Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors and CAR-T Cell Therapy: A Comprehensive Imaging-Based Review.

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent within the first few months. Any organ and tissue can be affected, ranging from mild to life-threatening. While some manifestations are common and more often mild, such as dermatitis and colitis, others are rarer and more severe, such as myocarditis. Management depends on the severity, with treatment being held for >grade 2 toxicities. Steroids are used in more severe cases, and immunosuppressive treatment may be considered for non-responsive toxicities, along with specific organ support. A multidisciplinary approach is mandatory for prompt identification and management. The diagnosis is primarily of exclusion. It often relies on imaging features, and, when possible, cytologic and/or pathological analyses are performed for confirmation. In case of clinical suspicion, imaging is required to assess the presence, extent, and features of abnormalities and to evoke and rule out differential diagnoses. This imaging-based review illustrates the diverse system-specific toxicities associated with immune checkpoint inhibitors and chimeric antigen receptor T-cells with a multidisciplinary perspective. Clinical characteristics, imaging features, cytological and histological patterns, as well as the management approach, are presented with insights into radiological tips to distinguish these toxicities from the most important differential diagnoses and mimickers-including tumor progression, pseudoprogression, inflammation, and infection-to guide imaging and clinical specialists in the pathway of diagnosing immune-related adverse events.

[Lung cancer screening : towards the implementation of a pilot project in Switzerland]. / Dépistage du cancer pulmonaire : vers l'implémentation d'un projet pilote en Suisse.

Lung cancer is responsible for one in five cancer-related deaths. Screening for lung cancer using low-dose chest CT (LDCT) is supported by several international studies targeting the at-risk population as part of an organised programme. Given the organisational challenges for the healthcare systems of the countries concerned, this involves setting up pilot screening projects. This requires close collaboration between the players involved, with a multidisciplinary approach structured around the participant, aiming to offer the expertise of the pulmonologist and the radiologist on the LDCT performed, interpreted with the help of artificial intelligence. Here we set out the elements needed to develop a screening programme, starting with the implementation of a pilot project.

Le cancer pulmonaire est responsable d'un décès lié au cancer sur cinq. Le dépistage du cancer pulmonaire par le scanner thoracique à faible dose (LDCT) est soutenu par plusieurs études internationales ciblant la population à risque dans le cadre d'un programme organisé. Vu les enjeux organisationnels pour le système de santé des pays concernés, cela passe par la mise en place de projets pilotes de dépistage. Cela requiert une collaboration étroite entre les différents acteurs, avec une approche multidisciplinaire structurée autour du participant visant à offrir l'expertise du pneumologue et du radiologue sur le LDCT effectué, interprété avec l'aide de l'intelligence artificielle. Nous exposons ici les éléments nécessaires à l'élaboration d'un programme de dépistage, en passant d'abord par la mise en place d'un projet pilote.

Investigating the Influence of High-Speed Gantry Rotation in Cardiac CT on Motion Artifacts in Aortic Stenosis Patients Not Premedicated with ß-Blockers: The FAST-CCT Randomized Trial Protocol.

BACKGROUND: Coronary CT angiography (CCTA) is increasingly used as a non-invasive tool to assess coronary artery disease (CAD). However, CCTA is subject to motion artifacts, potentially limiting its clinical utility. Despite faster (0.35 and 0.28 s/rot) gantry rotation times, low (60-65 bpm) heartbeat is recommended, and the use of ß-blockers is often needed. Technological advancements have resulted in the development of faster rotation speeds (0.23 s/rot). However, their added value in patients not premedicated with ß-blockers remains unclear. This prospective single-center, two-arm, randomized, controlled trial aims to assess the influence of fast rotation on coronary motion artifacts, diagnostic accuracy of CCTA for CAD, and patient safety. METHODS: We will randomize a total of 142 patients aged ≥ 50 scheduled for an aortic stenosis work-up to receive CCTA with either a fast (0.23) or standard (0.28 s/rot) gantry speed. PRIMARY OUTCOME: rate of CCTAs with coronary motion artifacts hindering interpretation. SECONDARY OUTCOMES: assessable coronary segments rate, diagnostic accuracy against invasive coronary angiography (ICA), motion artifact magnitude per segment, contrast-to-noise ratio (CNR), and patient ionizing radiation dose. The local ethics committee has approved the protocol. Potential significance: FAST-CCT may improve motion artifact reduction and diagnosis quality, thus eliminating the need for rate control and ß-blocker administration. CLINICALTRIALS: gov identifier: NCT05709652.

Optimizing Communication of Radiation Exposure in Medical Imaging, the Radiologist Challenge.

Since I started my residency program in Radiology, I have been committed to promoting radiation protection, paying particular attention to the justification and optimization of the examinations [...].

Impact of COVID-19 pneumonia on pulmonary vascular volume.

Background: Pulmonary manifestations of COVID-19 pneumonia are well known. However, COVID-19 is also associated with a range of vascular manifestations such as embolism, congestion, and perfusion changes. Regarding congestion, research from different groups has suggested arteriovenous anastomosis dysregulation as a contributing factor. In this study, we aim to better describe the changes in vascular volume in affected lung zones and to relate them to pathophysiological hypotheses. Methods: We performed automatic vascular volume extraction in 10 chest CTs of patients, including 2 female and 8 male with a mean age of 63.5 ± 9.3 years, diagnosed with COVID-19 pneumonia. We compared the proportion of vascular volumes between manually segmented regions of lung parenchyma with and without signs of pneumonia. Results: The proportion of vascular volume was significantly higher in COVID (CVasc) compared to non-COVID (NCVasc) areas. We found a mean difference (DVasc) of 5% and a mean ratio (RVasc) of 3.7 between the two compartments (p < 0.01). Conclusion: Vascular volume in COVID-19 affected lung parenchyma is augmented relative to normal lung parenchyma, indicating venous congestion and supporting the hypothesis of pre-existing intra-pulmonary arteriovenous shunts.

Radiation Exposure to Low-Dose Computed Tomography for Lung Cancer Screening: Should We Be Concerned?

Lung cancer screening (LCS) programs through low-dose Computed Tomography (LDCT) are being implemented in several countries worldwide. Radiation exposure of healthy individuals due to prolonged CT screening rounds and, eventually, the additional examinations required in case of suspicious findings may represent a concern, thus eventually reducing the participation in an LCS program. Therefore, the present review aims to assess the potential radiation risk from LDCT in this setting, providing estimates of cumulative dose and radiation-related risk in LCS in order to improve awareness for an informed and complete attendance to the program. After summarizing the results of the international trials on LCS to introduce the benefits coming from the implementation of a dedicated program, the screening-related and participant-related factors determining the radiation risk will be introduced and their burden assessed. Finally, future directions for a personalized screening program as well as technical improvements to reduce the delivered dose will be presented.

Cross-sectional evaluation of FGD-avid polyostotic fibrous dysplasia: MRI, CT and PET/MRI findings.

A 42-year-old male with left hip pain was diagnosed of several right femoral and tibial bone tumours. All lesions were osteolytic with sclerotic margins. The symptomatic lesion in the proximal femur also showed bone expansion and focal cortical thinning. Whole-body [18F]-fluorodeoxyglucose (FDG) PET/CT and segmental PET/MRI of the left hip and femur were performed for metabolic characterization of the lesions and for biopsy guidance. The lesions showed a heterogenous degree of FDG uptake corresponding to different metabolic stages of the disease. A biopsy of the tumour portion showing the highest FDG uptake revealed a fibrous dysplasia (FD). In conclusion, although generally affecting paediatric and adolescent subjects, polyostotic FD may be detected in the adulthood. Despite the benign nature of the disease, increased glucose metabolism can be seen in some lesions. Hybrid imaging combining morphological and functional information may help guide biopsy and better define the treatment strategy.

MR-enterography: role in the assessment of suspected anastomotic recurrence of Crohn disease after ileocolic resection.

PURPOSE: To determine the potential of magnetic resonance-enterography (MRE) in the assessment of the anastomotic status in patients with Crohn disease and prior ileocolic resection. METHODS: A total of 62 MRE examinations obtained in 52 patients with Crohn disease who had previously undergone ileocolic resection were retrospectively reviewed by two readers in consensus. MRE features (anastomotic wall thickening, wall stratification, wall enhancement pattern and degree, DWI signal intensity, ADC values, lymph nodes, comb sign and complications) were compared to clinical, endoscopic and histological findings that served as standard of reference. Sensitivity, specificity and accuracy of MRE were calculated. RESULTS: At univariate analysis, anastomotic wall thickening, anastomotic wall stratification, segmental wall enhancement, moderate wall enhancement, early and mucosal enhancement, and moderate/marked hyperintensity on diffusion-weighed imaging (DWI) were the most discriminative MRE features for differentiating between normal and abnormal anastomoses (p < 0.001 for all variables). Anastomotic wall thickening and segmental anastomotic wall enhancement were the two most sensitive and accurate MRE variables for the diagnosis of abnormal anastomosis with sensitivities of 82% (95% CI: 67-92%) and accuracies of 84% (95% CI: 72-92%). At univariate analysis, hyperintensity on DWI of the anastomotic site was the most sensitive finding for distinguishing between inflammatory recurrence and fibrostenosis (sensitivity, 89%; 95% CI: 67-99%). CONCLUSIONS: MRE provides objective and relatively specific morphological criteria that help detect abnormal ileocolic anastomosis, but performances are lower when differentiating between inflammatory recurrence and fibrostenosis. DWI may be useful in identifying pathologic anastomosis and, in particular, in distinguishing between inflammatory recurrence and fibrostenosis.

Non-occlusive mesenteric ischemia (NOMI) and prognostic signs at CT: reperfusion or not reperfusion that is the question!

PURPOSE: Non-occlusive mesenteric ischemia (NOMI) is a misdiagnosed and dangerous condition. To our knowledge, a comprehensive evaluation of CT parameters that can predict the outcome of patients suffering from NOMI is still missing. MATERIALS AND METHODS: Contrast-enhanced CT examination of 84 patients with a confirmed diagnosis of NOMI (37 with clinical and laboratory confirmation and 47 biopsy or surgery proven) was retrospectively reviewed by assessing vessels, mesentery, bowel, and peritoneal cavity CT quantitative and dichotomous parameters, and data were analyzed with Fisher's test. Diameter of superior mesenteric artery (SMA), celiac trunk (CT), inferior vena cava (IVC), superior mesenteric vein (SMV), and differences in CT HU (Delta HU) of the bowel wall before and after intravenous contrast media (ICM) administration were correlated to the patients' outcome using ANOVA test. Receiver operating characteristic (ROC) curves were elaborated after a binary logistic regression was performed. RESULTS: Increased number and diameter of vessels, bowel wall thickening, and hypervascularity were more frequent in patients with good prognosis. Conversely, pale mesentery, paper thin, hypovascularity, and aeroportia were more frequent in patients with bad prognosis. A significant correlation between diameters of SMA, CT, IVC, IMA, and SMV and outcome was found at univariate analysis. Also Delta HU resulted to be correlated with the outcome. At multivariate analysis only IVC and Delta HU were significant (p = 0.038 and 0.01) and the combined AUC resulted in 0.806 (CI 0.708-0.903). CONCLUSION: Dichotomous signs of reperfusion and quantitative CT parameters can predict the outcome of patients with NOMI. In particular the combination of IVC diameter and Delta HU of bowel wall allows to predict the prognosis with the highest accuracy.

Patient Perceptions and Knowledge of Ionizing Radiation From Medical Imaging.

Importance: Although imaging has become a standard tool of modern medicine, its widespread use has been paralleled by an increasing cumulative radiation dose to patients despite technological advancements and campaigns calling for better awareness and minimization of unnecessary exposures. Objective: To assess patients' knowledge about medical radiation and related risks. Design, Setting, and Participants: A survey study of hospitals in Italy was conducted; all patients in waiting rooms for medical imaging procedures before undergoing imaging examinations at 16 teaching and nonteaching hospitals were approached to take the survey. The survey was performed from June 1, 2019, to May 31, 2020. Main Outcomes and Measures: Survey respondents' basic knowledge of ionizing radiation levels and health risks, earlier imaging tests performed, and information and communication about radiation protection issues. Results: Among 3039 patients invited to participate, the response rate was 94.3% (n = 2866). Participants included 1531 women (53.4%); mean (SD) age was 44.9 (17.3) years. Of the 2866 participants, 1529 (53.3%) were aware of the existence of natural sources of ionizing radiation. Mammography (1101 [38.4%]) and magnetic resonance imaging (1231 [43.0%]) were categorized as radiation-based imaging modalities. More than half of the 2866 patients (1579 [55.1%]; P = .03) did not know that chest computed tomography delivers a larger dose of radiation than chest radiography, and only 1499 (52.3%) knew that radiation can be emitted after nuclear medicine examinations (P = .004). A total of 667 patients (23.3%) believed that radiation risks were unrelated to age, 1273 (44.4%) deemed their knowledge about radiation risks inadequate, and 2305 (80.4%) preferred to be informed about radiation risks by medical staff. A better knowledge of radiation issues was associated with receiving information from health care professionals (odds ratio [OR], 1.71; 95% CI, 1.43-2.03; P < .001) and having a higher educational level (intermediate vs low: OR, 1.48; 95% CI, 1.17-1.88; P < .001; high vs low: OR, 2.68; 95% CI, 2.09-3.43; P < .001). Conclusions and Relevance: The results of this survey suggest that patients undergoing medical imaging procedures have overall limited knowledge about medical radiation. Intervention to achieve better patient awareness of radiation risks related to medical exposures may be beneficial.

Imaging Features of Pulmonary Immune-related Adverse Events.

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.

Not all that glitters is COVID! Differential diagnosis of FDG-avid interstitial lung disease in low-prevalence regions.

Coronavirus disease-19 (COVID-19) is only one of the many possible infectious and non-infectious diseases that may occur with similar imaging features in patients undergoing [18F]-fluorodeoxyglucose (18FDG) monitoring, particularly in the most fragile oncologic patients. We briefly summarise some key radiological elements of differential diagnosis of interstitial lung diseases which, in our opinion, could be extremely useful for physicians reporting 18FDG PET/CT scans, not only during the COVID-19 pandemic, but also for their normal routine activity.

Relationship between pneumonitis induced by immune checkpoint inhibitors and the underlying parenchymal status: a retrospective study.

In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is a rare adverse event but may evolve to respiratory failure. Prompt management is required and usually consists of treatment interruption and immunosuppressive drug administration. The aim of this study was to evaluate relationships between immune-related pneumonitis and pre-existing parenchymal status, especially tumour location and history of chest radiotherapy. Computed tomography (CT) scans of patients with immune-related pneumonitis were retrospectively reviewed. Pattern, distribution and extent of pneumonitis were assessed in six lung regions. In patients who received radiotherapy, the extent of pneumonitis was evaluated according to the radiation field. Among 253 patients treated with immunotherapy, 15 cases of immune-related pneumonitis were identified. 10 had previous or concomitant chest radiotherapy in addition to immunotherapy. At CT scan, 29 (33%) out of 88 regions encompassed the primary tumour (n=4), a lung metastasis (n=4) and/or radiation fields (n=21). A significantly higher prevalence of parenchymal involvement by immune-related pneumonitis occurred within areas of primary or metastatic malignancy and/or radiation field (97%) as compared to other areas (3%, p=0.009). Lung regions affected by the primary tumour, metastasis or radiotherapy had a higher probability of immune-related pneumonitis than others (OR 10.8, p=0.024). An organising pneumonia (OP) pattern was more frequent after radiotherapy (70% versus 0%, p=0.024), whereas nonspecific interstitial pneumonia features were more commonly seen in radiotherapy-naive patients (100% versus 10%, p=0.002). In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is preferentially located within lung areas involved by tumour and/or radiation fields.

Imaging of tumour response to immunotherapy.

A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2-10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria-so-called immune-related response criteria and then immune-related RECIST (irRECIST)-were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of "unconfirmed progression", into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.

Renal Cell Carcinoma: the Oncologist Asks, Can PSMA PET/CT Answer?

PURPOSE OF REVIEW: To critically review the potential clinical applications of prostate-specific membrane antigen (PSMA) radioactive ligands in renal cell carcinoma (RCC). RECENT FINDINGS: Radioactive probes targeting PSMA hold promise in several malignancies in addition to prostate cancer, owing to the expression of PSMA by tumor neovasculature. The majority of clear cell RCCs (ccRCC), the most malignant RCC subtype, express PSMA on tumor-associated neovasculature. The endothelium of less aggressive RCC subtypes is PSMA positive in a lower, but still significant percentage of cases. PSMA might therefore represent an interesting theragnostic target in RCC. The preliminary data available suggest a potential role for PSMA-targeting radiopharmaceuticals in complementing conventional imaging for staging ccRCC patients at risk of nodal involvement and oligometastatic disease. Additional applications of PSMA imaging may be the selection and the response assessment of patients receiving anti-angiogenic treatments. The effectiveness of PSMA-targeting radionuclide therapy should also be investigated.

Validation of contrast-enhanced time-resolved magnetic resonance angiography in pre-ablation planning in patients with atrial fibrillation: comparison with traditional technique.

Bolus timing is critical to optimal magnetic resonance angiography (MRA) acquisitions but can be challenging in some patients. Our purpose was to evaluate whether contrast-enhanced time-resolved magnetic resonance angiography (TR-MRA), a dynamic multiphase sequence that does not rely on bolus timing, is a viable alternative method to conventional 3D fast-long angle shot contrast-enhanced magnetic resonance angiography (CE-MRA). Coronal subtracted conventional CE-MRA images in 50 consecutive patients presenting for pre-atrial fibrillation ablation pulmonary venous (PV) mapping were compared with 50 TR-MRA images performed in 50 subsequent patients. The TR-MRA protocol was modified to optimize spatial resolution with slightly reduced temporal resolution (6.1 s scan time). Three experienced readers evaluated each scan's image quality and relative left atrial (LA) opacification based on a 4-point scale and diagnostic PV visualization in a binary fashion. Additionally, LA signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and PV dimensions were measured for both techniques. TR-MRA had significantly higher overall image quality (3.10 ± 0.69 vs. 2.42 ± 0.69, p < 0.0001), and LA opacification scores (3.33 ± 0.70 vs. 2.15 ± 1.13, p < 0.0001) compared to CE-MRA. The proportion of diagnostically visualized pulmonary veins was 137/150 (91%) in the CE-MRA group vs. 147/150 (98%) with TR-MRA (p = 0.010). Both SNR and CNR were higher with TR-MRA vs. CE-MRA (277.9 ± 48.9 vs. 106.8 ± 41, p = 0.002 and 100.3 ± 41.7 vs. 70.7 ± 48.0, p = 0.002, respectively). Inter-reader variance of individual PV measurements for each of the MR techniques ranged between 0.62 and 1.47 mm and the ICC for vein measurements was higher with TR-MRA (range: 0.62-0.81) compared to CE-MRA (range: 0.47-0.64). TR-MRA, modified to maximize spatial resolution, offers an alternative method for performing high quality MRA examinations in patients with AF. TR-MRA offers greater overall image quality, PV visualization, and similarly reproducible PV measurements compared to traditional CE-MRA, without the challenges of proper bolus timing.

Structural and Functional Correlates of Myocardial T1 Mapping in 321 Patients With Hypertrophic Cardiomyopathy.

OBJECTIVE: The aim of this study was to evaluate the structural and functional correlates of T1 mapping in 321 patients with hypertrophic cardiomyopathy (HCM). METHODS: Three hundred twenty-one patients with HCM who underwent cardiac magnetic resonance from 2003 to 2013 were retrospectively identified from our institution's HCM registry. Left ventricular volume, function, late gadolinium enhancement (LGE), and Look-Locker T1 time were quantified. T1 time was normalized to blood pool to calculate T1 ratio. Correlations between LGE%, T1 ratio, and structural and functional features were performed using Pearson correlation coefficient. RESULTS: Late gadolinium enhancement showed stronger correlation with left ventricular mass index (r = 0.41, P < 0.001) compared with T1 ratio (r = -0.17, P = 0.004). Both LGE% and T1 ratio correlated with ejection fraction (r = -0.18 and P = 0.002 vs r = 0.21 and P < 0.001, respectively). E/e' showed correlation with LGE% but not with T1 ratio. CONCLUSIONS: Late gadolinium enhancement was more strongly correlated with the phenotypic expression of HCM compared with T1 ratio.

Evaluation of Hepatocellular Carcinoma Tumor Response After Transcatheter Arterial Chemoembolization Using Gadobenate Dimeglumine-Enhanced Liver Magnetic Resonance.

OBJECTIVE: Use of gadobenate dimeglumine-enhanced liver magnetic resonance (MR) for evaluation of hepatocellular carcinoma tumor response after transcatheter arterial chemoembolization (TACE). METHODS: Forty-five patients with hepatocellular carcinoma were imaged with multiphase gadobenate dimeglumine-enhanced MR examination at baseline and 1-month follow-up after TACE. Nodule size, enhancement, and apparent diffusion coefficient were measured for both examinations by 2 reviewers. Changes in tumor nodule size, enhancement, and apparent diffusion coefficient were evaluated using the Student t test. RESULTS: Nineteen of 45 patients completed the study, and a total of 34 hepatocellular carcinoma nodules were analyzed. On the posttreatment follow up, there was no significant change in nodule size. Target lesions demonstrated significant decrease in tumor enhancement after TACE (P < 0.001). Intense contrast accumulation along the periphery of the presumed necrotic tumor on the delayed hepatobiliary phase helped to differentiate viable from non-viable tumor. CONCLUSION: Gadobenate dimeglumine-enhanced liver MR may help differentiate between viable and necrotic tumor after TACE.