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Purpose Using multiparametric MRI data and the pathologic data from radical prostatectomy specimens, we simulated the treatment planning of dose-escalated high-dose-rate brachytherapy (HDR-BT) to the Multiparametric MRI dominant intraprostatic lesion (mpMRI-DIL) to compare the dose potentially delivered to the pathologically confirmed locations of the high-grade component of the cancer. Methods and Materials Pathologist-annotated prostatectomy midgland histology sections from 12 patients were registered to preprostatectomy mpMRI scans that were interpreted by four radiologists. To simulate realistic HDR-BT, we registered each observer's mpMRI-DILs and corresponding histology to two transrectal ultrasound images of other HDR-BT patients with a 15-Gy whole-gland prescription. We used clinical inverse planning to escalate the mpMRI-DILs to 20.25 Gy. We compared the dose that the histopathology would have received if treated with standard treatment plans to the dose mpMRI-targeting would have achieved. The histopathology was grouped as high-grade cancer (any Gleason Grade 4 or 5) and low-grade cancer (only Gleason Grade 3). Results 212 mpMRI-targeted HDR-BT plans were analyzed. For high-grade histology, the mpMRI-targeted plans achieved significantly higher median [IQR] D98 and D90 values of 18.2 [16.7–19.5] Gy and 19.4 [17.8–20.9] Gy, respectively, in comparison with the standard plans (p = 0.01 and p = 0.003). For low-grade histology, the targeted treatment plans would have resulted in a significantly higher median D90 of 17.0 [16.1–18.4] Gy in comparison with standard plans (p = 0.015); the median D98 was not significantly higher (p = 0.2). Conclusions In this retrospective pilot study of 12 patients, mpMRI-based dose escalation led to increased dose to high-grade, but not low-grade, cancer. In our data set, different observers and mpMRI sequences had no substantial effect on dose to histologic cancer.

Background PSMA-PET 1 has shown good concordance with histology, but there is a need to investigate the ability of PSMA-PET to delineate DIL 2 boundaries for guided biopsy and focal therapy planning. Objective To determine threshold and margin combinations that satisfy the following criteria: ≥95% sensitivity with max specificity and ≥95% specificity with max sensitivity. Design, setting and participants We registered pathologist-annotated whole-mount mid-gland prostatectomy histology sections cut in 4.4 mm intervals from 12 patients to pre-surgical PSMA-PET/MRI by mapping histology to ex-vivo imaging to in-vivo imaging. We generated PET-derived tumor volumes using boundaries defined by thresholded PET volumes from 1–100% of SUV 3 max in 1% intervals. At each interval, we applied margins of 0–30 voxels in one voxel increments, giving 3000 volumes/patient. Outcome measurements Mean and standard deviation of sensitivity and specificity for cancer detection within the 2D oblique histologic planes that intersected with the 3D PET volume for each patient. Results and limitations A threshold of 67% SUV max with an 8.4 mm margin achieved a (mean ± std.) sensitivity of 95.0 ± 7.8% and specificity of 76.4 ± 14.7%. A threshold of 81% SUV max with a 5.1 mm margin achieved sensitivity of 65.1 ± 28.4% and specificity of 95.1 ± 5.2%. Conclusions Preliminary evidence of thresholding and margin expansion of PSMA-PET images targeted at DILs validated with histopathology demonstrated excellent mean sensitivity and specificity in the setting of focal therapy/boosting and guided biopsy. These parameters can be used in a larger validation study supporting clinical translation.

Rebuilding the local vasculature is central to restoring the health of muscles subjected to ischemic injury. Arteriogenesis yields remodeled collateral arteries that circumvent the obstruction, and angiogenesis produces capillaries to perfuse the regenerating myofibers. However, the vital intervening network of arterioles that feed the regenerated capillaries is poorly understood and is an investigative challenge. We used machine learning and automated micromorphometry to quantify the arteriolar landscape in distal hindlimb muscles in mice that have regenerated after femoral artery excision. Assessment of 1,546 arteriolar sections revealed a striking (2-fold) increase in arteriolar density in regenerated muscle 14 and 28 days after ischemic injury. Lumen caliber was initially similar to that of control arterioles but after 4 wk lumen area was reduced by 46%. In addition, the critical smooth muscle layer was attenuated throughout the arteriolar network, across a 150- to 5-µm diameter range. To understand the consequences of the reshaped distal hindlimb arterioles, we undertook computational flow modeling, which revealed blunted flow augmentation. Moreover, impaired flow reserve was confirmed in vivo by laser-Doppler analyses of flow in response to directly applied sodium nitroprusside. Thus, in hindlimb muscles regenerating after ischemic injury, the arteriolar network is amplified, inwardly remodels, and is diffusely undermuscularized. These defects and the associated flow restraints could contribute to the deleterious course of peripheral artery disease and merit attention when considering therapeutic innovations.

PURPOSE Multiparametric MRI (mpMRI) has shown promise in the detection and localization of prostate cancer foci. Although techniques have been previously introduced to delineate lesions from mpMRI, these techniques were evaluated in datasets with T2 maps available. The generation of T2 map is not included in the clinical prostate mpMRI consensus guidelines; the acquisition of which requires repeated T2-weighted (T2W) scans and would significantly lengthen the scan time currently required for the clinically recommended acquisition protocol, which includes T2W, diffusion-weighted (DW), and dynamic contrast-enhanced (DCE) imaging. The goal of this study is to develop and evaluate an algorithm that provides pixel-accurate lesion delineation from images acquired based on the clinical protocol. METHODS Twenty-five pixel-based features were extracted from the T2-weighted (T2W), apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) images. The pixel-wise classification was performed on the reduced space generated by locality alignment discriminant analysis (LADA), a version of linear discriminant analysis (LDA) localized to patches in the feature space. Postprocessing procedures, including the removal of isolated points identified and filling of holes inside detected regions, were performed to improve delineation accuracy. The segmentation result was evaluated against the lesions manually delineated by four expert observers according to the Prostate Imaging-Reporting and Data System (PI-RADS) detection guideline. RESULTS The LADA-based classifier (60 ± 11%) achieved a higher sensitivity than the LDA-based classifier (51 ± 10%), thereby demonstrating, for the first time, that higher classification performance was attained on the reduced space generated by LADA than by LDA. Further sensitivity improvement (75 ± 14%) was obtained after postprocessing, approaching the sensitivities attained by previous mpMRI lesion delineation studies in which nonclinical T2 maps were available. CONCLUSION The proposed algorithm delineated lesions accurately and efficiently from images acquired following the clinical protocol. The development of this framework may potentially accelerate the clinical uses of mpMRI in prostate cancer diagnosis and treatment planning.

In magnetic resonance (MR)-targeted, 3-D transrectal ultrasound (TRUS)-guided biopsy, prostate motion during the procedure increases the needle targeting error and limits the ability to accurately sample MR-suspicious tumor volumes. The robustness of the 2-D-3-D registration methods for prostate motion compensation is impacted by local optima in the search space. In this paper, we analyzed the prostate motion characteristics and investigated methods to incorporate such knowledge into the registration optimization framework to improve robustness against local optima. Rigid motion of the prostate was analyzed adopting a mixture-of-Gaussian (MoG) model using 3-D TRUS images acquired at bilateral sextant probe positions with a mechanically assisted biopsy system. The learned motion characteristics were incorporated into Powell's direction set method by devising multiple initial search positions and initial search directions. Experiments were performed on data sets acquired during clinical biopsy procedures, and registration error was evaluated using target registration error (TRE) and converged image similarity metric values after optimization. After incorporating the learned initialization positions and directions in Powell's method, 2-D-3-D registration to compensate for motion during prostate biopsy was performed with rms ± std TRE of 2.33 ± 1.09 mm with ~3 s mean execution time per registration. This was an improvement over 3.12 ± 1.70 mm observed in Powell's standard approach. For the data acquired under clinical protocols, the converged image similarity metric value improved in ≥8% of the registrations whereas it degraded only ≤1% of the registrations. The reported improvements in optimization indicate useful advancements in robustness to ensure smooth clinical integration of a registration solution for motion compensation that facilitates accurate sampling of the smallest clinically significant tumors.

Three dimensional (3D) manual segmentation of the prostate on magnetic resonance imaging (MRI) is a laborious and time-consuming task that is subject to inter-observer variability. In this study, we developed a fully automatic segmentation algorithm for T2-weighted endorectal prostate MRI and evaluated its accuracy within different regions of interest using a set of complementary error metrics. Our dataset contained 42 T2-weighted endorectal MRI from prostate cancer patients. The prostate was manually segmented by one observer on all of the images and by two other observers on a subset of 10 images. The algorithm first coarsely localizes the prostate in the image using a template matching technique. Then, it defines the prostate surface using learned shape and appearance information from a set of training images. To evaluate the algorithm, we assessed the error metric values in the context of measured inter-observer variability and compared performance to that of our previously published semi-automatic approach. The automatic algorithm needed an average execution time of ∼60 s to segment the prostate in 3D. When compared to a single-observer reference standard, the automatic algorithm has an average mean absolute distance of 2.8 mm, Dice similarity coefficient of 82%, recall of 82%, precision of 84%, and volume difference of 0.5 cm in the mid-gland. Concordant with other studies, accuracy was highest in the mid-gland and lower in the apex and base. Loss of accuracy with respect to the semi-automatic algorithm was less than the measured inter-observer variability in manual segmentation for the same task. 3

Immunohistochemical tissue staining enhances microvasculature characteristics, including the smooth muscle in the medial layer of the vessel walls that is responsible for regulation of blood flow. The vasculature can be imaged in a comprehensive fashion using whole-slide scanning. However, since each such image potentially contains hundreds of small vessels, manual vessel delineation and quantification is not practically feasible. In this work, we present a fully automatic segmentation and vasculature quantification algorithm for whole-slide images. We evaluated its performance on tissue samples drawn from the hind limbs of wild-type mice, stained for smooth muscle using 3,3'-Diaminobenzidine (DAB) immunostain. The algorithm was designed to be robust to vessel fragmentation due to staining irregularity, and artefactual staining of nonvessel objects. Colour deconvolution was used to isolate the DAB stain for detection of vessel wall fragments. Complete vessels were reconstructed from the fragments by joining endpoints of topological skeletons. Automatic measures of vessel density, perimeter, wall area and local wall thickness were taken. The segmentation algorithm was validated against manual measures, resulting in a Dice similarity coefficient of 89%. The relationships observed between these measures were as expected from a biological standpoint, providing further reinforcement of the accuracy of this system. This system provides a fully automated and accurate means of measuring the arteriolar and venular morphology of vascular smooth muscle.

A common challenge when performing surface-based registration of images is ensuring that the surfaces accurately represent consistent anatomical boundaries. Image segmentation may be difficult in some regions due to either poor contrast, low slice resolution, or tissue ambiguities. To address this, we present a novel non-rigid surface registration method designed to register two partial surfaces, capable of ignoring regions where the anatomical boundary is unclear. Our probabilistic approach incorporates prior geometric information in the form of a statistical shape model (SSM), and physical knowledge in the form of a finite element model (FEM). We validate results in the context of prostate interventions by registering pre-operative magnetic resonance imaging (MRI) to 3D transrectal ultrasound (TRUS). We show that both the geometric and physical priors significantly decrease net target registration error (TRE), leading to TREs of 2.35 $\pm$ 0.81 mm and 2.81 $\pm$ 0.66 mm when applied to full and partial surfaces, respectively. We investigate robustness in response to errors in segmentation, varying levels of missing data, and adjusting the tunable parameters. Results demonstrate that the proposed surface registration method is an efficient, robust, and effective solution for fusing data from multiple modalities.

Objective: This paper presents the results of a new approach for selection of RF time series features based on joint independent component analysis for in vivo characterization of prostate cancer. Methods: We project three sets of RF time series features extracted from the spectrum, fractal dimension, and the wavelet transform of the ultrasound RF data on a space spanned by five joint independent components. Then, we demonstrate that the obtained mixing coefficients from a group of patients can be used to train a classifier, which can be applied to characterize cancerous regions of a test patient. Results: In a leave-one-patient-out cross validation, an area under receiver operating characteristic curve of 0.93 and classification accuracy of 84% are achieved. Conclusion: Ultrasound RF time series can be used to accurately characterize prostate cancer, in vivo without the need for exhaustive search in the feature space. Significance: We use joint independent component analysis for systematic fusion of multiple sets of RF time series features, within a machine learning framework, to characterize PCa in an in vivo study.

Radical prostatectomy is performed on approximately 40% of men with organ-confined prostate cancer. Pathologic information obtained from the prostatectomy specimen provides important prognostic information and guides recommendations for adjuvant treatment. The current pathology protocol in most centers involves primarily qualitative assessment. In this paper, we describe and evaluate our system for automatic prostate cancer detection and grading on hematoxylin & eosin-stained tissue images. Our approach is intended to address the dual challenges of large data size and the need for high-level tissue information about the locations and grades of tumors. Our system uses two stages of AdaBoost-based classification. The first provides high-level tissue component labeling of a superpixel image partitioning. The second uses the tissue component labeling to provide a classification of cancer versus noncancer, and low-grade versus high-grade cancer. We evaluated our system using 991 sub-images extracted from digital pathology images of 50 whole-mount tissue sections from 15 prostatectomy patients. We measured accuracies of 90% and 85% for the cancer versus noncancer and high-grade versus low-grade classification tasks, respectively. This system represents a first step toward automated cancer quantification on prostate digital histopathology imaging, which could pave the way for more accurately informed postprostatectomy patient care.

Background Changes in lung density on computed tomography (CT) are common after stereotactic ablative radiotherapy (SABR) and can confound the early detection of recurrence. We performed a systematic review to describe post-SABR findings on computed tomography (CT) and positron-emission tomography (PET), identify imaging characteristics that predict recurrence and propose a follow-up imaging algorithm. Methods A systematic review was conducted of studies providing detailed radiologic descriptions of anatomic and metabolic lung changes after SABR. Our search returned 824 studies; 26 met our inclusion criteria. Data are presented according to PRISMA guidelines. Results Acute changes post-SABR predominantly appear as consolidation or ground glass opacities. Late changes often demonstrate a modified conventional pattern of fibrosis, evolving beyond 2years after treatment. Several CT features, including an enlarging opacity, correlate with recurrence. Although PET SUVmax may rise immediately post-SABR, an SUVmax⩾5 carries a high predictive value of recurrence. Conclusions CT density changes are common post-SABR. The available evidence suggests that recurrent disease should be suspected if high-risk CT changes are seen with SUVmax⩾5 on PET. Further studies are needed to validate the predictive values of such metrics, and for advanced analysis of CT changes to allow early detection of potentially curable local recurrence.

Purpose: Three-dimensional ultrasound (3D US) of the carotid artery provides measurements of arterial wall and plaque [vessel wall volume (VWV)] that are complementary to the one-dimensional measurement of the carotid artery intima-media thickness. 3D US VWV requires an observer to delineate the media–adventitia boundary (MAB) and lumen–intima boundary (LIB) of the carotid artery. The main purpose of this work was to develop and evaluate a semiautomated segmentation algorithm for delineating the MAB and LIB of the carotid artery from 3D USimages.Methods: To segment the MAB and LIB, the authors used a level set method and combined several low-level image cues with high-level domain knowledge and limited user interaction. First, the operator initialized the algorithm by choosing anchor points on the boundaries, identified in the images. The MAB was segmented using local region- and edge-based energies and an energy that encourages the boundary to pass through anchor points from the preprocessed images. For the LIB segmentation, the authors used local and global region-based energies, the anchor point-based energy, as well as a constraint promoting a boundary separation between the MAB and LIB. The data set consisted of 231 2D images (11 2D images per each of 21 subjects) extracted from 3D USimages. The image slices were segmented five times each by a single observer using the algorithm and the manual method. Volume-based, region-based, and boundary distance-based metrics were used to evaluate accuracy. Moreover, repeated measures analysis was used to evaluate precision.Results: The algorithm yielded an absolute VWV difference of 5 . 0 % ± 4 . 3 % with a segmentation bias of - 0 . 9 % ± 6 . 6 % . For the MAB and LIB segmentations, the method gave absolute volume differences of 2 . 5 % ± 1 . 8 % and 5 . 6 % ± 3 . 0 % , Dice coefficients of 95 . 4 % ± 1 . 6 % and 93 . 1 % ± 3 . 1 % , mean absolute distances of 0 . 2 ± 0 . 1 and 0 . 2 ± 0 . 1 mm, and maximum absolute distances of 0 . 6 ± 0 . 3 and 0 . 7 ± 0 . 6 mm, respectively. The coefficients of variation of the algorithm ( 5 . 1 % ) and manual methods ( 3 . 9 % ) were not significantly different, but the average time saved using the algorithm (2.8 min versus 8.3 min) was substantial.Conclusions: The authors generated and tested a semiautomated carotid artery VWV measurement tool to provide measurements with reduced operator time and interaction, with high Dice coefficients, and with necessary required precision.

Purpose: 3D-TRUS-guided prostate biopsy permits a 3D record of biopsy cores, supporting the planning of targets to resample or avoid during repeat biopsy sessions. Image registration is required in order to map biopsy targets planned on a previous session’s 3D-TRUS image into the context of the current session. The authors evaluated the performance of surface- and intensity-based rigid and nonrigid registration algorithms for this task using a clinically motivated success criterion of a maximum 2.5 mm target registration error (TRE). Methods: The authors collected two 3D-TRUS images for each of 13 patients, where each image was collected in a separate biopsy session, and the sessions were 1 week apart. The authors tested the iterative closest point and thin-plate spline surface-based registration methods, and the block matching and B-spline intensity-based methods. Manually marked intrinsic fiducials (calcifications) were used to calculate a TRE for each of the tested methods. In addition, error ellipsoids, anisotropy, and variability due to image segmentation were analyzed. All analysis was performed separately for the peripheral zone since this area harbors up to 80% of all prostate cancer. Results: Only the intensity-based nonrigid registration method met the success criterion for both the whole gland and the peripheral zone. Segmentation was a substantial contributor to registration error variability for the surface-based methods, and the surface-based methods resulted in greater error volumes and anisotropy. Conclusions: Intensity-based rigid registration is clinically sufficient to register regions outside the peripheral zone, but nonrigid registration is required in order to register the peripheral zone with clinically needed accuracy. The clinical advantage of using nonrigid registration is questionable since the difference between the RMS TREs for rigid and nonrigid intensity-based registration could be considered to be small (0.3 mm) and is statistically significant. If the added clinical value in performing a nonrigid registration is insufficient given the additional time required for this computation, rigid registration alone may be suitable.

Purpose: Prostate biopsy is the clinical standard for the definitive diagnosis of prostate cancer. To overcome the limitations of 2D TRUS-guided biopsy systems when targeting preplanned locations, systems have been developed with 3D guidance to improve the accuracy of cancer detection. Prostate deformation due to needle insertion and biopsy gun firing is a potential source of error that can cause target misalignments during biopsies. Methods: The authors used nonrigid registration of 2D TRUSimages to quantify the deformation that occurs during the needle insertion and the biopsy gun firing procedure and compare this effect in biopsies performed using a hand-held TRUS probe to those performed using a mechanically assisted 3D TRUS-guided biopsy system. The authors calculated a spatially varying 95% confidence interval on the prostate tissue motion and analyzed this motion both as a function of distance to the biopsy needle and as a function of distance to the lower piercing point of the prostate. The former is relevant because biopsy targets lie along the needle axis, and the latter is of particular importance due to the reported high concentration of prostate cancer in the peripheral zone, a substantial portion of which lies on the posterior side of the prostate where biopsy needles enter the prostate after penetrating the rectal wall during transrectal biopsy. Results: The results show that for both systems, the tissue deformation is such that throughout the length of the needle axis, including regions proximal to the lower piercing point, spherical tumors with a radius of 2.1 mm or more can be sampled with 95% confidence under the assumption of zero error elsewhere in the biopsy system. More deformation was observed in the direction orthogonal to the needle axis compared to the direction parallel to the needle axis; this is of particular importance given the long, narrow shape of the biopsy core. The authors measured lateral tissue motion proximal to the needle axis of not more than 1.5 mm, with 95% confidence. The authors observed a statistically significant and clinically insignificant maximum difference of 0.38 mm in the deformation, resulting from the hand-held and mechanically assisted systems along the needle axis, and the mechanical system resulted in a lower relative increase in deformation proximal to the needle axis during needle insertion, as well as lower variability of deformation during biopsy gun firing. Conclusions: Given the clinical need to biopsy tumors of volume greater than or equal to 0.5 cm 3 , corresponding to spherical tumors with a radius of 5 mm or more, the tissue motion induced by needle insertion and gun firing is an important consideration when setting the design specifications for TRUS-guided prostate biopsy systems.

Supraspinatus muscle disorders are frequent and debilitating, resulting in pain and a limited range of shoulder motion. The gold standard for diagnosis involves an invasive surgical procedure. As part of a proposed clinical workflow for noninvasive computer-aided diagnosis (CAD) of the condition of the supraspinatus, we present a method to classify three-dimensional shapes of the muscle into relevant pathology groups, based on magnetic resonance (MR) images.We obtained MR images of the shoulder from 72 patients, separated into five pathology groups. The imaging protocol ensures that the supraspinatus is consistently oriented relative to the MR imaging plane for each scan. Next, we compute the Fourier coefficients of two-dimensional contours lying on parallel imaging planes and integrate the corresponding frequency components across all contours. To classify the shapes, we learn the Fourier coefficients that best distinguish the different classes.We show that our method leads to significant improvement when compared to previous work. We are able to distinguish between normal shapes and shapes that possess a pathology with an accuracy of almost 100%. Moreover, we can differentiate between the different pathology groups with an average accuracy of 86%.We confirm that analyzing the three-dimensional shape of the muscle has potential as a form of diagnosis reinforcement to assess the condition of the supraspinatus. Moreover, our proposed descriptor based on Fourier coefficients is able to distinguish the different pathology groups with accuracies higher than those obtained by previous work, indicating its potential application to support a system for CAD of the supraspinatus.

Medial representations of shapes are useful due to their use of an object-centered coordinate system that directly captures intuitive notions of shape such as thickness, bending, and elongation. However, it is well known that an object's medial axis transform (MAT) is unstable with respect to small perturbations of its boundary. This instability results in additional, unwanted branches in the skeletons, which must be pruned in order to recover the portions of the skeletons arising purely from the uncorrupted shape information. Almost all approaches to skeleton pruning compute a significance measure for each branch according to some heuristic criteria, and then prune the least significant branches first. Current approaches to branch significance computation can be classified as either local, solely using information from a neighborhood surrounding each branch, or global, using information about the shape as a whole. In this paper, we propose a third, groupwise approach to branch significance computation. We develop a groupwise skeletonization framework that yields a fuzzy significance measure for each branch, derived from information provided by the group of shapes. We call this framework the Groupwise Medial Axis Transform (G-MAT). We propose and evaluate four groupwise methods for computing branch significance and report superior performance compared to a recent, leading method. We measure the performance of each pruning algorithm using denoising, classification, and within-class skeleton similarity measures. This research has several applications, including object retrieval and shape analysis.

Purpose: Prostate biopsy, performed using two-dimensional (2D) transrectal ultrasound(TRUS) guidance, is the clinical standard for a definitive diagnosis of prostate cancer. Histological analysis of the biopsies can reveal cancerous, noncancerous, or suspicious, possibly precancerous, tissue. During subsequent biopsy sessions, noncancerous regions should be avoided, and suspicious regions should be precisely rebiopsied, requiring accurate needle guidance. It is challenging to precisely guide a needle using 2D TRUS due to the limited anatomic information provided, and a three-dimensional (3D) record of biopsy locations for use in subsequent biopsy procedures cannot be collected. Our tracked, 3D TRUS-guided prostate biopsy system provides additional anatomic context and permits a 3D record of biopsies. However, targets determined based on a previous biopsy procedure must be transformed during the procedure to compensate for intraprocedure prostate shifting due to patient motion and prostate deformation due to transducer probe pressure. Thus, registration is a critically important step required to determine these transformations so that correspondence is maintained between the prebiopsied image and the real-time image. Registration must not only be performed accurately, but also quickly, since correction for prostate motion and deformation must be carried outduring the biopsy procedure. The authors evaluated the accuracy, variability, and speed of several surface-based and image-based intrasession 3D-to-3D TRUSimage registration techniques, for both rigid and nonrigid cases, to find the required transformations. Methods: Our surface-based rigid and nonrigid registrations of the prostate were performed using the iterative-closest-point algorithm and a thin-plate spline algorithm, respectively. For image-based rigid registration, the authors used a block matching approach, and for nonrigid registration, the authors define the moving image deformation using a regular, 3D grid of B-spline control points. The authors measured the target registration error (TRE) as the postregistration misalignment of 60 manually marked, corresponding intrinsic fiducials. The authors also measured the fiducial localization error (FLE), the effect of segmentation variability, and the effect of fiducial distance from the transducer probe tip. Lastly, the authors performed 3D principal component analysis (PCA) on the x , y , and z components of the TREs to examine the 95% confidence ellipsoids describing the errors for each registration method. Results: Using surface-based registration, the authors found mean TREs of 2.13 ± 0.80 and 2.09 ± 0.77 mm for rigid and nonrigid techniques, respectively. Using image-based rigid and nonrigid registration, the authors found mean TREs of 1.74 ± 0.84 and 1.50 ± 0.83 mm , respectively. Our FLE was 0.21 mm and did not dominate the overall TRE. However, segmentation variability contributed substantially ( ∼ 50 % ) to the TRE of the surface-based techniques. PCA showed that the 95% confidence ellipsoid encompassing fiducial distances between the source and target registration images was reduced from 3.05 to 0.14 cm 3 , and 0.05 cm 3 for the surface-based and image-based techniques, respectively. The run times for both registration methods were comparable at less than 60 s. Conclusions: Our results compare favorably with a clinical need for a TRE of less than 2.5 mm, and suggest that image-based registration is superior to surface-based registration for 3D TRUS-guided prostate biopsies, since it does not require segmentation.

Three-dimensional (3D) prostate image segmentation is useful for cancer diagnosis and therapy guidance, but can be time-consuming to perform manually and involves varying levels of difficulty and interoperator variability within the prostatic base, midgland (MG), and apex. In this study, the authors measured accuracy and interobserver variability in the segmentation of the prostate on T2-weighted endorectal magnetic resonance (MR) imaging within the whole gland (WG), and separately within the apex, midgland, and base regions.The authors collected MR images from 42 prostate cancer patients. Prostate border delineation was performed manually by one observer on all images and by two other observers on a subset of ten images. The authors used complementary boundary-, region-, and volume-based metrics [mean absolute distance (MAD), Dice similarity coefficient (DSC), recall rate, precision rate, and volume difference (ΔV)] to elucidate the different types of segmentation errors that they observed. Evaluation for expert manual and semiautomatic segmentation approaches was carried out. Compared to manual segmentation, the authors' semiautomatic approach reduces the necessary user interaction by only requiring an indication of the anteroposterior orientation of the prostate and the selection of prostate center points on the apex, base, and midgland slices. Based on these inputs, the algorithm identifies candidate prostate boundary points using learned boundary appearance characteristics and performs regularization based on learned prostate shape information.The semiautomated algorithm required an average of 30 s of user interaction time (measured for nine operators) for each 3D prostate segmentation. The authors compared the segmentations from this method to manual segmentations in a single-operator (mean whole gland MAD = 2.0 mm, DSC = 82%, recall = 77%, precision = 88%, and ΔV = - 4.6 cm(3)) and multioperator study (mean whole gland MAD = 2.2 mm, DSC = 77%, recall = 72%, precision = 86%, and ΔV = - 4.0 cm(3)). These results compared favorably with observed differences between manual segmentations and a simultaneous truth and performance level estimation reference for this data set (whole gland differences as high as MAD = 3.1 mm, DSC = 78%, recall = 66%, precision = 77%, and ΔV = 15.5 cm(3)). The authors found that overall, midgland segmentation was more accurate and repeatable than the segmentation of the apex and base, with the base posing the greatest challenge.The main conclusions of this study were that (1) the semiautomated approach reduced interobserver segmentation variability; (2) the segmentation accuracy of the semiautomated approach, as well as the accuracies of recently published methods from other groups, were within the range of observed expert variability in manual prostate segmentation; and (3) further efforts in the development of computer-assisted segmentation would be most productive if focused on improvement of segmentation accuracy and reduction of variability within the prostatic apex and base.

In targeted 3D transrectal ultrasound (TRUS)-guided biopsy, patient and prostate movement during the procedure can cause target misalignments that hinder accurate sampling of preplanned suspicious tissue locations. Multiple solutions have been proposed for displacement compensation via registration of intraprocedural TRUS images to a baseline 3D TRUS image acquired at the beginning of the biopsy procedure. While 2D TRUS images are widely used for intraprocedural guidance, some solutions utilize richer intraprocedural images such as bi- or multiplanar TRUS or 3D TRUS, acquired by specialized probes. In this work, the impact of such richer intraprocedural imaging on displacement compensation accuracy was measured to evaluate the tradeoff between cost and complexity of intraprocedural imaging versus improved displacement compensation.Baseline and intraprocedural 3D TRUS images were acquired from 29 patients at standard sextant-template biopsy locations. Planes extracted from 3D TRUS images acquired at sextant positions were used to simulate 2D and 3D intraprocedural information available in different potential clinically relevant scenarios for co-registration with the baseline 3D TRUS image. In practice, intraprocedural 3D information can be acquired either via the use of specialized ultrasound probes (e.g., multiplanar or 3D probes) or via axial rotation of a tracked 2D TRUS probe. Registration accuracy was evaluated by calculating the target registration error (TRE) using manually identified homologous intrinsic fiducial markers (microcalcifications). The TRE was analyzed separately at the base, mid-gland and apex regions of the prostate.The results indicate that TRE improved gradually as the number of intraprocedural imaging planes used in registration was increased, implying that 3D TRUS information assisted the registration algorithm to robustly converge to more accurate solutions. The acquisition of a partial volume up to the angle of rotation supported more accurate displacement compensation than acquiring biplane configurations. Additional intraprocedural 3D TRUS image information was more beneficial to registration accuracy in the base and apex regions as compared with the mid-gland region.While the majority of the registrations using 2D TRUS images provided a clinically desired level of accuracy, intraprocedural 3D imaging helped improve the overall registration accuracy and robustness, especially in the base and apex regions of the prostate. These results are helpful for devising image-based registration methods for displacement compensation when designing 3D TRUS-guided biopsy systems.

Magnetic resonance imaging (MRI)-targeted, 3D transrectal ultrasound (TRUS)-guided "fusion" prostate biopsy intends to reduce the ∼23% false negative rate of clinical two-dimensional TRUS-guided sextant biopsy. Although it has been reported to double the positive yield, MRI-targeted biopsies continue to yield false negatives. Therefore, the authors propose to investigate how biopsy system needle delivery error affects the probability of sampling each tumor, by accounting for uncertainties due to guidance system error, image registration error, and irregular tumor shapes.T2-weighted, dynamic contrast-enhanced T1-weighted, and diffusion-weighted prostate MRI and 3D TRUS images were obtained from 49 patients. A radiologist and radiology resident contoured 81 suspicious regions, yielding 3D tumor surfaces that were registered to the 3D TRUS images using an iterative closest point prostate surface-based method to yield 3D binary images of the suspicious regions in the TRUS context. The probabilityP of obtaining a sample of tumor tissue in one biopsy core was calculated by integrating a 3D Gaussian distribution over each suspicious region domain. Next, the authors performed an exhaustive search to determine the maximum root mean squared error (RMSE, in mm) of a biopsy system that gives P ≥ 95% for each tumor sample, and then repeated this procedure for equal-volume spheres corresponding to each tumor sample. Finally, the authors investigated the effect of probe-axis-direction error on measured tumor burden by studying the relationship between the error and estimated percentage of core involvement.Given a 3.5 mm RMSE for contemporary fusion biopsy systems,P ≥ 95% for 21 out of 81 tumors. The authors determined that for a biopsy system with 3.5 mm RMSE, one cannot expect to sample tumors of approximately 1 cm(3) or smaller with 95% probability with only one biopsy core. The predicted maximum RMSE giving P ≥ 95% for each tumor was consistently greater when using spherical tumor shapes as opposed to no shape assumption. However, an assumption of spherical tumor shape for RMSE = 3.5 mm led to a mean overestimation of tumor sampling probabilities of 3%, implying that assuming spherical tumor shape may be reasonable for many prostate tumors. The authors also determined that a biopsy system would need to have a RMS needle delivery error of no more than 1.6 mm in order to sample 95% of tumors with one core. The authors' experiments also indicated that the effect of axial-direction error on the measured tumor burden was mitigated by the 18 mm core length at 3.5 mm RMSE.For biopsy systems with RMSE ≥ 3.5 mm, more than one biopsy core must be taken from the majority of tumors to achieveP ≥ 95%. These observations support the authors' perspective that some tumors of clinically significant sizes may require more than one biopsy attempt in order to be sampled during the first biopsy session. This motivates the authors' ongoing development of an approach to optimize biopsy plans with the aim of achieving a desired probability of obtaining a sample from each tumor, while minimizing the number of biopsies. Optimized planning of within-tumor targets for MRI-3D TRUS fusion biopsy could support earlier diagnosis of prostate cancer while it remains localized to the gland and curable.

Benign computed tomography (CT) changes due to radiation induced lung injury (RILI) are common following stereotactic ablative radiotherapy (SABR) and can be difficult to differentiate from tumor recurrence. The authors measured the ability of CT image texture analysis, compared to more traditional measures of response, to predict eventual cancer recurrence based on CT images acquired within 5 months of treatment.A total of 24 lesions from 22 patients treated with SABR were selected for this study: 13 with moderate to severe benign RILI, and 11 with recurrence. Three-dimensional (3D) consolidative and ground-glass opacity (GGO) changes were manually delineated on all follow-up CT scans. Two size measures of the consolidation regions (longest axial diameter and 3D volume) and nine appearance features of the GGO were calculated: 2 first-order features [mean density and standard deviation of density (first-order texture)], and 7 second-order texture features [energy, entropy, correlation, inverse difference moment (IDM), inertia, cluster shade, and cluster prominence]. For comparison, the corresponding response evaluation criteria in solid tumors measures were also taken for the consolidation regions. Prediction accuracy was determined using the area under the receiver operating characteristic curve (AUC) and two-fold cross validation (CV).For this analysis, 46 diagnostic CT scans scheduled for approximately 3 and 6 months post-treatment were binned based on their recorded scan dates into 2-5 month and 5-8 month follow-up time ranges. At 2-5 months post-treatment, first-order texture, energy, and entropy provided AUCs of 0.79-0.81 using a linear classifier. On two-fold CV, first-order texture yielded 73% accuracy versus 76%-77% with the second-order features. The size measures of the consolidative region, longest axial diameter and 3D volume, gave two-fold CV accuracies of 60% and 57%, and AUCs of 0.72 and 0.65, respectively.Texture measures of the GGO appearance following SABR demonstrated the ability to predict recurrence in individual patients within 5 months of SABR treatment. Appearance changes were also shown to be more accurately predictive of recurrence, as compared to size measures within the same time period. With further validation, these results could form the substrate for a clinically useful computer-aided diagnosis tool which could provide earlier salvage of patients with recurrence.

Three-dimensional (3D) transrectal ultrasound (TRUS)-guided systems have been developed to improve targeting accuracy during prostate biopsy. However, prostate motion during the procedure is a potential source of error that can cause target misalignments. The authors present an image-based registration technique to compensate for prostate motion by registering the live two-dimensional (2D) TRUS images acquired during the biopsy procedure to a preacquired 3D TRUS image. The registration must be performed both accurately and quickly in order to be useful during the clinical procedure.The authors implemented an intensity-based 2D-3D rigid registration algorithm optimizing the normalized cross-correlation (NCC) metric using Powell's method. The 2D TRUS images acquired during the procedure prior to biopsy gun firing were registered to the baseline 3D TRUS image acquired at the beginning of the procedure. The accuracy was measured by calculating the target registration error (TRE) using manually identified fiducials within the prostate; these fiducials were used for validation only and were not provided as inputs to the registration algorithm. They also evaluated the accuracy when the registrations were performed continuously throughout the biopsy by acquiring and registering live 2D TRUS images every second. This measured the improvement in accuracy resulting from performing the registration, continuously compensating for motion during the procedure. To further validate the method using a more challenging data set, registrations were performed using 3D TRUS images acquired by intentionally exerting different levels of ultrasound probe pressures in order to measure the performance of our algorithm when the prostate tissue was intentionally deformed. In this data set, biopsy scenarios were simulated by extracting 2D frames from the 3D TRUS images and registering them to the baseline 3D image. A graphics processing unit (GPU)-based implementation was used to improve the registration speed. They also studied the correlation between NCC and TREs.The root-mean-square (RMS) TRE of registrations performed prior to biopsy gun firing was found to be 1.87 ± 0.81 mm. This was an improvement over 4.75 ± 2.62 mm before registration. When the registrations were performed every second during the biopsy, the RMS TRE was reduced to 1.63 ± 0.51 mm. For 3D data sets acquired under different probe pressures, the RMS TRE was found to be 3.18 ± 1.6 mm. This was an improvement from 6.89 ± 4.1 mm before registration. With the GPU based implementation, the registrations were performed with a mean time of 1.1 s. The TRE showed a weak correlation with the similarity metric. However, the authors measured a generally convex shape of the metric around the ground truth, which may explain the rapid convergence of their algorithm to accurate results.Registration to compensate for prostate motion during 3D TRUS-guided biopsy can be performed with a measured accuracy of less than 2 mm and a speed of 1.1 s, which is an important step toward improving the targeting accuracy of a 3D TRUS-guided biopsy system.

Introduction: This study evaluates the clinical benefit of magnetic resonance-transrectal ultrasound (MR-TRUS) fusion biopsy over systematic biopsy between first-time and repeat prostate biopsypatients with prior atypical small acinar proliferation (ASAP).Methods: 100 patients were enrolled in a single-centre prospective cohort study: 50 for first biopsy, 50 for repeat biopsy with prior ASAP. Multiparameteric magnetic resonance imaging (MP-MRI) and standard 12-core ultrasound biopsy (Std-Bx) were performed on all patients. Targeted biopsy using MRI-TRUS fusion (Fn-Bx) was performed f suspicious lesions were identified on the prebiopsyMP-MRI. Classification of clinically significant disease was assessed independently for the Std-Bx vs. Fn-Bx cores to compare the two approaches.Results: Adenocarcinoma was detected in 49/100 patients (26 first biopsy, 23 ASAP biopsy), with 25 having significant disease (17 first, 8 ASAP). Fn-Bx demonstrated significantly higher per-core cancer detection rates, cancer involvement, and Gleason scores for first-time and ASAP patients. However, Fn-Bx was significantly more likely to detect significant cancer missed on Std-Bx for ASAP patients than first-time biopsy patients. The addition of Fn-Bx to Std-Bx for ASAP patients had a 166.7% relative risk reduction for missing Gleason ≥ 3 + 4 disease (number needed to image with MP-MRI=10 patients) compared to 6.3% for first biopsy (number to image=50 patients). Negative predictive value of MP-MRI for negative biopsy was 79% for first-time and 100% for ASAP patients, with median followup of 32.1 ± 15.5 months.Conclusions: MR-TRUS Fn-Bx has a greater clinical impact for repeat biopsy patients with prior ASAP than biopsy-naïve patients by detecting more significant cancers that are missed on Std-Bx.

Rotator cuff disorders are prevalent and can cause pain and reduced range of motion and strength. Accurate, noninvasive diagnosis of rotator cuff disorders is therefore important. In this work, we study the relationship between several three-dimensional (3D) shape measurements of the supraspinatus and its pathologic conditions. The objective is to explore the utility of 3D shape descriptors in distinguishing supraspinatus pathologies, leading to computer-aided diagnosis of rotator cuff disorders.We acquired magnetic resonance images of the shoulder from 73 patients, separated into five pathology groups: normal (14), tear (20), tear and atrophy (13), tear and retraction (15), and tear and atrophy and retraction (11). We segmented the 3D surface of the supraspinatus from each magnetic resonance image, and computed 11 3D shape characteristics for each. We performed an analysis of variance (ANOVA) test for each measurement to test the null hypothesis that the means of the pathology groups were equal. The most promising of the measurements, as determined by the ANOVA test, were used to train a support vector machine classifier to automatically assign new supraspinata to the correct pathology groups.The ANOVA test results rejected the null hypothesis (p.0045) for 7 of our 11 measurements. Highlights of the results from the support vector machine classifier were 79% accuracy in distinguishing normals from abnormals, and 82% accuracy in distinguishing atrophy from retraction, our main clinical motivation. These scores were tabulated based on leave-one-out cross-validation.From the results, we draw the conclusion that 3D shape analysis may be helpful in the diagnosis of rotator cuff disorders, but further investigation is required to develop a 3D shape descriptor that yields ideal pathology group separation. The results of this study suggest several promising avenues of future research to meet this goal.

volume is critical in treatment planning. Whether by expert guidelines, retrograde urethrography, bony landmark, ultrasound, or CT-based planning, there is discordant anatomic information regarding the distance between apex and the bulb, also known as the genitourinary diaphragm (GUD) or membranous urethra length (MUL). In this study, we use MRI with endorectal coil in a large series of patients to better characterize the MUL in radiation therapy planning. Materials/Methods: Patients with early stage, clinically localized prostate cancer (Gleason 6 and 7, cT1c-cT2b, PSA 85% interobserver agreement within 2 mm measurement. There was no association between MUL and patient age, T-stage, Gleason score, patient height, weight, or NCCN risk group. Conclusions: Although there remains variability, the median MUL, or GUD length, is 15 mm. This report likely represents the largest evaluation of the pre-treatment MUL in men with prostate cancer treated with external beam radiation. Our data challenges traditional guidelines between the apex and bulb from smaller series and adds to critical anatomic information of male urethral length and prostate apex anatomy. Prostate MRI with endorectal coil produces a reliable MUL and should be used to optimize target volume delineation at the prostate apex. Author Disclosure: N.K. Taunk: None. O. Akin: None. X. Pei: None. M. Zelefsky: None.

Purpose: Evaluation ofin vivo prostate imaging modalities for determining the spatial distribution and aggressiveness of prostate cancer ideally requires accurate registration of images to an accepted reference standard, such as histopathological examination of radical prostatectomy specimens. Three-dimensional (3D) reconstruction of prostate histology facilitates these registration-based evaluations by reintroducing 3D spatial information lost during histology processing. Because the reconstruction accuracy may constrain the clinical questions that can be answered with these data, it is important to assess the tradeoffs between minimally disruptive methods based on intrinsic image information and potentially more robust methods based on extrinsic fiducial markers. Methods: Ex vivo magnetic resonance (MR) images and digitized whole-mount histology images from 12 radical prostatectomy specimens were used to evaluate four 3D histology reconstruction algorithms. 3D reconstructions were computed by registering each histology image to the corresponding ex vivo MR image using one of two similarity metrics (mutual information or fiducial registration error) and one of two search domains (affine transformations or a constrained subset thereof). The algorithms were evaluated for accuracy using the mean target registration error (TRE) computed from homologous intrinsic point landmarks (3–16 per histology section; 232 total) identified on histology and MR images, and for the sensitivity of TRE to rotational, translational, and scaling initialization errors. Results: The algorithms using fiducial registration error and mutual information had mean ± standard deviation TREs of 0.7 ± 0.4 and 1.2 ± 0.7 mm, respectively, and one algorithm using fiducial registration error and affine transforms had negligible sensitivities to initialization errors. The postoptimization values of the mutual information-based metric showed evidence of errors due to both the optimizer and the similarity metric, and variation of parameters of the mutual information-based metric did not improve its performance. Conclusions: The extrinsic fiducial-based algorithm had lower mean TRE and lower sensitivity to initialization than the intrinsic intensity-based algorithm using mutual information. A model relating statistical power to registration error for certain imaging validation study designs estimated that a reconstruction algorithm with a mean TRE of 0.7 mm would require 27% fewer subjects than the method used to initialize the algorithms (mean TRE 1.3 ± 0.7 mm), suggesting the choice of reconstruction technique can have a substantial impact on the design of imaging validation studies, and on their overall cost.

Purpose: Three-dimensional (3D) transrectal ultrasound (TRUS)-guided systems have been developed to improve targeting accuracy during prostate biopsy. However, prostate motion during the procedure is a potential source of error that can cause target misalignments. The authors present an image-based registration technique to compensate for prostate motion by registering the live two-dimensional (2D) TRUS images acquired during the biopsy procedure to a preacquired 3D TRUS image. The registration must be performed both accurately and quickly in order to be useful during the clinical procedure. Methods: The authors implemented an intensity-based 2D-3D rigid registration algorithm optimizing the normalized cross-correlation (NCC) metric using Powell's method. The 2D TRUS images acquired during the procedure prior to biopsy gun firing were registered to the baseline 3D TRUS image acquired at the beginning of the procedure. The accuracy was measured by calculating the target registration error (TRE) using manually identified fiducials within the prostate; these fiducials were used for validation only and were not provided as inputs to the registration algorithm. They also evaluated the accuracy when the registrations were performed continuously throughout the biopsy by acquiring and registering live 2D TRUS images every second. This measured the improvement in accuracy resulting from performing the registration, continuously compensating for motion during the procedure. To further validate the method using a more challenging data set, registrations were performed using 3D TRUS images acquired by intentionally exerting different levels of ultrasound probe pressures in order to measure the performance of our algorithm when the prostate tissue was intentionally deformed. In this data set, biopsy scenarios were simulated by extracting 2D frames from the 3D TRUS images and registering them to the baseline 3D image. A graphics processing unit (GPU)-based implementation was used to improve the registration speed. They also studied the correlation between NCC and TREs. Results: The root-mean-square (RMS) TRE of registrations performed prior to biopsy gun firing was found to be 1.87 ± 0.81 mm. This was an improvement over 4.75 ± 2.62 mm before registration. When the registrations were performed every second during the biopsy, the RMS TRE was reduced to 1.63 ± 0.51 mm. For 3D data sets acquired under different probe pressures, the RMS TRE was found to be 3.18 ± 1.6 mm. This was an improvement from 6.89 ± 4.1 mm before registration. With the GPU based implementation, the registrations were performed with a mean time of 1.1 s. The TRE showed a weak correlation with the similarity metric. However, the authors measured a generally convex shape of the metric around the ground truth, which may explain the rapid convergence of their algorithm to accurate results. Conclusions: Registration to compensate for prostate motion during 3D TRUS-guided biopsy can be performed with a measured accuracy of less than 2 mm and a speed of 1.1 s, which is an important step toward improving the targeting accuracy of a 3D TRUS-guided biopsy system.