3D Prostate Research Articles

MP18-14 CAN SMALL LESIONS OF GLEASON 3+4 BE LEFT UNTREATED IN FOCAL THERAPY? ANALYSIS OF RADICAL PROSTATECTOMY SPECIMENS.

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy1 Apr 2016MP18-14 CAN SMALL LESIONS OF GLEASON 3+4 BE LEFT UNTREATED IN FOCAL THERAPY? ANALYSIS OF RADICAL PROSTATECTOMY SPECIMENS. Kent Kanao, Keishi Kajikawa, Ikuo Kobayashi, Hiroyuki Muramatsu, Shingo Morinaga, Genya Nishikawa, Takahiko Yoshizawa, Yoshiharu Kato, Masahito Watanabe, Kogenta Nakamura, and Makoto Sumitomo Kent KanaoKent Kanao More articles by this author , Keishi KajikawaKeishi Kajikawa More articles by this author , Ikuo KobayashiIkuo Kobayashi More articles by this author , Hiroyuki MuramatsuHiroyuki Muramatsu More articles by this author , Shingo MorinagaShingo Morinaga More articles by this author , Genya NishikawaGenya Nishikawa More articles by this author , Takahiko YoshizawaTakahiko Yoshizawa More articles by this author , Yoshiharu KatoYoshiharu Kato More articles by this author , Masahito WatanabeMasahito Watanabe More articles by this author , Kogenta NakamuraKogenta Nakamura More articles by this author , and Makoto SumitomoMakoto Sumitomo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2715AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Focal therapy as an emerging treatment modality for localized prostate cancer has gained interest in recent years. A focal therapy consensus meeting was held in London in June 2013 and many statements regarding eligibility for focal therapy had reached consensus. The panel agreed that it was acceptable not to treat lesions of Gleason score 3 + 3 up to a maximum cancer core length of 5 mm. However, the panel did not reach consensus on whether lesions of Gleason score 3 + 4 with a maximum cancer core length of 3 mm could be left untreated. The purpose of this study is to assess the size, Gleason score, extra prostatic extension (EPE), and occupied regions of all tumor foci in radical prostatectomy specimens and investigate whether small lesions of Gleason 3+4 could be left untreated in focal therapy. METHODS A total of 104 radical prostatectomy specimens were retrospectively analyzed. All tumor foci in each prostate were outlined on pathology slides, digitally scanned and exported to 3D slicer software (www.slicer.org) to reconstruct 3D prostate cancer models. All tumor foci were individually identified by the software. The region occupied by each tumor focus was individually determined. Gleason score and pathological stage were also individually determined. Volumes of all tumor foci were calculated using the program in the software. When multifocal disease was observed, index lesion was defined as largest tumor focus without considering its Gleason score. RESULTS A total of 441 tumor foci were detected in 104 specimens. Overall, 71 foci were greater than 0.5 cc. The median tumor volume was 0.035 cc (range 1.2 x 10-4 to 7.2). When region-targeted therapy is considered for tumor foci with volume greater than 0.5cc, the target region was set in quarter for 9 (14.5%), unilateral for 18 (29%), anterior bilateral for 11 (17.7%), posterior bilateral for 3 (4.8%), hockey stick for 13 (21%), whole prostate for 8 (12.9%) prostates, respectively. According to the consensus statements, 42 prostates with index lesion occupied more than half prostate and/or Gleason score 8 or higher and/or EPE were excluded from eligibility for focal therapy. In the remaining 62 prostates with 262 foci, there were 50 lesions with a volume of <0.5ml and Gleason score 3+4 besides index lesions. If lesions with a volume of <0.5ml and Gleason 3+4 could not be left in focal therapy, the 50 lesions should be treated in addition to index lesion. This may be contradictory to “index lesion theory” and the concept of focal therapy. CONCLUSIONS This study shows that there are many small lesions with Gleason 3+4 besides index lesions in patients with prostate cancer eligible for focal therapy. To treat those lesions is contradictory to the concept of focal therapy, and therefore it may be reasonable to left them untreated. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e198 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kent Kanao More articles by this author Keishi Kajikawa More articles by this author Ikuo Kobayashi More articles by this author Hiroyuki Muramatsu More articles by this author Shingo Morinaga More articles by this author Genya Nishikawa More articles by this author Takahiko Yoshizawa More articles by this author Yoshiharu Kato More articles by this author Masahito Watanabe More articles by this author Kogenta Nakamura More articles by this author Makoto Sumitomo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Random Walk Based Segmentation for the Prostate on 3D Transrectal Ultrasound Images.

This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem. Our segmentation algorithm is initialized with the user roughly marking the prostate and non-prostate points on the mid-gland slice which are fitted into an ellipse for obtaining more points. Based on these fitted seed points, we run the random walk algorithm to segment the prostate on the mid-gland slice. The segmented contour and the information from the decision tree classification are combined to determine the initial seed points for the other slices. The random walk algorithm is then used to segment the prostate on the adjacent slice. We propagate the process until all slices are segmented. The segmentation method was tested in 32 3D transrectal ultrasound images. Manual segmentation by a radiologist serves as the gold standard for the validation. The experimental results show that the proposed method achieved a Dice similarity coefficient of 91.37±0.05%. The segmentation method can be applied to 3D ultrasound-guided prostate biopsy and other applications.

3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments

Interactions between tumour cells and extracellular matrix proteins of the tumour microenvironment play crucial roles in cancer progression. So far, however, there are only a few experimental platforms available that allow us to study these interactions systematically in a mechanically defined three-dimensional (3D) context. Here, we have studied the effect of integrin binding motifs found within common extracellular matrix (ECM) proteins on 3D breast (MCF-7) and prostate (PC-3, LNCaP) cancer cell cultures, and co-cultures with endothelial and mesenchymal stromal cells. For this purpose, matrix metalloproteinase-degradable biohybrid poly(ethylene) glycol-heparin hydrogels were decorated with the peptide motifs RGD, GFOGER (collagen I), or IKVAV (laminin-111). Over 14days, cancer spheroids of 100–200μm formed. While the morphology of poorly invasive MCF-7 and LNCaP cells was not modulated by any of the peptide motifs, the aggressive PC-3 cells exhibited an invasive morphology when cultured in hydrogels comprising IKVAV and GFOGER motifs compared to RGD motifs or nonfunctionalised controls. PC-3 (but not MCF-7 and LNCaP) cell growth and endothelial cell infiltration were also significantly enhanced in IKVAV and GFOGER presenting gels. Taken together, we have established a 3D culture model that allows for dissecting the effect of biochemical cues on processes relevant to early cancer progression. These findings provide a basis for more mechanistic studies that may further advance our understanding of how ECM modulates cancer cell invasion and how to ultimately interfere with this process. Statement of SignificanceThreedimensional in vitro cancer models have generated great interest over the past decade. However, most models are not suitable to systematically study the effects of environmental cues on cancer development and progression. To overcome this limitation, we have developed an innovative hydrogel platform to study the interactions between breast and prostate cancer cells and extracellular matrix ligands relevant to the tumour microenvironment. Our results show that hydrogels with laminin- and collagen-derived adhesive peptides induce a malignant phenotype in a cell-line specific manner. Thus, we have identified a method to control the incorporation of biochemical cues within a three dimensional culture model and anticipate that it will help us in better understanding the effects of the tumour microenvironment on cancer progression.

스마트 케어 시스템에서의 3차원 전립선 암 가시화 도구 개발

In Korea, prostate cancer accounted for generating growth rate second the following thyroid cancer, because of western dietary habits. Survival rate of prostate cancer after clinical behavior is changed depend on follow-up management. A telemedicine have been applied to replacement of medical specialist in rural area, and a quick reaction to emergency situation. Our study developed prostate 3-dimensional (3D) visualization program and designed prostate aftercare system architecture, called smart care, using a device that can access the Internet. Region of interest (ROI) in prostate was manually segmented by physicians and visualized to 3D objects and sent to PACS Server as DICOM images. So, medical personnel could confirm patients' data along with 3D images not only PACS system, but also portable device like a smart phone. As a result, we conducted the aftercare service to 98 patients and visualize 3D prostate images. 3D images had advantage to instinctively apprehend where lesion is and make patients to understand state of their disease easily. In the future, should conduct an aftercare service to more patients, and will obtain numerical index through follow-up study to an accurate analysis.

Organoid culture systems for prostate epithelial and cancer tissue.

SummaryThis protocol describes a recently developed strategy to generate 3D prostate organoid cultures from healthy mouse and human prostate (either bulk or FAC-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumour cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumour. The stepwise establishment of these cultures and the fully defined serum-free conditioned medium that is required to sustain organoid growth are outlined. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery.

Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors.

Multicellular tumour spheroids (MTS) are three-dimensional cell cultures that possess their own microenvironments and provide a more meaningful model of tumour biology than monolayer cultures. As a result, MTS are becoming increasingly used as tumor models when measuring the efficiency of therapies. Monitoring the viability of live MTS is complicated by their 3D nature and conventional approaches such as fluorescence often require fixation and sectioning. In this paper we detail the use of Surface Enhanced Raman Spectroscopy (SERS) to measure the viability of MTS grown from prostate cancer (PC3) cells. Our results show that we can monitor loss of viability by measuring pH and redox potential in MTS and furthermore we demonstrate that SERS can be used to measure the effects of fractionation of a dose of radiotherapy in a way that has potential to inform treatment planning.

Correction: Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors.

Correction for 'Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors' by Victoria L. Camus, et al., Analyst, 2016, 141, 5056-5061.

Clinical implementation and error sensitivity of a 3D quality assurance protocol for prostate and thoracic IMRT.

This work aims at three goals: first, to define a set of statistical parameters and plan structures for a 3D pretreatment thoracic and prostate intensity‐modulated radiation therapy (IMRT) quality assurance (QA) protocol; secondly, to test if the 3D QA protocol is able to detect certain clinical errors; and third, to compare the 3D QA method with QA performed with single ion chamber and 2D gamma test in detecting those errors. The 3D QA protocol measurements were performed on 13 prostate and 25 thoracic IMRT patients using IBA's COMPASS system. For each treatment planning structure included in the protocol, the following statistical parameters were evaluated: average absolute dose difference (AADD), percent structure volume with absolute dose difference greater than 6% (ADD6), and 3D gamma test. To test the 3D QA protocol error sensitivity, two prostate and two thoracic step‐and‐shoot IMRT patients were investigated. Errors introduced to each of the treatment plans included energy switched from 6 MV to 10 MV, multileaf collimator (MLC) leaf errors, linac jaws errors, monitor unit (MU) errors, MLC and gantry angle errors, and detector shift errors. QA was performed on each plan using a single ion chamber and 2D array of ion chambers for 2D and 3D QA. Based on the measurements performed, we established a uniform set of tolerance levels to determine if QA passes for each IMRT treatment plan structure: maximum allowed AADD is 6%; maximum 4% of any structure volume can be with ADD6 greater than 6%, and maximum 4% of any structure volume may fail 3D gamma test with test parameters 3%/3 mm DTA. Out of the three QA methods tested the single ion chamber performed the worst by detecting 4 out of 18 introduced errors, 2D QA detected 11 out of 18 errors, and 3D QA detected 14 out of 18 errors.PACS number: 87.56.Fc

A novel 3D prostate cancer bone marrow metastasis in vitro model system

A novel 3D prostate cancer bone marrow metastasis in vitro model system

WE‐EF‐210‐08: BEST IN PHYSICS (IMAGING): 3D Prostate Segmentation in Ultrasound Images Using Patch‐Based Anatomical Feature

Purpose:Transrectal ultrasound (TRUS) is the standard imaging modality for the image‐guided prostate‐cancer interventions (e.g., biopsy and brachytherapy) due to its versatility and real‐time capability. Accurate segmentation of the prostate plays a key role in biopsy needle placement, treatment planning, and motion monitoring. As ultrasound images have a relatively low signal‐to‐noise ratio (SNR), automatic segmentation of the prostate is difficult. However, manual segmentation during biopsy or radiation therapy can be time consuming. We are developing an automated method to address this technical challenge.Methods:The proposed segmentation method consists of two major stages: the training stage and the segmentation stage. During the training stage, patch‐based anatomical features are extracted from the registered training images with patient‐specific information, because these training images have been mapped to the new patient’ images, and the more informative anatomical features are selected to train the kernel support vector machine (KSVM). During the segmentation stage, the selected anatomical features are extracted from newly acquired image as the input of the well‐trained KSVM and the output of this trained KSVM is the segmented prostate of this patient.Results:This segmentation technique was validated with a clinical study of 10 patients. The accuracy of our approach was assessed using the manual segmentation. The mean volume Dice Overlap Coefficient was 89.7±2.3%, and the average surface distance was 1.52 ± 0.57 mm between our and manual segmentation, which indicate that the automatic segmentation method works well and could be used for 3D ultrasound‐guided prostate intervention.Conclusion:We have developed a new prostate segmentation approach based on the optimal feature learning framework, demonstrated its clinical feasibility, and validated its accuracy with manual segmentation (gold standard). This segmentation technique could be a useful tool for image‐guided interventions in prostate‐cancer diagnosis and treatment.This research is supported in part by DOD PCRP Award W81XWH‐13‐1‐0269, and National Cancer Institute (NCI) Grant CA114313.

Enhancing Accumulation and Penetration of HPMA Copolymer-Doxorubicin Conjugates in 2D and 3D Prostate Cancer Cells via iRGD Conjugation with an MMP-2 Cleavable Spacer.

To enhance the accumulation and penetration of nanomedicines in tumor tissue, we developed and evaluated the biological properties of matrix metalloproteinase 2 (MMP-2)-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer drugs and tumor-penetrating peptide conjugates (P-DOX-PLGLAG-iRGD). Two different spacers were used in the design: a lysosomally (cathepsin B) cleavable tetrapeptide GFLG spacer conjugated doxorubicin (DOX) to HPMA copolymer, and an MMP-2-degradable linker (PLGLAG) connected tumor-homing and -penetrating cyclic peptide iRGD to HPMA copolymer. The accumulation of DOX in P-DOX-PLGLAG-iRGD-treated monolayer (2D) and multilayer (3D) DU-145 prostate cancer cells was higher than that of control groups (P-DOX and P-DOX + iRGD). The cell cycle arrest analysis and cytotoxicity data demonstrated that P-DOX-PLGLAG-iRGD produced a higher G2/M arrest and possessed stronger cytotoxicity against DU-145 cells than P-DOX + iRGD or P-DOX, which was consistent with the drug uptake results. Similarly, P-DOX-PLGLAG-iRGD demonstrated the highest penetration ability in 3D multicellular DU-145 tumor cell spheroids. The results indicate that covalent conjugation of iRGD via MMP-2-sensitive bonds enhances accumulation and penetration of nanomedicines into tumor cell monolayers and spheroids.

Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel-Conjugate Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D Models.

The 2D monolayer cell culture model is often the first step in the prediction of the success or failure of a nanoparticle-based drug delivery system. However, there is often poor translation between the 2D monolayer in vitro results and the nanoparticle-drug performance in vivo. One possible way of bridging this gap is the use of multicellular tumor spheroids (MCTSs) as an intermediate in vitro model due to its 3D structure. This paper aims to quantify and compare the results obtained from traditional 2D monolayer cell cultures and 3D MCTS by studying the cytotoxic effects of free paclitaxel (PTX) and paclitaxel, which has been conjugated to a poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer and self-assembled to give a micellar delivery system. The core of the micelle was cross-linked with a diamino nondegradable cross-linker to compare the effects of micelle stability on the results. Although the 2D prostate tumor cell culture results indicated that all micellar variants (IC50: 193-271 nM) were significantly less toxic than free paclitaxel (IC50: 15.2 nM), the micelles showed faster and higher cytotoxicity than free PTX in the 3D prostate MCTS. The cross-linking of micelles even showed accelerated antitumor activities to the MCTS compared with un-cross-linked micelles. The results indicate that DAO-cross-linked POEGMEA-b-PCEA-PTX conjugate micelles will be a useful nanodrug carrier for prostate cancer therapy. MCTS offers a very promising method of incorporating 3D structures into in vitro testing.

PD4-12 3D ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTICITY IMAGING OF PROSTATE CANCER: CORRELATION BETWEEN IN VIVO IMAGING AND WHOLE MOUNT HISTOLOGY

You have accessJournal of UrologyImaging/Radiology: Uroradiology I1 Apr 2015PD4-12 3D ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTICITY IMAGING OF PROSTATE CANCER: CORRELATION BETWEEN IN VIVO IMAGING AND WHOLE MOUNT HISTOLOGY Melissa Mendez, Mark Palmeri, Zachary Miller, Tyler Glass, Stephen Rosenzweig, Andrew Buck, John Madden, Thomas Polascik, and Kathryn Nightingale Melissa MendezMelissa Mendez More articles by this author , Mark PalmeriMark Palmeri More articles by this author , Zachary MillerZachary Miller More articles by this author , Tyler GlassTyler Glass More articles by this author , Stephen RosenzweigStephen Rosenzweig More articles by this author , Andrew BuckAndrew Buck More articles by this author , John MaddenJohn Madden More articles by this author , Thomas PolascikThomas Polascik More articles by this author , and Kathryn NightingaleKathryn Nightingale More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.324AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Novel imaging systems are becoming available that may allow for robust, real-time localization of aggressive prostate cancer [PCa] for targeted biopsy and focal therapy applications. In this study, Acoustic Radiation Force Impulse Imaging [ARFI] was assessed for its ability to localize aggressive and indolent disease through comparison to whole mount histopathology. METHODS 29 patients with biopsy confirmed Pca scheduled for radical prostatectomy underwent ARFI imaging using a Siemens Acuson SC2000 scanner with an ER7B side-fire probe. A 3D ARFI prostate volume was acquired immediately prior to surgery. The excised prostate was whole mount sectioned, stained, and inked for Pca. ARFI image volumes were then reviewed and regions suspicious for cancer [ROIs] were identified, blinded to histopathology, and assigned an index of suspicion based on a 3 point scale. The approximate centers of the ARFI ROIs and histopathology lesions were mapped to a standardized 27 region anatomic grid, and correlated using a nearest neighbor approach. Hisotopathology lesions were stratified into four categories: posterior/anterior aggressive and posterior/anterior indolent disease. Indolent disease was considered any lesion with a volume less than 0.5 cm3 and a Gleason grade of 3. Aggressive disease was considered any lesion with a volume more than 0.5 cm3 and/or a Gleason grade greater than 3. RESULTS A total of 49 lesions were identified on histopathology. ARFI identified 29 ROIs, and 27 of these ROIs [PPV: 93.1%, 27/29] correlated with histopathology lesions. We found that ARFI was more sensitive to posterior lesions [Overall: 65%, 26/40; Aggressive disease: 74%, 23/31; Indolent disease: 33%, 3/9] than anterior lesions [Overall: 11%, 1/9; Aggressive Disease: 14%, 1/7; Indolent Disease: none]. CONCLUSIONS ARFI consistently identified pathologically aggressive cancers more commonly than indolent lesions. ARFI's high PPV coupled with its sensitivity toward aggressive disease offers a promising low−cost, portable, real time imaging modality in both diagnostic targeted biopsy and focal, image−guided therapy. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e91 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Melissa Mendez More articles by this author Mark Palmeri More articles by this author Zachary Miller More articles by this author Tyler Glass More articles by this author Stephen Rosenzweig More articles by this author Andrew Buck More articles by this author John Madden More articles by this author Thomas Polascik More articles by this author Kathryn Nightingale More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Rotationally resliced 3D prostate TRUS segmentation using convex optimization with shape priors.

Efficient and accurate segmentations of 3D end-firing transrectal ultrasound (TRUS) images play an important role in planning of 3D TRUS guided prostate biopsy. However, poor image quality of the input 3D TRUS images, such as strong imaging artifacts and speckles, often makes it a challenging task to extract the prostate boundaries accurately and efficiently. In this paper, the authors propose a novel convex optimization-based approach to delineate the prostate surface from a given 3D TRUS image, which reduces the original 3D segmentation problem to a sequence of simple 2D segmentation subproblems over the rotational reslices of the 3D TRUS volume. Essentially, the authors introduce a novel convex relaxation-based contour evolution approach to each 2D slicewise image segmentation with the joint optimization of shape information, where the learned 2D nonlinear statistical shape prior is incorporated to segment the initial slice, its result is propagated as a shape constraint to the segmentation of the following slices. In practice, the proposed segmentation algorithm is implemented on a GPU to achieve the high computational performance. Experimental results using 30 patient 3D TRUS images show that the proposed method can achieve a mean Dice similarity coefficient of 93.4% ± 2.2% in 20 s for one 3D image, outperforming the existing local-optimization-based methods, e.g., level-set and active-contour, in terms of accuracy and efficiency. In addition, inter- and intraobserver variability experiments show its good reproducibility. A semiautomatic segmentation approach is proposed and evaluated to extract the prostate boundary from 3D TRUS images acquired by a 3D end-firing TRUS guided prostate biopsy system. Experimental results suggest that it may be suitable for the clinical use involving the image guided prostate biopsy procedures.

3D sandwich-type prostate specific antigen (PSA) immunosensor based on rGO–MWCNT–Pd nanocomposite

A signal amplifying sandwich-type immunosensor with a wide linear range and a low detection limit is developed with potential clinical and diagnostic applications.

The first clinical treatment with kilovoltage intrafraction monitoring (KIM): a real-time image guidance method.

Kilovoltage intrafraction monitoring (KIM) is a real-time image guidance method that uses widely available radiotherapy technology, i.e., a gantry-mounted x-ray imager. The authors report on the geometric and dosimetric results of the first patient treatment using KIM which occurred on September 16, 2014. KIM uses current and prior 2D x-ray images to estimate the 3D target position during cancer radiotherapy treatment delivery. KIM software was written to process kilovoltage (kV) images streamed from a standard C-arm linear accelerator with a gantry-mounted kV x-ray imaging system. A 120° pretreatment kV imaging arc was acquired to build the patient-specific 2D to 3D motion correlation. The kV imager was activated during the megavoltage (MV) treatment, a dual arc VMAT prostate treatment, to estimate the 3D prostate position in real-time. All necessary ethics, legal, and regulatory requirements were met for this clinical study. The quality assurance processes were completed and peer reviewed. During treatment, a prostate position offset of nearly 3 mm in the posterior direction was observed with KIM. This position offset did not trigger a gating event. After the treatment, the prostate motion was independently measured using kV/MV triangulation, resulting in a mean difference of less than 0.6 mm and standard deviation of less than 0.6 mm in each direction. The accuracy of the marker segmentation was visually assessed during and after treatment and found to be performing well. During treatment, there were no interruptions due to performance of the KIM software. For the first time, KIM has been used for real-time image guidance during cancer radiotherapy. The measured accuracy and precision were both submillimeter for the first treatment fraction. This clinical translational research milestone paves the way for the broad implementation of real-time image guidance to facilitate the detection and correction of geometric and dosimetric errors, and resultant improved clinical outcomes, in cancer radiotherapy.

Spatially varying accuracy and reproducibility of prostate segmentation in magnetic resonance images using manual and semiautomated methods.

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.

MRI Ultrasound Fusion-Guided Biopsy of the Prostate: Results of Initial Experience in a Radiation Oncology Department

Multiparametric MRI (MP-MRI) has been integrated into our radiation oncology practice to guide treatment for men who are seen for active surveillance (AS) management or for MP-MRI imaging after non-diagnostic biopsy. Standard 12 core transrectal ultrasound (TRUS)-guided prostate biopsy has poor sensitivity and specificity. We have adopted a targeted biopsy approach using real time MRI-ultrasound (US) fusion on a commercially available 3D US prostate biopsy system. In this report, we summarize our experience with MRI-US fusion-guided biopsy (MUFgBx) to evaluate the impact on therapeutic recommendations. There were 29 men identified retrospectively who underwent MUFgBx since Aug 2012. All patients had MP-MRI to identify dominant/suspicious prostate lesions, which were contoured in the system-specific software. The managing radiation oncologist requested MUFgBx by one urologist who utilized a TRUS end-fire probe to generate a 3D prostate image from both MRI and US modalities, which were registered using an adaptive focus deformable model. A total of 29 MUFgBx sessions were performed in patients with median age of 68 years (range, 53 - 86). There were 9 patients under AS at the time of MUFgBx. Following a non-diagnostic TRUS-guided biopsy, 4 patients underwent MUFgBx after MP-MRI revealed a suspicious lesion. MUFgBx was utilized in 13 patients to assess a lesion that would receive an RT boost dose as part of an in-house clinical protocol. There were 3 patients who had never received a biopsy prior to MUFgBx. Patients were divided into 2 groups to analyze the learning curve of the MUFgBx program. Group 1 (G1) included 18 MUFgBx sessions during the first 10 months and Group 2 (G2) included 11 MUFgBx sessions in the most recent 8 months. MUFgBx yielded a positive biopsy in 17 of 29 patients. G1 had a positive MUFgBx yield of 44.4% while G2 had a positive MUFgBx yield of 81.8%, which showed a trend toward significance (p = 0.11). MUFgBx upgraded 2 of 9 patients on active surveillance from Gleason 6 to 7, which converted them to primary treatment. Overall, 5 patients had Gleason upgrade after MUFgBx. There were 9 of 12 patients who had positive MUFgBx prior to boost RT dose for in-house protocol. In total, there were 42 of 187 positive MUFgBx cores (22.5%). The yield of positive MUFgBx cores in Group 1 was 11% (n = 109) and the yield for Group 2 was 38.5% (n = 78). Our experience with prostate MUFgBx suggests that the method provides a novel tool for targeted assessment of dominant lesions on MP-MRI. Based on our single institution experience, the learning curve appears to be approximately 20 procedures. Our encouraging preliminary results suggest that the radiation oncology community should further investigate utilization of this technology in the management of active surveillance patients and in patients that may benefit from RT boost to dominant lesions.

3D label-free prostate specific antigen (PSA) immunosensor based on graphene–gold composites

Highly sensitive and label-free detection of the prostate specific antigen (PSA) remains a challenge in the diagnosis of prostate cancer. Here, a novel three-dimensional (3D) electrochemical immunosensor capable of sensitive and label-free detection of PSA is reported. This unique immunosensor is equipped with a highly conductive graphene (GR)-based gold (Au) composite modified electrode. The GR-based Au composite is prepared using aerosol spray pyrolysis and the morphology of the composite is the shape of a crumpled GR ball decorated with Au nanoparticles. Unlike the previous research, this novel 3D immunosensor functions very well over a broad linear range of 0–10ng/mL with a low detection limit of 0.59ng/mL; furthermore, it exhibits a significantly increased electron transfer and high sensitivity toward PSA. The highest rate of current change with respect to the PSA concentration is 5μA/(ng/mL). Satisfactory selectivity, reproducibility, and stability of the 3D immunosensor are also exhibited.

The impact of stool and gas volume on intrafraction prostate motion in patients undergoing radiotherapy with daily endorectal balloon

PurposeThe aim of this study was to quantify the impact of rectal stool/gas volumes on intrafraction prostate motion for patients undergoing prostate radiotherapy with daily endorectal balloon (ERB). MethodsTotal and anterior stool/gas rectal volumes were quantified in 30 patients treated with daily ERB. Real-time intrafraction prostate motion from 494 treatment sessions, at most 6min in length, was evaluated using Calypso® tracking system. ResultsThe deviation of prostate intrafraction motion distribution was a function of stool/gas volume, especially when stool/gas is located in the anterior part of the rectum. Compared to patients with small anterior stool/gas volumes (<10cm3), those with large volume (10–60cm3) had a twofold increase in 3D prostate motion and interquartile data range within the 6th minute of treatment time. The 10% of the overall CBCT session where large anterior rectal volumes were observed demonstrated larger percentage of time at displacement greater than our proposed internal margin 3mm. ConclusionVolume and location of stool/gas can directly impact the ERB’s intrafraction immobilization ability. Although our patient preparation protocol and the 100cm3 daily ERB effectively stabilized prostate motion for 90% of the fractions, a larger-sized ERB may improve prostate fixation for patients with greater and/or variable daily rectal volume.