Multiparametric Ultrasound for Targeting Prostate Cancer: Combining ARFI,SWEI, QUS and B-Mode

Diagnosing prostate cancer through standard transrectal ultrasound (TRUS)-guided biopsy is challenging because of the sensitivity and specificity limitations of B-mode imaging. We used a linear support vector machine (SVM) to combine standard TRUS imaging data with acoustic radiation force impulse (ARFI) imaging data, shear wave elasticity imaging (SWEI) data and quantitative ultrasound (QUS) midband fit data to enhance lesion contrast into a synthesized multiparametric ultrasound volume. This SVM was trained and validated using a subset of 20 patients and tested on a second subset of 10 patients. Multiparametric US led to a statistically significant improvements in contrast, contrast-to-noise ratio (CNR) and generalized CNR (gCNR) when compared with standard TRUS B-mode and SWEI; in contrast and CNR when compared with MF; and in CNR when compared with ARFI. ARFI, MF and SWEI also outperformed TRUS B-mode in contrast, with MF outperforming B-mode in CNR and gCNR as well. ARFI, although only yielding statistically significant differences in contrast compared with TRUS B-mode, captured critical qualitative features for lesion identification. Multiparametric US enhanced lesion visibility metrics and is a promising technique for targeted TRUS-guided prostate biopsy in the future.     

Learning Non-rigid Deformations for Robust,Constrained Point-based Registration in Image-Guided MR-TRUS Prostate Intervention

Accurate and robust non-rigid registration of pre-procedure magnetic resonance (MR) imaging to intra-procedure trans-rectal ultrasound (TRUS) is critical for image-guided biopsies of prostate cancer. Prostate cancer is one of the most prevalent forms of cancer and the second leading cause of cancer-related death in men in the United States. TRUS-guided biopsy is the current clinical standard for prostate cancer diagnosis and assessment. State-of-the-art, clinical MR-TRUS image fusion relies upon semi-automated segmentations of the prostate in both the MR and the TRUS images to perform non-rigid surface-based registration of the gland. Segmentation of the prostate in TRUS imaging is itself a challenging task and prone to high variability. These segmentation errors can lead to poor registration and subsequently poor localization of biopsy targets, which may result in false-negative cancer detection. In this paper, we present a non-rigid surface registration approach to MR-TRUS fusion based on a statistical deformation model (SDM) of intra-procedural deformations derived from clinical training data. Synthetic validation experiments quantifying registration volume of interest overlaps of the PI-RADS parcellation standard and tests using clinical landmark data demonstrate that our use of an SDM for registration, with median target registration error of 2.98 mm, is significantly more accurate than the current clinical method. Furthermore, we show that the low-dimensional SDM registration results are robust to segmentation errors that are not uncommon in clinical TRUS data.     

Automatic Shape-Based Level Set Segmentation for Needle Tracking in 3-D TRUS-Guided Prostate Brachytherapy

Prostate brachytherapy is an effective treatment for early prostate cancer. The success depends critically on the correct needle implant positions. We have devised an automatic shape-based level set segmentation tool for needle tracking in 3-D transrectal ultrasound (TRUS) images, which uses the shape information and level set technique to localize the needle position and estimate the endpoint of needle in real-time. The 3-D TRUS images used in the evaluation of our tools were obtained using a 2-D TRUS transducer from Ultrasonix (Richmond, BC, Canada) and a computer-controlled stepper motor system from Thorlabs (Newton, NJ, USA). The accuracy and feedback mechanism had been validated using prostate phantoms and compared with 3-D positions of these needles derived from experts' readings. The experts' segmentation of needles from 3-D computed tomography images was the ground truth in this study. The difference between automatic and expert segmentations are within 0.1 mm for 17 of 19 implanted needles. The mean errors of automatic segmentations by comparing with the ground truth are within 0.25 mm. Our automated method allows real-time TRUS-based needle placement difference within one pixel compared with manual expert segementation.     

Association of automated and human observer lesion detecting ability using phantoms

A set of tissue-mimicking phantoms containing spherical negative contrast simulated lesions was employed to associate an automated method for determining detectability with human observers. Six alternative methods for computing the lesion signal-to-noise ratio (LSNR) were employed for quantifying automated detecting ability. The six methods differ regarding effective lesion area and whether or not gradients in local mean background echo levels were accounted for. The two-alternative-forced-choice (TAFC) technique was used to associate detecting ability of human observers with LSNR values. Although the six methods gave similar results, one method exhibited the least dependency on lesion diameter and is recommended; that method accounts for gradients in local mean background echo levels and employs an effective sphere area of 2/pi times the projected sphere area. A reasonable LSNR detection threshold value of -2.0 was found to apply for nominal transducer frequencies from 4 through 6 MHz and for lesion diameters from 2 through 5 mm. This result allows rapid human-observer-calibrated automated determination of the depth range of detectability as a function of sphere diameter and contrast.     

Prostate segmentation in transrectal ultrasound using magnetic resonance imaging priors

Purpose

In the current standard of care, real-time transrectal ultrasound (TRUS) is commonly used for prostate brachytherapy guidance. As TRUS provides limited soft tissue contrast, segmenting the prostate gland in TRUS images is often challenging and subject to inter-observer and intra-observer variability, especially at the base and apex where the gland boundary is hard to define. Magnetic resonance imaging (MRI) has higher soft tissue contrast allowing the prostate to be contoured easily. In this paper, we aim to show that prostate segmentation in TRUS images informed by MRI priors can improve on prostate segmentation that relies only on TRUS images.

Methods

First, we compare the TRUS-based prostate segmentation used in the treatment of 598 patients with a high-quality MRI prostate atlas and observe inconsistencies at the apex and base. Second, motivated by this finding, we propose an alternative TRUS segmentation technique that is fully automatic and uses MRI priors. The algorithm uses a convolutional neural network to segment the prostate in TRUS images at mid-gland, where the gland boundary can be clearly seen. It then reconstructs the gland boundary at the apex and base with the aid of a statistical shape model built from an MRI atlas of 78 patients.

Results

Compared to the clinical TRUS segmentation, our method achieves similar mid-gland segmentation results in the 598-patient database. For the seven patients who had both TRUS and MRI, our method achieved more accurate segmentation of the base and apex with the MRI segmentation used as ground truth.

Conclusion

Our results suggest that utilizing MRI priors in TRUS prostate segmentation could potentially improve the performance at base and apex.

     

Contrast‐Enhanced Transrectal Ultrasound for Follow‐up After Focal HIFU Ablation for Prostate Cancer

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast‐enhanced transrectal ultrasound (TRUS) in follow‐up of patients after high‐intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast‐enhanced TRUS findings were as follows: (1) contrast‐enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast‐enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image‐guided prostate biopsy, which showed prostate cancer; and (3) contrast‐enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.     

Frequency independent ultrasound contrast-detail analysis

An ultrasound contrast-detail phantom has been developed to evaluate the image quality of diagnostic ultrasound imaging systems. The phantom includes eight conical targets whose B-mode images show disk lesions such that the object contrast of each lesion relative to background is independent of the imaging device or transducer frequency/spectrum. By maintaining conditions for Rayleigh scattering and Rayleigh speckle statistics in the phantom gel, the object contrast of each lesion depends only on the scatterer concentration in the lesion relative to the scatterer concentration in the background. Experimental data confirmed this frequency independence. Results of contrast-detail performance of an ultrasound imaging system are shown, and a standard technique for error analysis of contrast-detail data is described.     

Phase Grouping-Based Needle Segmentation in 3-D Trans-rectal Ultrasound-Guided Prostate Trans-perineal Therapy

A robust and efficient needle segmentation method used to localize and track the needle in 3-D trans-rectal ultrasound (TRUS)-guided prostate therapy is proposed. The algorithmic procedure begins by cropping the 3-D US image containing a needle; then all voxels in the cropped 3-D image are grouped into different line support regions (LSRs) based on the outer product of the adjacent voxels' gradient vector. Two different needle axis extraction methods in the candidate LSR are presented: least-squares fitting and 3-D randomized Hough transform. Subsequent local optimization refines the position of the needle axis. Finally, the needle endpoint is localized by finding an intensity drop along the needle axis. The proposed methods were validated with 3-D TRUS tissue-mimicking agar phantom images, chicken breast phantom images and patient images obtained during prostate cryotherapy. The results of the in vivo test indicate that our method can localize the needle accurately and robustly with a needle endpoint localization accuracy <1.43 mm and detection accuracy >84%, which are favorable for 3-D TRUS-guided prostate trans-perineal therapy.     

MR-guided interventions for prostate cancer

MR imaging is currently the most effective diagnostic imaging tool for visualizing the anatomy and pathology of the prostate gland. Currently, the practicality and cost effectiveness of transrectal ultrasound dominates image guidance for needle-based prostate interventions. Challenges to the integration of diagnostic and interventional MR imaging have included the lack of real-time feed-back, the complexity of the imaging technique, and limited access to the perineum within the geometric constraints of the MR imaging scanner. Two basic strategies have been explored and clinically demonstrated in the literature: (1) coregistration of previously acquired diagnostic MR imaging to interventional TRUS or open scanner MR images, and (2) stereotactic needle interventions within conventional diagnostic scanners using careful patient positioning or the aid of simple manipulators. Currently, researchers are developing techniques that render MR imaging the method of choice for the direct guidance of many procedures. This article focuses on needle-based interventions for prostate cancer, including biopsy, brachytherapy, and thermal therapy With rapid progress in biologic imaging of the prostate gland, the authors believe that MR imaging guidance will play an increasing role in the diagnosis and treatment of prostate cancer.     

Robotic assistance for ultrasound-guided prostate brachytherapy

We present a robotically assisted prostate brachytherapy system and test results in training phantoms and Phase-I clinical trials. The system consists of a transrectal ultrasound (TRUS) and a spatially co-registered robot, fully integrated with an FDA-approved commercial treatment planning system. The salient feature of the system is a small parallel robot affixed to the mounting posts of the template. The robot replaces the template interchangeably, using the same coordinate system. Established clinical hardware, workflow and calibration remain intact. In all phantom experiments, we recorded the first insertion attempt without adjustment. All clinically relevant locations in the prostate were reached. Non-parallel needle trajectories were achieved. The pre-insertion transverse and rotational errors (measured with a Polaris optical tracker relative to the template's coordinate frame) were 0.25 mm (STD=0.17 mm) and 0.75 degrees (STD=0.37 degrees). In phantoms, needle tip placement errors measured in TRUS were 1.04 mm (STD=0.50mm). A Phase-I clinical feasibility and safety trial has been successfully completed with the system. We encountered needle tip positioning errors of a magnitude greater than 4mm in only 2 of 179 robotically guided needles, in contrast to manual template guidance where errors of this magnitude are much more common. Further clinical trials are necessary to determine whether the apparent benefits of the robotic assistant will lead to improvements in clinical efficacy and outcomes.     

超声多模态影像诊断前列腺癌及指导经直肠超声引导下靶向穿刺

目的 观察超声多模态影像诊断前列腺癌(PC)及指导经直肠超声(TRUS)引导下靶向穿刺的价值。方法 收集128例前列腺病变患者，包括61例PC及67例良性病变；根据前列腺影像报告和数据系统(PI-RADS)将其分为A组(PI-RADS 3分，n=64)、B组(PI-RADS 4分，n=29)及C组(PI-RADS 5分，n=35),观察TRUS、经直肠实时弹性成像(TRTE)及经直肠超声造影(TR-CEUS)联合诊断PC的效能，分析其用于TRUS引导下靶向穿刺的价值。结果 以TRUS、TRTE及TR-CEUS中存在任意2项阳性结果为截断值，超声多模态影像诊断PC的准确率、敏感度、特异度、阳性预测值、阴性预测值及曲线下面积分别为73.44%、77.05%、70.15%、70.15%、77.05%及0.766[95%CI(0.686,0.845)]。随病灶PI-RADS得分升高，超声多模态影像诊断PC的敏感度呈大致下降、而特异度呈上升趋势。结论 超声多模态影像有助于诊断PC及制定穿刺活检策略。     

Photoacoustic imaging of prostate brachytherapy seeds

Brachytherapy seed therapy is an increasingly common way to treat prostate cancer through localized radiation. The current standard of care relies on transrectal ultrasound (TRUS) for imaging guidance during the seed placement procedure. As visualization of individual metallic seeds tends to be difficult or inaccurate under TRUS guidance, guide needles are generally tracked to infer seed placement. In an effort to improve seed visualization and placement accuracy, the use of photoacoustic (PA) imaging, which is highly sensitive to metallic objects in soft tissue, was investigated for this clinical application. The PA imaging properties of bare (i.e., embedded in pure gelatin) and tissue-embedded (at depths of up to 13 mm) seeds were investigated with a multi-wavelength (750 to 1090 nm) PA imaging technique. Results indicate that, much like ultrasonic (US) imaging, an angular dependence (i.e., seed orientation relative to imaging transducer) of the PA signal exists. Despite this shortcoming, however, PA imaging offers improved contrast, over US imaging, of a seed in prostate tissue if sufficient local fluence is achieved. Additionally, although the PA signal of a bare seed is greatest for lower laser wavelengths (e.g., 750 nm), the scattering that results from tissue tends to favor the use of higher wavelengths (e.g., 1064 nm, which is the primary wavelength of Nd:YAG lasers) when the seed is located in tissue. A combined PA and US imaging approach (i.e., PAUS imaging) shows strong potential to visualize both the seed and the surrounding anatomical environment of the prostate during brachytherapy seed placement procedures.     

New contrast-detail phantoms for improved precision in lesion detection measurements

The previous design of our ultrasound contrast-detail (C-D) phantom is limited in its ability to evaluate the quality of diagnostic ultrasound imaging systems. There is uncertainty in the contrast-detail measurements due to the single available viewing angle for each target and the resulting single realization of the ultrasound speckle pattern. Two new contrast-detail phantom designs are described which enable many independent realizations of the speckle noise for observer C-D experiments of improved precision. In the first design, a single tissue-mimicking cone is located on the axis of a tissue-mimicking cylinder. Cross-sectional images of the cone which simulate focal lesions can be obtained from any orientation by rotating the cylinder under the transducer. In the second new design, a tissue-mimicking cone is positioned in a tissue-mimicking slurry of agar/graphite spheres. Gentle stirring of the slurry and rotation of the cone produce many independent realizations of the speckle. In both new phantoms, the lesion contrast can be specified and is frequency/transducer independent.     

A 5-MHz cylindrical dual-layer transducer array for 3-D transrectal ultrasound imaging

Two-dimensional transrectal ultrasound (TRUS) is being used in guiding prostate biopsies and treatments. In many cases, the TRUS probes are moved manually or mechanically to acquire volumetric information, making the imaging slow, user dependent, and unreliable. A real-time three-dimensional (3-D) TRUS system could improve reliability and volume rates of imaging during these procedures. In this article, the authors present a 5-MHz cylindrical dual-layer transducer array capable of real-time 3-D transrectal ultrasound without any mechanically moving parts. Compared with fully sampled 2-D arrays, this design substantially reduces the channel count and fabrication complexity. This dual-layer transducer uses PZT elements for transmit and P[VDF-TrFE] copolymer elements for receive, respectively. The mechanical flexibility of both diced PZT and copolymer makes it practical for transrectal applications. Full synthetic aperture 3-D data sets were acquired by interfacing the transducer with a Verasonics Data Acquisition System. Offline 3-D beamforming was then performed to obtain volumes of two wire phantoms and a cyst phantom. Generalized coherence factor was applied to improve the contrast of images. The measured -6-dB fractional bandwidth of the transducer was 62% with a center frequency of 5.66 MHz. The measured lateral beamwidths were 1.28 mm and 0.91 mm in transverse and longitudinal directions, respectively, compared with a simulated beamwidth of 0.92 mm and 0.74 mm.     

Development and Preliminary Evaluation of an Anthropomorphic Trans-rectal Ultrasound Prostate Brachytherapy Training Phantom

The quality of the trans-rectal ultrasound (TRUS) image, and thus seed placement during the prostate brachytherapy (PBT) procedure, relies on the user's technical and clinical competency. Simulation-based medical education can provide a structured approach for the acquisition of clinical competencies, but the efficacy of the training relies on the fidelity of the training simulators. In this work, the design, development and preliminary evaluation of an anthropomorphic training phantom for TRUS PBT is described. TRUS clinical patient data informed the design of 3-D printed moulds to fabricate prostate targets. Tissue-mimicking materials were included that had the sonographic characteristics of the prostate and overlying tissues, as well as the clinically relevant physical response, to provide haptic feedback to the user. Through an iterative design process, prototypes were constructed. These prototypes were quantitatively evaluated using a specification list and evaluated by an experienced clinical brachytherapy oncologist; their feedback was implemented, and the results of this evaluation are presented.     

A rare case of granulomatous prostatitis caused by Mycobacterium tuberculosis

We report a rare case of infective granulomatous prostatitis caused by Mycobacterium tuberculosis that may be mistaken for prostatic carcinoma, both on clinical examination and transrectal sonography (TRUS). A large hypoechoic mass was detected in the prostate of a 46-year-old man during TRUS and histopathologic examination after TRUS-guided biopsies reported the diagnosis of tuberculous prostatitis. We herein describe the clinical and TRUS findings of this case.     

A partial augmented reality system with live ultrasound and registered preoperative MRI for guiding robot-assisted radical prostatectomy

We propose an image guidance system for robot assisted laparoscopic radical prostatectomy (RALRP). A virtual 3D reconstruction of the surgery scene is displayed underneath the endoscope’s feed on the surgeon’s console. This scene consists of an annotated preoperative Magnetic Resonance Image (MRI) registered to intraoperative 3D Trans-rectal Ultrasound (TRUS) as well as real-time sagittal 2D TRUS images of the prostate, 3D models of the prostate, the surgical instrument and the TRUS transducer. We display these components with accurate real-time coordinates with respect to the robot system. Since the scene is rendered from the viewpoint of the endoscope, given correct parameters of the camera, an augmented scene can be overlaid on the video output. The surgeon can rotate the ultrasound transducer and determine the position of the projected axial plane in the MRI using one of the registered da Vinci instruments. This system was tested in the laboratory on custom-made agar prostate phantoms. We achieved an average total registration accuracy of 3.2  ±  1.3 mm. We also report on the successful application of this system in the operating room in 12 patients. The average registration error between the TRUS and the da Vinci system for the last 8 patients was 1.4  ±  0.3 mm and average target registration error of 2.1  ±  0.8 mm, resulting in an in vivo overall robot system to MRI mean registration error of 3.5 mm or less, which is consistent with our laboratory studies.     

Towards ultrasound probe positioning optimization during prostate needle biopsy using pressure feedback

Purpose

Accurate Transrectal Ultrasound (TRUS)-guided prostate needle biopsy requires registering preoperative 3D TRUS or MR image, in which tumors and other suspicious areas are visible, to intraoperative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, robotic needle biopsy systems can be used to place the US probe at the same position relative to the prostate during the 3D and 2D image acquisition to ensure similar prostate deformation. To have such similar deformation, only visual feedback is not sufficient as such feedback can be used to only guarantee that the whole prostate is within the field of view irrespective of the probe’s orientation. As such, contact pressure feedback can be utilized to ensure consistent minimum contact between the probe and prostate.

Method

A robotic system is proposed where a TRUS probe with pressure sensor array is used. The contact pressure can be measured during imaging and used to provide feedback in conjunction with an optimization algorithm for consistent probe positioning. The robotic system is driven by the feedback to position the probe such that pressure pattern of the sensors during 2D image acquisition is similar to the pressure pattern during 3D image acquisition. The proposed method takes into account the patient’s body movement expected during image acquisition. In this study, an in silico phantom is used where the simulated contact pressure distribution required in the optimization algorithm is obtained using a prostate finite element model.

Result

Starting from an arbitrary position where the probe contacts the phantom, this position was varied systematically until a position corresponding to maximum pressure pattern similarity between contact pressure patterns corresponding to the 2D and 3D imaging was achieved successfully.

Conclusion

Results obtained from the in silico phantom study indicate that the proposed technique is capable of ensuring having only minimal relative prostate deformation between preoperative image acquisition and intraoperative imaging used for guiding needle biopsy, paving the way for faster and more accurate registration.