Martin T. Freitag

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.

Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32)

The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participants REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patients impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.

Combined Clinical Parameters and Multiparametric Magnetic Resonance Imaging for Advanced Risk Modeling of Prostate Cancer—Patient-tailored Risk Stratification Can Reduce Unnecessary Biopsies

BACKGROUND Multiparametric magnetic resonance imaging (mpMRI) is gaining widespread acceptance in prostate cancer (PC) diagnosis and improves significant PC (sPC; Gleason score≥3+4) detection. Decision making based on European Randomised Study of Screening for PC (ERSPC) risk-calculator (RC) parameters may overcome prostate-specific antigen (PSA) limitations. OBJECTIVE We added pre-biopsy mpMRI to ERSPC-RC parameters and developed risk models (RMs) to predict individual sPC risk for biopsy-naïve men and men after previous biopsy. DESIGN, SETTING, AND PARTICIPANTS We retrospectively analyzed clinical parameters of 1159 men who underwent mpMRI prior to MRI/transrectal ultrasound fusion biopsy between 2012 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariate regression analyses were used to determine significant sPC predictors for RM development. The prediction performance was compared with ERSPC-RCs, RCs refitted on our cohort, Prostate Imaging Reporting and Data System (PI-RADS) v1.0, and ERSPC-RC plus PI-RADSv1.0 using receiver-operating characteristics (ROCs). Discrimination and calibration of the RM, as well as net decision and reduction curve analyses were evaluated based on resampling methods. RESULTS AND LIMITATIONS PSA, prostate volume, digital-rectal examination, and PI-RADS were significant sPC predictors and included in the RMs together with age. The ROC area under the curve of the RM for biopsy-naïve men was comparable with ERSPC-RC3 plus PI-RADSv1.0 (0.83 vs 0.84) but larger compared with ERSPC-RC3 (0.81), refitted RC3 (0.80), and PI-RADS (0.76). For postbiopsy men, the novel RMs discrimination (0.81) was higher, compared with PI-RADS (0.78), ERSPC-RC4 (0.66), refitted RC4 (0.76), and ERSPC-RC4 plus PI-RADSv1.0 (0.78). Both RM benefits exceeded those of ERSPC-RCs and PI-RADS in the decision regarding which patient to receive biopsy and enabled the highest reduction rate of unnecessary biopsies. Limitations include a monocentric design and a lack of PI-RADSv2.0. CONCLUSIONS The novel RMs, incorporating clinical parameters and PI-RADS, performed significantly better compared with RMs without PI-RADS and provided measurable benefit in making the decision to biopsy men at a suspicion of PC. For biopsy-naïve patients, both our RM and ERSPC-RC3 plus PI-RADSv1.0 exceeded the prediction performance compared with clinical parameters alone. PATIENT SUMMARY Combined risk models including clinical and imaging parameters predict clinically relevant prostate cancer significantly better than clinical risk calculators and multiparametric magnetic resonance imaging alone. The risk models demonstrate a benefit in making a decision about which patient needs a biopsy and concurrently help avoid unnecessary biopsies.

4D respiratory motion-compensated image reconstruction of free-breathing radial MR data with very high undersampling.

To develop four‐dimensional (4D) respiratory time‐resolved MRI based on free‐breathing acquisition of radial MR data with very high undersampling.

68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer.

Purpose The aim of our study is to assess the pharmacokinetics and biodistribution of 68Ga-PSMA-11 in patients suffering from primary prostate cancer (PC) by means of dynamic and whole-body PET/CT. Materials and methods Twenty-four patients with primary, previously untreated PC were enrolled in the study. All patients underwent dynamic PET/CT (dPET/CT) scanning of the pelvis and whole-body PET/CT studies with 68Ga-PSMA-11. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on two-tissue compartment modeling and a noncompartmental approach leading to the extraction of fractal dimension (FD). Results A total of 23/24 patients (95.8%) were 68Ga-PSMA-11 positive. In 9/24 patients (37.5%), metastatic lesions were detected. PC-associated lesions demonstrated the following mean values: SUVaverage = 14.3, SUVmax = 23.4, K1 = 0.24 (1/min), k3 = 0.34 (1/min), influx = 0.15 (1/min), and FD = 1.27. The parameters SUVaverage, SUVmax, k3, influx, and FD derived from PC-associated lesions were significantly higher than respective values derived from reference prostate tissue. Time-activity curves derived from PC-associated lesions revealed an increasing 68Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate but significant correlation between PSA levels and SUVaverage (r = 0.60) and SUVmax (r = 0.57), and a weak but significant correlation between Gleason score and SUVaverage (r = 0.33) and SUVmax (r = 0.28). Conclusion 68Ga-PSMA-11 PET/CT confirmed its capacity in detecting primary PC with a detection rate of 95.8%. Dynamic PET/CT studies of the pelvis revealed an increase in tracer uptake in PC-associated lesions during the 60 minutes of dynamic PET acquisition, a finding with potential applications in anti-PSMA approaches.

Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance

Background:Active surveillance (AS) is commonly based on standard 10–12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS.Methods:In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan–Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification.Results:A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score-upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS⩽2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification.Conclusions:Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI.

Suitable reference tissues for quantitative susceptibility mapping of the brain

Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease.

The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High-Risk Prostate Cancer: Try to Find a Standard

PURPOSE To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. PATIENTS AND METHODS In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. RESULTS Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. CONCLUSION Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS.

In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI

To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI).

Respiratory motion compensation for simultaneous PET/MR based on highly undersampled MR data

PURPOSE Positron emission tomography (PET) of the thorax region is impaired by respiratory patient motion. To account for motion, the authors propose a new method for PET/magnetic resonance (MR) respiratory motion compensation (MoCo), which uses highly undersampled MR data with acquisition times as short as 1 min/bed. METHODS The proposed PET/MR MoCo method (4D jMoCo PET) uses radial MR data to estimate the respiratory patient motion employing MR joint motion estimation and image reconstruction with temporal median filtering. Resulting motion vector fields are incorporated into the system matrix of the PET reconstruction. The proposed approach is evaluated for the thorax region utilizing a PET/MR simulation with 1 min MR acquisition time and simultaneous PET/MR measurements of six patients with MR acquisition times of 1 and 5 min and radial undersampling factors of 11.2 and 2.2, respectively. Reconstruction results are compared to 3D PET, 4D gated PET and a standard MoCo method (4D sMoCo PET), which performs iterative image reconstruction and motion estimation sequentially. Quantitative analysis comprises the parameters SUVmean, SUVmax, full width at half-maximum/lesion volume, contrast and signal-to-noise ratio. RESULTS For simulated PET data, our quantitative analysis shows that the proposed 4D jMoCo PET approach with temporal filtering achieves the best quantification accuracy of all tested reconstruction methods with a mean absolute deviation of 2.3% when compared to the ground truth. For measured PET patient data, the mean absolute deviation of 4D jMoCo PET using a 1 min MR acquisition for motion estimation is 2.1% relative to the 5 min MR acquisition. This demonstrates a robust behavior even in case of strong undersampling at MR acquisition times as short as 1 min. In contrast, 4D sMoCo PET shows considerable reduction of quantification accuracy for the 1 min MR acquisition time. Relative to 3D PET, the proposed 4D jMoCo PET approach with temporal filtering yields an average increase of SUVmean, SUVmax, and contrast of 29.9% and 13.8% for simulated and measured PET data, respectively. CONCLUSIONS Employing artifact-robust motion estimation enables PET/MR respiratory MoCo with MR acquisition times as short as 1 min/bed improving PET image quality and quantification accuracy.