MRI-guided biopsy of the prostate: correlation between the cancer detection rate and the number of previous negative TRUS biopsies

PURPOSEWe aimed to investigate prostate cancer detection rate of magnetic resonance imaging (MRI)-guided biopsy and to elucidate possible relations to the number of prior negative transrectal ultrasonography (TRUS)-guided biopsies.MATERIALS AND METHODSEighty-seven consecutive patients (mean age, 65.0 years; mean prostate-specific antigen, 13.3 ng/mL) with at least one prior negative TRUS-guided biopsy and persistent suspicion of prostate cancer were included in this study. All patients underwent MRI-guided biopsy after a diagnostic multiparametric MRI examination at 1.5 Tesla. Specimens were immediately fixated and subsequently evaluated by an experienced uropathologist. Prostate cancer detection rates were calculated. Prostate cancer-positive and -negative cores were compared. Correlation between number of prior biopsies and presence of prostate cancer was evaluated.RESULTSCancer detection rates for patients with one (n=24), two (n=25), three (n=18), and four or more (n=20) negative TRUS-guided biopsies were 29.2%, 40.0%, 66.7%, and 35.0%, respectively (P = 0.087). The median number of removed cores per patient was 3 (range, 1–8) without a significant difference between patients with and without cancer (P = 0.48). Thirty of 36 cancer patients were at intermediate or high risk according to the D´Amico clinical risk score. Eleven of 15 high risk cancers were localized in the transition zone (P = 0.002).CONCLUSIONSThis study demonstrates high cancer detection rates of MRI-guided biopsy independent of the number of previous TRUS-guided biopsies and the number of taken prostate cores. MRI-guided biopsy therefore represents a less invasive and effective diagnostic tool for patients with prostate cancer suspicion and previous negative TRUS-guided biopsies

Can magnetic resonance imaging replace conventional computerized tomography for follow-up of patients with testicular cancer? A systematic review

Purpose Follow-up protocols for patients with testicular cancer (TC) have significantly reduced the number of cross-sectional imaging studies to reduce radiation exposure. At present, it is unclear whether magnetic resonance imaging (MRI) could replace conventional computerized tomography (CT) imaging. The objective of this study is to summarize the scientific evidence on this topic and to review guideline recommendations with regard to the use of MRI. Methods A systematic literature review was performed searching Medline and Cochrane databases for prospective studies on patients with TC in the follow-up care (last search in February 2021). Additionally, guideline recommendations for TC were screened. Data extraction and quality assessment of included studies were performed and used for a descriptive presentation of results. Results A total of four studies including two ongoing trials were identified. Overall, the scientific evidence of prospective comparative studies is based on 102 patients. Data suggest that abdominal imaging with MRI can replace conventional CT for detection of lymph node metastasis of the retroperitoneum to spare radiation exposure and contrast media application. However, experienced radiologists are needed. Clinical guidelines are aware of the risk of diagnosis-induced secondary malignancy due to CT imaging and some have adapted their recommendations accordingly. Results of the two ongoing trials on 738 patients are expected soon to provide more reliable results on this topic. Conclusions There is growing evidence that abdominopelvic MRI imaging can replace CT imaging during follow-up of patients with TC in order to reduce radiation exposure and diagnosis-induced secondary malignancy

Unsupervised Anomaly Detection of Paranasal Anomalies in the Maxillary Sinus

Deep learning (DL) algorithms can be used to automate paranasal anomaly detection from Magnetic Resonance Imaging (MRI). However, previous works relied on supervised learning techniques to distinguish between normal and abnormal samples. This method limits the type of anomalies that can be classified as the anomalies need to be present in the training data. Further, many data points from normal and anomaly class are needed for the model to achieve satisfactory classification performance. However, experienced clinicians can segregate between normal samples (healthy maxillary sinus) and anomalous samples (anomalous maxillary sinus) after looking at a few normal samples. We mimic the clinicians ability by learning the distribution of healthy maxillary sinuses using a 3D convolutional auto-encoder (cAE) and its variant, a 3D variational autoencoder (VAE) architecture and evaluate cAE and VAE for this task. Concretely, we pose the paranasal anomaly detection as an unsupervised anomaly detection problem. Thereby, we are able to reduce the labelling effort of the clinicians as we only use healthy samples during training. Additionally, we can classify any type of anomaly that differs from the training distribution. We train our 3D cAE and VAE to learn a latent representation of healthy maxillary sinus volumes using L1 reconstruction loss. During inference, we use the reconstruction error to classify between normal and anomalous maxillary sinuses. We extract sub-volumes from larger head and neck MRIs and analyse the effect of different fields of view on the detection performance. Finally, we report which anomalies are easiest and hardest to classify using our approach. Our results demonstrate the feasibility of unsupervised detection of paranasal anomalies from MRIs with an AUPRC of 85% and 80% for cAE and VAE, respectively

Multiple Instance Ensembling For Paranasal Anomaly Classification In The Maxillary Sinus

Paranasal anomalies are commonly discovered during routine radiological screenings and can present with a wide range of morphological features. This diversity can make it difficult for convolutional neural networks (CNNs) to accurately classify these anomalies, especially when working with limited datasets. Additionally, current approaches to paranasal anomaly classification are constrained to identifying a single anomaly at a time. These challenges necessitate the need for further research and development in this area. In this study, we investigate the feasibility of using a 3D convolutional neural network (CNN) to classify healthy maxillary sinuses (MS) and MS with polyps or cysts. The task of accurately identifying the relevant MS volume within larger head and neck Magnetic Resonance Imaging (MRI) scans can be difficult, but we develop a straightforward strategy to tackle this challenge. Our end-to-end solution includes the use of a novel sampling technique that not only effectively localizes the relevant MS volume, but also increases the size of the training dataset and improves classification results. Additionally, we employ a multiple instance ensemble prediction method to further boost classification performance. Finally, we identify the optimal size of MS volumes to achieve the highest possible classification performance on our dataset. With our multiple instance ensemble prediction strategy and sampling strategy, our 3D CNNs achieve an F1 of 0.85 whereas without it, they achieve an F1 of 0.70. We demonstrate the feasibility of classifying anomalies in the MS. We propose a data enlarging strategy alongside a novel ensembling strategy that proves to be beneficial for paranasal anomaly classification in the MS

Technical developments, experimental and clinical results

Titelblatt, Inhaltsverzeichnis, Danksagung, Erklärung Vorbemerkungen Einleitung MRT der Prostata Eigene Literatur Diskussion und Ausblick Zusammenfassung LiteraturDas Prostatakarzinom ist das häufigste Malignom des Mannes. Zur Früherkennung des Prostatakarzinoms wird Männern ab dem 50. Lebensjahr eine jährliche digitale rektale Untersuchung und die Bestimmung des PSA-Wertes im Serum empfohlen. Bei auffälligen Befunden erfolgt zur histologischen Sicherung eine durch den transrektalen Ultraschall gesteuerte systematische Prostatabiopsie mit mindestens 6 Biopsien. Die systematische Prostatabiopsie ist jedoch häufig (ca. 70 %) negativ. Angesichts dieser Probleme wurden im Rahmen der hier beschriebenen Projekte experimentelle und klinische Studien und Entwicklungen zur Verbesserung der MR-Diagnostik des Prostatakarzinoms durchgeführt. Zunächst stellte sich die Frage, mit welcher Spulentechnik eine optimale Bildqualität für die hochauflösende Darstellung der Prostata zu erreichen ist und ob im Zuge der technischen Entwicklung auf die für den Patienten unangenehme Endorektalspule verzichtet werden kann. Dabei hat sich in einer intraindividuellen Vergleichsuntersuchung von drei verschiedenen Spulensystemen bei 49 Patienten mit gesichertem Prostatakarzinom die kombinierte Endorektal-Körper-Phased-Array-Spule bezüglich der Abbildungsqualität gegenüber der Endorektalspule alleine und der Körper- Phased-Array-Spule alleine überlegen gezeigt (Originalarbeit 1). Bei einer Treffsicherheit von 59 % für die Stadieneinteilung fand sich jedoch für die Abgrenzbarkeit von Stagingkriterien kein signifikanter Unterschied. Mit der optimierten Spulenkombination konnte in einer prospektiven Untersuchung bei 44 Patienten mit erhöhtem PSA-Wert über 4 ng/ml oder suspekter Ratio von freiem zu gebundenem PSA von unter 15 % eine Sensitivität von 83 % für den Tumornachweis bei einer erneuten Prostatabiopsie erreicht werden. Sie ist damit höher als mit dem transrektalen US und der digitalen rektalen Untersuchung mit jeweils 33 % (Originalarbeit 3). Seither wird bei diesem Problempatientengut die MR-Untersuchung der Prostata routinemäßig zur Problemlösung durchgeführt. Die Spezifität des Tumornachweises ist mit 62 % in der T2-gewichteten Bildgebung jedoch gering. Schwierigkeiten bei der Abgrenzung von Tumoren ergeben sich z.B. bei zusätzlicher Prostatitis (Originalarbeit 3). Weitere Probleme bei der Abgrenzung von Prostatakarzinomen ergeben sich bei Einblutungen, nach Hormonbehandlung und nach Radiatio. In einer Studie bei 23 Patienten die 6 bis 24 Monate nach kombinierter Radiatio eines Prostatakarzinoms untersucht wurden, fand sich in allen Fällen eine verminderte Signalintensität und aufgehobene zonale Gliederung der Prostata. Deshalb konnten Tumorrezidive bzw. eine Tumorpersistenz erst ab einer Größe von 10 mm Durchmesser innerhalb der fibrotisch veränderten Prostata abgegrenzt werden (Originalarbeit 2). Der Einsatz von Hochfeldgeräten mit einer Feldstärke von 3 Tesla lässt prinzipiell ein verbessertes Signal-zu-Rausch- Verhältnis erwarten. Jedoch waren für Geräte dieser Feldstärke zum Zeitpunkt der Studie noch keine Endorektalspulen verfügbar. Deshalb wurde eine intraindividuelle Vergleichsuntersuchung bei 24 Patienten mit Prostatakarzinom an Geräten mit 1,5 und 3 Tesla Feldstärke mit der jeweils besten zur Verfügung stehenden Spulentechnik durchgeführt. Dabei zeigte sich die Untersuchung bei 1,5 Tesla mit der kombinierten Endorektal-Körper-Phased-Array-Spule der Untersuchung bei 3 Tesla mit der Torso-Phased-Array-Spule bezüglich der Bildqualität, Abgrenzbarkeit der zonalen Anatomie und Abgrenzbarkeit des Tumors überlegen (p < 0,001). Deshalb bleibt derzeit in unserer Arbeitsgruppe die Untersuchung bei 1,5 Tesla mit kombinierter Endorektal-Körper-Phased- Array-Spule der Standard für den Nachweis von Prostatakarzinomen (Originalarbeit 4). Auch bei Einsatz einer optimalen Gerätetechnik bleibt die MR-tomographische Abgrenzung von Prostatakarzinomen mit konventionellen Pulssequenzen problematisch. Tumoren unterscheiden sich von gesundem Prostatagewebe durch eine unterschiedliche Mikrogefäßdichte. Eine Differenzierung zwischen Tumorgewebe und gesundem Prostatagewebe ist deshalb auch anhand der Bestimmung von Parametern der Perfusion möglich. Anders als die konventionelle T1-gewichtete Bildgebung mit Spin-Echo-Sequenzen nach KM- Applikation, die keine eindeutigen Vorteile gegenüber der nativen T2-gewichteten Bildgebung bietet, ist die dynamische MRT mit schnellen Sequenzen wie z.B. einer fast-low-angle-shot-Sequenz in der Lage, die unterschiedliche Perfusion darzustellen. Im Tierversuch ließ sich dieses Kriterium bei 15 Ratten mit orthotop implantierten Prostatakarzinomen innerhalb der gesunden Prostata als vermehrtes Flussvolumen und vermehrte Extravasation darstellen (Originalarbeit 5). Eine weitere Verbesserung erwarten wir durch eine pharmakokinetische Analyse der dynamischen MRT-Daten mit dem Ziel physiologische Gewebeparameter wie Blutvolumen, interstitielles Volumen und Zellvolumen sowie Gefäßpermeabilitäten zu gewinnen. Hierzu wurde eine Dual-Kontrast-Sequenz entwickelt, die eine Quantifizierung der arteriellen Inputfunktion ermöglicht. Nach einem speziell konstruierten Postprozessing lassen sich die Daten einer eigens dafür entwickelten pharmakokinetischen Analyse unterziehen und ergeben die gesuchten Parameter (Originalarbeit 6). Ergebnisse klinischer Studien stehen für diese Technik noch aus. Um im MRT nachgewiesene tumorsuspekte Areale innerhalb der Prostata einer histologischen Untersuchung zuzuführen, wurde in Kooperation mit einer kleinen Firma eine MR-kompatible Vorrichtung entwickelt, mit deren Hilfe tumorsuspekte Areale in der Prostata im geschlossenen MRT bei 1,5 Tesla biopsiert werden können. Mit dieser Technik konnten bei 18 Patienten mit suspekten Arealen in der Prostata bei 8 Patienten ein Prostatakarzinom gesichert werden (Originalarbeit 7). Insgesamt lassen die technischen Entwicklungen darauf hoffen, dass zukünftig ggf. durch kombinierten Einsatz der hier beschriebenen Techniken einerseits behandlungsbedürftige Prostatakarzinome sicherer, und damit in einem kurativen Stadium nachgewiesen werden können, und andererseits unnötige Biopsien bei PSA-Erhöhungen benigner Ursache vermieden werden können.Prostate cancer is the most common malignancy in males. Men aged 50 and older are recommended to undergo an annual digital rectal examination (DRE) and determination of prostate-specific antigen (PSA) in serum for early detection. However, prostate biopsy guided by transrectal ultrasound (TRUS) is negative for cancer in many patients with PSA levels elevated above 4 ng/ml. T2-weighted magnetic resonance imaging (MRI) is able to visualize the zonal anatomy of the prostate and to depict suspicious areas with a low signal in the high-intensity peripheral zone. Data of our own comparatative study on different coil types are presented. In patients with prior negative core biopsy, MRI has a higher sensitivity for detecting prostate cancer than DRE and TRUS. Data of our own study are presented. However, its specificity is poor since other abnormalities such as prostatic intraepithelial neoplasia (PIN), prostatitis, scars, or haemorrhage have a similar MRI appearance. Data of our own study are presented. Newly developed biopsy devices allow for removing targeted biopsies from areas that are suspicious on MRI. Results of own developments are shown. Experimental results of our development of a postprocessing method for dynamic contrast enhanced MRI on the one hand and results in a study with an animal model are presented

Non-metastatic castrate-resistant prostate cancer: a call for improved guidance on clinical management.

BACKGROUND Guidelines on the clinical management of non-metastatic castrate-resistant prostate cancer (nmCRPC) generally focus on the need to continue androgen deprivation therapy and enrol patients into clinical trials of investigational agents. This guidance reflects the lack of clinical trial data with established agents in the nmCRPC patient population and the need for trials of new agents. AIM To review the evidence base and consider ways of improving the management of nmCRPC. CONCLUSION Upon the development of castrate resistance, it is essential to rule out the presence of metastases or micrometastases by optimising the use of bone scans and possibly newer procedures and techniques. When nmCRPC is established, management decisions should be individualised according to risk, but risk stratification in this diverse population is poorly defined. Currently, prostate-specific antigen (PSA) levels and PSA doubling time remain the best method of assessing the risk of progression and response to treatment in nmCRPC. However, optimising imaging protocols can also help assess the changing metastatic burden in patients with CRPC. Clinical trials of novel agents in nmCRPC are limited and have problems with enrolment, and therefore, improved risk stratification and imaging may be crucial to the improved management. The statements presented in this paper, reflecting the views of the authors, provide a discussion of the most recent evidence in nmCRPC and provide some advice on how to ensure these patients receive the best management available. However, there is an urgent need for more data on the management of nmCRPC

Prognostic factors in patients with clinical stage I nonseminoma-beyond lymphovascular invasion: a systematic review

Objective To systematically evaluate evidence on prognostic factors for tumor recurrence in clinical stage I nonseminoma patients other than lymphovascular invasion (LVI). Methods We performed a systematic literature search in the biomedical databases Medline (via Ovid) and Cochrane Central Register of Controlled Trials (search period January 2010 to February 2021) for full text publications in English and German language, reporting on retro- or prospectively assessed prognostic factors for tumor recurrence in patients with stage I nonseminomatous germ cell tumors. Results Our literature search yielded eleven studies reporting on 20 potential prognostic factors. Results are based on cohort studies of mostly moderate to low quality. Five out of eight studies found a significant association of embryonal carcinoma (EC) in the primary tumor with relapse. Among the different risk definitions of embryonal carcinoma (presence, predominance, pure), presence of EC alone seems to be sufficient for prognostification. Interesting results were found for rete testis invasion, predominant yolk sac tumor, T-stage and history of cryptorchidism, but the sparse data situation does not justify their clinical use. Conclusions No additional factors that meet the prognostic value of LVI, especially when determined by immunohistochemistry, could be identified through our systematic search. The presence of EC might serve as a second, subordinate prognostic factor for clinical use as the data situation is less abundant than the one of LVI. Further efforts are necessary to optimize the use of these two prognostic factors and to evaluate and validate further potential factors with promising preliminary data