Martin Biermann

Loss of dopaminergic neurons in the substantia nigra (SN) pars compacta (SNc) is a pathological hallmark of Parkinson’s disease (PD). This is accompanied by a reduction of the dopamine synthesis byproduct neuromelanin (NM), which can be detected in vivo with NM-sensitive MRI, showing potential as a biomarker of PD. This relies on delineating the NM-rich region, which is achieved by applying manual or automated methods. Currently, there is a lack of publicly available tools for this task, so we trained a deep neural network intended for publishing, while exploring the effects of incorporating multiparametric MRI for segmenting the NM hyperintensity of the SN. We obtained multiple MRI contrasts, including NM-sensitive magnetization transfer contrast from 109 individuals (87 PD, 22 healthy controls) comprising a Norwegian and a Canadian cohort. The method was further evaluated on 209 MRIs from the Parkinson’s Progressive Markers Initiative (PPMI). We observed that models trained naively on images from a single site tended to perform very poorly when exposed to similar data from different sites, emphasizing the importance of validating on out-of-distribution data. By applying aggressive data augmentation, we could largely attenuate the problem. We also observed a small additional regularizing effect from training the neural network on multiparametric MRIs. Volume and contrast-to-noise ratio (CNR) of the SN hyperintensity to the crus cerebri were used to distinguish patients from controls, with an area under the receiver operating characteristic (AUROC) of 0.863. CNR was found to be a better marker of disease status than volume, and we discuss a potential confusion in discerning the two measures. No contralateral association was observed between the severity of motor symptoms and volume or CNR.

Despite major reforms of specialist training in the Nordic countries towards concrete learning outcomes and promoting active learning, most specialist courses continue to be based on lectures. We redesigned our mandatory 5‐day course in clinical nuclear medicine (NM) that was last held in 2016 towards active learning. Thirty 1‐h lectures were replaced with 10 thematic blocks of 3 h each. Each block was taught by a single teacher in a blend of short introductory lectures alternating with small groups of residents reading NM cases from our newly established national case library in diagnostic format. Due to COVID‐19, the entire course in 2021 needed to be run on a videoconferencing system rather than in a computer laboratory as had been originally planned. At the end of the course, we conducted the same anonymized survey as in 2016. All 19 course participants responded. 74% fully agreed that the e‐course format had been ‘good’. One hundred per cent fully agreed that the practical exercises were ‘useful’ versus 50% in 2016 (p < 0.001). In their free text answers on the merits or downsides of e‐learning, 12/12 respondents only mentioned advantages. Our newly established library of anonymized teaching cases within our national health network is an effective tool for organising courses based on active learning. Despite the change towards distance learning enforced by the pandemic, course participants reported the same high levels of satisfaction with active learning in small groups as in the earlier traditional lecture‐based course format.

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 10⁸) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.

Aims We observed hitherto unreported layering of radioactivity in the bladder on PET/CT in prostate cancer (PC) when combined with contrast-enhanced CT (CECT). This effect facilitates assessment of the prostate bed in PC. Methods Among 128 patients imaged with [¹⁸F]PSMA-1007, we selected all 8 studies without and 28 studies with CECT. 20 patients also underwent PET/MR. As controls, we chose 20 and 16 males studied with [¹⁸F]FDG for extrapelvic disease with and without CECT. Posterior anterior (PA) ratio was calculated as SUV_post/SUV_ant * 100 % based on maximal standard uptake values (SUV) in 20 mm spheres in the anterior and posterior bladder. Four nuclear physicians scored assessibility of the bladder base on a 3-point Likert scale (3 = optimal, 1 = poor). We acquired serial PET/CT over 4 hours of a flask with layering of 100 ml intravenous contrast agent and 100 ml physiological saline with 40 MBq of [¹⁸F]PSMA-1007, while a control flask was shaken at the start of the experiment. Results Layering of tracer was observed in all PET/CT studies with CE-CT, but not in studies without contrast. Median PA ratios were 44 % (interquartile range 33–62) for [¹⁸F]PSMA-1007 and 73 % (52–67) for [¹⁸F]FDG, respectively. Intravenous contrast improved assessibility scores in PET of the bladder base, but the effect only reached significance in the PET/MR data. In the in vitro data, radioactivity was retained in the aqueous supernatant over the entire experiment whereas there was no separation of phases in the control flask over time. Conclusion When performing PET combined with CECT, sedimentation of contrast agent in the bladder leads to upward displacement of radioactivity, enhancing clarity of PET images in the posterior bladder and the prostate bed on both PET/CT and PET/MR. Ziel Bei der PET/CT-Untersuchung von Prostatakarzinomen (PC) in Kombination mit kontrastverstärkter CT (CECT) beobachteten wir eine bis dato nicht berichtete Schichtung von Radioaktivität in der Blase. Dieser Effekt erleichtert die Beurteilung des Prostatabettes bei PC. Methoden Von 128 Patienten, die mit [¹⁸F]PSMA-1007 untersucht wurden, haben wir alle 8 Studien ohne CECT und 28 Studien mit CECT ausgewählt. Bei 20 Patienten wurde auch eine PET/MRT durchgeführt. Als Kontrollen wählten wir 20 bzw. 16 Männer aus, die mit [¹⁸F]FDG auf extrapelvine Erkrankungen mit und ohne CECT untersucht wurden. Die Posterior-anterior (PA)-Ratio wurde berechnet als SUV_post/SUV_ant * 100% auf Grundlage der maximalen standardisierten Aufnahmewerte (SUV) in 20mm großen Kugeln in der vorderen und hinteren Blase. Vier Nuklearmediziner bewerteten die Beurteilbarkeit des Blasenbodens auf einer 3-Punkte-Likert-Skala (3 = optimal, 1 = schlecht). Wir haben serielle PET/CT-Aufnahmen über 4 Stunden in einer Flasche mit einer Schichtung von 100ml intravenösem Kontrastmittel und 100ml physiologischer Kochsalzlösung mit 40MBq [¹⁸F]PSMA-1007 durchgeführt, während eine Kontrollflasche zu Beginn des Experiments geschüttelt wurde. Ergebnisse In allen PET/CT-Studien mit CECT wurde eine Schichtung des Tracers beobachtet, nicht jedoch in Studien ohne Kontrastmittel. Die mittleren PA-Ratios betrugen 44% (Interquartile: 33–62) für [¹⁸F]PSMA-1007 bzw. 73% (52–67) für [¹⁸F]FDG. Die intravenöse Kontrastmittelgabe verbesserte die Beurteilbarkeit bei der PET-Untersuchung des Blasenbodens, aber der Effekt war nur bei den PET/MR-Daten signifikant. Bei den In-vitro-Daten wurde die Radioaktivität während des gesamten Experiments im wässrigen Überstand zurückgehalten, während in der Kontrollflasche keine Phasentrennung über die Zeit erfolgte. Schlussfolgerung Bei der Durchführung von PET in Kombination mit CECT führt die Sedimentation des Kontrastmittels in der Blase zu einer Verdrängung der Radioaktivität nach oben, wodurch die Klarheit der PET-Bilder in der hinteren Blase und im Prostatabett sowohl bei der PET/CT als auch bei der PET/MRT verbessert wird. Received: 23 September 2021 Accepted after revision: 04 April 2022 Article published online: 14 June 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Objective: Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule. Patients and Methods: In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI). Results: We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric (r_s = − 0.31, p = 0.007), small bowel (r_s = − 0.41, p < 0.001) and colonic (r_s = − 0.33, p = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index (r_s = − 0.81, p < 0.001) and mean stomach pressure (r_s = − 0.64, p = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel (r_s = − 0.77, p < 0.001) and colon (r_s = − 0.74, p = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index (r_s = − 0.34, p = 0.012), and mean pressure of the colon correlated with upper abdominal pain (r_s = − 0.37, p = 0.007). We found no association between symptoms, gastric emptying nor any other transit times. Conclusion: In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.

Aims Since 2017, medical students at the University of Bergen were taught PET/CT “hands-on” by viewing PET/CT cases in native format on diagnostic workstations in the hospital. Due to the COVID-19 pandemic, students were barred access. This prompted us to launch and evaluate a new freeware PET/CT viewing system hosted in the university network. Methods We asked our students to install the multiplatform Fiji viewer with Beth Israel PET/CT plugin (http://petctviewer.org) on their personal computers and connect to a central image database in the university network based on the public domain orthanc server (https://orthanc-server.com). At the end of course, we conducted an anonymous student survey. Results The new system was online within eight days, including regulatory approval. All 76 students (100 %) in the fifth year completed their course work, reading five anonymized PET/CT cases as planned. 41 (53 %) students answered the survey. Fiji was challenging to install with a mean score of 1.8 on a 5-point Likert scale (5 = easy, 1 = difficult). Fiji was more difficult to use (score 3.0) than the previously used diagnostic workstations in the hospital (score 4.1; p < 0.001, paired t-test). Despite the technical challenge, 47 % of students reported having learnt much (scores 4 and 5); only 11 % were negative (scores 1 and 2). 51 % found the PET/CT tasks engaging (scores 4 and 5) while 20 % and 5 % returned scores 2 and 1, respectively. Conclusion Despite the initial technical challenge, “hands-on” learning of PET/CT based on the freeware Fiji/orthanc PET/CT-viewer was associated with a high degree of student satisfaction. We plan to continue running the system to give students permanent access to PET/CT cases in native format regardless of time or location.

Purpose of review: Thyroid cancer is the most common endocrine cancer in adults with rising incidence. Challenges in imaging thyroid cancer are twofold: distinguishing thyroid cancer from benign thyroid nodules, which occur in 50% of the population over 50 years; and correct staging of thyroid cancer to facilitate appropriate radical surgery in a single session. The clinical management of thyroid cancer patients has been covered in detail by the 2015 guidelines of the American Thyroid Association (ATA). The purpose of this review is to state the principles underlying optimal multimodal imaging of thyroid cancer and aid clinicians in avoiding important pitfalls. Recent findings: Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of nodules for fine needle biopsy (FNB) and the evaluation of new radioactive tracers for imaging thyroid cancer. Summary: The mainstay of diagnosing thyroid cancer is thyroid ultrasound with ultrasound-guided FNB. Contrast-enhanced computed tomography and PET with [¹⁸F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [¹⁸F]FDOPA and [⁶⁸Ga]DOTATOC are the preferred tracers for medullary thyroid cancer.

Radiology and nuclear medicine have traditionally been taught in a series of lectures and seminars concluded by an examination testing knowledge rather than skills. To emphasize skills in the students’ learning process, we developed and evaluated a new e-learning framework for teaching medical imaging. The framework consists of electronic lectures, a learning management system (LMS), and a diagnostic viewing system. Students were to review positron emission tomography/computed tomography (PET/CT) examinations of five cases of lung cancer. The framework was evaluated in an objective structured clinical examination (OSCE) taken by 139 undergraduate students at the end of their third year, and in a comparative survey of two groups of 85 and 84 students in the fifth and sixth year who were taught the same oncology course with and without mandatory PET/CT exercises, respectively. Of the 139 third-year students, 134 (96%) passed the OSCE PET/CT station according to the predefined criteria. While 85/85 (100%) of the fifth-year students had taken exercises when they were mandatory, only 2/84 (2%) of the sixth-year students had reviewed the cases on a voluntary basis (P < 0.001). Of the 25 survey responders in the fifth year, 24 (96%) agreed that the mandatory PET/CT exercises had promoted their learning while the sixth-year students, whose course concluded with a multiple-choice examination, emphasized the utility of online lectures. The new e-learning framework teaches students basic competency in PET/CT navigation and interpretation and is associated with a high degree of student satisfaction.

Background: While e-learning has become an important tool in teaching medical students, the training of specialists in medical imaging is still dominated by lecture-based courses. Purpose: To assess the potential of e-learning in specialist education in medical imaging. Material and Methods: An existing lecture-based five-day course in Clinical Nuclear Medicine (NM) was enhanced by e-learning resources and activities, including practical exercises. An anonymized survey was conducted after participants had completed and passed the multiple choice electronic course examination. Results: Twelve out of 15 course participants (80%) responded. Overall satisfaction with the new course format was high, but 25% of the respondents wanted more interactive elements such as discussions and practical exercises. The importance of lecture handouts and supplementary online material such as selected original articles and professional guidelines was affirmed by all the respondents (92% fully, 8% partially), while 75% fully and 25% partially agreed that the lectures had been interesting and relevant. Conclusion: E-learning represents a hitherto unrealized potential in the education of medical specialists. It may expedite training of medical specialists while at the same time containing costs.