Search

Targeted radionuclide therapy (TRT) using targeting moieties labeled with α-particle-emitting radionuclides (α-TRT) is an intensely investigated treatment approach as the short range of α-particles allows effective treatment of local lesions and micrometastases. However, profound assessment of the immunomodulatory effect of α-TRT is lacking in literature. Methods: Using flow cytometry of tumors, splenocyte restimulation, and multiplex analysis of blood serum, we studied immunologic responses ensuing from TRT with an antihuman CD20 single-domain antibody radiolabeled with 225Ac in a human CD20 and ovalbumin expressing B16-melanoma model. Results: Tumor growth was delayed with α-TRT and increased blood levels of various cytokines such as interferon-γ, C-C motif chemokine ligand 5, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1. Peripheral antitumoral T-cell responses were detected on α-TRT. At the tumor site, α-TRT modulated the cold tumor microenvironment (TME) to a more hospitable and hot habitat for antitumoral immune cells, characterized by a decrease in protumoral alternatively activated macrophages and an increase in antitumoral macrophages and dendritic cells. We also showed that α-TRT increased the percentage of programmed death-ligand 1 (PD-L1)-positive (PD-L1pos) immune cells in the TME. To circumvent this immunosuppressive countermeasure we applied immune checkpoint blockade of the programmed cell death protein 1-PD-L1 axis. Combination of α-TRT with PD-L1 blockade potentiated the therapeutic effect, however, the combination aggravated adverse events. A long-term toxicity study revealed severe kidney damage ensuing from α-TRT. Conclusion: These data suggest that α-TRT alters the TME and induces systemic antitumoral immune responses, which explains why immune checkpoint blockade enhances the therapeutic effect of α-TRT. However, further optimization is warranted to avoid adverse events.

Background: The ramus artery contributes to the development of turbulence, which may influence computed tomography (CT) derived fractional flow reserve (FFR CT) even without coronary artery disease (CAD). The relationship between ramus-induced turbulence and FFR CT is unclear. Method and Results: A total of 120 patients with

Introduction Immune-mediated interstitial pneumonitis may be treated with anti-CD20 therapy after failure of conventional therapies. However, clinical response is variable. It was hypothesized that autoreactive CD20-positive cells may play an important role in this variability. This prospective study aims to elucidate if imaging of CD20-positive cells in the lungs allows prediction of the response to anti-CD20 treatment. Methods Twenty-one patients with immune-mediated interstitial lung disease (ILD) with deteriorated pulmonary function received a dose of 1000 mg rituximab on day 1 and day 14 spiked with a tracer dose of radiolabeled [89Zr]-rituximab. PET/CT was performed on days 3 and 6. Standardized uptake values (SUV) were calculated as a measure for pulmonary CD20 expression. Based on pulmonary function tests (PFT), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), prior to and 6 months after treatment, patients were classified as responder (stable disease or improvement) or non-responder. Results Fifteen patients (71%) were classified as responder. Pulmonary [89Zr]-rituximab PET SUVmean was significantly correlated with the change in FVC and DLCO (K = 0.49 and 0.56, respectively) when using target-to-background ratios, but not when using SUVmean alone. [89Zr]-rituximab SUVmean was significantly higher in responders than in non-responders (0.35 SD 0.09 vs. 0.23 SD 0.06; P = 0.02). Conclusion Rituximab treatment was effective in the majority of patients. As a higher pulmonary uptake of [89Zr]-rituximab correlated with improvement of PFT and treatment outcome, [89Zr]-rituximab PET imaging may serve as a potential predictive biomarker for anti-CD20 therapy. Trial registration Clinicaltrials.gov identifier NCT02251964

The opposable thumb provides both stability and mobility and is needed to accomplish different prehensile tasks. The trapezium is a complex bone, with a distal articular surface that is convex in the sagittal plane of the thumb and concave in the coronal plane of the thumb. The numerous additional articulations with the carpus and the oblique orientation to the main plane of the hand makes it difficult to evaluate the trapeziometacarpal joint using standard hand or wrist radiographic views. This review gives an overview of the different radiological views that have been described for the thumb with an emphasis on their historical origin and positioning during radiography. We also describe different measurements and classifications that can be obtained using different thumb radiographs.

Self-control is of vital importance for human wellbeing. Hare et al. (2009) were among the first to provide empirical evidence on the neural correlates of self-control. This seminal study profoundly impacted theory and empirical work across multiple fields. To solidify the empirical evidence supporting self-control theory, we conducted a preregistered replication of this work. Further, we tested the robustness of the findings across analytic strategies. Participants underwent functional magnetic resonance imaging while rating 50 food items on healthiness and tastiness and making choices about food consumption. We closely replicated the original analysis pipeline and supplemented it with additional exploratory analyses to follow-up on unexpected findings and to test the sensitivity of results to key analytical choices. Our replication data provide support for the notion that decisions are associated with a value signal in ventromedial prefrontal cortex (vmPFC), which integrates relevant choice attributes to inform a final decision. We found that vmPFC activity was correlated with goal values regardless of the amount of self-control and it correlated with both taste and health in self-controllers but only taste in non-self-controllers. We did not find strong support for the hypothesized role of left dorsolateral prefrontal cortex (dlPFC) in self-control. The absence of statistically significant group differences in dlPFC activity during successful self-control in our sample contrasts with the notion that dlPFC involvement is required in order to effectively integrate longer-term goals into subjective value judgments. Exploratory analyses highlight the sensitivity of results (in terms of effect size) to the analytical strategy, for instance, concerning the approach to region-of-interest analysis.

The synthesis of deuteriated tri-tert-butyl phosphine is reported. This synthesis is an adaptation of the known procedure for tri-tert-butyl phosphine via a Grignard intermediate.

Endometriosis represents one of the most common causes of life-impacting chronic pelvic pain and female infertility. Magnetic resonance imaging (MRI) plays an increasing role in the diagnosis and mapping of endometriosis, while diagnostic laparoscopy currently tends to be reserved for the patients with negative imaging results. The #Enzian, published in 2021, proposes a new comprehensive classification system of endometriosis, combining a complete staging of deep infiltrative endometriosis with the evaluation of peritoneal/ovarian/tubal localizations and the presence of adenomyosis. This article addresses in detail the applicability of the #Enzian classification, primarily based on surgical findings, to the MRI evaluation of the endometriosis. Overall, there is a significant matching between MRI features and the #Enzian classification criteria, two different perspectives of endometriosis mapping, with different goals and levels of detail. The main discrepancy lies in the evaluation of tubo-ovarian condition, which is not fully assessable by MRI. Furthermore, as endometriosis is a complex disease, usually multifocal, that can present with a myriad of imaging findings, MRI reporting should be clear and well organized. The authors group, both radiologists and gynecologists, propose a structured MRI report of endometriosis in correlation with the #Enzian classification, merging the detailed anatomical and pre-operative information provided by the MRI with the benefits of a comprehensive classification system of endometriosis in the clinical practice and research field. Critical relevance statement This article addresses in detail the applicability of the #Enzian classification, primarily based on surgical findings, to the MRI evaluation of the endometriosis and proposes a #Enzian-based structured MRI report. Graphical abstract: [Figure not available: see fulltext.] publishersversion published

Funding Information: The authors thank ESGO, ESTRO, and ESP for their support. The authors also thank the 155 international reviewers (physicians and patient representatives, see Appendix 2 in Online Supplemental File 2) for their valuable comments and suggestions. The authors thank the ESGO office, especially Kamila Macku, Tereza Cicakova, and Kateřina Šibravová, provided invaluable logistical and administrative support throughout the process. The development group (including all authors) is collectively responsible for the decision to submit for publication. DC (chair), JL (chair), MRR (chair) and FP (methodologist) wrote the first draft of the manuscript. All other contributors have actively given personal input, reviewed the manuscript, and have given final approval before submission. DC is responsible for the overall content as the guarantor. Initiated through the ESGO the decision to develop multidisciplinary guidelines was made jointly by the ESGO, ESTRO, and ESP. The ESGO provided administrative support. The ESGO, ESTRO and ESP are nonprofit knowledgeable societies. *These guidelines were developed by ESGO, ESTRO and ESP and are published in the Int J Gynecol Cancer, Radiother Oncol and Virchows Archiv. CCh has reported advisory boards for GSK, MSD and EISAI; SFL has reported advisory boards for MSD, GSK, AstraZeneca and Novartis; DL has reported consultant honoria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen and PharmaMar, advisory boards for AstraZeneca, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept and Sutro, research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar, research sponsored by AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Roche, Seagen and Novartis, and speakers’ bureau activities for AstraZeneca, Clovis Oncology, GSK, MSD and PharmaMar; UM has reported advisory boards for AstraZeneca (Steering committee member for CALLA Study); RN has reported research grants from Elekta, Varian, Accuray, Dutch Research Council, and Dutch Cancer Society; AO has reported personal fees for advisory board membersip from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, F. Hoffmann-La Roche, Genmab/Seagen, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de Espana, SA, Mersana Thereapeutics, Novocure, PharmaMar, piIME Oncology, Roche, Sattucklabs, Sutro Biopharma and Tesaro, and personal fees for travel/accomodation from AstraZeneca, PharmaMar and Roche; DQ has reported advisory boards for Mimark inc; MPS has reported research grants and personal fees for workshops from Elekta AB; DC, MRR, FP, CC, AF, DF, DJK, FJ, CK, PM, RN, FPec, JP, SR, AS, VS, KT, IZ and JCL have reported no conflicts of interest. Not commissioned; internally peer reviewed. Not applicable. Not applicable. David Cibula, Maria Rosaria Raspollini, François Planchamp, Carlos Centeno, Cyrus Chargari, Ana Felix, Daniela Fischerova, Daniela Jahn-Kuch, Florence Joly, Christhardt Kohler, Sigurd F. Lax, Domenica Lorusso, Umesh Mahantshetty, Patrice Mathevet, Raj Naik, Remi Nout, Ana Oaknin, Fedro Peccatori, Jan Persson, Denis Querleu, Sandra Rubio, Maximilian Paul Schmid, Artem Stepanyan, Valentyn Svintsitskyi, Karl Tamussino, Ignacio Zapardiel, Jacob Christian Lindegaard. All data relevant to the study are included in the article or uploaded as supplementary information. Funding Information: CCh has reported advisory boards for GSK, MSD and EISAI; SFL has reported advisory boards for MSD, GSK, AstraZeneca and Novartis; DL has reported consultant honoria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen and PharmaMar, advisory boards for AstraZeneca, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept and Sutro, research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar, research sponsored by AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Roche, Seagen and Novartis, and speakers’ bureau activities for AstraZeneca, Clovis Oncology, GSK, MSD and PharmaMar; UM has reported advisory boards for AstraZeneca (Steering committee member for CALLA Study); RN has reported research grants from Elekta, Varian, Accuray, Dutch Research Council, and Dutch Cancer Society; AO has reported personal fees for advisory board membersip from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, F. Hoffmann-La Roche, Genmab/Seagen, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de Espana, SA, Mersana Thereapeutics, Novocure, PharmaMar, piIME Oncology, Roche, Sattucklabs, Sutro Biopharma and Tesaro, and personal fees for travel/accomodation from AstraZeneca, PharmaMar and Roche; DQ has reported advisory boards for Mimark inc; MPS has reported research grants and personal fees for workshops from Elekta AB; DC, MRR, FP, CC, AF, DF, DJK, FJ, CK, PM, RN, FPec, JP, SR, AS, VS, KT, IZ and JCL have reported no conflicts of interest. Publisher Copyright: © 2023 ESGO, ESTRO, ESP In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined. publishersversion published

A 35 year-old right-handed female presented with persistent wrist pain lasting two years. Imaging disclosed an accessory tendon-shaped structure, identified as a Flexor Carpi Radialis Brevis, strangling the Flexor Carpi Radialis tendon at the wrist during effort. Surgical exploration found the insertion of the Flexor Carpi Radialis Brevis to be bifid. Resection of the stenosing branch and the fibrotic tendon sheath restored strength in the right wrist and painless symmetrical motion compared to the left wrist ten weeks postoperatively.

Purpose For many low- and middle-income countries (LMICs), breast cancer (BC) screening based on mammography is not a viable option. Clinical breast examination (CBE) may represent a pragmatic and cost-effective alternative. This paper examines the cost-effectiveness of CBE screening programme among a patient group for whom its cost-effectiveness is likely to be least evident (HER2-positive patients) and discuss the wider implications for BC screening in LMICs. Methods A Markov model was used to examine clinical and economic outcomes over a life-time horizon from the patient, public payer, and healthcare sector perspective. HER2-positive patients entered the model at either disease-free survival or metastatic BC state. The downstaging effect of CBE determined the starting probabilities in the no-screening and screening scenarios. The model used a monthly cycle length, with half-cycle correction. Costs and outcomes were discounted at 1.5% annually. Results Compared with no-screening, the cost-effectiveness ratio (ICER) per quality-adjusted life-year gained for the CBE screening programme was $1801, $2381, and $4179 from three mentioned perspectives, respectively. The finding of cost-effectiveness remained robust to a range of sensitivity analyses. The parameters to which ICERs are most sensitive are average age of cohorts, reduction in proportion of metastatic patients at diagnosis, cost of CBE, and BC detection rate of the programme. Conclusion For HER2-positive patients and compared with no-screening, CBE screening programme in Vietnam is cost-effective from all investigated perspectives. CBE is a ‘good value’ intervention and should be considered for implementation throughout Vietnam as well as in LMICs where mammography is not feasible.

Background: Both quantitative flow ratio (QFR) and fractional flow reserve derived from computed tomography (FFRCT) have shown significant correlations with invasive wire-based fractional flow reserve. However, the correlation between QFR and FFRCT is not fully investigated in patients with complex coronary artery disease (CAD). The aim of this study is to investigate the correlation and agreement between QFR and FFRCT in patients with de novo three-vessel disease and/or left main CAD. Methods: This is a post-hoc sub-analysis of the international, multicenter, and randomized SYNTAX III REVOLUTION trial, in which both invasive coronary angiography and coronary computed tomography angiography were prospectively obtained prior to the heart team discussion. QFR was performed in an independent core laboratory and compared with FFRCT analyzed by HeartFlow™. The correlation and agreement between QFR and FFRCT were assessed per vessel. Furthermore, independent factors of diagnostic discordance between QFR and FFRCT were evaluated. Results: Out of 223 patients, 40 patients were excluded from this analysis due to the unavailability of FFRCT and/or QFR, and a total of 469 vessels (183 patients) were analyzed. There was a strong correlation between QFR and FFRCT (R ​= ​0.759; p ​< ​0.001), and the Bland-Altman analysis demonstrated a mean difference of −0.005 and a standard deviation of 0.116. An independent predictor of diagnostic concordance between QFR and FFRCT was the lesion location in right coronary artery (RCA) (odds ratio 0.395; 95% confidence interval 0.174–0.894; P ​= ​0.026). Conclusion: In patients with complex CAD, QFR and FFRCT were strongly correlated. The location of the lesion in RCA was associated with the highest diagnostic concordance between QFR and FFRCT.

Background and purposeRadiomics features derived from medical images have the potential to act as imaging biomarkers to improve diagnosis and predict treatment response in oncology. However, the complex relationships between radiomics features and the biological characteristics of tumours are yet to be fully determined. In this study, we developed a preclinical cone beam computed tomography (CBCT) radiomics workflow with the aim to use in vivo models to further develop radiomics signatures.Materials and methodsCBCT scans of a mouse phantom were acquired using onboard imaging from a small animal radiotherapy research platform (SARRP, Xstrahl). The repeatability and reproducibility of radiomics outputs were compared across different imaging protocols, segmentation sizes, pre-processing parameters and materials. Robust features were identified and used to compare scans of two xenograft mouse tumour models (A549 and H460).ResultsChanges to the radiomics workflow significantly impact feature robustness. Preclinical CBCT radiomics analysis is feasible with 119 stable features identified from scans imaged at 60 kV, 25 bin width and 0.26 mm slice thickness. Large variation in segmentation volumes reduced the number of reliable radiomics features for analysis. Standardization in imaging and analysis parameters is essential in preclinical radiomics analysis to improve accuracy of outputs, leading to more consistent and reproducible findings.ConclusionsWe present the first optimised workflow for preclinical CBCT radiomics to identify imaging biomarkers. Preclinical radiomics has the potential to maximise the quantity of data captured in in vivo experiments and could provide key information supporting the wider application of radiomics.

Introduction Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty. Case presentation Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li–Fraumeni syndrome. Discussion Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li–Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li–Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation. Conclusion In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension.

Objective. To test and compare different intensity standardization approaches for whole-body multi-parametric MR images, aiming to compensate voxel intensity differences between scans. These differences, common for magnetic resonance imaging, pose problems in image quantification, assessment of changes between a baseline and follow-up scan, and hinder performance of image processing and machine learning algorithms. Approach. In this work, we present a comparison on the accuracy of intensity standardization approaches with increasing complexity, for intra- and inter-patient multi-parametric whole-body MRI. Several approaches were used: z-scoring of the intensities, piecewise linear mapping and deformable mapping of intensity distributions into established reference intensity space. For each method, the impact on standardization algorithm on the use of single image or average population distribution reference; as well as, whole image and region of interest were additionally investigated. All methods were validated on a data set of 18 whole-body anatomical and diffusion-weighted MR scans consisting of baseline and follow-up examinations acquired from advanced prostate cancer patients and healthy volunteers. Main results. The piecewise linear intensity standardisation approach provided the best compromise between standardization accuracy and method stability, with average deviations in intensity profile of 0.011-0.027 and mean absolute difference of 0.29-0.37 standard score (intra-patient) and 0.014-0.056 (inter-patient), depending on the type of used MR modality. Significance. Linear piecewise approaches showed the overall best performance across multiple validation metrics, mostly because of its robustness. The inter-patient standardization proved to perform better when using population average reference image; in contrary to intra-patient approach, where the best results were achieved by standardizing towards a reference image taken as the baseline scan.

BACKGROUND: Personalized long term vital prognosis plays a key role in deciding between percutaneous coronary intervention (PCI) and CABG in patients with complex coronary artery disease. The FASTTRACK CABG trial enrolls patients with the sole guidance of coronary computed tomographic angiography (CCTA) and fractional flow reserve CCTA (FFRCT). The feasibility/non-feasibility of this approach is determined by the surgeon request to have access to the invasive coronary angiography. METHODS: This interim analysis, which was requested by the Data and Safety Monitoring Board (DSMB), compared the treatment decision of the "on site" Heart team to the recommended treatment as per the SYNTAX Score II 2020 (SS-2020), which was prospectively assessed by the central core laboratory in the first 57 consecutive patients (half of the planned population) enrolled in this First in Man study. RESULTS: The average anatomical SYTAX Score is 35.6 ± 11.5. The SS-2020 predicted 5-year MACE and 10-year all-cause mortality are 14.7 % and 21.6 % following CABG, and 23.0 % and 30.4 % following PCI. Among the enrolled patients the SS-2020 predicts long-term PCI outcomes similar to CABG (absolute risk difference ≤0 % in favor of PCI) in only two patients whilst the remaining 55 patients had a predicted survival benefit with CABG. CONCLUSIONS: According to the SS-2020, the first 57 patients recruited into the FASTTRACK CABG trial received the appropriate modality of revascularization and the DSMB allowed the investigators to complete the study.

This Roadmap paper covers the field of precision preclinical x-ray radiation studies in animal models. It is mostly focused on models for cancer and normal tissue response to radiation, but also discusses other disease models. The recent technological evolution in imaging, irradiation, dosimetry and monitoring that have empowered these kinds of studies is discussed, and many developments in the near future are outlined. Finally, clinical translation and reverse translation are discussed.

Funding Information: The APC was financed by Instituto Politécnico de Setúbal. Publisher Copyright: © 2023 by the authors. The current paper presents a hyper parameterization optimization process for a convolutional neural network (CNN) applied to pipe burst locations in water distribution networks (WDN). The hyper parameterization process of the CNN includes the early stopping termination criteria, dataset size, dataset normalization, training set batch size, optimizer learning rate regularization, and model structure. The study was applied using a case study of a real WDN. Obtained results indicate that the ideal model parameters consist of a CNN with a convolutional 1D layer (using 32 filters, a kernel size of 3 and strides equal to 1) for a maximum of 5000 epochs using a total of 250 datasets (using data normalization between 0 and 1 and tolerance equal to max noise) and a batch size of 500 samples per epoch step, optimized with Adam using learning rate regularization. This model was evaluated for distinct measurement noise levels and pipe burst locations. Results indicate that the parameterized model can provide a pipe burst search area with more or less dispersion depending on both the proximity of pressure sensors to the burst or the noise measurement level. publishersversion published

Cavernous malformations (CMs) are benign vascular malformations that maybe seen anywhere in the central nervous system. They are dynamic lesions, growing or shrinking over time and only rarely remaining stable. Size varies from a few millimeters to a few centimeters. CMs can be sporadic or familial, and while most of them are congenital, de novo and acquired lesions may also be seen. Etiology is still unknown. A genetic molecular mechanism has been proposed since a cerebral cavernous malformation gene loss of function was found in both familial and sporadic lesions. Additionally, recent studies suggest that formation of CMs in humans may be associated with a distinctive bacterial gut composition (microbioma). Imaging is fairly typical but may vary according to age, location, and etiology. Follow-up is not well established because CMs patients have a highly unpredictable clinical course. Angiogenic and inflammatory mechanisms have been implicated in disease activity, as well as lesional hyperpermeability and iron deposition. Imaging and serum biomarkers of these mechanisms are under current investigation. Treatment options, including surgery or radiosurgery, are not well defined and are dependent upon multiple factors, including clinical presentation, lesion location, number of hemorrhagic events, and medical comorbidities. Our purpose is to review the imaging features of CMs based on their size, location, and etiology, as well as their differential diagnosis and best imaging approach. New insights in etiology will be briefly considered. Follow-up strategies, including serum and imaging biomarkers, and treatment options will also be discussed. publishersversion published

Introduction: Although the use of 68Ga has increased substantially in nuclear medicine over the last decade, there is limited information available on occupational exposure due to 68Ga. The purpose of this study is to determine the occupational extremity exposure during the preparation, dispensing and administration of 68Ga-labelled radiopharmaceuticals. Method: Workers in eight centres wore a ring dosimeter for all tasks involving 68Ga-labelled radiopharmaceuticals for a minimum of one month. Additionally, the fingertip dose was monitored in two centres and the hand with the highest ring dose during 68Ga procedures was also identified in one centre. Results: The median normalised ring dose for 68Ga procedures was found to be 0.25 mSv GBq−1 (range 0.01–3.34). The normalised 68Ga ring doses recorded in this study are similar to that found in the literature for 18F. This study is consistent with previous findings that the highest extremity dose is found on the non-dominant hand. A limited sub study in two of the centres showed a median fingertip to base of the finger dose ratio of 4.3. Based on this median ratio, the extrapolated annual 68Ga fingertip dose for 94% of the workers monitored in this study would be below Category B dose limit (150 mSv) and no worker would exceed Category A dose limit (500 mSv). Conclusion: When appropriate shielding and radiation protection practices are employed, the extremity dose due to 68Ga is comparable to that of 18F and is expected to be well below the regulatory limits for the majority of workers.

A 79-year-old male with chronic coronary syndrome with complex coronary artery disease was included in the first-in-man trial of surgical revascularization guided solely by coronary computed tomography angiography (CCTA) and fractional flow reserve derived from CCTA (FFRCT). In CCTA analysis, the patient had calcified three-vessel disease, with a global anatomical SYNTAX score of 27. In contrast, in the initial FFRCT, only the ramus intermediate stenosis was physiologically significant, with no other vessels having an FFRCT ≤ 0.80 (functional SYNTAX score of 2). Discordance between the results of the CCTA and FFRCT necessitated an in-depth analysis by using both invasive and non-invasive coronary angiography. Angiography-derived fractional flow reserve (FFR) confirmed that the stenosis in the proximal left anterior descending artery (LAD) was physiologically significant, while it remained functionally negative in the second assessment of FFRCT. Extensive calcification is the most plausible explanation for the underestimation of the stenosis of proximal LAD in CCTA-derived FFR technology.

Computed tomography-derived fractional flow reserve decreases from the proximal to the distal with coronary stenosis. According to the principles of fluid dynamics, paradoxical computed tomography-derived fractional flow reserve changes require an unconventional vessel mor-phology and specific site of the vessels with a high driving force. Therefore, only a few articles have reported a paradoxical increase of computed tomography-derived fractional flow reserve. We present a case report of marked computed tomography-derived fractional flow reserve elevation in the middle left anterior descending artery with a severe coronary stenosis. Computed tomography-derived fractional flow reserve was 0.94 just proximal to the stenotic lesion and decreased to 0.65 at the maximum stenosis area but recovered to 0.80 in the distal segment. We speculated that the vessel morphology could have caused a pressure recovery phenomenon, resulting in paradoxical computed tomography-derived fractional flow reserve changes.

BACKGROUND: Extremity exposure during the handling of unsealed radioactive sources is a matter of concern for nuclear medicine workers. Next to 99mTc and 18F, other radiopharmaceuticals have seen an increase in their use over the last decade. However, limited information on their impact on extremity dose is available. This study aimed to gain insight into the status of extremity exposure and dose monitoring in Europe. METHODS: A survey was conducted at the end of 2020 among the European Association of Nuclear Medicine community. It contained 24 questions considering department characteristics, worker tasks, dosimeter use, typical worker extremity dose, department workload for selected radionuclides (99mTc, 18F, 68Ga, 177Lu, 90Y) and protective measures. RESULTS: A total of 106 replies were received, 92% of which were from Europe. About half of the respondents were from academic hospitals. Ninety-nine departments implement extremity dose monitoring for a total of 1335 workers. Most workers (95%) wear a ring dosimeter, generally on the non-dominant hand, and 44% on the index finger. Monthly doses were generally low (median values at different ring position: 0.4-1.8 mSv), although higher doses were reported (20.8-38.8 mSv). About 1/3 of workers performed the full task range (preparation, dispensing, and administration). Administration is associated with significantly lower extremity doses. Interestingly, no correlation between department workload and collective dose was found. The adoption of vial and syringe shielding, as well as distance tools, was common. The workers dispensing 99mTc without syringe shielding or PET nuclides without automated system received a significantly higher dose. Handling 68Ga, 177Lu and 90Y did not appear to have an impact on the reported doses. CONCLUSIONS: Protective measures play a significant role in lowering extremity doses, while department workload and more recently introduced radionuclides seem not to be major dose determinants.

Dermatofibrosarcoma protuberans is a low-grade cutaneous sarcoma typically located on the trunk or proximal extremities. Less common locations include the head, face, and neck area. This tumour is slow growing with variable clinical appearance. It is known for its locally invasive nature and low metastatic propensity. Because imaging findings are rather nonspecific, biopsy is needed for definite diagnosis. This case describes an unusually large example of dermatofibrosarcoma protuberans in the less common preauricular region.

Purpose Proton computed (transmission) tomography (pCT) refers to the process of imaging an object by letting protons pass through it, while measuring their energy after, and their position and (optionally) direction both before and after their traversal through that object. The so far experimental technique has potential to improve treatment planning of proton therapy by enabling the direct acquisition of a proton stopping power map of tissue, thus removing the need to obtain it by converting X-ray CT attenuation data and thereby eliminating uncertainties which arise in the mentioned conversion process. The image reconstruction in pCT requires accurate estimates of the proton trajectories. In experimental pCT detector setups where the direction of the protons is not measured, the air gap between the detector planes and the imaged object worsens the spatial resolution of the image obtained. In this work we determined the mean proton paths and the corresponding spatial uncertainty, taking into account the presence of the air gap. Methods We used Monte Carlo simulations of radiation transport to systematically investigate the effect of the air gap size between detector and patient on the spatial resolution of proton (ion) computed tomography for protons with an energy of 200 MeV and 250 MeV as well as for helium ions (He-4) with an energy of 798 MeV. For the simulations we used TOPAS which itself is based on Geant4. Results For all particles, which are detected at the same entrance and exit coordinate, the average ion path and the corresponding standard deviation was computed. From this information, the dependence of the spatial resolution on the air gap size and the angular confusion of the particle beam was inferred. Conclusion The presence of the airgap does not pose a problem for perfect fan beams. In realistic scenarios, where the initial angular confusion is around 5 mrad and for typical air gap sizes up to 10 cm, using an energy of 200 MeV a spatial resolution of about 1.6 mm can be achieved. Using protons with E = 250 MeV a spatial resolution of about 1.1 mm and using helium ions (He-4) with E = 798 MeV even a spatial resolution below 0.7 mm respectively is attainable.

A total of 1335 outpatients with suspected coronary artery disease and who underwent computed tomography derived fractional flow reserve (FFRCT ) analysis were examined. Only four patients showed reverse increase of FFRCT from the proximal to the distal vessel and all of them had a large ramus artery (RAM). Of all parameters (vessel length, lumen volume, plaque volume, and left ventricular mass), only the bifurcation angle was significantly higher in reverse increase of FFRCT with RAM group (106.0 ± 15.8°) than normal FFRCT with RAM group (82.6 ± 21.7°) and normal FFRCT without RAM group (66.9 ± 21.1°).

OBJECTIVE: The aim of the study was to assess DWI with ROI-ADC and WL-ADC measurements in early response after NAC in breast cancer. METHODS: Between January 2016 and December 2019, 55 women were enrolled in this prospective single-center study. MRI was performed at three time points for each patient: before treatment (MRI 1: DW and DCE MRI), after one cycle of NAC (MRI 2: noncontrast DW MRI), and after completion of NAC before surgery (MRI 3: DW and DCE MRI). ROI-ADC and WL-ADC measurements were obtained on MRI and were compared to histology findings and to the RCB class. Patients were categorized as having pCR or non-pCR. RESULTS: Among 48 patients, 9 experienced pCR. An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 88.9% and a specificity of 63.4% in predicting pCR, whereas WL-ADC did not predict pCR. An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 83.3% and a specificity of 64.9% in predicting radiologic complete response. An increase of WL-ADC between MRI 1 and 2 of more than 25.5% had a sensitivity of 83.3% and a specificity of 75.5% in predicting radiologic complete response. CONCLUSION: After one cycle of NAC, a significant increase in breast tumor ROI-ADC at DWI predicted complete pathologic and radiologic responses. KEY POINTS: • An increase of WL-ADC between MRI 1 and 2 of more than 25.5% had a sensitivity of 83.3% and a specificity of 75.5% in predicting radiologic complete response. • An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 88.9% and a specificity of 63.4% in predicting pCR, and a sensitivity of 83.3% and a specificity of 64.9% in predicting radiologic complete response. • A significant increase in breast tumor ROI-ADC at DWI predicted complete pathologic and radiologic responses.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (99mTc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD. 99mTc-cAbVCAM1-5 uptake strongly correlates with liver histological inflammatory score and with molecular inflammatory markers. The diagnostic power to detect any degree of liver inflammation is excellent (AUROC 0.85–0.99). These data build the rationale to investigate 99mTc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.

ObjectivesThis study will list the most common comorbidities of congenital facial nerve palsy and how to detect and treat them, with special attention for ENT-problems such as hearing loss. Congenital facial nerve palsy is a very rare entity but in UZ Brussels hospital there was a follow-up of 16 children in the last 30 years.MethodsLiterature review has been done, combined with thorough research of our own series of 16 children with congenital facial nerve palsy.ResultsCongenital facial nerve palsy can be part of a known syndrome, most commonly Moebius syndrome, but can also appear solely. It appears often bilateral and with a severe gradation. In our series, hearing loss is frequently seen in association with congenital facial nerve palsy. Other abnormalities are dysfunction of the abducens nerve, ophthalmological problems, retro- or micrognathism and abnormalities of limbs or heart. The majority of the children in our series underwent radiological imaging (CT and/or MRI): the facial nerve but also the vestibulocochlear nerve and middle and inner ear can be evaluated.ConclusionA multidisciplinary approach of congenital facial nerve palsy is recommended as it can affect various bodily functions. Radiological imaging needs to be done to acquire additional information that can be useful for diagnostic and therapeutic purposes. Although congenital facial nerve palsy may not be treatable itself, its comorbidities can be treated and improve the quality of life of the affected child.

PURPOSE: (1) to assess the influence of medial or lateral imaging plane inclination on the measurement of sulcus angle, trochlear depth, and facet asymmetry on transverse cross-sectional images. (2) to assess the effect of measurement level (height) on these respective parameters. MATERIALS AND METHODS: Twenty dry femurs (9 left, 11 right) were imaged with CT. A 3D dataset was obtained from which axial images were reconstructed in the ideal plane without inclination as well as with 8° of medial and lateral inclination. Sulcus angle, trochlear depth, and facet asymmetry were measured on the 3 image sets. In addition, the measurements were performed at 5 mm and 10 mm from the superior margin of the medial trochlear facet. Statistical analysis consisted of the Wilcoxon test and calculation of measurement variation. RESULTS: There were no statistically significant differences between the indicated measurements on the reference set compared to medial or lateral inclination. All measurements were significantly different depending on measurement height. CONCLUSION: Medial or lateral inclination in the transverse imaging plane of 8° does not influence the values of typical parameters used for the assessment of trochlear dysplasia. The measurement height has a significant influence, and a consensus should be found as to which is the optimal measurement height.

Purpose: Radiation cardiotoxicity (RC) is a clinically significant adverse effect of treatment for patients with thoracic malignancies. Clinical studies in lung cancer have indicated that heart substructures are not uniformly radiosensitive, and that dose to the heart base drives RC. In this study, we aimed to characterize late changes in gene expression using spatial transcriptomics in a mouse model of base regional radiosensitivity. Methods and Materials: An aged female C57BL/6 mouse was irradiated with 16 Gy delivered to the cranial third of the heart using a 6 × 9 mm parallel opposed beam geometry on a small animal radiation research platform, and a second mouse was sham-irradiated. After echocardiography, whole hearts were collected at 30 weeks for spatial transcriptomic analysis to map gene expression changes occurring in different regions of the partially irradiated heart. Cardiac regions were manually annotated on the capture slides and the gene expression profiles compared across different regions. Results: Ejection fraction was reduced at 30 weeks after a 16 Gy irradiation to the heart base, compared with the sham-irradiated controls. There were markedly more significant gene expression changes within the irradiated regions compared with nonirradiated regions. Variation was observed in the transcriptomic effects of radiation on different cardiac base structures (eg, between the right atrium [n = 86 dysregulated genes], left atrium [n = 96 dysregulated genes], and the vasculature [n = 129 dysregulated genes]). Disrupted biological processes spanned extracellular matrix as well as circulatory, neuronal, and contractility activities. Conclusions: This is the first study to report spatially resolved gene expression changes in irradiated tissues. Examination of the regional radiation response in the heart can help to further our understanding of the cardiac base's radiosensitivity and support the development of actionable targets for pharmacologic intervention and biologically relevant dose constraints.

Objectives: To compare the amount of fluid in synovial sheaths of the ankle before and after running. Our hypothesis was that this amount would increase, and that the threshold for what is normally acceptable should be adjusted after physical activity.Methods: Twenty-one healthy volunteers (n=42 ankles) ran for 40 minutes on a treadmill. They underwent 3T MRI before and immediately after running using a dedicated ankle coil. The images were stored and subsequently measured in a standardized way and independently read by two readers for fluid in the tendon sheaths in the retro and inframalleolar area. Statistics were performed for each tendon (Wilcoxon signed rank test), and also for the pooled data. Intraclass correlation coefficients were calculated.Results: For reader 1, for all tendons the values after running increased without reaching statistical significance. For reader 2 this was not the case for all tendons but for most. When all the data were pooled (n=800 measurements), the statistical difference before and after running was significant (p< 0.001).Conclusion: Data pre and post running show a trend of increasing synovial fluid, however not significant for each individual tendon. The pooled data for all tendons, (n=800) show a statistically significant increase after running (p< 0.001). The clinical implication is that the threshold for normally acceptable fluid should be adjusted if the patient undergoes an MR study after recent physical activity.

Funding Information: The authors thank Pedro Pereira from Canon, Portugal, for providing the 2D Wall Motion Tracking software for speckle tracking echocardiography. The EchoCrit Group is a collaboration group of the Intensive Care Department of Hospital Garcia de Orta, Almada, Portugal, dedicated to the advanced Echocardiography and POCUS in critical care, formed by the following physicians: Rui Gomes, Jacobo Bacariza, Rita Varudo, João Leote, Vera Pereira, Dário Batista, Vânia Brito, Corinna Lohmann, João Gouveia, Joana Manuel, Liliana Santos, Sara Lança, Lucinda Oliveira, Tiago Ferreira, Joana Ferreira, João Sampaio, José Seoane, Inês Pimenta, Cristina Martins, Ricardo Meireles, Francisco D’Orey, Maria Inês Ribeiro, Antero Fernandes (Head of Intensive Care Department). The authors would like the names of the individual members of the Group to be searchable through their individual PubMed records. Funding: funding sources: Foundation—015_595935779—Foundation for Science and Technology (FCT), in collaboration with the Agency for Clinical Research and Biomedical Innovation (AICIB), open special funding, “RESEARCH 4 COVID-19”, to R&D projects and initiatives that respond to the needs of the National Health Service (SNS) as a response to this and future pandemics in a very short time horizon. Project: “Early recognition of cardiac injury associated with COVID-19 and clinical outcomes.” Publisher Copyright: © 2023, The Author(s). Introduction: SARS-CoV-2 infection is associated with multiple cardiac manifestations. Left atrial strain (LA-S) by speckle tracking echocardiography (STE) is a novel transthoracic echocardiography (TTE) measure of LA myocardial deformation and diastolic dysfunction, which could lead to early recognition of cardiac injury in severe COVID-19 patients with possible implications on clinical management, organ dysfunction, and mortality. Cardiac injury may occur by direct viral cytopathic effects or virus-driven immune activation, resulting in heart infiltration by inflammatory cells, despite limited and conflicting data are available on myocardial histology. Purpose: We aimed to explore LA-S and immune profiles in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: We enrolled 30 patients > 18 years with positive SARS-CoV-2 RT-PCR, admitted to ICU. Acute myocardial infarction and pulmonary embolism were exclusion criteria. On days D1, D3, and D7 after ICU admission, patients performed TTE, hemogram, cardiac (pro-BNP; troponin) and inflammatory biomarkers (ESR; ferritin; IL1β; IL6; CRP; d-dimer; fibrinogen; PCT; adrenomedullin, ADM), and immunophenotyping by flow cytometry. Results: Patient’s mean age was 60.7 y, with 63% males. Hypertension was the most common risk factor (73%; with 50% of patients under ACEi or ARA), followed by obesity (40%, mean BMI = 31 kg/m2). Cardiac dysfunction was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. Mortality, hospitalization days, remdesivir use, organ dysfunction, cardiac and serum biomarkers were not different between patients with (DYS) and without cardiac dysfunction (nDYS), except for ADM (increased in nDYS group at D7). From the 77 TTE, there was a striking difference between diastolic dysfunction evaluation by classic criteria compared to STE (28.6% vs. 57.1%, p = 0.0006). Lower reservoir (Ɛ) and contraction (ƐCT) LA-S correlated with IL-6 (Ɛ, p = 0.009, r = − 0.47; ƐCT, p = 0.0002, r = − 0.63) and central memory CD4 T-cells (ƐCT, p = 0.049, r = − 0.24). Along all timepoints, DYS patients showed persistent low lymphocyte counts that recovered at D7 in nDYS patients. DYS patients had lower platelets at D3 and showed a slower recovery in platelet counts and CRP levels; the latter significantly decreased at D7 in nDYS patients (p = 0.009). Overall, patients recovered with an increasing P/F ratio, though to a lesser extent in DYS patients. Discussion: Our study shows that LA-S may be a more sensitive marker for diastolic dysfunction in severe COVID-19, which could identify patients at risk for a protracted inflammatory state. A differential immune trait in DYS patients at ICU admission, with persistent lymphopenia, enriched CM T-cells, and higher IL-6 may suggest distinct inflammatory states or migration patterns in patients that develop cardiac injury. publishersversion published

To compare region of interest (ROI)-apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) measurements and Ki-67 proliferation index before and after neoadjuvant chemotherapy (NACT) for breast cancer. 55 women were enrolled in this prospective single-center study, with a final population of 47 women (49 cases of invasive breast cancer). ROI-ADC measurements were obtained on MRI before and after NACT and were compared to histological findings, including the Ki-67 index in the whole study population and in subgroups of “pathologic complete response” (pCR) and non-pCR. Nineteen percent of women experienced pCR. There was a significant inverse correlation between Ki-67 index and ROI-ADC before NACT (r = − 0.443, p = 0.001) and after NACT (r = − 0.614, p –3 mm2/s before NACT to 1.533 × 10–3 mm2/s after NACT (p Clinical trial registration number: clinicaltrial.gov NCT02798484, date: 14/06/2016.

Molecular fluorescence-guided surgery using near-infrared light has the potential to improve the rate of complete resection of cancer. Typically, monoclonal antibodies are being used as targeting moieties, however smaller fragments, such as single-domain antibodies (i.e., Nanobodies®) improve tumor specificity and enable tracer injection on the same day as surgery. In this study, the feasibility of a carcinoembryonic antigen-targeting Nanobody (NbCEA5) conjugated to two zwitterionic dyes (ZW800-1 Forte [ZW800F] and ZW800-1) for visualization of pancreatic ductal adenocarcinoma (PDAC) was investigated. After site-specific conjugation of NbCEA5 to the zwitterionic dyes, binding specificity was evaluated on human PDAC cell lines with flow cytometry. A dose escalation study was performed for both NbCEA5-ZW800F and NbCEA5-ZW800-1 in mice with subcutaneously implanted pancreatic tumors. Fluorescence imaging was performed up to 24 h after intravenous injection. Furthermore, the optimal dose for NbCEA5-ZW800-1 was injected in mice with orthotopically implanted pancreatic tumors. A dose-escalation study showed superior mean fluorescence intensities for NbCEA5-ZW800-1 compared to NbCEA5-ZW800F. In the orthotopic tumor models, NbCEA5-ZW800-1 accumulated specifically in pancreatic tumors with a mean in vivo tumor-to-background ratio of 2.4 (SD = 0.23). This study demonstrated the feasibility and potential advantages of using a CEA-targeted Nanobody conjugated to ZW800-1 for intraoperative PDAC imaging.

Purpose. The objective of this study was to analyse the possibilities of using 4D CT scanning for the tracking of patients’ mandibles. Methods. A clinical 256-slice Revolution CT was used in obtaining 4D CT scans without table movement, with a novel mandibular phantom, mounted on a programmable six degrees-of-freedom Stewart Platform in motion. The phantom was used to simulate mandibular motions which are combinations of rotations with translations (depression, elevation, protrusion, retrusion and laterotrusion). The phantom was scanned five times during identical motion patterns with a dynamic CT acquisition protocol. An image processing workflow consisting of a pairwise rigid registration and semi-automatic segmentation was developed to extract kinematic parameters (cardan angles and point-of-interest displacements) from the dynamic sequences. Reproducibility was investigated by the 95% confidence interval and the absorbed organ dose to organs of interest in the primary beam were also estimated and compared to those of a standard CT scan of the brain Results. The maximum average 95% confidence interval for the displacement across all time points for the five repetitions was 0.61 mm (Y axis). In terms of rotations, the maximum average 95% confidence interval across all time points for the five repetitions was 1.39° (X axis). The effective dose for the dynamic scan was found to be 1.3 mSv, for a CTDIvol of 63.95 mGy and a DLP of 1023.14 mGycm. The absorbed organ doses were similar to organ doses during a clinical head CT scan. Conclusions. A framework is proposed to use 4D CT scanning as a possible methodology to evaluate the motion of the temporomandibular joint. The scanning protocol allows to visualise the motion by applying a semi-automated segmentation and registration. A graphical representation of all displacements in the three spatial dimensions can depict multiple points-of-interest at once during the same acquisition. A novel type of phantom was also introduced which simulates mandibular movement with six degrees-of-freedom (three translations and three rotations).

Publisher Copyright: © 2023, Turkish Society of Radiology. All rights reserved. Ovarian dysgerminoma (OD) is a rare germ cell tumor accounting for 1%–2% of all malignant ovar­ian tumors and is generally associated with a good prognosis. The condition is more frequent in young women and can arise in dysgenetic gonads that contain gonadoblastomas. While the defini­tive diagnosis of OD is only possible histologically, certain radiological features can provide facilitat­ing clues. A large, unilateral, solid, lobulated ovarian tumor with markedly enhancing septa should raise the suspicion of OD in young women. Serum lactate dehydrogenase is characteristically ele­vated in this tumor type and can complement its diagnosis and postoperative follow-up; however, it is a nonspecific marker. Moreover, knowing the mimickers of OD is essential to optimizing the radiological image interpretation and allowing for adequate management and timely treatment. Therefore, in this article, the radiological and clinical-pathologic features of ODs were reviewed to allow radiologists to become familiarized with them and narrow the diagnostic possibilities when facing this type of tumor. publishersversion published

Funding Information: Filipe Veloso Gomes has received research grants from Terumo; educational grants from Terumo, Medtronic, Guerbet; speaker honoraria from Bayer, Guerbet, Medtronic, Roche. Thierry-de-Baere has received consulting fees from Astra-Zeneca, Boston-Scientific, Guerbet, Medtronic and Terumo. Gontran Verset has received honoraria for lectures from Terumo, BTG, Bayer. Élia Coimbra—no conflicts of interest Gerardo Tovar-Felice has received a research grant from Terumo. Katerina Malagari has received honoraria for lectures from Merit Medical, BTG, Boston Scientific, Terumo. Jordi Bruix has received consulting fees from AbbVie, Adaptimmune, Arqule, Astra-Medimmune, Basilea, Bayer-Shering Pharma, Bio-Alliance, BMS, BTG- Biocompatibles, Eisai, Gilead, Incyte, Ipsen, Kowa, Lilly, MSD, Nerviano, Novartis, Polaris, Quirem, Roche, Sirtex, Sanofi, Terumo; honararia for lectures from Bayer, Eisai, BTG/Boston Scientific, Sirtex, Terumo, Ipsen, Astra-Zeneca. Publisher Copyright: © 2023, The Author(s). Purpose: To evaluate survival, efficacy and safety of transarterial chemoembolization (TACE) in the treatment of patients with hepatocellular carcinoma (HCC), through a pooled analysis of patients with BCLC 0, A and B HCC stages, treated with polyethylene glycol drug eluting microspheres (PEG-DEM) TACE. Materials and Methods: Patients from 3 retrospective and 2 prospective registries were included. Overall survival (OS), progression-free survival (PFS), tumour response and safety were evaluated. Multivariate Cox regression analysis was performed to evaluate predictors of OS. Results: A total of 580 patients (72.1% males, mean age 66.9 ± 10.3 years) were included. 43.5% had BCLC A, and 41.0% BCLC B disease stage, and 85.8% were Child–Pugh class A. Complete and partial response (mRECIST or RECIST1.1) were achieved in 60.14% and 27.11% of patients, with overall response and disease control rates of 87.30% and 94.60%, respectively. Median OS was 50.8 months for the total population, and 61.2 and 38.1 months for BCLC 0 + A and BCLC B patients, respectively. Median PFS for the total population, BCLC 0 + A and BCLC B groups was 15.6, 21.6 and 12.7 months, respectively. Conclusions: This multicentric pooled analysis confirmed efficacy and safety of PEG-DEM TACE, with a median OS of 50.8 months. publishersversion epub_ahead_of_print

Amyloidoisis in patients with Waldenström macroglobulinemia (WM) mostly involves the heart, peripheral nerves and kidneys. Retroperitoneal amyloidosis is a rare finding. We describe a 62-year-old man with an incidental finding of a monoclonal gammopathy and elevated inflammatory parameters. Bilateral moderately active retroperitoneal infiltration with punctiform calcifications was found on fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging. Taken together, these findings are suggestive of Waldenström associated amyloidosis. Computed tomography-guided retroperitoneal biopsy confirmed the diagnosis.

OBJECTIVESMyocardial bridging is mostly diagnosed as an incidental imaging finding but can result in severe vessel compression and significant clinical adverse complications. Since there is still an ongoing debate when to propose surgical unroofing, we studied a group of patients where this was performed as an isolated procedure.METHODSIn 16 patients (38.9 ± 15.7 years, 75% men) who had surgical unroofing for symptomatic isolated myocardial bridges of the left anterior descending artery, we retrospectively analysed symptomatology, medication, imaging modalities used, operative techniques, complications and long-term outcome. Computed tomographic fractional flow reserve was calculated to understand its potential value for decision-making.RESULTSMost procedures were performed on-pump (75%, mean cardiopulmonary bypass 56.5 ± 27.9 min, mean aortic cross-clamping 36.4 ± 19.7 min). Three patients needed a left internal mammary artery bypass since the artery dived inside the ventricle. There were no major complications or deaths. The mean follow-up was 5.5 years. Although there was a dramatic improvement in symptoms, still 31% experienced atypical chest pain at various moments during follow-up. Postoperative radiological control was performed in 88%, showing no residual compression or recurrent myocardial bridge and patent bypass if performed. All postoperative computed tomographic flow calculations (7) showed a normalization of coronary flow.CONCLUSIONSSurgical unroofing for symptomatic isolated myocardial bridging is a safe procedure. Patient selection remains difficult but introducing standard coronary computed tomographic angiography with flow calculations could be helpful in preoperative decision-making and during follow-up.

RATIONALE AND OBJECTIVES: Real-time polymerase chain reaction (RT-PCR) remains the gold standard for confirmation of Coronavirus Disease 2019 (COVID-19) despite having many disadvantages. Here, we investigated the diagnostic performance of chest computed tomography (CT) as an alternative to RT-PCR in patients with clinical suspicion of COVID-19 infection. METHODS: In this descriptive cross-sectional study, 27,824 patients with clinical suspicion of COVID-19 infection who underwent unenhanced low-dose chest CT from 20 February, 2020 to 21 May, 2020 were evaluated. Patients were recruited from seven specifically designated hospitals for patients with COVID-19 infection affiliated to Shahid Beheshti University of Medical Sciences. In each hospital, images were interpreted by two independent radiologists. CT findings were considered as positive/negative for COVID-19 infection based on RSNA diagnostic criteria. Then, the correlation between the number of daily positive chest CT scans and number of daily PCR-confirmed cases and COVID-19-related deaths in Tehran province during this three-month period was assessed. The trends of admission rate and patients with positive CT scans were also evaluated. RESULTS: A strong positive correlation between the numbers of daily positive CT scans and daily PCR-confirmed COVID-19 cases (r = 0.913, p < 0.001) was observed. Furthermore, in hospitals located in regions with a lower socioeconomic status, the admission rate and number of positive cases within this three-month period was higher as compared to other hospitals. CONCLUSION: Low-dose chest CT is a safe, rapid and reliable alternative to RT-PCR for the diagnosis of COVID-19 in high-prevalence regions. In addition, our study provides further evidence for considering patients' socioeconomic status as an important risk factor for COVID-19.

Background For patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2), spinal cord stimulation (SCS) may serve as an effective minimally invasive treatment. Despite the evidence that SCS can improve return to work (RTW), only 9.5 to 14% of patients implanted with SCS are effectively capable of returning to work. Thus, it seems that current post-operative interventions are not effective for achieving RTW after SCS implantation in clinical practice. The current objective is to examine whether a personalised biopsychosocial rehabilitation programme specifically targeting RTW alters the work ability in PSPS-T2 patients after SCS implantation compared to usual care. Methods A two-arm, parallel-group multicentre randomised controlled trial will be conducted including 112 patients who will be randomised (1:1) to either (a) a personalised biopsychosocial RTW rehabilitation programme of 14 weeks or (b) a usual care arm, both with a follow-up period until 12 months after the intervention. The primary outcome is work ability. The secondary outcomes are work status and participation, pain intensity, health-related quality of life, physical activity and functional disability, functional capacities, sleep quality, kinesiophobia, self-management, anxiety, depression and healthcare expenditure. Discussion Within the OPERA project, we propose a multidisciplinary personalised biopsychosocial rehabilitation programme specifically targeting RTW for patients implanted with SCS, to tackle the high socio-economic burden of patients that are not re-entering the labour market. The awareness is growing that the burden of PSPS-T2 on our society is expected to increase over time due to the annual increase of spinal surgeries. However, innovative and methodologically rigorous trials exploring the potential to decrease the socio-economic burden when patients initiate a trajectory with SCS are essentially lacking. Trial registration ClinicalTrials.gov NCT05269212. Registered on 7 March 2022.

OBJECTIVES: To quantitatively evaluate the impact of a cardiac acquisition CT mode on motion artifacts in comparison to a conventional cine mode for dynamic musculoskeletal (MSK) imaging. METHODS: A rotating PMMA phantom with air-filled holes drilled at varying distances from the disk center corresponding to linear hole speeds of 0.75 cm/s, 2.0 cm/s, and 3.6 cm/s was designed. Dynamic scans were obtained in cardiac and cine modes while the phantom was rotating at 48°/s in the CT scanner. An automated workflow to compute the Jaccard distance (JD) was established to quantify degree of motion artifacts in the reconstructed phantom images. JD values between the cardiac and cine scan modes were compared using a paired sample t-test. In addition, three healthy volunteers were scanned with both modes during a cyclic flexion-extension motion of the knee and analysed using the proposed metric. RESULTS: For all hole sizes and speeds, the cardiac scan mode had significantly lower (p-value

Adult extracorporal membrane oxygenation utilization in the ICU has rapidly increased. Newer technology and cannulation strategies and the complex hemodynamics make imaging interpretation challenging. There is also a high rate of complications. This review details the common indications, cannulation strategies, relevant hemodynamics and complications which impact imaging interpretation. Recommendations for modifying computed tomography protocols and techniques to obtain diagnostic images and some of the imaging pitfalls are also discussed.

Abstract This document from the European Society of Thoracic Imaging (ESTI) and the European Society of Radiology (ESR) discusses the role of imaging in the long-term follow-up of COVID-19 patients, to define which patients may benefit from imaging, and what imaging modalities and protocols should be used. Insights into imaging features encountered on computed tomography (CT) scans and potential pitfalls are discussed and possible areas for future review and research are also included. Key Points • Post-COVID-19 pneumonia changes are mainly consistent with prior organizing pneumonia and are likely to disappear within 12 months of recovery from the acute infection in the majority of patients. • At present, with the longest series of follow-up examinations reported not exceeding 12 months, the development of persistent or progressive fibrosis in at least some individuals cannot yet be excluded. • Residual ground glass opacification may be associated with persisting bronchial dilatation and distortion, and might be termed “fibrotic-like changes” probably consistent with prior organizing pneumonia.

Lyophilization is commonly used in the production of pharmaceutical compounds to increase the stability of the Active Pharmaceutical Ingredient (API) by removing solvents. This study investigates the possibility to lyophilize an anti-HER2 and an anti-MMR single-domain antibody fragment (sdAb)-based precursor as a first step in the development of a diagnostic kit for PET imaging. Methods NOTA-sdAb precursors have been lyophilized with the following formulation: 100 µg NOTA-sdAb in 0.1 M NaOAc (NaOAc), 5% (w/v%) mannitol-sucrose mix at a 2:1 ratio and 0.1 mg/mL polysorbate 80. During development of the formulation and drying cycle, factors such as cake appearance, glass transition temperature and residual moisture were analyzed to ensure qualitative and stable lyophilized samples. Stability studies of lyophilized precursor were conducted up to 18 months after storage at 2–8 °C by evaluating the precursor integrity, aggregation, functionality and 68Ga-labeling efficiency. A comparative biodistribution study (lyophilized vs non-lyophilized precursor) was conducted in wild type mice (n = 3) and in tumor bearing mice (n = 6). Results The lyophilized NOTA-anti-HER2 precursor shows consistent stability data in vitro for up to 12 months at 2–8 °C in three separate batches, with results indicating stability even for up to T18m. No aggregation, degradation or activity loss was observed. Radiochemical purity after 68Ga-labeling is consistent over a period of 12 months (RCP ≥ 95% at T12m). In vivo biodistribution analyses show a typical [68Ga]Ga-NOTA-anti-HER2 sdAb distribution profile and a comparable tumor uptake for the lyophilized compound vs non-lyophilized (5.5% vs 5.7 %IA/g, respectively). In vitro results of lyophilized NOTA-anti-MMR precursor indicates stability for up to 18 months, while in vivo data show a comparable tumor uptake (2.5% vs 2.8 %IA/g, respectively) and no significant difference in kidney retention (49.4% vs 47.5 %IA/g, respectively). Conclusion A formulation and specific freeze-drying cycle were successfully developed to lyophilize NOTA-sdAb precursors for long-term storage at 2–8 °C. In vivo data show no negative impact of the lyophilization process on the in vivo behavior or functionality of the lyophilized precursor. These results highlight the potential to develop a kit for the preparation of 68Ga-sdAb-based radiopharmaceuticals.

This review provides a dynamical systems perspective on psychiatric symptoms and disease, and discusses its potential implications for diagnosis, prognosis, and treatment. After a brief introduction into the theory of dynamical systems, we will focus on the idea that cognitive and emotional functions are implemented in terms of dynamical systems phenomena in the brain, a common assumption in theoretical and computational neuroscience. Specific computational models, anchored in biophysics, for generating different types of network dynamics, and with a relation to psychiatric symptoms, will be briefly reviewed, as well as methodological approaches for reconstructing the system dynamics from observed time series (like fMRI or EEG recordings). We then attempt to outline how psychiatric phenomena, associated with schizophrenia, depression, PTSD, ADHD, phantom pain, and others, could be understood in dynamical systems terms. Most importantly, we will try to convey that the dynamical systems level may provide a central, hub-like level of convergence which unifies and links multiple biophysical and behavioral phenomena, in the sense that diverse biophysical changes can give rise to the same dynamical phenomena and, vice versa, similar changes in dynamics may yield different behavioral symptoms depending on the brain area where these changes manifest. If this assessment is correct, it may have profound implications for the diagnosis, prognosis, and treatment of psychiatric conditions, as it puts the focus on dynamics. We therefore argue that consideration of dynamics should play an important role in the choice and target of interventions.

Background: Adolescence is a critical period for the development of not only personality but also psychopathology. These processes may be specific to sex, and brain reward circuits may have a role. Here, we studied how reward processing and temperament associations differ across adolescent and adult females. Methods: A total of 29 adolescent girls and 41 adult women completed temperament assessments and performed a classical taste conditioning paradigm during brain imaging. Data were analyzed for the dopamine-related prediction error response. In addition, unexpected stimulus receipt or omission and expected receipt response were also analyzed. Heat maps identified cortical-subcortical brain response associations. Results: Adolescents showed stronger prediction error and unexpected receipt and omission responses (partial η2 = 0.063 to 0.166; p = .001 to .043) in insula, orbitofrontal cortex (OFC), and striatum than adults. Expected stimulus receipt response was similar between groups. In adolescents versus adults, persistence was more strongly positively related to prediction error (OFC, insula, striatum; Fisher's z = 1.704 to 3.008; p = .001 to .044) and unexpected stimulus receipt (OFC, insula; Fisher's z = 1.843 to 2.051; p = .014 to .033) and negatively with omission (OFC, insula, striatum; Fisher's z = −1.905 to −3.069; p = .001 to .028). Reward sensitivity and reward dependence correlated more positively with unexpected stimulus receipt and more negatively with stimulus omission response in adolescents. Adolescents showed significant correlations between the striatum and FC for unexpected stimulus receipt and omission that correlated with persistence but were absent in adults. Conclusions: Associations between temperamental traits and brain reward response may provide neurotypical markers that contribute to developing adaptive or maladaptive behavior patterns when transitioning from adolescence to adulthood.

To evaluate coronary artery disease (CAD) with computed tomography coronary angiography (CTCA)-derived fractional flow reserve (FFR) in patients with atrial fibrillation (AF) requiring ablation. The study population consisted of 151 patients who underwent CTCA before AF ablation (AF group), and a control group of 151 patients from the outpatient clinic who underwent CTCA without any history of AF (non-AF group), matched for age, sex, BMI, and angina symptomatology. All study patients underwent CTCA with subdivision of coronary lesion type into severe (≥ 70% luminal narrowing), moderate (50% ≤ luminal narrowing < 70%), and mild stenosis (< 50% luminal narrowing). In patients with ≥ 1 moderate or severe stenosis, non-invasive FFR was calculated from CTCA (FFR CT). Baseline characteristics and CAD risk factors were similar between the 2 groups. During CTCA, 38% of the patients in the AF group were in ongoing atrial arrhythmia (either AF or regular atrial tachycardia). The number of patients with severe (10 (6.6%) vs 10 (6.6%), P = 1.00), moderate (14 (9.5%) vs 10 (6.7%), P = 0.4), and mild stenosis (43 (28.5%) vs 56 (37.1%), P = 0.11) was not significantly different between the 2 groups. Performance of FFR CT was feasible in 32/44 patients (73%), and failed in 27% of the patients (7 and 5 patients in the AF and non-AF group, respectively, P = 0.74). No difference was observed in the prevalence of hemodynamically significant stenosis (FFR CT ≤ 0.80) (15 (9.9%) vs 12 (7.9%), P = 0.85). Our study showed technical feasibility of CTCA in all patients of both groups, including the patients with AF as presenting rhythm. The FFR CT add-on analysis failed equally frequent in patients of the AF versus non-AF group. An equal rate of CAD was observed in the AF group and non-AF group, favoring the concept of shared associated risk factors for CAD and AF.

BACKGROUND AND PURPOSE: Data from neuro-imaging techniques allow us to estimate a brain's age. Brain age is easily interpretable as 'how old the brain looks' and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility by investigating the relationship between brain age and cognitive performance in multiple sclerosis (MS). METHODS: A linear regression model was trained to predict age from brain magnetic resonance imaging volumetric features and sex in a healthy control dataset (HC_train, n = 1673). This model was used to predict brain age in two test sets: HC_test (n = 50) and MS_test (n = 201). Brain-predicted age difference (BPAD) was calculated as BPAD = brain age minus chronological age. Cognitive performance was assessed by the Symbol Digit Modalities Test (SDMT). RESULTS: Brain age was significantly related to SDMT scores in the MS_test dataset (r = -0.46, p