The pattern of prostate cancer local recurrence after radiation and salvage cryoablation.

OBJECTIVE: We assessed the pattern of local recurrence after salvage cryoablation of the prostate, and the impact of local recurrence on intermediate-term outcome. METHODS: One hundred twenty-two patients who underwent salvage cryoablation were studied after a mean follow-up of 56 months. Serial prostate biopsy was carried out after cryoablation. The histopathology of prostate biopsies before and after cryoablation were compared. The prognostic value of post-cryoablation biopsy was assessed with the Cox regression method. RESULTS: 23.1% of patients had a positive biopsy for prostate cancer following salvage cryoablation. Most cancer recurrences occurred in the apex (51.5%), base (21.2%) and seminal vesicles (18.2%). The presence of cancer at the base of the prostate was found to be a prognostic factor for eventual biochemical failure. Overall 5-year biochemical disease-free survival (bDFS) was 28%, however patients with cancer at the base of the prostate had a 5-year bDFS of 0%. CONCLUSION: Cancer recurrences occurred in areas where aggressive freezing was avoided as it might result in serious problems (e.g., urethro-rectal fistula and incontinence). Post-cryoablation biopsies and the location of persistent disease are of prognostic value.

Contemporary technique of intraoperative 3-dimensional ultrasonography-guided transperineal prostate cryotherapy.

Successful cryotherapy of the prostate for neoplasms relies on imaging to achieve good oncological outcomes with minimal complications. Traditional prostatic cryotherapy relies on 2-dimensional ultrasonography (2DUS) guidance, which often makes it difficult to track the passage of needles in an oblique plane. We describe our initial 3-dimensional ultrasonography (3DUS) system, and the subsequent improvements that have been made during the last 10 years. Our imaging system uses a Philips HDI 5000 ultrasonography unit, a standard PC, a Matrox Meteor II video frame grabber and 3DUS developed at Robarts Research Institute. For the cryotherapy we use ultrathin (17-gauge) IceRod needles. After image acquisition, preplanning is performed using the 3-dimensional (3D) software, and then the IceRod needles are inserted into the prostate. As the freezing process commences, continuous 3DUS images are taken and analyzed during the double freeze-thaw cycles to monitor the progress of the ice ball formation. Real-time intraoperative 3D imaging of the prostate during cryotherapy has allowed us to accurately preplan and then monitor the progression of ice ball formation, which represents a significant advantage over conventional 2DUS.

Fast prostate segmentation in 3D TRUS images based on continuity constraint using an autoregressive model.

In this article a new slice-based 3D prostate segmentation method based on a continuity constraint, implemented as an autoregressive (AR) model is described. In order to decrease the propagated segmentation error produced by the slice-based 3D segmentation method, a continuity constraint was imposed in the prostate segmentation algorithm. A 3D ultrasound image was segmented using the slice-based segmentation method. Then, a cross-sectional profile of the resulting contours was obtained by intersecting the 2D segmented contours with a coronal plane passing through the midpoint of the manually identified rotational axis, which is considered to be the approximate center of the prostate. On the coronal cross-sectional plane, these intersections form a set of radial lines directed from the center of the prostate. The lengths of these radial lines were smoothed using an AR model. Slice-based 3D segmentations were performed in the clockwise and in the anticlockwise directions, where clockwise and anticlockwise are defined with respect to the propagation directions on the coronal view. This resulted in two different segmentations for each 2D slice. For each pair of unmatched segments, in which the distance between the contour generated clockwise and that generated anticlockwise was greater than 4 mm, a method was used to select the optimal contour. Experiments performed using 3D prostate ultrasound images of nine patients demonstrated that the proposed method produced accurate 3D prostate boundaries without manual editing. The average distance between the proposed method and manual segmentation was 1.29 mm. The average intraobserver coefficient of variation (i.e., the standard deviation divided by the average volume) of the boundaries segmented by the proposed method was 1.6%. The average segmentation time of a 352 x 379 x 704 image on a Pentium IV 2.8 GHz PC was 10 s.

Salvage cryoablation of the prostate: followup and analysis of predictive factors for outcome.

PURPOSE: We assessed the efficacy of cryoablation of the prostate with an emphasis on finding predictive factors that lead to improved outcome. MATERIALS AND METHODS: A total of 187 patients with locally recurrent prostate cancer after radiotherapy underwent salvage cryoablation of the prostate, and were studied after a mean followup of 39 months. Survival analysis was performed with the Kaplan-Meier method. Several variables were tested for predictive value using the Cox regression model including serum prostate specific antigen before radiotherapy, serum prostate specific antigen at cryoablation, clinical stage before radiotherapy, Gleason score before radiotherapy, Gleason score at cryoablation, number of positive biopsy cores and use of neoadjuvant hormonal therapy before cryoablation. RESULTS: Serum prostate specific antigen at cryoablation was a predictive factor for biochemical recurrence on univariate and multivariate analysis (p <0.001). Patients with pre-cryoablation prostate specific antigen less than 4 ng/ml had a 5 and 8-year biochemical recurrence-free survival of 56% and 37%, respectively. In contrast, patients with pre-cryoablation prostate specific antigen 10 ng/ml or greater had a 5 and 8-year biochemical recurrence-free survival of only 1% and 7%, respectively. Patients with pre-cryoablation prostate specific antigen from 4 to 9.99 ng/ml had intermediate survival outcomes. Of the patients 32% were started on hormonal therapy for disease progression at a mean of 31 months postoperatively. Overall 5 and 8-year survival was 97% and 92%, respectively. CONCLUSIONS: Salvage cryoablation is a viable treatment option for patients with prostate cancer in whom radiation therapy has failed. Salvage cryoablation should be performed when serum prostate specific antigen is still relatively low because in these patients the procedure may potentially be curative. Even when cryoablation fails to eradicate the disease in some patients, it allows hormonal therapy to be deferred for a significant period of time in that cohort.

Needle and seed segmentation in intra-operative 3D ultrasound-guided prostate brachytherapy.

In order to guide the needle to the correct location in 3D US-guided brachytherapy, the needle is continuously tracked as it is being inserted. A pre-scan before the needle insertion and a post-scan after the needle insertion are subtracted to obtain a difference image containing the needle. The image is projected along two orthogonal directions approximately perpendicular to the needle, and the 3D needle is reconstructed from the segmented needles in the two projected images. The seeds implanted with the needle are located in the cropped volume along the needle. Thus, the seeds are segmented using a tri-bar model and 3D line segment patterns. Finally, the positions of the seeds are determined using a peak detection technique. Experiments with agar and turkey/chicken phantoms as well as patient data demonstrated that our needle segmentation technique could segment the needle in near real-time with an accuracy of 0.6 mm in position and 1.0 degrees in orientation. The true-positive rate for seed segmentation is 100% for the agar phantom and 93% for the chicken phantom. The average distance to manual seed segmentation was 1.0mm for the agar phantom and 1.7 mm for the chicken phantom.

Automated localization of implanted seeds in 3D TRUS images used for prostate brachytherapy.

An algorithm has been developed in this paper to localize implanted radioactive seeds in 3D ultrasound images for a dynamic intraoperative brachytherapy procedure. Segmentation of the seeds is difficult, due to their small size in relatively low quality of transrectal ultrasound (TRUS) images. In this paper, intraoperative seed segmentation in 3D TRUS images is achieved by performing a subtraction of the image before the needle has been inserted, and the image after the seeds have been implanted. The seeds are searched in a "local" space determined by the needle position and orientation information, which are obtained from a needle segmentation algorithm. To test this approach, 3D TRUS images of the agar and chicken tissue phantoms were obtained. Within these phantoms, dummy seeds were implanted. The seed locations determined by the seed segmentation algorithm were compared with those obtained from a volumetric cone-beam flat-panel micro-CT scanner and human observers. Evaluation of the algorithm showed that the rms error in determining the seed locations using the seed segmentation algorithm was 0.98 mm in agar phantoms and 1.02 mm in chicken phantoms.

Prostate boundary segmentation from ultrasound images using 2D active shape models: optimisation and extension to 3D.

Boundary outlining, or segmentation, of the prostate is an important task in diagnosis and treatment planning for prostate cancer. This paper describes an algorithm based on two-dimensional (2D) active shape models (ASM) for semi-automatic segmentation of the prostate boundary from ultrasound images. Optimisation of the 2D ASM for prostatic ultrasound was done first by examining ASM construction and image search parameters. Extension of the algorithm to three-dimensional (3D) segmentation was then done using rotational-based slicing. Evaluation of the 3D segmentation algorithm used distance- and volume-based error metrics to compare algorithm generated boundary outlines to gold standard (manually generated) boundary outlines. Minimum description length landmark placement for ASM construction, and specific values for constraints and image search were found to be optimal. Evaluation of the algorithm versus gold standard boundaries found an average mean absolute distance of 1.09+/-0.49 mm, an average percent absolute volume difference of 3.28+/-3.16%, and a 5x speed increase versus manual segmentation.

High-frequency ultrasound: a useful tool for evaluating the abdominal wall following free TRAM and DIEP flap surgery.

BACKGROUND: This is the first study to use a standardized ultrasound protocol to evaluate hernia and abdominal wall laxity following free transverse rectus abdominis myocutaneous (TRAM) and deep inferior epigastric perforator (DIEP) flap surgery. METHODS: All patients who underwent free TRAM and DIEP flap surgery performed by the senior author between the years 1994 and 2003 were recruited for physical examination and ultrasound of the abdominal wall for the dynamic evaluation of hernia and abdominal wall laxity. RESULTS: A total of 25 of 28 patients were followed up (89 percent). Eleven were in the DIEP flap group (44 percent) and 14 were in the free TRAM flap group (56 percent). Age- and body habitus-matched female volunteers (n = 12) were also used in this study. The mean follow-up was 3.8 years (range, 0.8 to 8.2 years). Although the kappa coefficient was +1 for detection of hernia on physical examination between two independent examiners, the interobserver correlation was poor for detection of bulges (kappa coefficient, +0.53). Ultrasound showed that abdominal wall laxity was statistically highest in the upright position, followed by 30 degrees of truncal flexion, and lowest in the supine position. The amount of abdominal wall laxity detected by ultrasound was significantly higher in the free TRAM flap group than in the free DIEP flap group. Two hernias were detected in the TRAM flap group by ultrasound and one hernia was previously known in the DIEP flap group. CONCLUSION: This is the first study to establish a standardized ultrasound protocol as an adjunct diagnostic tool to clinical examination for the dynamic evaluation of postoperative hernia and abdominal wall laxity.

Oblique needle segmentation and tracking for 3D TRUS guided prostate brachytherapy.

An algorithm was developed in order to segment and track brachytherapy needles inserted along oblique trajectories. Three-dimensional (3D) transrectal ultrasound (TRUS) images of the rigid rod simulating the needle inserted into the tissue-mimicking agar and chicken breast phantoms were obtained to test the accuracy of the algorithm under ideal conditions. Because the robot possesses high positioning and angulation accuracies, we used the robot as a "gold standard," and compared the results of algorithm segmentation to the values measured by the robot. Our testing results showed that the accuracy of the needle segmentation algorithm depends on the needle insertion distance into the 3D TRUS image and the angulations with respect to the TRUS transducer, e.g., at a 10 degrees insertion anglulation in agar phantoms, the error of the algorithm in determining the needle tip position was less than 1 mm when the insertion distance was greater than 15 mm. Near real-time needle tracking was achieved by scanning a small volume containing the needle. Our tests also showed that, the segmentation time was less than 60 ms, and the scanning time was less than 1.2 s, when the insertion distance into the 3D TRUS image was less than 55 mm. In our needle tracking tests in chicken breast phantoms, the errors in determining the needle orientation were less than 2 degrees in robot yaw and 0.7 degrees in robot pitch orientations, for up to 20 degrees needle insertion angles with the TRUS transducer in the horizontal plane when the needle insertion distance was greater than 15 mm.

A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model.

Prostate cancer is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered mouse models, because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited because autopsy was the only reliable method to evaluate treatment efficacy in longitudinal studies. This article reports the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94-amino acid prostate secretory protein gene-directed transgenic prostate cancer model. Qualitative comparisons of three-dimensional ultrasound images with serial histology sections of prostate tumors show the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. Ultrasound imaging identified tumors ranging from 2.4 to 14 mm maximum diameter. The correlation coefficient of tumor diameter measurements done in vivo with three-dimensional ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both >90% when diagnoses were based on repeated ultrasound examinations done on separate days. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated volume doubling times of 5 and 13 days for two prostate tumors. Compared with other microimaging and molecular imaging modalities, the application of three-dimensional ultrasound imaging to prostate cancer in mice showed advantages, such as high spatial resolution and contrast in soft tissue, fast and uncomplicated protocols, and portable and economical equipment that will likely enable ultrasound to become a new microimaging modality for mouse preclinical trial studies.

Brachytherapy needle deflection evaluation and correction.

In prostate brachytherapy, an 18-gauge needle is used to implant radioactive seeds. This thin needle can be deflected from the preplanned trajectory in the prostate, potentially resulting in a suboptimum dose pattern and at times requiring repeated needle insertion to achieve optimal dosimetry. In this paper, we report on the evaluation of brachytherapy needle deflection and bending in test phantoms and two approaches to overcome the problem. First we tested the relationship between needle deflection and insertion depth as well as whether needle bending occurred. Targeting accuracy was tested by inserting a brachytherapy needle to target 16 points in chicken tissue phantoms. By implanting dummy seeds into chicken tissue phantoms under 3D ultrasound guidance, the overall accuracy of seed implantation was determined. We evaluated methods to overcome brachytherapy needle deflection with three different insertion methods: constant orientation, constant rotation, and orientation reversal at half of the insertion depth. Our results showed that needle deflection is linear with needle insertion depth, and that no noticeable bending occurs with needle insertion into the tissue and agar phantoms. A 3D principal component analysis was performed to obtain the population distribution of needle tip and seed position relative to the target positions. Our results showed that with the constant orientation insertion method, the mean needle targeting error was 2.8 mm and the mean seed implantation error was 2.9 mm. Using the constant rotation and orientation reversal at half insertion depth methods, the deflection error was reduced. The mean needle targeting errors were 0.8 and 1.2 mm for the constant rotation and orientation reversal methods, respectively, and the seed implantation errors were 0.9 and 1.5 mm for constant rotation insertion and orientation reversal methods, respectively.

3D ultrasound imaging of the carotid arteries.

Although ultrasonography is an important cost-effective imaging modality, technical improvements are needed before its full potential is realized for accurate and reproducible monitoring of carotid disease and plaque burden. 2D viewing of 3D anatomy, using conventional ultrasonography limits our ability to quantify and visualize carotid disease and is partly responsible for the reported variability in diagnosis and monitoring of disease progression. Efforts of investigators have focused on overcoming these deficiencies by developing 3D ultrasound imaging techniques that are capable of acquiring B-mode, color Doppler and power Doppler images of the carotid arteries using existing conventional ultrasound systems, reconstructing the information into 3D images, and then allowing interactive viewing of the 3D images on inexpensive desktop computers. In addition, the availability of 3D ultrasound images of the carotid arteries has allowed the development of techniques to quantify plaque volume and surface morphology as well as allowing registration with other 3D imaging modalities. This paper describes 3D ultrasound imaging techniques used to image the carotid arteries and summarizes some of the developments aimed at quantifying plaque volume and morphology.

Serial histopathology results of salvage cryoablation for prostate cancer after radiation failure.

PURPOSE: There has been a paucity of long-term followup reports of cryoablation for prostate cancer. In particular, little is known regarding the long-term histological results following salvage cryoablation. We report serial biopsy results of up to 43 months on 106 patients who underwent cryoablation after radical radiotherapy failed. MATERIALS AND METHODS: A total of 110 cryoablation procedures were done in 106 patients for biopsy proven, clinically localized radiation failure. Postoperatively transrectal ultrasound guided biopsy (usually 4 cores) was done at approximately 3, and/or 6, 12 and 24 months, and thereafter as indicated by prostate specific antigen, which was measured every 6 months. RESULTS: Of 818 biopsy cores a total of 23 (2.8%) from 15 patients (14.2%) were positive. Of the positive cores 73.9% were found within year 1 following cryoablation. Residual viable prostate glands and stroma were found in 42.4% and 27.4% of patients, respectively, at various time points. The frequency of various histological features, the most common being necrosis and fibrosis, was tabulated from the serial biopsy histology reports. CONCLUSIONS: The results of serial biopsies have improved our understanding of the histopathological changes as well as the capabilities and limitations of salvage cryoablation. The biopsy positivity rate is acceptable, although the finding of persistent viable prostatic tissue in a substantial proportion of patients implies that vigilant long-term followup is mandatory.

Three-dimensional ultrasound imaging and its use in quantifying organ and pathology volumes.

Although ultrasonography is an important cost-effective imaging modality, technical improvements are needed before its full potential is realized for accurate and reproducible monitoring of disease progression or regression. Two-dimensional viewing of three-dimensional anatomy, using conventional ultrasonography, limits our ability to quantify and visualize pathology and is partly responsible for the reported variability in diagnosis and monitoring of disease progression. Efforts of investigators have focused on overcoming these deficiencies by developing 3D ultrasound imaging techniques that are capable of acquiring B-mode images using existing conventional ultrasound systems, reconstructing the information into 3D images, and then allowing interactive viewing of the 3D images on inexpensive desktop computers. In addition, the availability of 3D ultrasound images has allowed the development of manual and semi-automated techniques to quantify normal and abnormal anatomical volumes. In this paper we review our semi-automated 3D segmentation approaches for segmenting the surface of the carotid arteries and plaques, and segmenting the prostate. These techniques demonstrate that efficient segmentation techniques can be used with 3D ultrasound images to quantify anatomical organ volumes and morphology.

Testing and optimization of a semiautomatic prostate boundary segmentation algorithm using virtual operators.

Image analysis tasks such as size measurement and landmark-based registration require the user to select control points in an image. The output of such algorithms depends on the choice of control points. Since the choice of points varies from one user to the next, the requirement for user input introduces variability into the output of the algorithm. In order to test and/or optimize such algorithms, it is necessary to assess the multiplicity of outputs generated by the algorithm in response to a large set of inputs; however, the input of data requires substantial time and effort from multiple users. In this paper we describe a method to automate the testing and optimization of algorithms using "virtual operators," which consist of a set of spatial distributions describing how actual users select control points in an image. In order to construct the virtual operator, multiple users must repeatedly select control points in the image on which testing is to be performed. Once virtual operators are generated, control points for initializing the algorithm can be generated from them using a random number generator. Although an initial investment of time is required from the users in order to construct the virtual operator, testing and optimization of the algorithm can be done without further user interaction. We illustrate the construction and use of virtual operators by testing and optimizing our prostate boundary segmentation algorithm. The algorithm requires the user to select four control points on the prostate as input.

Prostate boundary segmentation from 3D ultrasound images.

Segmenting, or outlining the prostate boundary is an important task in the management of patients with prostate cancer. In this paper, an algorithm is described for semiautomatic segmentation of the prostate from 3D ultrasound images. The algorithm uses model-based initialization and mesh refinement using an efficient deformable model. Initialization requires the user to select only six points from which the outline of the prostate is estimated using shape information. The estimated outline is then automatically deformed to better fit the prostate boundary. An editing tool allows the user to edit the boundary in problematic regions and then deform the model again to improve the final results. The algorithm requires less than 1 min on a Pentium III 400 MHz PC. The accuracy of the algorithm was assessed by comparing the algorithm results, obtained from both local and global analysis, to the manual segmentations on six prostates. The local difference was mapped on the surface of the algorithm boundary to produce a visual representation. Global error analysis showed that the average difference between manual and algorithm boundaries was -0.20 +/- 0.28 mm, the average absolute difference was 1.19 +/- 0.14 mm, the average maximum difference was 7.01 +/- 1.04 mm, and the average volume difference was 7.16% +/- 3.45%. Variability in manual and algorithm segmentation was also assessed: Visual representations of local variability were generated by mapping variability on the segmentation mesh. The mean variability in manual segmentation was 0.98 mm and in algorithm segmentation was 0.63 mm and the differences of about 51.5% of the points comprising the average algorithm boundary are insignificant (P < or = 0.01) to the manual average boundary.

Training module to teach ultrasound-guided breast biopsy skills to residents improves accuracy.

OBJECTIVE: To evaluate the effectiveness of a training module in teaching residents the skills necessary to perform accurate and safe ultrasound-guided breast biopsies (USGBB). METHODS: Twelve residents with no USGBB experience, but variable ultrasound (US) experience, were randomly assigned to 2 groups; 1 group participated in a training module, and the other received no training. Each resident then attempted 30 core biopsies of "lesions" implanted in breast phantoms. Successful biopsies extracted some "lesion" material. "Chest wall" hits were also counted. RESULTS: The trained residents had significantly fewer "chest wall" hits than the untrained group (p < 0.002), but there was no significant difference in the number of successful biopsies (73% v. 43%, p = 0.09). The subgroup of residents who were USGBB trained but inexperienced in US (n = 4) achieved more successful biopsies (p < 0.05) and fewer "chest wall" hits (p < 0.01) than their matched untrained cohort (n = 3). The trained US-experienced subgroup (n = 2) had fewer "chest wall" hits than the matched untrained subgroup (n = 3; p < 0.05) but similar biopsy success rates. Untrained US-experienced residents (n = 3) had more successful biopsies than untrained US-inexperienced residents (n = 3; p < 0.001) and similar "chest wall" hits. CONCLUSION: Residents with training perform USGBBs more safely, and training significantly improves accuracy of USGBB in residents with no US experience. US experience improves biopsy success rates but does not affect safety levels of residents with no USGBB training.

Semiautomatic three-dimensional segmentation of the prostate using two-dimensional ultrasound images.

In this paper, we report on two methods for semiautomatic three-dimensional (3-D) prostate boundary segmentation using 2-D ultrasound images. For each method, a 3-D ultrasound prostate image was sliced into the series of contiguous 2-D images, either in a parallel manner, with a uniform slice spacing of 1 mm, or in a rotational manner, about an axis approximately through the center of the prostate, with a uniform angular spacing of 5 degrees. The segmentation process was initiated by manually placing four points on the boundary of a selected slice, from which an initial prostate boundary was determined. This initial boundary was refined using the Discrete Dynamic Contour until it fit the actual prostate boundary. The remaining slices were then segmented by iteratively propagating this result to an adjacent slice and repeating the refinement, pausing the process when necessary to manually edit the boundary. The two methods were tested with six 3-D prostate images. The results showed that the parallel and rotational methods had mean editing rates of 20% and 14%, and mean (mean absolute) volume errors of -5.4% (6.5%) and -1.7% (3.1%), respectively. Based on these results, as well as the relative difficulty in editing, we conclude that the rotational segmentation method is superior.

Comparison of core needle breast biopsy techniques: freehand versus three-dimensional US guidance.

RATIONALE AND OBJECTIVES: No single method is generally accepted for evaluating the accuracy of breast biopsy techniques before their clinical implementation. The purpose of this study was to test a new process for evaluating biopsy techniques by using it in the evaluation of a prototype three-dimensional ultrasound (US)-guided biopsy device. MATERIALS AND METHODS: The biopsy accuracy of a new three-dimensional US-guided breast biopsy device was compared to that of the accepted clinical practice of biopsy by expert radiologists with two-dimensional freehand US guidance. Biopsies were performed in chicken tissue phantoms containing 3.2-mm lesions made of poly(vinyl alcohol) cryogel. The criterion for a successful biopsy was the presence of lesion in the sample. The equivalence limit difference tested was 10% by using a power of 90% and a two-sided test significance level, a, of 10%. RESULTS: The biopsy success rate of the three-dimensional US-guided system (96%) was equivalent to that of expert radiologists using two-dimensional freehand US guidance (94.5%) in tissue phantoms containing poly(vinyl alcohol) cryogel lesions. CONCLUSION: This evaluation procedure is a valuable precursor to clinical trials in the assessment of biopsy techniques. The three-dimensional US-guided breast biopsy system provides a suitable alternative to two-dimensional freehand US guidance for biopsy of breast cancer.