Prostate cancer is a commonly diagnosed cancer in men in the United States, second only to skin cancer. One of the most commonly used treatment modalities for prostate cancer is transperineal interstitial permanent prostate brachytherapy (TIPPB), which involves permanent implantation of 35-140 radioactive seeds into the prostate gland according to a preplan. Prostate brachytherapy is generally considered to be an effective treatment modality for early stage prostate cancer. However, as with many medical therapies, the success rates have varied markedly between medical practitioners. At least part of the difference in clinical outcomes is related to technical differences or implant quality. There is a complex, largely undefined relationship between dosimetric parameters and cancer control rates. The most widely reported parameters related to biochemical cancer control with radioactive seeds are the D90 dose (the minimum dose delivered to 90% of the prostate), and the V100 dose (the percent of the postimplant prostate volume covered by the prescription dose). These quality parameters are traditionally derived from a postimplant computed tomography (CT) scan.
During a prostate brachytherapy procedure, transrectal ultrasound (TRUS) and fluoroscopy imaging modalities complement each other by separately providing good visualization of the soft tissue at the treatment site, and of the implanted seeds, respectively, enabling the medical practitioner to separately view images of the prostate gland and images of the implanted seeds. Due to several factors such as prostate swelling, needle deviation from the planned direction, seed movement along the needle tracks, and change in patient positioning, some deviations from the preplan used for implant of the seeds are inevitable. Therefore, the postimplant CT scan is performed to compute the dose that will be received by the prostate with the initial implanted seeds. If inadequate isodose patterns are detected in the CT scan, a patient is considered for further treatment, such as an external beam radiation therapy or a second implant. However, a return trip to the operating room for implant of additional seeds clearly inconveniences the patient and increases the cost of healthcare. Instead, it would be desirable to intraoperatively assess the seed implant dosage parameters or isodose patterns at the time of the initial seed implant, and implant additional seeds as appropriate at that time before the initial prostate brachytherapy is completed. However, conventional prostate brachytherapy techniques do not provide any acceptable approach for evaluating the dosage parameters during the actual implant procedure.
If dosimetry evaluation could be performed intraoperatively, physicians could implant additional seeds into the under-dosed portions of the prostate while the patient remains on the operating table, thus obviating further treatment at a later time. Several researchers have attempted to perform dosimetry using ultrasound imaging modality only. However, ultrasound imaging is suboptimal in terms of seed visibility, and at least 95% of the implanted seeds need to be detected to provide an accurate estimation of dose parameters. Although some improvement in seed visibility has been achieved by using an alternating magnetic field, vibroacoustography, transurethral ultrasound, 3-D TRUS imaging, suture-mounted seeds, and seeds with a textured surface, all of these methods have either fallen significantly short of the required seed detection rate or have not been evaluated with real clinical data to determine their efficacy.
Seed detection in ultrasound images is clearly very important as one of the steps necessary to enable a clinician to evaluate the dosage that will be delivered by implanted seeds. No image modality is suitable for both implanted seeds and the prostate gland in the operating room. Both the fluoroscopy and TRUS images can be produced at that time, but currently, the two types of images are not easily correlated. In the fluoroscope images, soft tissues are not delineated, but the seeds are very clear; while in TRUS images, the prostate boundaries are clearly evident, but only part of the seed images appears and can be confused with non-seed structures, such as gas bubbles and calcifications, or other image elements or artifacts.
Accordingly, seed detection in TRUS images is an active area of medical image analysis. Research in this area has resulted in the development of an algorithm for seed detection based on the constant false alarm rate detection, and also, an algorithm for three-dimensional (3-D) seed detection. Another algorithm for seed detection has been developed that uses ultrasound radio frequency signals. However, as reported in the prior art, these experiments were not based on analysis of real clinical images, but instead, on phantom images. Still another prior art approach that did evaluate clinical data made use of the seed implant needle as an external fiducial, but that approach is believed likely too cumbersome for clinical use.
Based on empirical experience, only about 20% of the implanted seeds can typically be detected in TRUS images acquired by using the longitudinal transducer of a bi-planar TRUS probe. Due to the poor seed visibility in TRUS images, some researchers have used the locations of needle tips when seeds were placed to compute an estimate of dosimetry. However, this method is inaccurate, since it does not account for prostate swelling or seed movement.
In contrast to TRUS images, all of the implanted seeds are evident in three or more fluoroscopy images acquired from different angles. Since TRUS complements fluoroscopy by providing good visualization of the soft tissue, the combination of these two imaging modalities could enable effective and efficient determination of intraoperative dosimetry. However, a suitable TRUS-fluoroscopy registration method has not been developed or suggested in the prior art that can determine all of the seed locations in relation to the prostate boundaries.
To perform TRUS-fluoroscopy registration, markers that are visible in both imaging modalities, such as needle tips and radio-opaque fiducial markers, have been used. However, these methods are cumbersome and further complicate the brachytherapy procedure, since there is barely enough space inside a seed-implanted prostate to insert needles or implant fiducial markers. Furthermore, these markers are not used in routine seed implant procedures and increase the cost.
Other researchers have proposed the use of embedded markers on a modified ultrasound probe and fiducial markers above the abdomen. These external fiducial markers can be identified in fluoroscopy images and are assumed to be in known calibrated pose with respect to the TRUS coordinate system. But, the distance between the prostate and fiducial markers leads to error propagation, thus reducing the accuracy in registering seeds to the prostate boundaries. If this distance is too great, fiducial markers may not even be visible in fluoroscopy images acquired from oblique views. External fiducial marker-based approaches are also very sensitive to patient motion, which is a major limitation, especially for procedures performed under local anesthesia, since patients often move during image acquisition.
Therefore, it would clearly be desirable to develop an efficient approach for identifying seeds in TRUS images, and for then performing a registration between the seeds in the fluoroscopic and TRUS images. In this manner, it should be possible to find the relative locations of seeds within the prostate boundary to evaluate dosage parameters. Furthermore, it would be preferable to automatically detect the seeds in fluoroscopic images, either manually or automatically detect the locations of at least some of the seeds in the TRUS images, and then automatically perform the registration between the two types of images using the seed location data from each. A medical practitioner should then be able to intraoperatively determine if more seeds need to be implanted and implant the additional seeds where needed.
In consideration of the preceding discussion, a method has been developed for performing a prostate brachytherapy procedure on a patient, in which radioactive seeds are implanted at a treatment site in the patient, and enabling intraoperative determination of a dosage parameter for implanted seeds during the brachytherapy procedure. After implanting a plurality of radioactive seeds at the treatment site, X-ray data are acquired that identify locations of a majority (typically all) of the implanted seeds. In addition, ultrasound data are collected that identify a location of the prostate, as well as the locations of each of only a minority of the implanted seeds relative to the prostate. It should be noted, that the minority of implanted seeds and their locations relative to the prostate are identified without solely relying on cross-sectional images of the seeds. Indeed, the seeds are more evident in longitudinal ultrasound images of the treatment site. Next, the method registers the X-ray data with the ultrasound data to determine the locations of the majority of the implanted seeds relative to the prostate. The registration of the seeds in the two different types of images enables a dosage parameter for the implanted seeds to be determined, based on the locations of the majority of the seeds relative to the prostate.
The longitudinal ultrasound images are along an axis that is generally aligned with a longitudinal axis of each implanted seed. The step of identifying the minority of seeds can be done automatically, as follows. Bright structures in the longitudinal ultrasound images are readily identified because they have a reflected ultrasound power level that is substantially greater than a background ultrasound power level. The structures thus appear as bright objects in the longitudinal images. The method then identifies any of the bright objects identified in the longitudinal ultrasound images that correspond to line structures and detects each of the line structures that includes an adjacent mirror structure reflection. The presence of an adjacent mirror structure reflection is an indication that the line structure is an implanted seed.
The step of acquiring the ultrasound data can include the step of rectally inserting an ultrasound probe to enable transrectal ultrasound (TRUS) image data of the treatment site to be collected in orthogonally different orientations. Alternatively, a 3-D rectally inserted probe can be employed to produce volumetric ultrasound data that correspond to both axial and longitudinal images of the prostate. As a further alternative, an ultrasound probe can be inserted through a patient's urethra to enable transurethral ultrasound images to be collected in orthogonally different orientations.
The step of acquiring X-ray data includes the step of collecting a plurality of fluoroscopic images of the treatment site at different angular orientations, after the seeds have been implanted, so that spatial locations of the seeds can be determined. This step can be implemented automatically or manually.
The step of determining a dosage parameter for the implanted seeds can include the step of determining isodose contours for the implanted seeds relative to the prostate. In an exemplary embodiment, the method further includes the step of displaying the isodose contours of the implanted seeds in relation to the prostate. A medical practitioner viewing the isodose contours can then intraoperatively determine whether additional seeds should be implanted and if so, where the additional seeds should be implanted during the procedure to achieve a desired radiation dosage effect on the prostate.
The step of registering the X-ray data with the ultrasound data can include the step of iteratively performing an optimization loop that transforms the X-ray data and correlates the resulting transformed X-ray data with the ultrasound data. The step of iteratively performing the optimization loop can include the steps of performing a rigid body transformation of the X-ray data based on a current pose parameter set, thereby producing the transformed X-ray data, and computing an optimal assignment of the transformed X-ray data to the ultrasound data. Until a solution to the optimal assignment converges, the method repetitively adjusts the current pose parameter set and carries out the steps of performing the rigid body transformation, and computing the optimal assignment.
The step of registering the X-ray data with the ultrasound data further can include the steps of recording the solution that has converged and the associated costs of the solution. Until the optimization loop has been entered a predefined maximum number of times that is greater than a predefined maximum number of iterations, a new pose parameter set is sampled for use as the current pose parameter set. The optimization loop is then reentered with the new pose parameter set, which now comprises the current pose parameter set. The steps comprising the optimization loop are then repeated until the solution again converges. A current solution that has converged is recorded, along with a current associated cost of said solution. The iterative process is finally concluded, returning the current solution and the current associated cost, after the optimization loop has been entered more times than the predefined maximum number of iterations.
Another aspect of this novel approach is directed to an exemplary system for performing a prostate brachytherapy procedure on a patient. The system includes an ultrasound system having a probe configured to produce ultrasound data corresponding to volumetric images or both axial and longitudinal ultrasound images of the treatment site. The longitudinal images are generally aligned with a longitudinal axis of seeds that have been implanted, and the axial images are generally transverse to the longitudinal axis of the seeds. The ultrasound data can be evaluated to indicate a location of only a minority of the seeds that have been implanted relative to the prostate of the patient.
Also included in the system is a fluoroscope that is configured for producing X-ray data for the treatment site, indicating a majority of the seeds that have been implanted. A computing device is provided for processing the ultrasound data and the X-ray data and carrying out a plurality of functions. These functions are generally consistent with the steps of the method described above.
This Summary has been provided to introduce a few concepts in a simplified form that are further described in detail below in the Description. However, this Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
Various aspects and attendant advantages of one or more exemplary embodiments and modifications thereto will become more readily appreciated as the same becomes better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:
Exemplary embodiments are illustrated in referenced Figures of the drawings. It is intended that the embodiments and Figures disclosed herein are to be considered illustrative rather than restrictive. No limitation on the scope of the technology and of the claims that follow is to be imputed to the examples shown in the drawings and discussed herein.
In one embodiment, a Hitachi Corporation HI VISION 5500™ ultrasound machine (not shown in this Figure) and a U-533™ biplanar TRUS probe were used with a Civco EXII™ stepper drive. The fluoroscopic images were produced by an Elektra SLS-14™ fluoroscope. The biplanar TRUS probe that was used includes both a longitudinal transducer and an axial transducer, so that orthogonal views of the prostate can be produced. The data acquisition procedure positions the biplanar TRUS probe within the patient using the stepper driver and produces data corresponding to the axial and rotational angular position of the TRUS probe provided from a position encoder on the stepper drive, thus providing geometrical information for all acquired ultrasound images, with respect to a reference coordinate system.
Using the longitudinal transducer of the TRUS probe, a first set of images are acquired by rotating the longitudinal ultrasound transducer in either a clockwise or counterclockwise direction about its longitudinal axis, while the corresponding angle and depth information provided by the position encoder are recorded. This first set of images are referred to herein, as “rotational images.” Rotational images can be acquired at 1° angular increments (or at other angular increments, as desired). By using the axial transducer of the TRUS probe, a second set of images can be captured at 1 mm increments along the longitudinal axis, using the stepper driver to move the ultrasound axial transducer in the craniocaudal direction. The corresponding depth and angle information provided by the position encoder of the stepper drive is recorded for these two sets of images. The images in the second set of images are referred to herein as “axial images.”
In conventional prostate brachytherapy, only the axial ultrasound images are typically used, and generally, no attempt is made to identify seeds in these ultrasound images. In axial images, the seeds would be imaged in transverse cross-section and thus, are barely visible as dots—unless fiducial markers are used. In contrast, the rotational (or other longitudinal) images produced by the longitudinal transducer in the biplanar TRUS probe enable a subset (e.g., 20%) of the total number of seeds implanted to be detected. While the seeds are more visible in their longitudinal aspect than in their cross-sectional aspect, noise, other artifacts, and poor visibility of the seeds in the ultrasound rotational or other longitudinal images make detection difficult. The detection of the minority of the total seeds comprising this subset can be done either manually or automatically, as explained below.
It will be evident that the cross-sectional aspect of a seed 88 in the axial images is much less evident than the longitudinal aspect of the seed in the rotational or other types of longitudinal images. However, as will be evident in an exemplary rotational TRUS image 100 of the prostate shown in
A step 122 provides for collecting X-ray data, for example using a fluoroscope, which indicates the 3-D locations of seeds in space—but not in relation to the prostate. Since the fluoroscopic images do not show the prostate or even its outline, the location of the seeds within these fluoroscopic images alone cannot be related to their position within the prostate, and the dosage parameters for the prostate cannot be determined solely from the fluoroscopic images. Multiple fluoroscopic images are acquired (e.g., −15°, 0° and +15° degrees in case of three) by rotating the gantry of the X-ray fluoroscopy machine about an isocenter (which is in general not a requirement). It may be desirable to collect more or fewer fluoroscopic images at other rotational positions about this axis. An exemplary, well known, seed reconstruction algorithm, which can be used to determine the locations of the implanted seeds, assumes an isocentric imaging geometry, but other techniques can be employed that do not impose this constraint.
In contrast to step 122, a step 124 provides for collecting ultrasound longitudinal (e.g., rotational, coronal, or sagittal images) for the region of the prostate. These TRUS images include sufficient information to enable the locations of a subset (i.e., a minority) of the total number of seeds implanted to be determined. However, the seeds are not all visible in the longitudinal TRUS images, although, it is typically possible to identify the locations of at least 20% of the total number of implanted seeds. Details of an exemplary procedure for identifying the locations of the seeds comprising this subset are discussed below. The axial TRUS image data show seeds only as dots, but provide a clear indication of the limits of the prostate that is geometrically related to the subset of seeds determined from the rotational or other type of longitudinal ultrasound data.
A step 126 then performs a registration between the fluoroscopic or x-ray set of seed locations, referred to as the “N-point model set,” and the TRUS set of seed locations, referred to as the “M-point data set.” An exemplary registration algorithm that is used for this step is referred to as an iterative optimal assignment (IOA) algorithm. The IOA first establishes a one-to-one correspondence between the model set and data set and then computes the sum of error distances between the matching seeds. Further details of the IOA algorithm are discussed below, in connection with
Once the registration between the two sets of ultrasound and X-ray data has been achieved in step 126, a step 128 calculates the dosimetry based on seed emission factors and seed locations in the prostate defined as a result of registration of the two types of data. Each type of seed that is used for prostate brachytherapy has a characteristic radiation emission that can be used in evaluating the dosage on the prostate, relative to the location of the seeds in the prostate, their density, and other spatial characteristics. Accordingly, this step provides data that indicates the effectiveness of the seeds that have been implanted in achieving the desired radiation therapy of the prostate. Optionally (but likely to be employed in each instance), a step 130 provides for displaying isodose contours on the prostate image to enable a medical practitioner to more readily determine whether additional seeds should be implanted and if so, where the additional seeds should be placed to achieve optimal therapy of the prostate.
In step 148, a signal of 16-pixel length is synthesized by:
s(n)=−(sin(0.15 πn)+sin(0.3 πn)) (1)
and an image pattern is created by this signal. Every vertical line in the pattern is a linear mapping from s(n) to a range from 0 to 255, and the pattern is 30 pixels wide.
Because the image signal is too short for spectrum analysis, it is necessary to extend a 2-D image pattern 240 having lines 242, 244, and 246 to a 1-D signal 248, as shown in
Only a structure with high local contrast is considered as a seed. While other techniques might be used for carrying out spectrum analysis of the 1-D signal produced by extending the 2-D image patterns, experiments have shown that the multiples signal classification (MUSIC) algorithm provides good results for detecting seeds in TRUS images, as indicated in a step 148 of
In these preceding steps, each vertical line in the TRUS image is treated as a scan line of the ultrasound beam. The smooth seed surface should produce a specular reflection of the ultrasound beam, so the power at the seed is relatively great compared to the background power. In step 144 of
In clinical TRUS images, the non-seed structures (calcification and/or air bubbles) in the prostate may appear as a bright line structure similar to that of seeds. A non-seed structure can be distinguished from a seed not by its own appearance, but because a seed has a mirror structure above it that does not exist in a calcification and/or air bubble trapped along a needle track. In TRUS images, a seed appears to have a mirror above it that is caused by the specular reflection between the two smooth surfaces of the seed. A non-seed structure does not exhibit this characteristic, because its surface is rough, and no specular reflection happens on the rough surface. Accordingly, if two peaks on a line are close to each other and the one nearer to the transducer has a higher value, this peak is selected as identifying a seed position, because the other peak is caused by the mirror effect of the seed.
In a step 150 of
An exemplary approach used in connection with the present novel technology uses IOA to achieve registration between the model set (i.e., the locations of all of the implanted seeds as determined from the fluoroscopic images), and the data set (the locations of the subset of implanted seeds determined by analysis of the TRUS images). IOA is similar to a prior art approach called “iterative closest point” (ICP) in the sense that transformation parameters and a correspondence matrix are used to refine each other in each iteration. However, recognizing the weakness of the nearest-neighbor approach, correspondence establishment is formulated as an optimal assignment problem that is solved with the Hungarian method. Thus, for a given set of seed pose parameters, a one-to-one correspondence with a minimum associated cost is established. Then, IOA searches iteratively through the parameter space to find the pose parameters that provide the best alignment between the data set and model set.
The following describes the IOA algorithm implemented using the Hungarian method. An assignment A is a one-to-one mapping from K to L. Since |K|≦|L|, for each kεK, there exists a match lεL, where I=a(k). Let q(k, l) be the cost of associating kεK with IεL, then the cost of an assignment A is given as:
The optimal assignment problem involves minimizing q(A) over all assignments under the assumption that |K|=|L|. If |K|≦|L|, |L|−|K| dummy elements should be added to the data set such that the cost of associating the newly added elements with every lεL is zero. Let Q be an |L|×|L| matrix with elements q(k, l) after augmenting K with dummy elements as described above. In this setting, the optimal assignment is reduced to minimizing the sum of |L| elements chosen from Q such that no two chosen elements are on the same column or row. A brute-force algorithm can solve this problem by computing the cost of all |L|! possible assignments and finding the minimum. However, this approach has an exorbitantly large computational cost.
The algorithm known as the Hungarian method, which was proposed by Kuhn based on the early works of two Hungarian mathematicians, Egervary and Konig, and later modified by Munkres, can solve the optimal assignment problem with O(|K|2|L|) run-time complexity. Since the Hungarian method is well known in the art, it is unnecessary to describe it in detail herein. Knuth's implementation was used in an exemplary embodiment.
Using the terminology introduced above, the registration problem can be rephrased as follows. Find a set of transformation parameters, ξ, such that after applying the corresponding transformation on the model set, the total cost of the resulting optimal assignment between the data and model sets is minimal.
Typically, a transformation is applied on the data set. However, to perform dosimetry, it is necessary to superimpose the seeds that have been reconstructed from fluoroscopic images on the axial TRUS images. Therefore, in the present case, the model set is transformed while the data set is kept stationary. Let (x, y, z) be the data reference frame and (x′, y′, z′) be the model reference frame. The optimum pose parameters can be found by minimizing the following criterion function:
where F (ξ) is given as the transformation matrix. In the case of rigid-body registration, the pose parameter set consists of six parameters, xo, yo, zo for translation and κ, φ, ω for rotation. Then, the transformation matrix is given as:
IOA attempts to find the set of optimum pose parameters ξ* in Eq. (3) based on the flowchart shown in
Exemplary logical steps 160 of the IOA procedure are illustrated in
The present approach for determining dosage parameters while a patient is undergoing prostate brachytherapy to enable additional seeds to be implanted has been implemented during tests conducted on 25 consecutive patients. These 25 unselected patients with American Joint Commission on Cancer clinical state T1c-T2 prostate cancer were treated with Pd-103 seed implantation, and the dosimetry was evaluated using the real-time postimplant fusion of TRUS and fluoroscopically derived isodoses, to enable intraoperative corrections to maximize dosimetric parameters that were achieved. The isodose data were determined based on using the procedure described above.
In nine of the patients, no seeds were added after the intraoperative dose evaluation. Their average intraoperative V100s and D90s were 99±1.5% and 176±23%. In 16 patients, an average of 4±1.8 additional seeds was added, based on the initial intraoperative evaluation. The initial intraoperative V100 and D90s were 86±8% and 94±18%, respectively. The corrected intraoperative V100 and D90s were 93±4% and 109±12%, respectively. The average improvement in the V100 and D90 parameters was 7.0% (p=0.005) and 8% (p=0.011), respectively. The V200s and V300s were minimally affected.
Imaging System for Prostate Brachytherapy with Intraoperative Dosimetry
A combined ultrasound and fluoroscopic imaging system 400 for providing prostate brachytherapy with intraoperative dosimetry, as described above, is illustrated in
Also included in system 400 is a conventional fluoroscope 408 that uses X-rays to image the prostate region to provide images showing the disposition of all implanted seeds. Output signals from ultrasound signal source and processor 404 and from fluoroscope 408 are input to a controller 450, which may be a computing device—either hardwired or programmed, such as a personal computer (PC). This controller also controls the fluoroscope and ultrasound system, as well as ultrasound probe positioner 406, so that ultrasound probe 402 collects the desired ultrasound images in which the prostate and disposition of each of a subset of the implanted seeds are indicated, and the fluoroscope collects the images in which the disposition of all of the implanted seeds is indicated. Controller 450 processes both of these types of images to produce the model set and data set discussed above, and then determines the registration between the two types of images so that dosage parameters can be determined intraoperatively. The medical practitioner can provide text or make selections with one or more user input devices 410. The images of the prostate region, as well as isodose contours relative to axial views of the prostate can be displayed on a display 412, enabling the medical practitioner to intraoperatively assess whether additional seeds should be implanted and where they should be implanted to achieve an optimal treatment of the prostate, as explained above.
The user employs computer 464 to process the images produced by the fluoroscopic system and the ultrasound probe. Processor 462 executes the machine instructions stored in memory 466. These machine instructions cause the processor to determine the model set and the data set from the fluoroscopic images and TRUS images, respectively, and then based upon the registration of these sets, determines dosage parameters and/or isodose contours that can be viewed on display 468. The results can be stored on storage 460, or on a separate storage—not shown in
Although the concepts disclosed herein have been described in connection with the preferred form of practicing them and modifications thereto, those of ordinary skill in the art will understand that many other modifications can be made thereto within the scope of the claims that follow. Accordingly, it is not intended that the scope of these concepts in any way be limited by the above description, but instead be determined entirely by reference to the claims that follow.
This application is based on a prior copending provisional application Ser. No. 60/912,371, filed on Apr. 17, 2007, the benefit of the filing date of which is hereby claimed under 35 U.S.C. § 119(e).
This invention was made with government support under Contract No. DAMD 17-03-1-0033 awarded by the Department of Defense (DOD). The government has certain rights in the invention.
Number | Date | Country | |
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60912371 | Apr 2007 | US |