Jochen Kruecker

Magnetic Resonance Imaging/Ultrasound Fusion Guided Prostate Biopsy Improves Cancer Detection Following Transrectal Ultrasound Biopsy and Correlates With Multiparametric Magnetic Resonance Imaging

PURPOSE A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported. MATERIALS AND METHODS This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy. RESULTS Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging. CONCLUSIONS Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.

Magnetic Resonance Imaging/Ultrasound–Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy

BACKGROUND Gleason scores from standard, 12-core prostate biopsies are upgraded historically in 25-33% of patients. Multiparametric prostate magnetic resonance imaging (MP-MRI) with ultrasound (US)-targeted fusion biopsy may better sample the true gland pathology. OBJECTIVE The rate of Gleason score upgrading from an MRI/US-fusion-guided prostate-biopsy platform is compared with a standard 12-core biopsy regimen alone. DESIGN, SETTING, AND PARTICIPANTS There were 582 subjects enrolled from August 2007 through August 2012 in a prospective trial comparing systematic, extended 12-core transrectal ultrasound biopsies to targeted MRI/US-fusion-guided prostate biopsies performed during the same biopsy session. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The highest Gleason score from each biopsy method was compared. INTERVENTIONS An MRI/US-fusion-guided platform with electromagnetic tracking was used for the performance of the fusion-guided biopsies. RESULTS AND LIMITATIONS A diagnosis of prostate cancer (PCa) was made in 315 (54%) of the patients. Addition of targeted biopsy led to Gleason upgrading in 81 (32%) cases. Targeted biopsy detected 67% more Gleason ≥4+3 tumors than 12-core biopsy alone and missed 36% of Gleason ≤3+4 tumors, thus mitigating the detection of lower-grade disease. Conversely, 12-core biopsy led to upgrading in 67 (26%) cases over targeted biopsy alone but only detected 8% more Gleason ≥4+3 tumors. On multivariate analysis, MP-MRI suspicion was associated with Gleason score upgrading in the targeted lesions (p<0.001). The main limitation of this study was that definitive pathology from radical prostatectomy was not available. CONCLUSIONS MRI/US-fusion-guided biopsy upgrades and detects PCa of higher Gleason score in 32% of patients compared with traditional 12-core biopsy alone. Targeted biopsy technique preferentially detects higher-grade PCa while missing lower-grade tumors.

Real-time MRI-TRUS fusion for guidance of targeted prostate biopsies

Targeted prostate biopsy is challenging because no currently established imaging modality is both accurate for prostate cancer diagnosis and cost-effective for real-time procedure guidance. A system that fuses real-time transrectal ultrasound images with previously acquired endorectal coil MRI images for prostate biopsy guidance is presented here. The system uses electromagnetic tracking and intraoperative image registration to superimpose the MRI data on the ultrasound image. Prostate motion is tracked and compensated for without the need for fiducial markers. The accuracy of the system in phantom studies was shown to be 2.4 ± 1.2 mm. The fusion system has been used in more than 20 patients to guide biopsies with almost no modification of the conventional protocol. Retrospective clinical evaluation suggests that clinically acceptable spatial accuracy can be achieved.

Multiparametric Magnetic Resonance Imaging and Ultrasound Fusion Biopsy Detect Prostate Cancer in Patients with Prior Negative Transrectal Ultrasound Biopsies

PURPOSE Patients with negative transrectal ultrasound biopsies and a persistent clinical suspicion are at risk for occult but significant prostate cancer. The ability of multiparametric magnetic resonance imaging/ultrasound fusion biopsy to detect these occult prostate lesions may make it an effective tool in this challenging scenario. MATERIALS AND METHODS Between March 2007 and November 2011 all men underwent prostate 3 T endorectal coil magnetic resonance imaging. All concerning lesions were targeted with magnetic resonance imaging/ultrasound fusion biopsy. In addition, all patients underwent standard 12-core transrectal ultrasound biopsy. Men with 1 or more negative systematic prostate biopsies were included in our cohort. RESULTS Of the 195 men with previous negative biopsies, 73 (37%) were found to have cancer using the magnetic resonance imaging/ultrasound fusion biopsy combined with 12-core transrectal ultrasound biopsy. High grade cancer (Gleason score 8+) was discovered in 21 men (11%), all of whom had disease detected with magnetic resonance imaging/ultrasound fusion biopsy. However, standard transrectal ultrasound biopsy missed 12 of these high grade cancers (55%). Pathological upgrading occurred in 28 men (38.9%) as a result of magnetic resonance imaging/ultrasound fusion targeting vs standard transrectal ultrasound biopsy. The diagnostic yield of combined magnetic resonance imaging/ultrasound fusion platform was unrelated to the number of previous negative biopsies and persisted despite increasing the number of previous biopsy sessions. On multivariate analysis only prostate specific antigen density and magnetic resonance imaging suspicion level remained significant predictors of cancer. CONCLUSIONS Multiparametric magnetic resonance imaging with a magnetic resonance imaging/ultrasound fusion biopsy platform is a novel diagnostic tool for detecting prostate cancer and may be ideally suited for patients with negative transrectal ultrasound biopsies in the face of a persistent clinical suspicion for cancer.

Initial clinical experience with real‐time transrectal ultrasonography‐magnetic resonance imaging fusion‐guided prostate biopsy

To evaluate the feasibility and utility of registration and fusion of real‐time transrectal ultrasonography (TRUS) and previously acquired magnetic resonance imaging (MRI) to guide prostate biopsies.

Utility of Multiparametric Magnetic Resonance Imaging Suspicion Levels for Detecting Prostate Cancer

PURPOSE We determine the usefulness of multiparametric magnetic resonance imaging in detecting prostate cancer, with a specific focus on detecting higher grade prostate cancer. MATERIALS AND METHODS Prospectively 583 patients who underwent multiparametric magnetic resonance imaging and subsequent prostate biopsy at a single institution were evaluated. On multiparametric magnetic resonance imaging, lesions were identified and scored as low, moderate or high suspicion for prostate cancer based on a validated scoring system. Magnetic resonance/ultrasound fusion guided biopsies of magnetic resonance imaging lesions in addition to systematic 12-core biopsies were performed. Correlations between the highest assigned multiparametric magnetic resonance imaging suspicion score and presence of cancer and biopsy Gleason score on the first fusion biopsy session were assessed using univariate and multivariate logistic regression models. Sensitivity, specificity, negative predictive value and positive predictive value were calculated and ROC curves were developed to assess the discriminative ability of multiparametric magnetic resonance imaging as a diagnostic tool for various biopsy Gleason score cohorts. RESULTS Significant correlations were found between age, prostate specific antigen, prostate volume, and multiparametric magnetic resonance imaging suspicion score and the presence of prostate cancer (p<0.0001). On multivariate analyses controlling for age, prostate specific antigen and prostate volume, increasing multiparametric magnetic resonance imaging suspicion was an independent prognosticator of prostate cancer detection (OR 2.2, p<0.0001). Also, incremental increases in multiparametric magnetic resonance imaging suspicion score demonstrated stronger associations with cancer detection in patients with Gleason 7 or greater (OR 3.3, p<0.001) and Gleason 8 or greater (OR 4.2, p<0.0001) prostate cancer. Assessing multiparametric magnetic resonance imaging as a diagnostic tool for all prostate cancer, biopsy Gleason score 7 or greater, and biopsy Gleason score 8 or greater separately via ROC analyses demonstrated increasing accuracy of multiparametric magnetic resonance imaging for higher grade disease (AUC 0.64, 0.69, and 0.72, respectively). CONCLUSIONS Multiparametric magnetic resonance imaging is a clinically useful modality to detect and characterize prostate cancer, particularly in men with higher grade disease.

Intravoxel incoherent motion MR imaging for prostate cancer: An evaluation of perfusion fraction and diffusion coefficient derived from different b-value combinations

There has been a resurgent interest in intravoxel incoherent motion (IVIM) MR imaging to obtain perfusion as well as diffusion information on lesions, in which the diffusion was modeled as Gaussian diffusion. However, it was observed that this diffusion deviated from expected monoexponential decay at high b‐values and the reported perfusion in prostate is contrary to the findings in dynamic contrast‐enhanced (DCE) MRI studies and angiogenesis. Thus, this work is to evaluate the effect of different b‐values on IVIM perfusion fractions (f) and diffusion coefficients (D) for prostate cancer detection. The results show that both parameters depended heavily on the b‐values, and those derived without the highest b‐value correlated best with the results from DCE‐MRI studies; specifically, f was significantly elevated (7.2% vs. 3.7%) in tumors when compared with normal tissues, in accordance with the volume transfer constant (Ktrans; 0.39 vs. 0.18 min−1) and plasma fractional volume (vp; 8.4% vs. 3.4%). In conclusion, it is critical to choose an appropriate range of b‐values in studies or include the non‐Gaussian diffusion contribution to obtain unbiased IVIM measurements. These measurements could eliminate the need for DCE‐MRI, which is especially relevant in patients who cannot receive intravenous gadolinium‐based contrast media. Magn Reson Med, 2013.

Multimodality image fusion-guided procedures: technique, accuracy, and applications.

Personalized therapies play an increasingly critical role in cancer care: Image guidance with multimodality image fusion facilitates the targeting of specific tissue for tissue characterization and plays a role in drug discovery and optimization of tailored therapies. Positron-emission tomography (PET), magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CT) may offer additional information not otherwise available to the operator during minimally invasive image-guided procedures, such as biopsy and ablation. With use of multimodality image fusion for image-guided interventions, navigation with advanced modalities does not require the physical presence of the PET, MRI, or CT imaging system. Several commercially available methods of image-fusion and device navigation are reviewed along with an explanation of common tracking hardware and software. An overview of current clinical applications for multimodality navigation is provided.

Discrete Deformable Model Guided by Partial Active Shape Model for TRUS Image Segmentation

Automatic prostate segmentation in transrectal ultrasound (TRUS) images is highly desired in many clinical applications. However, robust and automated prostate segmentation is challenging due to the low SNR in TRUS and the missing boundaries in shadow areas caused by calcifications or hyperdense prostate tissues. This paper presents a novel method of utilizing a priori shapes estimated from partial contours for segmenting the prostate. The proposed method is able to automatically extract prostate boundary from 2-D TRUS images without user interaction for shape correction in shadow areas. During the segmentation process, missing boundaries in shadow areas are estimated by using a partial active shape model, which takes partial contours as input but returns a complete shape estimation. With this shape guidance, an optimal search is performed by a discrete deformable model to minimize an energy functional for image segmentation, which is achieved efficiently by using dynamic programming. The segmentation of an image is executed in a multiresolution fashion from coarse to fine for robustness and computational efficiency. Promising segmentation results were demonstrated on 301 TRUS images grabbed from 19 patients with the average mean absolute distance error of 2.01 mm ± 1.02 mm.

Simultaneous integrated boost of biopsy proven, MRI defined dominant intra-prostatic lesions to 95 Gray with IMRT: early results of a phase I NCI study

BackgroundTo assess the feasibility and early toxicity of selective, IMRT-based dose escalation (simultaneous integrated boost) to biopsy proven dominant intra-prostatic lesions visible on MRI.MethodsPatients with localized prostate cancer and an abnormality within the prostate on endorectal coil MRI were eligible. All patients underwent a MRI-guided transrectal biopsy at the location of the MRI abnormality. Gold fiducial markers were also placed. Several days later patients underwent another MRI scan for fusion with the treatment planning CT scan. This fused MRI scan was used to delineate the region of the biopsy proven intra-prostatic lesion. A 3 mm expansion was performed on the intra-prostatic lesions, defined as a separate volume within the prostate. The lesion + 3 mm and the remainder of the prostate + 7 mm received 94.5/75.6 Gray (Gy) respectively in 42 fractions. Daily seed position was verified to be within 3 mm.ResultsThree patients were treated. Follow-up was 18, 6, and 3 months respectively. Two patients had a single intra-prostatic lesion. One patient had 2 intra-prostatic lesions. All four intra-prostatic lesions, with margin, were successfully targeted and treated to 94.5 Gy. Two patients experienced acute RTOG grade 2 genitourinary (GU) toxicity. One had grade 1 gastrointestinal (GI) toxicity. All symptoms completely resolved by 3 months. One patient had no acute toxicity.ConclusionThese early results demonstrate the feasibility of using IMRT for simultaneous integrated boost to biopsy proven dominant intra-prostatic lesions visible on MRI. The treatment was well tolerated.