Interactive Explainable Deep Learning Model Informs Prostate Cancer Diagnosis at MRI.

Background Clinically significant prostate cancer (PCa) diagnosis at MRI requires accurate and efficient radiologic interpretation. Although artificial intelligence may assist in this task, lack of transparency has limited clinical translation. Purpose To develop an explainable artificial intelligence (XAI) model for clinically significant PCa diagnosis at biparametric MRI using Prostate Imaging Reporting and Data System (PI-RADS) features for classification justification. Materials and Methods This retrospective study included consecutive patients with histopathologic analysis-proven prostatic lesions who underwent biparametric MRI and biopsy between January 2012 and December 2017. After image annotation by two radiologists, a deep learning model was trained to detect the index lesion; classify PCa, clinically significant PCa (Gleason score ≥ 7), and benign lesions (eg, prostatitis); and justify classifications using PI-RADS features. Lesion- and patient-based performance were assessed using fivefold cross validation and areas under the receiver operating characteristic curve. Clinical feasibility was tested in a multireader study and by using the external PROSTATEx data set. Statistical evaluation of the multireader study included Mann-Whitney U and exact Fisher-Yates test. Results Overall, 1224 men (median age, 67 years; IQR, 62-73 years) had 3260 prostatic lesions (372 lesions with Gleason score of 6; 743 lesions with Gleason score of ≥ 7; 2145 benign lesions). XAI reliably detected clinically significant PCa in internal (area under the receiver operating characteristic curve, 0.89) and external test sets (area under the receiver operating characteristic curve, 0.87) with a sensitivity of 93% (95% CI: 87, 98) and an average of one false-positive finding per patient. Accuracy of the visual and textual explanations of XAI classifications was 80% (1080 of 1352), confirmed by experts. XAI-assisted readings improved the confidence (4.1 vs 3.4 on a five-point Likert scale; P = .007) of nonexperts in assessing PI-RADS 3 lesions, reducing reading time by 58 seconds (P = .009). Conclusion The explainable AI model reliably detected and classified clinically significant prostate cancer and improved the confidence and reading time of nonexperts while providing visual and textual explanations using well-established imaging features. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chapiro in this issue.

Injectable autologous chondrocyte implantation in acetabular cartilage defects: 2-year minimum clinical and MRI results.

INTRODUCTION: Early results using injectable autologous chondrocyte implantation (ACI) for the treatment of full thickness acetabular cartilage defects have been promising. However, so far there is no information on radiological results after injectable ACI using spheroids. The purpose of this sturdy was to (1) investigate the quality of tissue repair on MRI and (2) investigate the correlation between the MRI results and clinical results at a minimum follow-up of 24 months after third generation ACI in full thickness acetabular cartilage defects. It was hypothesized that ACI shows good MRI results in patients with large full thickness acetabular cartilage defects 24 months after surgery. It was also hypothesized that there is a correlation between postoperative clinical and MRI morphological results at a minimum follow-up of 24 months. STUDY DESIGN: Retrospective case series. MATERIALS AND METHODS: Patients with ACI for full thickness acetabular cartilage defects > 2 cm2 were evaluated by preoperative and postoperative clinical scoring tools including the modified Harris Hip Score (mHHS), the International Hip Outcome Tool (iHOT-33), and the Subjective Hip Value (SHV) as well as a high resolution indirect arthro-MRI 24 months after surgery utilizing an identical imaging protocol for all patients. The magnetic resonance observation of cartilage repair tissue (MOCART) scoring system was used to classify the repair tissue on MRI. Demographic patient data was evaluated for influencing factors for pre- and postoperative clinical as well as radiological results. RESULTS: Thirty six consecutive patients (5 women/31 men, average age 32.9 years) had undergone two stage ACI procedure. The average size of the cartilage defect was 5.0 (2-6) cm2. The average follow-up was 29.9 (24-42) months. Four patients were not available for the final follow-up (follow-up rate 89%). The postoperative average MOCART score was 82.2 (± 14.2). MOCART score showed medium correlation of the item defect fill and the postoperative mHHS (r = 0.384, p = 0.043). There was no correlation of the other items or the total score with postoperative results. The patients showed significant improvement in the outcome measurements between preoperative and postoperative in the mHHS, the iHOT-33, and the SHV. CONCLUSIONS: Despite the large acetabular cartilage defects included in this study, ACI showed good MRI results with complete defect fill in 87.5% after a minimum 24-month follow-up. Statistically significant correlation of MRI and clinical results could only be seen with the item defect fill. Further research with longer follow-up is needed to evaluate the long-term results of ACI in acetabular cartilage defects.

[Predictors of Legal Probation after Forensic Addiction Treatment: Review of the Determinants of Success of a Treatment order According to sec. 64 of the German Criminal Code - Part II]. / Prädiktoren der Legalbewährung nach forensischer Suchtbehandlung ­ Zweiter Teil einer Übersichtsarbeit zu Erfolgsdeterminanten einer Unterbringung gemäß § 64 StGB.

BACKGROUND: Before a forensic addiction treatment can be ordered by the court according to sec. 64 of the German Criminal Code (StGB), a prognosis of success must be made and affirmed. In recent years, several studies have been devoted to the search for appropriate predictors of a "sufficiently concrete" prospect of success. Legal probation after release is the legally stipulated criterion for success in forensic addiction treatment. OBJECTIVE: As the second part of a two-part review on the determinants of success in forensic addiction treatment, this paper aims to provide an overview of the current evidence on predictors of legal probation after forensic addiction treatment and relates this to the evidence to the predictors of the discharge mode. METHODOLOGY: Based on systematic literature research, the results of eight empirical studies published between 2002-2019 were processed in depth and presented in an overview table. RESULTS: Despite heterogeneous findings in detail, the presence of motivational, practical life and social resources, on the one hand, and criminal history and characteristics of current delinquency, on the other hand, show relatively clear relationships to legal probation after successful forensic addiction treatment. At the same time, the exclusive consideration of legal probation as the only criterion for the prognosis of treatment success reveals conceptual imprecision, since this is then overlaid by the criminal prognosis. CONCLUSION: The limitations of the current state of research suggest a two-step approach for the preparation of a treatment prognosis: first, the predictors of the discharge mode could be used to examine the question of the likelihood of success of a regular course of treatment; then, the predictors of legal probation could be used to examine whether any conclusions can be drawn on the relapse-preventive effect of forensic addiction treatment. Both parts of the review can thus support forensic psychiatric experts in making a reliable prognosis of treatment prospects. In addition, consideration should be given to whether the information base for experts could be improved, for example, through a probationary phase.

[Predictors of the discharge mode from forensic addiction treatment: Review of the determinants of success of a treatment order according to sec. 64 of the German Criminal Code (Part I)]. / Prädiktoren des Entlassmodus aus forensischer Suchtbehandlung ­ Erster Teil einer Übersichtsarbeit zu Erfolgsdeterminanten einer Unterbringung gemäß § 64 StGB.

BACKGROUND: Before a forensic addiction treatment can be ordered by court according to sec. 64 of the German Criminal Code (StGB), a success prognosis must be made and affirmed. The search for appropriate predictors for a "sufficiently concrete prospect of success" was the focus of several studies in recent years. In addition to legal probation, the mode of release from the measure, i.e. whether regular release on probation or an end of the accommodation due to a lack of prospect of success, represents the central success criterion of forensic addiction treatment. OBJECTIVES: As the first part of a two-part overview of the determinants of success in forensic addiction treatment, the aim of this paper was to provide an overview of the current state of knowledge on predictors of the discharge mode, both univariate and multivariate. METHODOLOGY: Based on a systematic literature search, the results of 16 empirical studies from the period 1999 to 2019 are summarized and presented in detail. Univariate findings on individual predictors are presented in an overview table, while multivariate results are summarized in "typical" treatment discontinuations. RESULTS: On a univariate level, the findings were predominantly heterogeneous. The factors personality disorder and psychopathy as well as "static" anamnestic factors such as criminal background could be considered as reasonably reliable predictors. Multivariate, in particular the combination of an early onset of delinquency, a problematic social and/or occupational or educational background together with certain personality components, indicated a very high risk of premature discharge. CONCLUSION: The current state of research cannot provide an exhaustive answer to the question of decisive determinants of success or failure of a treatment acc. to sec. 64 StGB - measured by the discharge mode. However, the overview can assist forensic psychiatric experts in making a reliable prognosis of treatment prospects.

Combined tumor plus nontumor interim FDG-PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer.

We have investigated the prognostic value of two novel interim 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters in patients undergoing chemoradiation (CRT) for esophageal squamous cell carcinoma (ESCC): one tumor parameter (maximal standardized uptake ratio rSUR) and one normal tissue parameter (change of FDG uptake within irradiated nontumor-affected esophagus ∆SUVNTO ). PET data of 134 European and Chinese patients were analyzed. Parameter establishment was based on 36 patients undergoing preoperative CRT plus surgery, validation was performed in 98 patients receiving definitive CRT. Patients received PET imaging prior and during fourth week of CRT. Clinical parameters, baseline PET parameters, and interim PET parameters (rSUR and ∆SUVNTO ) were analyzed and compared to event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Combining rSUR and ∆SUVNTO revealed a strong prognostic impact on EFS, OS, LRC and FFDM in patients undergoing preoperative CRT. In the definitive CRT cohort, univariate analysis with respect to EFS revealed several staging plus both previously established interim PET parameters as significant prognostic factors. Multivariate analyses revealed only rSUR and ∆SUVNTO as independent prognostic factors (p = 0.003, p = 0.008). Combination of these parameters with the cutoff established in preoperative CRT revealed excellent discrimination of patients with a long or short EFS (73% vs. 17% at 2 years, respectively) and significantly discriminated all other endpoints (OS, p < 0.001; LRC, p < 0.001; FFDM, p = 0.02), even in subgroups. Combined use of interim FDG-PET derived parameters ∆SUVNTO and rSUR seems to have predictive potential, allowing to select responders for definitive CRT and omission of surgery.

Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience.

BACKGROUND: The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context. METHODS: Here, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by including n = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019. RESULTS: Median progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6-16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen in n = 11 (34%) cases, whereas n = 21 (66%) patients showed progressive disease (PD). In n = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out of n = 5 patients receiving additional regional hyperthermia, n = 3 achieved PR or SD. CONCLUSIONS: This single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS.

Validation of the PI-RADS language: predictive values of PI-RADS lexicon descriptors for detection of prostate cancer.

OBJECTIVES: To assess the discriminatory power of lexicon terms used in PI-RADS version 2 to describe MRI features of prostate lesions. METHODS: Four hundred fifty-four patients were included in this retrospective, institutional review board-approved study. Patients received multiparametric (mp) MRI and subsequent prostate biopsy including MRI/transrectal ultrasound fusion biopsy and 10-core systematic biopsy. PI-RADS lexicon terms describing lesion characteristics on mpMRI were assigned to lesions by experienced readers. Positive and negative predictive values (PPV, NPV) of each lexicon term were assessed using biopsy results as a reference standard. RESULTS: From a total of 501 lesions, clinically significant prostate cancer (csPCa) was present in 175 lesions (34.9%). Terms related to findings of restricted diffusion showed PPVs of up to 52.0%/43.9% and NPV of up to 91.8%/89.7% (peripheral zone or PZ/transition zone or TZ). T2-weighted imaging (T2W)-related terms showed a wide range of predictive values. For PZ lesions, high PPVs were found for "markedly hypointense," "lenticular," "lobulated," and "spiculated" (PPVs between 67.2 and 56.7%). For TZ lesions, high PPVs were found for "water-drop-shaped" and "erased charcoal sign" (78.6% and 61.0%). The terms "encapsulated," "organized chaos," and "linear" showed to be good predictors for benignity with distinctively low PPVs between 5.4 and 6.9%. Most T2WI-related terms showed improved predictive values for TZ lesions when combined with DWI-related findings. CONCLUSIONS: Lexicon terms with high discriminatory power were identified (e.g., "markedly hypointense," "water-drop-shaped," "organized chaos"). DWI-related terms can be useful for excluding TZ cancer. Combining T2WI- with DWI findings in TZ lesions markedly improved predictive values. KEY POINTS: • Lexicon terms describing morphological and functional features of prostate lesions on MRI show a wide range of predictive values for prostate cancer. • Some T2-related terms have favorable PPVs, e.g., "water-drop-shaped" and "organized chaos" while others show less distinctive predictive values. DWI-related terms have noticeable negative predictive values in TZ lesions making DWI feature a useful tool for exclusion of TZ cancer. • Combining DWI- and T2-related lexicon terms for assessment of TZ lesions markedly improves PPVs. Most T2-related lexicon terms showed a significant decrease in PPV when combined with negative findings for "DW hyperintensity."

Additive Value of Transrectal Systematic Ventral Biopsies in Combination with Magnet Resonance Imaging/Ultrasound Fusion-Guided Biopsy in Patients with 3 or More Negative Prostate Biopsies.

INTRODUCTION: Patients with consistent suspicion for prostate cancer (PCa) and multiple negative prebiopsies prior to multiparametric magnetic resonance imaging (mpMRI) are still frequently evaluated for an image-guided biopsy and are reported with heterogeneous detection rates. The inclusion of a systematic biopsy (SB) is also still recommended with predominant sampling within the posterior/peripheral zone of the prostate. The aim of this study was (I) to evaluate PCa detection rates using a modified 10 core SB template including anterior biopsies in combination with mpMRI/ultrasound fusion-guided targeted biopsy (TB) in patients with 3 or more negative prebiopsies and (II) to compare mpMRI index lesion localization with histologically confirmed locali-zation from associated prostatectomy samples. METHODS: Overall 1,337 consecutive patients underwent sensor-based registration TB of the prostate and a subsequent 10-core SB between January 2012 and December 2015 at our institution. For this study, 101 patients with ≥3 negative prebiopsies and prostate imaging - reporting data system lesions ≥3 were pooled prospectively and underwent TB and a modified SB including 2 ventral (anterior) biopsies. Detection rates were estimated for the modified SB, TB, and its combination. A subgroup analysis of 35 patients undergoing prostatectomy was performed by a head-to-head comparison of mpMRI index lesion and histologically confirmed PCa index lesion localization. RESULTS: The overall detection rate for PCa was 54.5%. The combination of TB and SB detected 14 (25.4%) more cases missed by TB alone (p < 0.001) and 7 (12.7%) more cases missed by SB alone (p = 0.016), respectively. A postoperative Gleason upgrade was seen in 12/35 (34.3%) cases within the TB group and in 14/35 (40.0%) in the SB group, respectively. The subgroup analysis showed a predominant location of PCa index lesions anteriorly at the level of the midgland. The MRI detection rate of the anteriorly located index lesions was 70.4% (15/21 cases) with a clinically significant Gleason score (≥3 + 4 = 7a [International Society of Urological Pathology grade 2]) in 80.9%. Interestingly a modified SB template detected 90.5% (19/21) of the anteriorly located index lesions. CONCLUSION: Our data suggest that in patients with multiple prebiopsies PCa seems to be predominantly located anteriorly. We suggest the general integration of anterior biopsies despite TB in repeat biopsy patients.

PARP-1 expression as a prognostic factor in Desmoid-type fibromatosis.

Desmoid-type fibromatoses (or desmoid tumors) are entities of intermediate biological potential and are locally invasive. Radical surgery, as state of the art therapy, is frequently limited by incomplete resections. Hormone modifying therapies are promising but further research is required. Poly Adenosine Diphosphate Ribose Polymerase-1 (PARP-1), a DNA repairing enzyme, might be a pathogenetic factor and could become a potential target for therapy as shown by the successful treatment of selected carcinomas and sarcomas by PARP-inhibition. In this study, we investigated the expression of estrogen receptors (ER) α (1) and ß (2), progesterone receptor (PR), androgen receptor (AR), as well as PARP-1 via immunohistochemistry and quantitative RT-PCR in 69 tissue samples of desmoid tumors. Immunohistochemistry was quantified using the Immunoreactivity Score (IRS). Overall expression patterns were correlated with clinical-pathologic parameters to determine their value as a prognostic factor. Among the investigated hormone receptors only ERß showed partial cytoplasmic reactivity. PARP-1 revealed variable nuclear positivity with IRS ranging from 0 to 6. Univariate survival analysis showed that higher expression of estrogen receptor 1 was associated with shorter disease-free survival (p = 0.005). Uni- (p = 0.03) and multivariate (p = 0.003) analyses of mRNA data revealed that higher PARP-1 expression correlated with earlier recurrence. According to this study PARP-1 expression is associated with poorer prognosis, that is faster recurrence, highlighting the possibility of PARP-1-targeting agents as a therapeutic option. Hormone receptors were of minor prognostic relevance in this study.

The influence of posture and scapulothoracic orientation on the choice of humeral component retrotorsion in reverse total shoulder arthroplasty.

BACKGROUND: The literature suggests implantation of the humeral component in reverse total shoulder arthroplasty (RTSA) in 0°-40° of retrotorsion without further specification. We hypothesized that optimal humeral component retrotorsion to avoid notching and gain balanced rotational capacity would depend on scapular position and posture. METHODS: We investigated 200 shoulders in 100 patients with available whole-body computed tomography scans and created 3-dimensional models. Implantation of a humeral component in 20° of retrotorsion was simulated, and a correction angle (CA) to yield perfect opposition to the glenosphere was calculated. Patient-specific variables such as age, sex, posture, and scapular orientation parameters were correlated with this CA. RESULTS: Scapular orientation showed large interindividual differences. A highly significant correlation was seen between the CA and scapular internal rotation (R = 0.71, P < .001) and protraction (R = 0.39, P < .001). When the CA was adjusted for glenoid retroversion, the correlation coefficient of scapular internal rotation increased even further (R = 0.91, P < .001). Scapular internal rotation itself showed a correlation with thoracic kyphosis (R = 0.27, P < .001), protraction (R = 0.57, P < .001), tilt (R = 0.29, P < .001), and scapular translation (R = -0.23, P < .001). CONCLUSION: Scapular orientation and posture should be integrated into the determination process of humeral component retrotorsion in RTSA. In theory, implantation of the humeral component with increased retrotorsion leads to improved neutral opposition of the RTSA components in patients with extensive internal rotation of the scapula. On the basis of varying scapular internal rotation, we propose the distinction of 3 different posture types (A-C) for enhanced appraisal of scapulothoracic orientation.

Image-guided Irreversible Electroporation of Localized Prostate Cancer: Functional and Oncologic Outcomes.

Background Irreversible electroporation (IRE) is a nonthermal ablative method based on the formation of nanoscale defects in cell membranes leading to cell death. Clinical experience with the technique for treatment of prostate cancer remains limited. Purpose To evaluate urogenital toxicity and oncologic outcome of MRI-transrectal US fusion-guided IRE of localized prostate cancer. Materials and Methods In this prospective study, men with biopsy-proven, treatment-naive, low- to intermediate-risk prostate cancer (prostate-specific antigen [PSA], ≤15 ng/mL; Gleason score, ≤3 + 4; clinical stage, ≤T2c; lesion size at multiparametric MRI, ≤20 mm) underwent focal MRI/transrectal US fusion-guided IRE between July 2014 and July 2017. Primary end point was the urogenital toxicity profile of focal IRE by using participant-reported questionnaires. Secondary end points were biochemical, histologic, and imaging measures of oncologic control. Analyses were performed by using nonparametric and χ2 test statistics. Results Thirty men were included (median age, 65.5 years); mean PSA level was 8.65 ng/mL and mean tumor size was 13.5 mm. One grade III adverse event (urethral stricture) was recorded. The proportion of men with erection sufficient for penetration was 83.3% (25 of 30) at baseline and 79.3% (23 of 29; P > .99) at 12 months. Leak-free and pad-free continence rate was 90% (27 of 30) at baseline and 86.2% (25 of 29; P > .99) at 12 months. Urogenital function remained stable at 12 months according to changes in the modified International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms, or ICIQ-MLUTS, and the International Index of Erectile Function, or IIEF-5, questionnaires (P = .58 and P = .07, respectively). PSA level decreased from a baseline median value of 8.65 ng/mL (interquartile range, 5-11.4 ng/mL) to 2.35 ng/mL (interquartile range, 1-3.4 ng/mL) at 12 months (P < .001). At 6 months, 28 of 30 participants underwent posttreatment biopsy. The rate of in-field treatment failure was 17.9% (five of 28) as determined with multiparametric prostate MRI and targeted biopsies at 6 months. Conclusion After a median follow-up of 20 months, focal irreversible electroporation of localized prostate cancer was associated with low urogenital toxicity and promising oncologic outcomes. © RSNA, 2019 Online supplemental material is available for this article.

Impact of 68Ga-DOTATOC PET/MRI on robotic radiosurgery treatment planning in meningioma patients: first experiences in a single institution.

OBJECTIVEFor stereotactic radiosurgery (SRS) planning, precise contouring of tumor boundaries and organs at risk is of utmost importance. Correct interpretation of standard neuroimaging (i.e., CT and MRI) can be challenging after previous surgeries or in cases of skull base lesions with complex shapes. The aim of this study was to evaluate the impact of 68Ga-DOTATOC PET/MRI on treatment planning for image-guided SRS by CyberKnife.METHODSThe authors retrospectively identified 11 meningioma treatments in 10 patients who received a 68Ga-DOTATOC PET/MRI prior to SRS. The planning target volume (PTV) used for the patients' treatment was defined as the reference standard. This was contoured by a treating radiosurgeon (RS0) using fused planning CT and PET/MRI data sets. The same tumors were then contoured by another experienced radiosurgeon (RS1) and by a less-experienced radiosurgeon (RS2), both blinded to PET data sets. A comparison of target volumes with focus on volume-based metrics and distance to critical structures was performed. RS1 and RS2 also filled in a questionnaire analyzing the confidence level and the subjective need for the implementation of PET data sets for contouring.RESULTSAnalysis showed a subjective personal preference for PET/MRI in all cases for both radiosurgeons, particularly in proximity to critical structures. The analysis of the planning volumes per physician showed significantly smaller RS2-PTV in comparison to RS1-PTV and to RS0-PTV, whereas the median volumes were comparable between RS1-PTV and RS2-PTV (median: RS0: 4.3 cm3 [IQR 3.4-6.5 cm3] and RS1: 4.5 cm3 [IQR 2.7-6 cm3] vs RS2: 2.6 cm3 [IQR 2-5 cm3]; p = 0.003). This was also reflected in the best spatial congruency between the 2 experienced physicians (RS0 and RS1). The percentage of the left-out volume contoured by RS1 and RS2 compared to RS0 with PET/MRI demonstrated a relevant left-out-volume portion in both cases with greater extent for the less-experienced radiosurgeon (RS2) (RS1: 19.1% [IQR 8.5%-22%] vs RS2: 40.2% [IQR 34.2%-53%]). No significant differences were detected regarding investigated critical structures.CONCLUSIONSThis study demonstrated a relevant impact of PET/MRI on target volume delineation of meningiomas. The extent was highly dependent on the experience of the treating physician. This preliminary study supports the relevance of 68Ga-DOTATOC PET/MRI as a tool for radiosurgical treatment planning of meningiomas.

Contrast-Enhanced Ultrasound (CEUS) and Quantitative Perfusion Analysis in Patients with Suspicion for Prostate Cancer.

PURPOSE: The aim of this study was to investigate contrast-enhanced ultrasound (CEUS) parameters acquired by software during magnetic resonance imaging (MRI) US fusion-guided biopsy for prostate cancer (PCa) detection and discrimination. MATERIALS AND METHODS: From 2012 to 2015, 158 out of 165 men with suspicion for PCa and with at least 1 negative biopsy of the prostate were included and underwent a multi-parametric 3 Tesla MRI and an MRI/US fusion-guided biopsy, consecutively. CEUS was conducted during biopsy with intravenous bolus application of 2.4 mL of SonoVue® (Bracco, Milan, Italy). In the latter CEUS clips were investigated using quantitative perfusion analysis software (VueBox, Bracco). The area of strongest enhancement within the MRI pre-located region was investigated and all available parameters from the quantification tool box were collected and analyzed for PCa and its further differentiation was based on the histopathological results. RESULTS: The overall detection rate was 74 (47 %) PCa cases in 158 included patients. From these 74 PCa cases, 49 (66 %) were graded Gleason ≥ 3 + 4 = 7 (ISUP ≥ 2) PCa. The best results for cancer detection over all quantitative perfusion parameters were rise time (p = 0.026) and time to peak (p = 0.037). Within the subgroup analysis (> vs ≤ 3 + 4 = 7a (ISUP 2)), peak enhancement (p = 0.012), wash-in rate (p = 0.011), wash-out rate (p = 0.007) and wash-in perfusion index (p = 0.014) also showed statistical significance. CONCLUSION: The quantification of CEUS parameters was able to discriminate PCa aggressiveness during MRI/US fusion-guided prostate biopsy.

Ga-68-PSMA PET/CT in treatment-naïve patients with prostate cancer: Which clinical parameters and risk stratification systems best predict PSMA-positive metastases?

PURPOSE: To evaluate the accuracy of clinical parameters and established pre-treatment risk stratification systems for prostate cancer (PCa) in predicting PSMA-positive metastases in men undergoing Ga-68-PSMA PET/CT as initial staging examination. MATERIALS AND METHODS: A retrospective analysis in 108 consecutive treatment-naïve patients with biopsy-proven PCa undergoing Ga-68-PSMA PET/CT (median age, 72 years [range, 49-82 years]) was performed. Prediction of PSMA-positive metastases by serum PSA, clinical T stage (cT), ISUP group, percentage of positive biopsy cores, and derived risk scores (D'Amico risk classification system, Roach [RF], Yale formula [YF], and Briganti nomogram [BN]) was examined with ROC analysis. RESULTS: Any PSMA-positive metastases were found in 36 of 108 patients, including LN metastases in 28 patients, extrapelvic LN metastases in 15 patients, and organ metastases in 19 patients (bone, 19; lung, 1). AUCs for PSA, cT, ISUP, and percentage of positive biopsy cores regarding PSMA-positive metastases did not differ significantly (range, 0.6-0.8; each P > 0.05). D'Amico (AUC, 0.61-0.64) was inferior to RF (0.76-0.83), YF (0.81-0.86), and BN (0.73 to 0.88; each P < 0.05). Among the 89 high-risk patients (D'Amico), decision for or against PET imaging based on RF (cut-off, >18.0), YF (>10.8), or BN (>8.0) would have prevented PSMA PET/CT in 4 (5%), 15 (17%), or 18 patients (20%), respectively, while preserving a sensitivity ≥95% for PSMA-positive metastases. CONCLUSIONS: Clinical parameters and established risk stratification systems for PCa can predict Ga-68-PSMA PET-positive metastases in treatment-naïve patients. Especially YF and BN may improve identification of patients with the highest probability of metastatic disease detected by Ga-68-PSMA PET/CT.

Mesenteric Fibrosis in Midgut Neuroendocrine Tumors: Functionality and Radiological Features.

BACKGROUND: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD). METHODS: A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed. RESULTS: Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043). CONCLUSIONS: We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.

A direct comparison of contrast-enhanced ultrasound and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer detection and prediction of aggressiveness.

INTRODUCTION: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) analyse tissue vascularization. We evaluated if CEUS can provide comparable information as DCE-MRI for the detection of prostate cancer (PCa) and prediction of its aggressiveness. MATERIAL AND METHODS: A post-hoc evaluation of 92 patients was performed. In each patient CEUS and DCE-MRI parameters of the most suspicious lesion identified on MRI were analysed. The predictive values for discrimination between benign lesions, low-/intermediate- and high-grade PCa were evaluated. Results of targeted biopsy served as reference standard (benign lesions, n=51; low- and intermediate-grade PCa [Gleason grade group 1 and 2], n=22; high-grade PCa [≥ Gleason grade group 3], n=19). RESULTS: In peripheral zone lesions of all tested CEUS parameters only time to peak (TTPCEUS) showed significant differences between benign lesions and PCa (AUC 0.65). Of all tested DCE-MRI parameters, rate constant (Kep) was the best discriminator of high-grade PCa in the whole prostate (AUC 0.83) and in peripheral zone lesions (AUC 0.89). CONCLUSION: DCE-MRI showed a superior performance for detection of PCa and prediction of its aggressiveness. CEUS and DCE-MRI performed better in peripheral zone lesions than in transition zone lesions. KEY POINTS: • DCE-MRI gathers information about vascularization and capillary permeability characteristics of tissues. • DCE-MRI can detect PCa and predict its aggressiveness. • CEUS also gathers information about vascularization of tissues. • For detection of PCa and prediction of aggressiveness DCE-MRI performed superiorly. • Both imaging techniques performed better in peripheral zone lesions.

Increased Activity of the Immunoregulatory Enzyme Indoleamine-2,3-Dioxygenase with Consecutive Tryptophan Depletion Predicts Death in Patients with Neuroendocrine Neoplasia.

BACKGROUND/AIMS: Data from a considerable number of malignancies demonstrate that depletion of the essential amino acid tryptophan via induction of the immunoregulatory enzyme indoleamine-2,3-dioxygenase (IDO) serves as an important tumour escape strategy and is of prognostic importance. Here we investigate the predictive value of the activity of IDO as well as levels of tryptophan and respective downstream catabolites in a large cohort of patients with neuroendocrine neoplasms (NEN). METHODS: 142 consecutive Caucasian patients (62 male, aged 60.3 ± 11.9 years) with histologically confirmed NEN were systematically analysed in a retrospective blinded end point analysis. Patients were followed up for a mean period of about 3.9 ± 1.9 years. Clinical outcome, levels of established biomarkers, and tryptophan degradation markers (assessed using tandem mass spectrometry) including estimated IDO activity were recorded. Cox proportional hazards regression models were performed for the assessment of prognostic power. RESULTS: We found that baseline tryptophan levels were significantly lower and IDO activity was significantly increased in non-survivors. The risk for death inclined stepwise and was highest in patients in the upper tertile of IDO activity. Cox proportional regression models identified IDO activity as an independent predictor of death. CONCLUSIONS: In this retrospective analysis, we observed that baseline activity of the immunoregulatory enzyme IDO was significantly increased in non-survivors. IDO activity was identified as an independent predictor of death in this cohort of NEN patients. Whether IDO activity or tryptophan depletion serves to guide future therapeutic interventions in NEN remains to be established.

Influence of fractional anisotropy thresholds on diffusion tensor imaging tractography of the periprostatic neurovascular bundle and selected pelvic tissues: do visualized tracts really represent nerves?

Background Diffusion tensor imaging (DTI) tractography has recently been shown to successfully visualize periprostatic tracts allegedly representing the neurovascular bundle. Purpose To examine the impact of different fractional anisotropy (FA) thresholds on the results of DTI tractography in the male pelvis as well as to evaluate the resulting specificity for nerve tracts. Material and Methods Ten healthy male volunteers were examined at 3 Tesla. DTI tractography was performed based on seed points placed circularly around the prostate, in the rectoprostatic angle, the peripheral zone of the prostate, the sciatic nerve, and in addition the urinary bladder using FA thresholds of 0.20, 0.05, and 0.01. DTI tract number and DTI tract length measured with different FA thresholds were compared. ANOVA with repeated measures was used for statistics. Results DTI tract number and tract length were significantly dependent on FA thresholds. While a FA threshold of 0.20 visualized the typical distribution of DTI tracts in the sciatic nerve, a FA threshold of ≤0.05 was necessary to yield results visually mimicking the distribution of nerve tracts in the NVB. However, with such low FA thresholds even in the filled urinary bladder DTI tracts could be visualized. With FA thresholds of 0.20, the number and length of periprostatic DTI tracts did not differ from those measured within the prostate. Conclusion DTI tractography can be used to visualize DTI tracts periprostatically. However, one may doubt that these DTI tracts represent nerve tracts and that the periprostatic neurovascular bundle can be evaluated in a meaningful way with the current methods available.

Maximizing Information From Routine Staging Computed Tomography in Functional Neuroendocrine Neoplasms: Are There Findings Indicating the Presence of Carcinoid Heart Disease?

PURPOSE: The aim of this study was to evaluate signs of right-sided heart dysfunction on staging computed tomography (CT) as indirect indicators of carcinoid heart disease. PATIENTS AND METHODS: Patients with functionally active neuroendocrine neoplasm and different grades of tricuspid valve regurgitation (TR) were identified. Two readers independently reviewed contrast-enhanced staging CT performed within 90 days before or after echocardiography. Logistic regression and receiver operating analyses were used to asses the predictive value of right ventricle-left ventricle ratio (RV-LV ratio), ventricular septal bowing, retrograde contrast filling of the hepatic veins during contrast injection, and time to aortal enhancement greater than 100 Hounsfield units during bolus tracking for TR. RESULTS: Forty-four examinations were evaluated (11 with TR = 0, 16 with TR = 1, 9 with TR = 2, and 8 with TR = 3). Right ventricle-LV ratio was found to predict TR less than or equal to 1 versus TR greater than 1 (P = 0.0188) and TR less than or equal to 1 versus TR equals 2 (P = 0.0082). A prolonged time to aortal enhancement greater than 100 Hounsfield units during bolus tracking predicted TR less than or equal to 1 versus TR greater than 1 (P = 0.0077). Area under the curve for RV-LV ratio was 0.86 when differentiating TR less than or equal to 1 versus TR equals 2. With a cutoff of 1.07, sensitivity was 0.89, and specificity was 0.72. CONCLUSIONS: In patients with functionally active neuroendocrine neoplasm, an RV-LV ratio of more than 1.07 predicted TR with a relatively high sensitivity and moderate specificity and thus could serve as an indicator of subclinical carcinoid heart disease on routine staging CT.

Diagnostic imaging of pancreatic neuroendocrine neoplasms (pNEN): tumor detection, staging, prognosis, and response to treatment.

Pancreatic neuroendocrine neoplasms (pNEN) are rare malignancies arising from neuroendocrine cells of the pancreas. Functional tumors can present with specific clinical syndromes due to hormonal secretion. These tumors can present as incidental findings on imaging performed for unrelated purposes or they are diagnosed when workup is initiated in patients with specific syndromes or metastases. This article presents an overview of available imaging techniques focusing on computed tomography and magnetic resonance imaging. Recommendations regarding examination protocols are given. Typical imaging features of pNEN and metastases are described. Their potential value for the evaluation of prognosis as well as tumor response under treatment is discussed.