placements permits compound eluting spacer placement independent of source placement and thereby allowing a further increase in the therapeutic ratio. Additional work is needed to understand the in vivo spatial distribution of compound around eluters, and to incorporate time dependence of both compound release and radiation dose.

Real-time inverse high-dose-rate brachytherapy planning with catheter optimization by compressed sensing-inspired optimization strategies.

This paper demonstrates that optimization strategies derived from the field of compressed sensing (CS) improve computational performance in inverse treatment planning (ITP) for high-dose-rate (HDR) brachytherapy. Following an approach applied to low-dose-rate brachytherapy, we developed a reformulation of the ITP problem with the same mathematical structure as standard CS problems. Two greedy methods, derived from hard thresholding and subspace pursuit are presented and their performance is compared to state-of-the-art ITP solvers. Applied to clinical prostate brachytherapy plans speed-up by a factor of 56-350 compared to state-of-the-art methods. Based on a Wilcoxon signed rank-test the novel method statistically significantly decreases the final objective function value (p < 0.01). The optimization times were below one second and thus planing can be considered as real-time capable. The novel CS inspired strategy enables real-time ITP for HDR brachytherapy including catheter optimization. The generated plans are either clinically equivalent or show a better performance with respect to dosimetric measures.

Balancing dose and image registration accuracy for cone beam tomosynthesis (CBTS) for breast patient setup.

PURPOSE: To balance dose reduction and image registration accuracy in breast setup imaging. In particular, the authors demonstrate the relationship between scan angle and dose delivery for cone beam tomosynthesis (CBTS) when employed for setup verification of breast cancer patients with surgical clips. METHODS: The dose measurements were performed in a female torso phantom for varying scan angles of CBTS. Setup accuracy was measured using three registration methods: Clip centroid localization accuracy and the accuracy of two semiautomatic registration algorithms. The dose to the organs outside of the ipsilateral breast and registration accuracy information were compared to determine the optimal scan angle for CBTS for breast patient setup verification. Isocenter positions at the center of the patient and at the breast-chest wall interface were considered. RESULTS: Image registration accuracy was within 1 mm for the CBTS scan angles theta above 20 degrees for some scenarios and as large as 80 degrees for the worst case, depending on the imaged breast and registration algorithm. Registration accuracy was highest based on clip centroid localization. For left and right breast imaging with the isocenter at the chest wall, the dose to the contralateral side of the patient was very low (<0.5 cGy) for all scan angles considered. For central isocenter location, the optimal scan angles were 30 degrees - 50 degrees for the left breast imaging and 40 degrees - 50 degrees for the right breast imaging, with the difference due to the geometric asymmetry of the current clinical imaging system. CONCLUSIONS: The optimal scan angles for CBTS imaging were found to be between 10 degrees and 50 degrees, depending on the isocenter location and ipsilateral breast. Use of the isocenter at the breast-chest wall locations always resulted in greater accuracy of image registration (<1 mm) at smaller angles (10 degrees - 20 degrees) and at lower doses (<0.1 cGy) to the contralateral organs. For chest wall isocenters, doses delivered to organs outside of the target breast were much smaller than the scattered and leakage doses of the treatment beams. The complete volumetric information of all clips in the region of interest, combined with the small dose to the contralateral organs and the small scan angle, could result in an advantage for small angle CBTS with off center isocenters over simple orthogonal pairs.

GAF film dosimetry of a tandem positioned beta-emitting intravascular brachytherapy source train.

Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath 90Sr/90Y 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%.

A practical method to achieve prostate gland immobilization and target verification for daily treatment.

PURPOSE: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. METHODS AND MATERIALS: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. RESULTS: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to < or =1 mm from 4 mm. CONCLUSIONS: Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.

Evaluation of three-dimensional finite element-based deformable registration of pre- and intraoperative prostate imaging.

In this report we evaluate an image registration technique that can improve the information content of intraoperative image data by deformable matching of preoperative images. In this study, pretreatment 1.5 tesla (T) magnetic resonance (MR) images of the prostate are registered with 0.5 T intraoperative images. The method involves rigid and nonrigid registration using biomechanical finite element modeling. Preoperative 1.5 T MR imaging is conducted with the patient supine, using an endorectal coil, while intraoperatively, the patient is in the lithotomy position with a rectal obturator in place. We have previously observed that these changes in patient position and rectal filling produce a shape change in the prostate. The registration of 1.5 T preoperative images depicting the prostate substructure [namely central gland (CG) and peripheral zone (PZ)] to 0.5 T intraoperative MR images using this method can facilitate the segmentation of the substructure of the gland for radiation treatment planning. After creating and validating a dataset of manually segmented glands from images obtained in ten sequential MR-guided brachytherapy cases, we conducted a set of experiments to assess our hypothesis that the proposed registration system can significantly improve the quality of matching of the total gland (TG), CG, and PZ. The results showed that the method statistically-significantly improves the quality of match (compared to rigid registration), raising the Dice similarity coefficient (DSC) from prematched coefficients of 0.81, 0.78, and 0.59 for TG, CG, and PZ, respectively, to 0.94, 0.86, and 0.76. A point-based measure of registration agreement was also improved by the deformable registration. CG and PZ volumes are not changed by the registration, indicating that the method maintains the biomechanical topology of the prostate. Although this strategy was tested for MRI-guided brachytherapy, the preliminary results from these experiments suggest that it may be applied to other settings such as transrectal ultrasound-guided therapy, where the integration of preoperative MRI may have a significant impact upon treatment planning and guidance.

Optimizing target coverage by dosimetric feedback during prostate brachytherapy.

PURPOSE: Postimplant dosimetry of permanent prostate implants shows a loss of coverage compared to the preplan. One contributing factor is needle misplacement. The significance of needle misplacement and the clinical utility of dosimetric feedback were analyzed in the setting of interventional magnetic resonance (IMR) guided prostate brachytherapy. METHODS AND MATERIALS: Information provided by an intraoperative planning system was analyzed for 10 patients. Needle misplacement was measured and the dosimetric consequences calculated. Additional catheters and sources were placed following the insertion of all planned catheters to compensate for nonideal needle placement. RESULTS: Source misplacement ranged from 0.0 to 1.0 cm (median, 0.3 cm). The resulting loss of coverage ranged from 1% to 13%, and the intraoperative dosimetric feedback allowed a recovery of from 0% to 12% coverage. Between 0 and 3 (median, 2) additional needles and from 0 to 10 (median, 8) additional sources were required to restore coverage of the target. Final planned coverage exceeded 94% for all patients. CONCLUSION: The discrepancy between planned and achieved needle placement leads to a loss of dosimetric coverage of the target volume. Dosimetric feedback allows compensation for needle divergence. The technique of real-time dosimetric feedback does not require an IMR system, and could be generalized to ultrasound-guided implants.

Feasibility of transperineal prostate biopsy under interventional magnetic resonance guidance.

A patient, who was not suited for ultrasound-guided biopsy, was biopsied in an interventional magnetic resonance unit at Brigham and Women's Hospital. Real-time magnetic resonance imaging provided verification of placement before tissue samples were taken. This technique successfully sampled tissue from the prostate and led to a diagnosis of cancer.

A clinical method for real-time dosimetric guidance of transperineal 125I prostate implants using interventional magnetic resonance imaging.

PURPOSE: The clinical utility of an interventional magnetic resonance (IMR)-guided implant technique with real-time dosimetric feedback is presented. METHODS AND MATERIALS: The work was carried out at a IMR unit at Brigham and Women's Hospital. Planning and dosimetric feedback were provided by a software system that provides an interface to the IMR images, anatomy demarcation, template registration, dose calculation engine for planning, and evaluating the implant. Planning during the procedure permits the incorporation of actual needle trajectories in the dose calculations. RESULTS: Fifteen patients were planned in the treatment position. During source placement, actual needle locations were incorporated into the dose calculations. After accounting for the observed needle trajectories of the planned needles, 14 of 15 patients (93%) required additional sources to achieve the desired coverage of the target volume. CONCLUSION: A brachytherapy implant procedure which provides clinically significant advances has been implemented. Specifically, the planning system allows dosimetric validation of the needle placement. This procedure is effective in delivering brachytherapy to the target volume and assuring that the implant is delivered in accordance with the preplan. The dosimetric feedback could be incorporated in ultrasound-guided implants.

A software system for interventional magnetic resonance image-guided prostate brachytherapy.

OBJECTIVE: Current prostatic brachytherapy implant procedures use ultrasound imaging for geometric guidance during surgery, with pre-surgical planning based on ultrasound images and post-surgical dosimetry based on computed tomography (CT). This procedure suffers from the poor soft-tissue contrast of ultrasound and CT and problems inherent in the repositioning of the patient at surgery. We have designed and implemented an integrated real-time imaging and treatment-planning software system that combines the superior soft-tissue contrast of magnetic resonance (MR) images with the real-time acquisition of those images for localization, verification, and dosimetric purposes. The system permits the surgeon and patient to complete all phases of treatment in one setting. MATERIALS AND METHODS: We utilize an intra-operative MR unit that permits real-time imaging and stereotactic localization during a surgical procedure. Our software system integrates with the unit and features (i) a calibration schema to calibrate the prostatic surgical implant template within the unit, (ii) full volumetric data acquisition of the prostate, (iii) interactive three-dimensional (3D) treatment planning with volumetric dose evaluation, and (iv) geometric and dosimetric feedback during the surgical procedure. We utilize a software architecture that uses mediators between the abstract data types, or objects. These mediators communicate state changes in individual objects (e.g., a change in a catheter position) to other objects (e.g., a dose-volume histogram) that depend on these changes. A consistent 3D representation of the treatment volumes allows interactive reconstruction of the volumes on arbitrary MR image sections and real-time dose computations. RESULTS: We have successfully implemented the system clinically and have treated 143 patients (as of August 2000). The system supports four clinical phases. The first consists of calibrating the implant template with respect to the patient's anatomy and the MR unit. The second consists of acquiring a complete volumetric MR data set of the prostatic volume. The third consists of delineating the treatment volume (often a sub-volume of the prostate) and the dose-limiting critical volumes. These volumes are used in determining the surgical treatment plan based on catheter and seed placement in the prostate and a dosimetric evaluation of all volumes. The final phase consists of implanting the catheters with the radioactive seeds, where each catheter is imaged and compared to the planned position of the catheter, thus allowing a direct comparison, and possible adjustment, of the implanted versus planned catheter position. CONCLUSIONS: The system is highly interactive, and has great flexibility in its design, maintainability, and clinical practice. The system provides an efficient model to support the surgical procedure. The system significantly improves the diagnostic information provided to the clinician and the treatment planner and the geometric accuracy of the surgical procedure compared to ultrasound procedures. The system allows excellent critical structure sparing, both through interactive placement of the catheters with high geometric accuracy and through the definition of the actual sub-prostatic volumes possible with MR.

A stereotactic radiation therapy device for retinoblastoma using a noncircular collimator and intensity filter.

The proximity of the lens to the retina makes the treatment of retinoblastoma a challenge for external beam radiation therapy. The approximately 1 mm separation between the posterior edge of the lens and the anterior region of the retina causes a trade-off between coverage of the entire retina and excessive dose to the lens. A stereotactic, LINAC based, lens sparing technique for treating retinoblastoma is presented. The technique uses noncoplanar arcs with the lens at isocenter. A special noncircular collimator blocks the lens but it also causes the dose distribution to vary across the retina. A fluence modulation filter is used to reduce the dose inhomogeneity across the target. The resulting dose distribution is roughly hemispheric, providing both anterior coverage of the retina and lens blocking unlike conventional techniques. The method used to develop the collimator and filter assembly is presented. Dosimetry of the assembly was carried out using radiochromic film, and the results were entered in a treatment planning system. The dose distribution as measured in a phantom is provided and compared to calculations.

Beam profiles for x-ray rotation therapy.

Determining the beam configuration necessary to deliver a desired dose distribution with rotation therapy is equivalent to solving an integral equation. The equation has been solved analytically for a handful of dose distributions having specific radial variation and either rotational or reflective angular symmetry. In this work a numerical method for calculating beam profiles appropriate for producing distributions having arbitrary radial variation and angular symmetry of order l > or = 2 is presented. The accuracy of the technique is demonstrated by comparison with one of the few dose distributions for which an analytic solution exists, and the ability to produce both more general and conformal distributions is also shown. The problems of negative intensity and scatter are discussed.

A problem in rotation therapy with X-rays: dose distributions with an axis of symmetry.

We give the equations which need to be solved to extend the work of Brahme, Roos, and Lax to dose distributions which are not circularly symmetrical. These equations do not contain the linear absorption coefficient, mu, explicitly so they are valid in principle for any mu. The general solution of these equations has not been found, but the solution given by Brahme, Roos, and Lax is used to extend their work to simple dose distributions with an axis of symmetry. Some examples are given and discussed.