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ObjectivesTo present a framework to develop and implement a fast-track artificial intelligence (AI) curriculum into an existing radiology residency program, with the potential to prepare a new generation of AI conscious radiologists.MethodsThe AI-curriculum framework comprises five sequential steps: (1) forming a team of AI experts, (2) assessing the residents’ knowledge level and needs, (3) defining learning objectives, (4) matching these objectives with effective teaching strategies, and finally (5) implementing and evaluating the pilot. Following these steps, a multidisciplinary team of AI engineers, radiologists, and radiology residents designed a 3-day program, including didactic lectures, hands-on laboratory sessions, and group discussions with experts to enhance AI understanding. Pre- and post-curriculum surveys were conducted to assess participants’ expectations and progress and were analyzed using a Wilcoxon rank-sum test.ResultsThere was 100% response rate to the pre- and post-curriculum survey (17 and 12 respondents, respectively). Participants’ confidence in their knowledge and understanding of AI in radiology significantly increased after completing the program (pre-curriculum means 3.25 ± 1.48 (SD), post-curriculum means 6.5 ± 0.90 (SD), p-value = 0.002). A total of 75% confirmed that the course addressed topics that were applicable to their work in radiology. Lectures on the fundamentals of AI and group discussions with experts were deemed most useful.ConclusionDesigning an AI curriculum for radiology residents and implementing it into a radiology residency program is feasible using the framework presented. The 3-day AI curriculum effectively increased participants’ perception of knowledge and skills about AI in radiology and can serve as a starting point for further customization.Critical relevance statementThe framework provides guidance for developing and implementing an AI curriculum in radiology residency programs, educating residents on the application of AI in radiology and ultimately contributing to future high-quality, safe, and effective patient care.Key points• AI education is necessary to prepare a new generation of AI-conscious radiologists.• The AI curriculum increased participants’ perception of AI knowledge and skills in radiology.• This five-step framework can assist integrating AI education into radiology residency programs.

PET-based tumor delineation is an error prone and labor intensive part of image analysis. Especially for patients with advanced disease showing bulky tumor FDG load, segmentations are challenging. Reducing the amount of user-interaction in the segmentation might help to facilitate segmentation tasks especially when labeling bulky and complex tumors. Therefore, this study reports on segmentation workflows/strategies that may reduce the inter-observer variability for large tumors with complex shapes with different levels of user-interaction. Twenty PET images of bulky tumors were delineated independently by six observers using four strategies: (I) manual, (II) interactive threshold-based, (III) interactive threshold-based segmentation with the additional presentation of the PET-gradient image and (IV) the selection of the most reasonable result out of four established semi-automatic segmentation algorithms (Select-the-best approach). The segmentations were compared using Jaccard coefficients (JC) and percentage volume differences. To obtain a reference standard, a majority vote (MV) segmentation was calculated including all segmentations of experienced observers. Performed and MV segmentations were compared regarding positive predictive value (PPV), sensitivity (SE), and percentage volume differences. The results show that with decreasing user-interaction the inter-observer variability decreases. JC values and percentage volume differences of Select-the-best and a workflow including gradient information were significantly better than the measurements of the other segmentation strategies (p-value<0.01). Interactive threshold-based and manual segmentations also result in significant lower and more variable PPV/SE values when compared with the MV segmentation. FDG PET segmentations of bulky tumors using strategies with lower user-interaction showed less inter-observer variability. None of the methods led to good results in all cases, but use of either the gradient or the Select-the-best workflow did outperform the other strategies tested and may be a good candidate for fast and reliable labeling of bulky and heterogeneous tumors.

Bridging therapy before CD19-directed chimeric antigen receptor (CAR) T-cell infusion is frequently applied in patients with relapsed or refractory Large B-cell lymphoma (r/r LBCL). This study aimed to assess the influence of quantified MATV and MATV-dynamics, between pre-apheresis (baseline) and pre-lymphodepleting chemotherapy (pre-LD) MATV, on CAR T-cell outcomes and toxicities in patients with r/r LBCL. MATVs were calculated semi-automatically at baseline ( n  = 74) and pre-LD ( n  = 68) in patients with r/r LBCL who received axicabtagene ciloleucel. At baseline, patients with a low MATV (< 190 cc) had a better time to progression (TTP) and overall survival (OS) compared to high MATV patients ( p  < 0.001). High MATV patients who remained stable or reduced upon bridging therapy showed a significant improvement in TTP ( p  = 0.041) and OS ( p  = 0.015), compared to patients with a high pre-LD MATV (> 480 cc). Furthermore, high MATV baseline was associated with severe cytokine release syndrome (CRS, p  = 0.001). In conclusion, patients with low baseline MATV had the best TTP/OS and effective reduction or controlling MATV during bridging improved survival outcomes in patients with a high baseline MATV, providing rationale for the use of more aggressive bridging regimens.

This review describes the main benefits of using long axial field of view (LAFOV) PET in clinical applications. As LAFOV PET is the latest development in PET instrumentation, many studies are ongoing that explore the potentials of these systems, which are characterized by ultra-high sensitivity. This review not only provides an overview of the published clinical applications using LAFOV PET so far, but also provides insight in clinical applications that are currently under investigation. Apart from the straightforward reduction in acquisition times or administered amount of radiotracer, LAFOV PET also allows for other clinical applications that to date were mostly limited to research, e.g., dual tracer imaging, whole body dynamic PET imaging, omission of CT in serial PET acquisition for repeat imaging, and studying molecular interactions between organ systems. It is expected that this generation of PET systems will significantly advance the field of nuclear medicine and molecular imaging.

Background The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177 Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial. Changes in methods and materials Two important changes were made to the original protocol: (1) the study will now use 177 Lu-PSMA-617 instead of 177 Lu-PSMA-I&T and (2) responding patients with residual disease on 18 F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177 Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177 Lu-PSMA-617 will also receive an interim 18 F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; “Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer” and is now partly supported by Advanced Accelerator Applications, a Novartis Company. Conclusions We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177 Lu-PSMA-I&T under the previous protocol will be replaced. Trial registration ClinicalTrials.gov NCT04443062 . First posted: June 23, 2020.

BackgroundExcellent performance characteristics of the Vision Quadra PET/CT, e.g. a substantial increase in sensitivity, allow for precise measurements of image-derived input functions (IDIF) and tissue time activity curves. Previously we have proposed a method for a reduced 30 min (as opposed to 60 min) whole body 18F-FDG Patlak PET imaging procedure using a previously published population-averaged input function (PIF) scaled to IDIF values at 30–60 min post-injection (p.i.). The aim of the present study was to apply this method using the Vision Quadra PET/CT, including the use of a PIF to allow for shortened scan durations.MethodsTwelve patients with suspected lung malignancy were included and received a weight-based injection of 18F-FDG. Patients underwent a 65-min dynamic PET acquisition which were reconstructed using European Association of Nuclear Medicine Research Ltd. (EARL) standards 2 reconstruction settings. A volume of interest (VOI) was placed in the ascending aorta (AA) to obtain the IDIF. An external PIF was scaled to IDIF values at 30–60, 40–60, and 50–60 min p.i., respectively, and parametric 18F-FDG influx rate constant (Ki) images were generated using a t* of 30, 40 or 50 min, respectively. Herein, tumour lesions as well as healthy tissues, i.e. liver, muscle tissue, spleen and grey matter, were segmented.ResultsGood agreement between the IDIF and corresponding PIF scaled to 30–60 min p.i. and 40–60 min p.i. was obtained with 7.38% deviation in Ki. Bland–Altman plots showed excellent agreement in Ki obtained using the PIF scaled to the IDIF at 30–60 min p.i. and at 40–60 min p.i. as all data points were within the limits of agreement (LOA) (− 0.004–0.002, bias: − 0.001); for the 50–60 min p.i. Ki, all except one data point fell in between the LOA (− 0.021–0.012, bias: − 0.005).ConclusionsParametric whole body 18F-FDG Patlak Ki images can be generated non-invasively on a Vision Quadra PET/CT system. In addition, using a scaled PIF allows for a substantial (factor 2 to 3) reduction in scan time without substantial loss of accuracy (7.38% bias) and precision (image quality and noise interference).

Background High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. Methods The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m 2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. Discussion This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. Trial registration Netherlands Trial Register NL8902 , registered on 2020–09-15.

Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN , TET2 (35%), and ARID1A , IGLL5 , and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring.

BackgroundEarly detection of recurrent or progressive HCC remains the strongest prognostic factor for survival. Dual tracer PET/CT imaging with [11C]CH and [18F]FDG can further increase detection rates as both tracers entail different metabolic pathways involved in HCC development. We investigated dual-tracer PET/CT in clinical decision making in patients suspected of recurrent or progressive HCC. All HCC patients who underwent both [11C]CH and [18F]FDG PET/CT in our institute from February 2018 to December 2021 were included. Both tracer PET/CT were within 4 weeks of each other with at least 6-month follow-up. Patients underwent dual tracer PET/CT because of unexplained and suspicious CT/MRI or sudden rise of serum tumour markers. A detected lesion was considered critical when the finding had prognostic consequences leading to treatment changes.ResultsNineteen patients who underwent [11C]CH and [18F]FDG PET/CT were included of which all but six patients were previously treated for HCC. Dual-tracer critical finding detection rate was 95%, with [18F]FDG 68%, and [11C]CH 84%. Intrahepatic HCC recurrence finding rate was 65% for both tracers. [18F]FDG found more ablation site recurrences (4/5) compared to [11C]CH (2/5). Only [11C]CH found two needle tract metastases. Both tracers found 75% of the positive lymph nodes. Two new primary tumours were found, one by [18F]FDG and both by [11C]CH.ConclusionsOur study favours a dual-tracer approach in HCC staging in high-risk patients or when conventional imaging is non-conclusive.

Background/objectives: Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. 18 F-PSMA-1007 is increasingly used because of its favorable imaging characteristics. However, increased non-specific skeletal uptake may be an important pitfall of this radioligand. Therefore, we aimed to assess the interobserver variation in reporting skeletal 18 F-PSMA-1007 uptake on PET/CT. Design/methods: In total, 33 18 F-PSMA-1007 PET/CT scans of 21 patients with primary PCa and 12 patients with biochemical recurrence were included, and a total of 85 skeletal lesions were evaluated by three independent observers. The primary endpoint was the interobserver variability of the likelihood of malignancy of the skeletal lesions on both patient and lesion level (kappa analysis). Results: Observers qualified most lesions as not malignant (81–91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95–100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%. Conclusion: This interobserver analysis of skeletal 18 F-PSMA-1007 uptake resulted in moderate agreement, in line with rates reported in literature. Importantly, the presence of non-specific skeletal uptake without CT substrate, as a potential shortcoming of 18 F-PSMA-1007, did not impair interobserver agreement.