Randomized trial comparing cryoablation and external beam radiotherapy for T2C-T3B prostate cancer.

The objective was to evaluate the relative efficacy of cryoablation (CRYO) versus external beam radiation (EBRT) for clinically locally advanced prostate cancer in a randomized clinical trial. Patients with histologically proven, clinically staged as T2C, T3A or T3B disease were randomized with 6 months of perioperative hormone therapy to one of the two procedures. Owing largely to a shift in practice to longer term adjuvant hormonal therapy and higher doses of radiation for T3 disease, only 64 out of the planned 150 patients were accrued. Twenty-one of 33 (64%) in the CRYO group and 14 of 31 (45%) in the EBRT-treated group who had met the ASTRO definition of failure were also classified as treatment failure. The mean biochemical disease-free survival (bDFS) was 41 months for the EBRT group compared to 28 months for the CRYO group. The 4-year bDFS for EBRT and CRYO groups were 47 and 13%, respectively. Disease-specific survival (DSS) and overall survival (OS) for both groups were very similar. Serious complications were uncommon in either group. EBRT patients exhibited gastrointestinal (GI) adverse effects more frequently. Taking into account the relative deficiency in numbers and the original trial design, this prospective randomized trial indicated that the results of CRYO were less favorable compared to those of EBRT, and was suboptimal primary therapy in locally advanced prostate cancer.

Stereotactic mammography imaging combined with 3D US imaging for image guided breast biopsy.

Stereotactic X-ray mammography (SM) and ultrasound (US) guidance are both commonly used for breast biopsy. While SM provides three-dimensional (3D) targeting information and US provides real-time guidance, both have limitations. SM is a long and uncomfortable procedure and the US guided procedure is inherently two dimensional (2D), requiring a skilled physician for both safety and accuracy. The authors developed a 3D US-guided biopsy system to be integrated with, and to supplement SM imaging. Their goal is to be able to biopsy a larger percentage of suspicious masses using US, by clarifying ambiguous structures with SM imaging. Features from SM and US guided biopsy were combined, including breast stabilization, a confined needle trajectory, and dual modality imaging. The 3D US guided biopsy system uses a 7.5 MHz breast probe and is mounted on an upright SM machine for preprocedural imaging. Intraprocedural targeting and guidance was achieved with real-time 2D and near real-time 3D US imaging. Postbiopsy 3D US imaging allowed for confirmation that the needle was penetrating the target. The authors evaluated 3D US-guided biopsy accuracy of their system using test phantoms. To use mammographic imaging information, they registered the SM and 3D US coordinate systems. The 3D positions of targets identified in the SM images were determined with a target localization error (TLE) of 0.49 mm. The z component (x-ray tube to image) of the TLE dominated with a TLEz of 0.47 mm. The SM system was then registered to 3D US, with a fiducial registration error (FRE) and target registration error (TRE) of 0.82 and 0.92 mm, respectively. Analysis of the FRE and TRE components showed that these errors were dominated by inaccuracies in the z component with a FREz of 0.76 mm and a TREz of 0.85 mm. A stereotactic mammography and 3D US guided breast biopsy system should include breast compression for stability and safety and dual modality imaging for target localization. The system will provide preprocedural x-ray mammography information in the form of SM imaging along with real-time US imaging for needle guidance to a target. 3D US imaging will also be available for targeting, guidance, and biopsy verification immediately postbiopsy.

3D ultrasound guided breast biopsy system.

Stereotactic X-ray mammography (SM) and ultrasound (US) guidance are commonly used techniques for breast biopsy. While SM provides 3D targeting information and US provides real-time guidance, both techniques have limitations. SM is a long and uncomfortable procedure and the US guided procedure is inherently 2D, requiring a skilled physician for both safety and accuracy. We have developed a 3D US-guided biopsy system to integrate with SM. The dual modality breast biopsy system combines the advantages of both approaches with 3D US and SM targeting, near real-time 3D and real-time 2D US guidance, breast stabilisation and a confined needle trajectory. Our goal is to be able to biopsy a larger percentage of suspicious masses using ultrasound, by clarifying ambiguous structures with mammographic imaging. Using breast phantoms, we have shown that our ultrasound guided biopsy system was capable of targeting artificial lesions that were 3.2 mm in diameter, with a 96% success rate. Through this study, we also demonstrated that our system was equivalent to current clinical practice, for an in vitro biopsy task. Metal beads in known relative positions allowed us to determine the geometry of the SM system, so that stereotactic mammography could be registered to 3D US images. The target registration error was found to be 1.6 mm. This error was dominated by positioning error in the vertical direction (perpendicular to the film surface). As an adjunct to SM, we propose that 3D US could provide more complete imaging information for target identification and real-time monitoring of needle insertion, as well as providing a means for rapid confirmation of biopsy success.

The development and evaluation of a three-dimensional ultrasound-guided breast biopsy apparatus.

We have designed a prototype three-dimensional ultrasound guidance (3D USB) apparatus to improve the breast biopsy procedure. Features from stereotactic mammography and free-hand US-guided biopsy have been combined with 3D US imaging. This breast biopsy apparatus accurately guides a needle into position for the sampling of target tissue. We have evaluated this apparatus in three stages. First, by testing the placement accuracy of a needle in a tissue mimicking phantom. Second, with tissue mimicking phantoms that had embedded lesions for biopsy. Finally, by comparison to free-hand US-guided biopsy, using chicken breast phantoms. The first two stages of evaluation quantified the mechanical biases in the 3D USB apparatus. Compensating for these, a 96% success rate in targeting 3.2 mm "lesions" in chicken breast phantoms was achieved when using the 3D USB apparatus. The expert radiologists performing biopsies with free-hand US guidance achieved a 94.5% success rate. This has proven an equivalence between our apparatus, operated by non-experts, and free-hand biopsy performed by expert radiologists, for 3.2 mm lesions in vitro, with a 95% confidence.

Three-dimensional ultrasound-guided core needle breast biopsy.

A new core needle breast biopsy system guided by 3-D ultrasound (US) is proposed. Our device provides rapid imaging and real-time guidance, as well as breast stabilization and a needle guidance apparatus using 3-D imaging. The targeting accuracy of our device was tested by inserting a 14-gauge biopsy needle into agar phantoms under 3-D US guidance. A total of 18 0.8-mm stainless-steel beads embedded in the phantoms defined each of the four target positions tested. Positioning accuracy was calculated by comparing needle tip position to the preinsertion bead position, as measured by three observers three times each on 3-D US. The interobserver standard error of measurement was no more than 0.14 mm for the beads and 0.27 mm for the needle tips. A 3-D principal component analysis was performed to obtain the population distribution of needle tip position relative to the target beads for the four target positions. The 3-D 95% confidence intervals were found to have total widths ranging from 0.43 to 1.71 mm, depending on direction and bead position.

Three-dimensional ultrasound imaging.

Ultrasound is an inexpensive and widely used imaging modality for the diagnosis and staging of a number of diseases. In the past two decades, it has benefited from major advances in technology and has become an indispensable imaging modality, due to its flexibility and non-invasive character. In the last decade, research investigators and commercial companies have further advanced ultrasound imaging with the development of 3D ultrasound. This new imaging approach is rapidly achieving widespread use with numerous applications. The major reason for the increase in the use of 3D ultrasound is related to the limitations of 2D viewing of 3D anatomy, using conventional ultrasound. This occurs because: (a) Conventional ultrasound images are 2D, yet the anatomy is 3D, hence the diagnostician must integrate multiple images in his mind. This practice is inefficient, and may lead to variability and incorrect diagnoses. (b) The 2D ultrasound image represents a thin plane at some arbitrary angle in the body. It is difficult to localize the image plane and reproduce it at a later time for follow-up studies. In this review article we describe how 3D ultrasound imaging overcomes these limitations. Specifically, we describe the developments of a number of 3D ultrasound imaging systems using mechanical, free-hand and 2D array scanning techniques. Reconstruction and viewing methods of the 3D images are described with specific examples. Since 3D ultrasound is used to quantify the volume of organs and pathology, the sources of errors in the reconstruction techniques as well as formulae relating design specification to geometric errors are provided. Finally, methods to measure organ volume from the 3D ultrasound images and sources of errors are described.

Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications.

PURPOSE: We conduct a critical evaluation of cryoablation of prostate cancer after failure of full dose radiotherapy to identify predictors of treatment failure and complications. MATERIALS AND METHODS: A total of 125 cryoablation procedures were performed in 118 patients with proved local recurrence after full dose radiotherapy. Followup includes serial prostate specific antigen (PSA) and biopsy at 6,12 and 24 months. Kaplan-Meier plots were constructed for different PSA cutoffs. We separately analyzed different cohorts based on T stage, Gleason score, PSA before cryoablation and endocrine therapy status. RESULTS: Of the 118 patients 114 had serum PSA nadir less than 0.5 ng./ml. Median followup was 18.6 months (range 3 to 54). Of the biopsy cores 3.1% (23 of 745) from 7 patients contained persistent viable cancer. Kaplan-Meier plots showed patients free of histological failure leveling at 87% and free from biochemical failure at 68%, 55% and 34%, respectively, with PSA greater than 4, 2 and 0.5 ng./ml. PSA greater than 10 ng./ml. before cryoablation, Gleason score 8 or greater before radiation and stage T3/T4 disease appeared to predict an unfavorable biochemical outcome. Serious complications included 4 rectourethral fistulas (3.3%) and severe incontinence (6.7%). Strong predictors of complications included bulky disease for fistulas and prior transurethral surgery. CONCLUSIONS: Salvage cryoablation after radiation can achieve reasonable biochemical and histological results with acceptable morbidity. Cryoablation appears to be a reasonable treatment option for this patient population with few viable therapeutic options, provided vigorous patient selection criteria are adhered to.

Prostate boundary segmentation from 2D ultrasound images.

Outlining, or segmenting, the prostate is a very important task in the assignment of appropriate therapy and dose for cancer treatment; however, manual outlining is tedious and time-consuming. In this paper, an algorithm is described for semiautomatic segmentation of the prostate from 2D ultrasound images. The algorithm uses model-based initialization and the efficient discrete dynamic contour. Initialization requires the user to select only four points from which the outline of the prostate is estimated using cubic interpolation functions and shape information. The estimated contour is then deformed automatically to better fit the image. The algorithm can easily segment a wide range of prostate images, and contour editing tools are included to handle more difficult cases. The performance of the algorithm with a single user was compared to manual outlining by a single expert observer. The average distance between semiautomatically and manually outlined boundaries was found to be less than 5 pixels (0.63 mm), and the accuracy and sensitivity to area measurements were both over 90%.

An algorithm for automatic needle localization in ultrasound-guided breast biopsies.

An algorithm was developed in order to reduce operator dependence in ultrasound-guided breast biopsy, by automatically locating the needle in the ultrasound image, and displaying its location on the image for the user. Ultrasound images of a typical breast biopsy needle inserted in a tissue-mimicking agar were obtained to test the algorithm. The resulting images were examined by a group of observers who recorded the values of the angle, intercept and tip coordinates of the needle in the image, and inter- and intra-observer variability studies were performed on the results. The results of the algorithm segmentation were compared to the values recorded by the observers, and physical measurements recorded at the time the images were acquired. The algorithm segmentation was precise enough to successfully (when considering angle and tip segmentation) target 90% of tumors of 4.5 mm in diameter situated at the center of the image.

Clinical utility of three-dimensional US.

Three-dimensional (3D) ultrasonography (US) is rapidly gaining popularity as it moves out of the research environment and into the clinical setting. This modality offers several distinct advantages over conventional US, including 3D image reconstruction with a single pass of the US beam, virtually unlimited viewing perspectives; accurate assessment of long-term effects of treatment; and more accurate, repeatable evaluation of anatomic structures and disease entities. In obstetric imaging, 3D US provides a novel perspective on the fetal anatomy, makes anomalies easier to recognize, facilitates maternal-fetal bonding, and helps families better understand fetal abnormalities. Three-dimensional pelvic US allows volume data sets to be acquired with both transvaginal and transabdominal probes. Viewing multiple 3D power Doppler US images in a fast cine loop has proved useful in angiographic applications. Three-dimensional prostate US can help make accurate volume assessments for dosimetry planning or for estimating prostate-specific antigen levels. In breast imaging, 3D US has the capacity to demonstrate lesion margins and topography, thereby helping differentiate benign from malignant masses. Three-dimensional US can also help determine the need for biopsy and help facilitate needle localization and guidance during biopsy. With recent advances in computer technology and display techniques, 3D US will likely play an increasingly important role in medicine.

Variability and accuracy of measurements of prostate brachytherapy seed position in vitro using three-dimensional ultrasound: an intra- and inter-observer study.

This paper is a step in investigating whether three-dimensional (3D) ultrasound can be used intraoperatively to replace Computed Tomography (CT) for localization of brachytherapy seeds. In order to quantify the accuracy and variability of seed localization without introducing effects due to tissues, we first report our results with test phantoms. An inter- and intra-observer study was performed to assess the variability of 2 3D ultrasound scan acquisition methods: Tilt 3D scanning and pull-back 3D scanning. Seven observers measured the positions of gold seed markers in an agar phantom twice in each of the three orthogonal image planes. An analysis of variance (ANOVA) was performed to determine the intra- and inter-observer standard errors of measurement (SEM) and the minimum detectable changes in marker position (deltap). Average intra- and inter-observer SEMs for the tilt scan 3D image were 0.36 and 0.40 mm, respectively. Measurements of the pull-back scan 3D image yielded average intra- and inter-observer SEM of 0.46 and 0.49 mm, respectively. A paired difference analysis showed that the lower SEM for the tilt 3D scan image were statistically significant at a significance level of alpha= 0.05. The accuracy of the US measurements was tested by determining marker coordinates from CT images of the phantom in a stereotactic head frame. CT coordinates were matched to the ultrasound (US) coordinates by means of an affine transform. Average matching errors in x, y, and z were 0.02, 0.10, and -0.02 mm, respectively.

Three-dimensional ultrasound imaging.

Two-dimensional viewing of three-dimensional anatomy by conventional ultrasound limits our ability to quantify and visualize a number of diseases and is partly responsible for the reported variability in diagnosis. Over the past two decades, many investigators have addressed this limitation by developing three-dimensional imaging techniques, including three-dimensional ultrasound imaging. In this paper we describe the development of a number of three-dimensional ultrasound imaging systems that make use of B mode, color Doppler, and power Doppler. In these systems, the conventional ultrasound transducer is scanned mechanically or by a freehand technique. The ultrasound images are digitized and then reconstructed into a three-dimensional volume, which can be viewed and manipulated interactively by the diagnostician with a variety of image-rendering techniques. These developments as well as future trends are discussed with regard to their applications and limitations.

Three-dimensional ultrasound and magnetic resonance imaging of pelvic anatomy: potential for complications from minimally invasive procedures.

OBJECTIVE: Several new minimally invasive therapies have recently been popularized for both malignant and benign prostate disorders, including interstitial implantation of radioactive seeds and high-radiofrequency wires, cryoablation, transurethral thermotherapy, and laser prostatectomy. Complications can be incurred during the various procedures, often as a result of injury to adjacent anatomic structures. Some of the complications are inadvertent, whereas others are inherent in the particular treatment process. We hope to increase awareness and understanding of some of the potential complications. METHODS AND MATERIALS: Magnetic resonance (MR) and three-dimensional transrectal ultrasonography (TRUS) imaging were utilized to illustrate the relevant pelvic anatomy in, respectively, a healthy volunteer and four patients undergoing evaluation for prostate symptoms. In addition, data from the Visible Human dataset (the Visible Human Project is part of the National Library of Medicine 1986 Long-Range Plan) were used. RESULTS: The potential complications relating to urinary sphincter and anal sphincter control, sexual function, pelvic musculature, and pelvic nerve physiology could be explained on the basis of the MR and TRUS findings using cryoablation for illustrative purposes. CONCLUSION: A clear understanding of the relevant anatomy and physiology is essential for the physician to provide patient counseling preoperatively regarding anticipated sequelae and to avoid preventable intraoperative complications related to minimally invasive therapeutic procedures for the prostate.

Perineal prostate cancer seeding along needle tract following cryosurgery.

We report a case of tumor seeding along the path of a cryoprobe during cryotherapy for prostate cancer. Seeding was reported as a potential problem in the era of transperineal biopsies, but we suspect that it may again resurface in modern minimally invasive surgical treatments that develop a transperineal tract. Minimizing prostate trauma and bleeding during minimally invasive therapies such as cryosurgery and brachytherapy may decrease the risk of tumor seeding. We believe that the perineum of all patients who have undergone transperineal procedures should be thoroughly checked during follow-up.

Three-dimensional transrectal ultrasound guided cryoablation for localized prostate cancer in nonsurgical candidates: a feasibility study and report of early results.

PURPOSE: A 3-dimensional (D) transrectal ultrasound imaging system was incorporated into the cryoablation routine for prostate cancer to assess its feasibility and use. The objective was to improve visibility for probe placement and for intraoperative monitoring. MATERIALS AND METHODS: A commercially available transrectal ultrasound unit was coupled with a custom designed software system to construct 3-dimensional prostate images. A total of 52 patients with clinically localized prostate cancer, in whom radiotherapy had failed (45) or who were otherwise judged to be nonsurgical candidates (7) were treated with cryoablation, using 3-D transrectal ultrasound for intraoperative guidance. RESULTS: In all cases the intraoperative 3-D transrectal ultrasound images provided a unique coronal view of the prostate, revealing useful information and facilitating more precise probe placement and treatment monitoring. Early postoperative histological and biochemical results and complication rates compare well with other contemporary series. CONCLUSIONS: Although the precise role of cryoablation in the management of prostate cancer remains unclear and long-term results are pending, incorporation of a 3-D transrectal ultrasound imaging system into the cryoablation routine proved to be feasible and appeared to be a worthwhile effort to facilitate the procedure, and deserves further evaluation.

Receiver operating characteristic (ROC) curve analysis of transrectal ultrasonographic prostate cancer detection.

PURPOSE: To provide an overview of receiver operating characteristics (ROC) curve theory and create an ROC curve describing transrectal ultrasound (TRUS) detection of prostate cancer (PCa). METHODS: One hundred thirty-two patients with either an abnormal digital rectal exam (DRE) or a prostate-specific antigen (PSA) above 4 ng/ml or both underwent TRUS and biopsy of the peripheral zone (PZ) of each quadrant. ROC software was used to create an ROC curve. RESULTS: One hundred seventy-nine of 528 quadrants (34%) harbored PCa. The performance of TRUS in detection of PCa as defined by the area below the ROC is 0,809. CONCLUSIONS: Future investigators are encouraged to employ ROC analysis of TRUS to permit more meaningful comparisons of performance.

Accuracy of prostate volume measurements in vitro using three-dimensional ultrasound.

RATIONALE AND OBJECTIVES: We assessed the ability of a three-dimensional (3D) ultrasound imaging system to measure accurately prostate volume. METHODS: Multiple two-dimensional ultrasound images of cadaver prostates scanned in a water bath were reconstructed into three-dimensional (3D) images. The volumes of the prostates were calculated from these 3D images and compared with the actual volumes. Multiple 3D ultrasound volume readings were evaluated for precision. RESULTS: The slope of the best-fit line correlating 3D ultrasound estimated volume and true volume was 1.006 +/- 0.007. The average error was 0.36 +/- 1.17 cm3; the coefficient of determination (r2), which is the measure of the straight-line relationship, was .9997; and the standard error was 1.15 cm3. CONCLUSION: Three-dimensional ultrasound images accurately reflect true prostate volumes measured in vitro.

Three-dimensional prostate ultrasound and its application to cryosurgery.

Transrectal ultrasound (TRUS), despite its undeniable utility in prostate imaging, employs a spatially flexible and variable 2-dimensional (2-D) imaging technique to visualize a 3-dimensional (3-D) disease process and anatomy. To circumvent some of the limitations of 2-D TRUS, 3-D TRUS was developed. The system consists of a motorized assembly (to hold a standard ultrasound transducer) and a computer with a video frame grabber. The microcomputer, using software developed in our laboratory, rapidly reconstructs a series of linear ultrasound images into a 3-D image. The 3-D TRUS technology has been incorporated into our program for cryoablation of the prostate. With intraoperative 3-D TRUS providing a unique coronal view, cryoprobe placement is facilitated to detect malalignment and avoid subsequent suboptimal cryoablation. In our use of 3-D TRUS guidance, in all 21 initial patients, probe malalignment, otherwise not apparent on standard 2-D TRUS, was detected and corrected before cryosurgery. With median follow-up of just < 1 year, only 2 of 44 biopsy cores (from the same site of 1 patient) were positive at 3 and 6 months. 3-D TRUS appears to be a valuable adjunctive tool in prostate imaging, especially in providing guidance for cryoblation of prostate cancer.

Three-dimensional ultrasound imaging of the eye.

We assessed whether an inexpensive, three-dimensional (3D) ultrasound (US) imaging system could produce clinically useful 3D images, without causing patient discomfort. Five patients were examined. The 3D US system consisted of a transducer holder containing a mechanical motor, and a microcomputer. During data acquisition the transducer was mechanically rotated for 22 seconds, while 200 two-dimensional (2D) US images were collected and formed into a 3D image by the computer. The 3D image was viewed on the computer monitor. The 3D images correlated with the clinical and radiological findings. The new perspectives were helpful in diagnosing eye abnormalities and no patient discomfort occurred. The device was easy to use. It is concluded that, as good-quality 3D and 2D US images were produced quickly, with no patient discomfort, and the device is inexpensive, uncomplicated, and easily attached to existing ultrasound machines, it will probably be useful in clinical practice.