Matthias Roethke

A Novel Stereotactic Prostate Biopsy System Integrating Pre-Interventional Magnetic Resonance Imaging and Live Ultrasound Fusion

PURPOSE We developed an effective way to precisely diagnose prostate cancer using a novel prostate biopsy system that integrates pre-interventional magnetic resonance imaging with peri-interventional ultrasound for perineal navigated prostate biopsy. MATERIALS AND METHODS A total of 106 men with findings suspicious for prostate cancer (median age 66 years, prostate specific antigen 8.0 ng/ml and prostate volume 47 ml) underwent multiparametric 3 Tesla magnetic resonance imaging. Suspicious lesions were marked and data were transferred to the novel biopsy system. Using a custom-made biplane transrectal ultrasound probe mounted on a stepper we gathered 3-dimensional ultrasound data and fused them with magnetic resonance imaging data. As a result, suspicious magnetic resonance imaging lesions were superimposed over the transrectal ultrasound data. Three-dimensional biopsy planning was done, including systematic biopsies. Perineal biopsies were taken under live ultrasound guidance and the precise site of each biopsy was documented in 3 dimensions. We evaluated feasibility, safety and cancer detection. RESULTS Prostate cancer was detected in 63 of 106 patients (59.4%). Magnetic resonance imaging findings correlated positively with histopathology in 71 of 103 patients (68.9%). In magnetic resonance imaging lesions marked as highly suspicious, the detection rate was 95.8% (23 of 24 cases). Lesion targeted cores had a significantly higher positivity rate than nontargeted cores. The procedural targeting error of the first 2,461 biopsy cores was 1.7 mm. Regarding adverse effects, 2 patients experienced urinary retention and 1 had a perineal hematoma. Urinary tract infections did not develop. CONCLUSIONS Perineal stereotactic prostate biopsies guided by the combination of magnetic resonance imaging and ultrasound enable effective examination of suspicious magnetic resonance imaging lesions. Each biopsy core taken is documented accurately for its location in 3 dimensions, enabling magnetic resonance imaging validation and tailored treatment planning. The morbidity of the procedure was minimal.

Critical Evaluation of Magnetic Resonance Imaging Targeted, Transrectal Ultrasound Guided Transperineal Fusion Biopsy for Detection of Prostate Cancer

PURPOSE Diagnosis and precise risk stratification of prostate cancer is essential for individualized treatment decisions. Magnetic resonance imaging/transrectal ultrasound fusion has shown encouraging results for detecting clinically significant prostate cancer. We critically evaluated magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy in routine clinical practice. MATERIALS AND METHODS Included in this prospective study were 347 consecutive patients with findings suspicious for prostate cancer. Median age was 65 years (range 42 to 84) and mean prostate specific antigen was 9.85 ng/ml (range 0.5 to 104). Of the men 49% previously underwent transrectal ultrasound guided biopsies, which were negative, and 51% underwent primary biopsy. In all patients 3 Tesla multiparametric magnetic resonance imaging was done. Systematic stereotactic prostate biopsies plus magnetic resonance imaging targeted, transrectal ultrasound guided biopsies were performed in those with abnormalities on magnetic resonance imaging. Imaging data and biopsy results were analyzed. A self-designed questionnaire was sent to all men on further clinical history and biopsy adverse effects. RESULTS Of 347 patients biopsy samples of 200 (58%) showed prostate cancer and 73.5% of biopsy proven prostate cancer were clinically relevant according to National Comprehensive Cancer Network (NCCN) criteria. On multiparametric magnetic resonance imaging 104 men had findings highly suspicious for prostate cancer. The tumor detection rate was 82.6% (86 of 104 men) with a Gleason score of 7 or greater in 72%. Overall targeted cores detected significantly more cancer than systematic biopsies (30% vs 8.2%). Of 94 patients without cancer suspicious lesions on magnetic resonance imaging 11 (11.7%) were diagnosed with intermediate risk disease. Regarding adverse effects, 152 of 300 patients (50.6%) reported mild hematuria, 26% had temporary erectile dysfunction and 2.6% needed short-term catheterization after biopsy. Nonseptic febrile urinary tract infections developed in 3 patients (1%). CONCLUSIONS Magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy provides high detection of clinically significant tumors. Since multiparametric magnetic resonance imaging still has some limitations, systematic biopsies should currently not be omitted. The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting.

Comparative Analysis of Transperineal Template Saturation Prostate Biopsy Versus Magnetic Resonance Imaging Targeted Biopsy with Magnetic Resonance Imaging-Ultrasound Fusion Guidance

PURPOSE Multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy may improve the detection of clinically significant prostate cancer. However, standardized prospective evaluation is limited. MATERIALS AND METHODS A total of 294 consecutive men with suspicion of prostate cancer (186 primary, 108 repeat biopsies) enrolled in 2013 underwent 3T multiparametric magnetic resonance imaging (T2-weighted, diffusion weighted, dynamic contrast enhanced) without endorectal coil and systematic transperineal cores (median 24) independently of magnetic resonance imaging suspicion and magnetic resonance imaging targeted cores with software registration (median 4). The highest Gleason score from each biopsy method was compared. McNemars tests were used to evaluate detection rates. Predictors of Gleason score 7 or greater disease were assessed using logistic regression. RESULTS Overall 150 cancers and 86 Gleason score 7 or greater cancers were diagnosed. Systematic, transperineal biopsy missed 18 Gleason score 7 or greater tumors (20.9%) while targeted biopsy did not detect 11 (12.8%). Targeted biopsy of PI-RADS 2-5 alone overlooked 43.8% of Gleason score 6 tumors. McNemars tests for detection of Gleason score 7 or greater cancers in both modalities were not statistically significant but showed a trend of superiority for targeted primary biopsies (p=0.08). Sampling efficiency was in favor of magnetic resonance imaging targeted prostate biopsy with 46.0% of targeted biopsy vs 7.5% of systematic, transperineal biopsy cores detecting Gleason score 7 or greater cancers. To diagnose 1 Gleason score 7 or greater cancer, 3.4 targeted and 7.4 systematic biopsies were needed. Limiting biopsy to men with PI-RADS 3-5 would have missed 17 Gleason score 7 or greater tumors (19.8%), demonstrating limited magnetic resonance imaging sensitivity. PI-RADS scores, digital rectal examination findings and prostate specific antigen greater than 20 ng/ml were predictors of Gleason score 7 or greater disease. CONCLUSIONS Compared to systematic, transperineal biopsy as a reference test, magnetic resonance imaging targeted biopsy alone detected as many Gleason score 7 or greater tumors while simultaneously mitigating the detection of lower grade disease. The gold standard for cancer detection in primary biopsy is a combination of systematic and targeted cores.

Multiparametric Magnetic Resonance Imaging (MRI) and MRI–Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen

BACKGROUND Multiparametric magnetic resonance imaging (mpMRI) and MRI fusion targeted biopsy (FTB) detect significant prostate cancer (sPCa) more accurately than conventional biopsies alone. OBJECTIVE To evaluate the detection accuracy of mpMRI and FTB on radical prostatectomy (RP) specimen. DESIGN, SETTING AND PARTICIPANTS From a cohort of 755 men who underwent transperineal MRI and transrectal ultrasound fusion biopsy under general anesthesia between 2012 and 2014, we retrospectively analyzed 120 consecutive patients who had subsequent RP. All received saturation biopsy (SB) in addition to FTB of lesions with Prostate Imaging Reporting and Data System (PI-RADS) score ≥2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The index lesion was defined as the lesion with extraprostatic extension, the highest Gleason score (GS), or the largest tumor volume (TV) if GS were the same, in order of priority. GS 3+3 and TV ≥1.3ml or GS ≥3+4 and TV ≥0.55ml were considered sPCa. We assessed the detection accuracy by mpMRI and different biopsy approaches and analyzed lesion agreement between mpMRI and RP specimen. RESULTS AND LIMITATIONS Overall, 120 index and 71 nonindex lesions were detected. Overall, 107 (89%) index and 51 (72%) nonindex lesions harbored sPCa. MpMRI detected 110 of 120 (92%) index lesions, FTB (two cores per lesion) alone diagnosed 96 of 120 (80%) index lesions, and SB alone diagnosed 110 of 120 (92%) index lesions. Combined SB and FTB detected 115 of 120 (96%) index foci. FTB performed significantly less accurately compared with mpMRI (p=0.02) and the combination for index lesion detection (p=0.002). Combined FTB and SB detected 97% of all sPCa lesions and was superior to mpMRI (85%), FTB (79%), and SB (88%) alone (p<0.001 each). Spearmans rank correlation coefficient for index lesion agreement between mpMRI and RP was 0.87 (p<0.001). Limitations included the retrospective design, multiple operators, and nonblinding of radiologists. CONCLUSIONS MpMRI identified 92% of index lesions compared with RP histopathology. The combination of FTB and SB was superior to both approaches alone, reliably detecting 97% of sPCa lesions. PATIENT SUMMARY Multiparametric magnetic resonance imaging detects the index lesion accurately in 9 of 10 patients; however, the combined biopsy approach, while missing less significant cancer, comes at the cost of detecting more insignificant cancer.

Quantitative Susceptibility Mapping Differentiates between Blood Depositions and Calcifications in Patients with Glioblastoma

Objectives The application of susceptibility weighted imaging (SWI) in brain tumor imaging is mainly used to assess tumor-related “susceptibility based signals” (SBS). The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM), is able to distinguish between both entities reliably. Materials and Methods SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication). Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps. Results 43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps. Conclusions QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of calcification in the context of different therapy regimes.

Primary Central Nervous System Lymphoma and Atypical Glioblastoma: Multiparametric Differentiation by Using Diffusion-, Perfusion-, and Susceptibility-weighted MR Imaging

PURPOSE To compare multiparametric diagnostic performance with diffusion-weighted, dynamic susceptibility-weighted contrast material-enhanced perfusion-weighted, and susceptibility-weighted magnetic resonance (MR) imaging for differentiating primary central nervous system lymphoma (PCNSL) and atypical glioblastoma. MATERIALS AND METHODS This retrospective study was institutional review board-approved and informed consent was waived. Pretreatment MR imaging was performed in 314 patients with glioblastoma, and a subset of 28 patients with glioblastoma of atypical appearance (solid enhancement with no visible necrosis) was selected. Parameters of diffusion-weighted (apparent diffusion coefficient [ADC]), susceptibility-weighted (intratumoral susceptibility signals [ITSS]), and dynamic susceptibility-weighted contrast-enhanced perfusion-weighted (relative cerebral blood volume [rCBV]) imaging were evaluated in these 28 patients with glioblastoma and 19 immunocompetent patients with PCNSL. A two-sample t test and χ(2) test were used to compare parameters.The diagnostic performance for differentiating PCNSL from glioblastoma was evaluated by using logistic regression analyses with leave-one-out cross validation. RESULTS Minimum, maximum, and mean ADCs and maximum and mean rCBVs were significantly lower in patients with PCNSL than in those with glioblastoma (P < .01, respectively), whereas mean ADCs and mean rCBVs allowed the best diagnostic performance. Presence of ITSS was significantly lower in patients with PCNSL (32% [six of 19]) than in those with glioblastoma (82% [23 of 28]) (P < .01). Multiparametric assessment of mean ADC, mean rCBV, and presence of ITSS significantly increased the probability for differentiating PCNSL and atypical glioblastoma compared with the evaluation of one or two imaging parameters (P < .01), thereby correctly predicting histologic results in 95% (18 of 19) of patients with PCNSL and 96% (27 of 28) of patients with atypical glioblastoma. CONCLUSION Combined evaluation of mean ADC, mean rCBV, and presence of ITSS allowed reliable differentiation of PCNSL and atypical glioblastoma in most patients, and these results support an integration of advanced MR imaging techniques for the routine diagnostic workup of patients with these tumors.

Histology core‐specific evaluation of the European Society of Urogenital Radiology (ESUR) standardised scoring system of multiparametric magnetic resonance imaging (mpMRI) of the prostate

To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single‐core histology. To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI.

Evaluation of Diffusion Kurtosis Imaging Versus Standard Diffusion Imaging for Detection and Grading of Peripheral Zone Prostate Cancer.

ObjectivesThe purpose of the study was to evaluate and validate diffusion kurtosis imaging (DKI) for detection grading of peripheral zone prostate cancer (PCa) compared with standard diffusion-weighted imaging (DWI) in a cohort of patients with biopsy-proven PCa. Materials and MethodsIn this retrospective, single-institutional study, 55 patients (age, 67.5 ± 6.9 years; range, 52–84 years) who underwent multiparametric magnetic resonance imaging (MRI) before transperineal magnetic resonance/transrectal ultrasound-guided fusion biopsy were included. Suspicious lesions identified in multiparametric MRI underwent image-guided targeted biopsy procedure using a hybrid magnetic resonance/transrectal ultrasound-guided fusion biopsy system. Multiparametric MRI examinations were performed at 3.0 T using a 16-channel phased array coil. Diffusion kurtosis imaging has been acquired with 9 b values (0, 50, 250, 500, 750, 1000, 1250, 1500, and 2000 s/mm2). In patients with histologically proven PCa, a representative tumor region was determined as region of interest (ROI) on axial T2-weighted images in consensus by 2 board-certified radiologists. For quantitative evaluation, ROIs located in malignant and contralateral tumor-free regions were transferred to diffusion-weighted images. Diffusion kurtosis imaging parameters (Dapp and Kapp) and apparent diffusion coefficient (ADC) values of the ROIs in tumor and contralateral remote areas were calculated. Estimation of the kurtosis-derived parameters was performed using a voxel-by-voxel fit followed by an ROI-based averaging and a second fit to ROI-averaged signal values. A subgroup analysis was performed to determine the influence of aggressiveness of PCa using ADC, Dapp, and Kapp. The receiver operating characteristic (ROC) curves were calculated for DKI parameters and ADC values. ResultsIn the 55 patients, the average prostate-specific antigen level was 12.4 ± 12.6 ng/mL (range, 2.7–75.0 ng/mL), and the median Gleason score was 7 (range, 6–10). Dapp (units, 10−3 mm2/s) was significantly lower in tumor compared with control regions (1.48 ± 0.35 vs 2.00 ± 0.32, P < 0.05), and Kapp was significantly higher (1.01 ± 0.21 vs 0.76 ± 0.14, P < 0.05). Dapp was significantly higher than standard ADC (units, 10−3 mm2/s) both in tumor regions and in controls (1.48 ± 0.35 vs 1.10 ± 0.25 and 2.00 ± 0.32 vs 1.43 ± 0.25, P < 0.05). Neither the ROI-based calculation of the kurtosis parameters nor the application of the noise correction significantly changed the DKI parameter estimation. There was no significant difference for the applied fitting method for DKI-derived parameters considering the differentiation between tumor and control tissue. Subsequent ROC analyses did not reveal a significant difference between DKI and ADC for detection of PCa. Sensitivities derived by Youden J statistics cutoff values ranged from 69% to 91% for DKI parameters; specificities ranged from 71% to 89%. Subgroup analysis for DKI (Dapp, Kapp) and ADC for assessing aggressiveness of PCa found significant difference (P < 0.05) for discrimination between high- and low-grade findings. However, no significant difference could be obtained between standard DWI- and DKI-derived parameters. ConclusionsThe results of this study demonstrated no significant benefit of DKI for detection and grading of PCa as compared with standard ADC in the peripheral zone determined from b values of 0 and 800 s/mm2. For clinical routine application, ADC derived from monoexponential fitting of DWI data remains the standard for characterizing peripheral zone cancer of the prostate.

PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer

Ga-labelled PSMA ligandGlu-NH-CO-NH-Lys(Ahx)-HBED-CC.A 68-year-old patient was referred to our institution for radi-ation therapy planning and exclusion of distant metastases 4-months after biopsy-proven dia gnosis of left peripheral prostatecancer(PSA18.5ng/ml,Gleason score7).Whole-bodyPET/CT1 hour after injection of 171 MBq

Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg Study Group for Enhanced Prostate Diagnostics.

To define terms and processes and agree on a minimum dataset in relation to transperineal prostate biopsy procedures and enhanced prostate diagnostics. To identify the need for further evaluation and establish a collaborative research practice.