3D genomic mapping reveals multifocality of human pancreatic precancers.

Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study1. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution. To elucidate genetic relationships between and within PanINs, we developed a workflow in which 3D modelling guides multi-region microdissection and targeted and whole-exome sequencing. From these samples, we calculated a mean burden of 13 PanINs per cm3 and extrapolated that the normal intact adult pancreas harbours hundreds of PanINs, almost all with oncogenic KRAS hotspot mutations. We found that most PanINs originate as independent clones with distinct somatic mutation profiles. Some spatially continuous PanINs were found to contain multiple KRAS mutations; computational and in situ analyses demonstrated that different KRAS mutations localize to distinct cell subpopulations within these neoplasms, indicating their polyclonal origins. The extensive multifocality and genetic heterogeneity of PanINs raises important questions about mechanisms that drive precancer initiation and confer differential progression risk in the human pancreas. This detailed 3D genomic mapping of molecular alterations in human PanINs provides an empirical foundation for early detection and rational interception of pancreatic cancer.

Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model.

BACKGROUND: PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2 cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). PATIENTS AND METHODS: An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. RESULTS: Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2 cm). CONCLUSIONS: Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.

Performance of explainable artificial intelligence in guiding the management of patients with a pancreatic cyst.

BACKGROUND/OBJECTIVES: Pancreatic cyst management can be distilled into three separate pathways - discharge, monitoring or surgery- based on the risk of malignant transformation. This study compares the performance of artificial intelligence (AI) models to clinical care for this task. METHODS: Two explainable boosting machine (EBM) models were developed and evaluated using clinical features only, or clinical features and cyst fluid molecular markers (CFMM) using a publicly available dataset, consisting of 850 cases (median age 64; 65 % female) with independent training (429 cases) and holdout test cohorts (421 cases). There were 137 cysts with no malignant potential, 114 malignant cysts, and 599 IPMNs and MCNs. RESULTS: The EBM and EBM with CFMM models had higher accuracy for identifying patients requiring monitoring (0.88 and 0.82) and surgery (0.66 and 0.82) respectively compared with current clinical care (0.62 and 0.58). For discharge, the EBM with CFMM model had a higher accuracy (0.91) than either the EBM model (0.84) or current clinical care (0.86). In the cohort of patients who underwent surgical resection, use of the EBM-CFMM model would have decreased the number of unnecessary surgeries by 59 % (n = 92), increased correct surgeries by 7.5 % (n = 11), identified patients who require monitoring by 122 % (n = 76), and increased the number of patients correctly classified for discharge by 138 % (n = 18) compared to clinical care. CONCLUSIONS: EBM models had greater sensitivity and specificity for identifying the correct management compared with either clinical management or previous AI models. The model predictions are demonstrated to be interpretable by clinicians.

Adrenal cysts less than 10 cm can be safely observed.

BACKGROUND: Adrenal cysts are rare and appropriate management is unclear due to a lack of data on their natural history. Understanding adrenal cyst growth patterns would assist in clinical management. METHODS: This single-institution study included all adult patients diagnosed with simple adrenal cysts between 2004 and 2021. Baseline characteristics and outcomes of those who underwent resection (ADX) or observation (OBS) were compared using the chi-squared test, student's t-test, and Wilcoxon rank-sum test. Growth curves and sensitivity analysis were plotted for all patients who had follow-up imaging. RESULTS: We identified 77 patients with imaging-confirmed adrenal cysts. The majority were female (75.3%) and more than half were white (55.8%). One-third of patients underwent ADX, and the remaining were observed. ADX patients were younger (median age [IQR]: 55.5 y [45.0-68.2 y] vs. 44.2 y [38.7-55.0 y], p = 0.01) and more likely to be Hispanic (12% vs. 0%, p = 0.05). ADX patients presented with larger cysts (5.6 vs. 2.6 cm, p = 0.002). The median time from diagnosis to last follow-up was 1.1 y for ADX and 4.1 y for OBS. Average growth for OBS was 0.3 cm/y, while average growth for ADX was 3.9 cm/y. In ADX patients, cysts >10 cm grew significantly faster than cysts <10 cm (median growth rate 13.2 cm/y vs. 0.3 cm/y, p < 0.05). There was no adrenal malignancy diagnosis, hyperfunctionality, or observation-related complications (e.g., rupture). CONCLUSION: While size >4-6 cm has guided surgical referral for solid adrenal masses, this study demonstrates a size threshold of 10 cm, below which asymptomatic, simple adrenal cysts can safely be observed.

Flank pain, hypertension, and hematuria: CT and 3D cinematic rendering in the evaluation of renal artery emergencies-a pictorial essay.

Non-traumatic acute renal artery emergencies encompass a spectrum of etiologies, including renal artery stenosis, arteriovenous malformations, aneurysms and pseudoaneurysms, dissections, thrombosis, and vasculitis. Prompt and accurate diagnosis in the emergency setting is crucial due to the potential for significant morbidity and mortality. Computed tomography (CT) and CT angiography (CTA) are the mainstay imaging modalities, offering rapid acquisition and high diagnostic accuracy. The integration of 3D postprocessing techniques, such as 3D cinematic rendering (CR), improves the diagnostic workflow by providing photorealistic and anatomically accurate visualizations. This pictorial essay illustrates the diagnostic utility of CT and CTA, supplemented by 3D CR, through a series of 10 cases of non-traumatic renal artery emergencies. The added value of 3D CR in improving diagnostic confidence, surgical planning, and understanding of complex vascular anatomy is emphasized.

Expanded experience with cardiovascular black blood cinematic rendering.

Black blood cinematic rendering (BBCR) is a newly described preset for cinematic rendering, which creates photorealistic displays from volumetric data sets with the contrast-enhanced blood pool displayed as dark and transparent. That set of features potentially provides for enhanced visualization of endomyocardial and intraluminal pathology, as well as cardiac devices. The similarity of the images to black-blood magnetic resonance imaging (MRI) may allow for expansion of the evaluation of certain types of pathology into patient populations unable to undergo MRI. In the emergency setting, the rapid acquisition time and reasonable post-processing time make this technique clinically feasible. In this expanded experience, we demonstrate an expanded clinical experience with the BBCR technique, highlighting the applications for intraluminal cardiovascular evaluation, especially focused on current and potential emergency radiology applications.

3D Cinematic rendering for evaluating femoral pseudoaneurysms in injection drug users.

The inguinal region, specifically the femoral vasculature, is a commonly used site of injection for intravenous drug users (IVDU). Repeated puncture of the vessel wall results in breakdown and subsequent arterial pseudoaneurysm- dilatations or outpouching of blood vessels, which, if left untreated, can result in fatal complications such as rupture with hemorrhage, sepsis, or even limb loss. The current modalities for arterial pseudoaneurysms include Doppler ultrasound and computed tomography (CT) angiography, both of which play important roles in management and surgical planning. However, 3D cinematic rendering (CR), a novel CT post-processing technique, offers timely, highly detailed photorealistic images that more clearly display the relation of anatomical structures, allowing for greater diagnostic confidence and precise surgical planning, particularly useful in the emergency setting. In this pictorial review, we demonstrate role of 3D CR in diagnosis and management of femoral pseudoaneurysms in IVDU through 9 illustrative cases.

The role of 3D cinematic rendering in the evaluation of upper extremity trauma.

Traumatic upper extremity injuries are a common cause of emergency department visits, comprising between 10-30% of traumatic injury visits. Timely and accurate evaluation is important to prevent severe complications such as permanent deformities, ischemia, or even death. Computed tomography (CT) and CT angiography (CTA) are the favored non-invasive imaging techniques for assessing upper extremity trauma, playing a crucial role in both the treatment planning and decision-making processes for such injuries. In CT postprocessing, a novel 3D rendering method, cinematic rendering (CR), employs sophisticated lighting models that simulate the interaction of multiple photons with the volumetric dataset. This technique produces images with realistic shadows and improved surface detail, surpassing the capabilities of volume rendering (VR) or maximal intensity projection (MIP). Considering the benefits of CR, we demonstrate its use and ability to achieve photorealistic anatomic visualization in a series of 11 cases where patients presented with traumatic upper extremity injuries, including bone, vascular, and skin/soft tissue injuries, adding to diagnostic confidence and intervention planning.

Cinematic rendering of non-traumatic thoracic aorta emergencies: a new look at an old problem.

Non-traumatic thoracic aorta emergencies are acute conditions associated with substantial morbidity and mortality. In the emergency setting, timely detection of aortic injury through radiological imaging is crucial for prompt treatment planning and favorable patient outcomes. 3D cinematic rendering (CR), a novel rendering algorithm for computed tomography (CT) image processing, allows for life-like visualization of spatial details and contours of highly complex anatomic structures such as the thoracic aorta and its vessels, generating a photorealistic view that not just adds to diagnostic confidence, but is especially useful for non-radiologists, including surgeons and emergency medicine physicians. In this pictorial review, we demonstrate the utility of CR in the setting of non-traumatic thoracic aorta emergencies through 10 cases that were processed at a standalone 3D CR station at the time of presentation, including its role in diagnosis and management.

Cinematic Rendering of Pancreatic Neuroendocrine Tumours: Opportunities for Clinical Implementation: Part 2: Preoperative Planning and Evaluation of Metastatic Disease.

Pancreatic neuroendocrine tumours (PNETs) are a rare subset of pancreatic tumours that have historically comprised up to 3% of all clinically detected pancreatic tumours. In recent decades, however, advancements in imaging have led to an increased incidental detection rate of PNETs and imaging has played an increasingly central role in the initial diagnostics and surgical planning of these tumours. Cinematic rendering (CR) is a 3D post-processing technique that generates highly photorealistic images through more realistically modelling the path of photons through the imaged volume. This allows for more comprehensive visualization, description, and interpretation of anatomical structures. In this 2-part review article, we present the first description of the various CR appearances of PNETs in the reported literature while providing commentary on the unique clinical opportunities afforded by the adjunctive utilization of CR in the workup of these rare tumours. This second instalment focuses on the applications of CR in optimizing preoperative planning of PNETs.

Cinematic Rendering of Pancreatic Neuroendocrine Tumours: Opportunities for Clinical Implementation: Part 1: Tumour Detection and Characterization.

Pancreatic neuroendocrine tumours (PNETs) are a rare subset of pancreatic tumours that have historically comprised up to 3% of all clinically detected pancreatic tumours. In recent decades, however, advancements in imaging have led to an increased incidental detection rate of PNETs and imaging has played an increasingly central role in the initial diagnostics and surgical planning of these tumours. Cinematic rendering (CR) is a 3D post-processing technique that generates highly photorealistic images through more realistically modelling the path of photons through the imaged volume. This allows for more comprehensive visualization, description, and interpretation of anatomical structures. In this 2-part review article, we present the first description of the various CR appearances of PNETs in the reported literature while providing commentary on the unique clinical opportunities afforded by the adjunctive utilization of CR in the workup of these rare tumours. The first of these 2 instalments highlights the utility of CR in optimizing PNET detection and characterization.

Bilateral Persistent Sciatic Arteries.

Online supplemental material is available for this article.

Musculoskeletal CT Imaging: State-of-the-Art Advancements and Future Directions.

CT is one of the most widely used modalities for musculoskeletal imaging. Recent advancements in the field include the introduction of four-dimensional CT, which captures a CT image during motion; cone-beam CT, which uses flat-panel detectors to capture the lower extremities in weight-bearing mode; and dual-energy CT, which operates at two different x-ray potentials to improve the contrast resolution to facilitate the assessment of tissue material compositions such as tophaceous gout deposits and bone marrow edema. Most recently, photon-counting CT (PCCT) has been introduced. PCCT is a technique that uses photon-counting detectors to produce an image with higher spatial and contrast resolution than conventional multidetector CT systems. In addition, postprocessing techniques such as three-dimensional printing and cinematic rendering have used CT data to improve the generation of both physical and digital anatomic models. Last, advancements in the application of artificial intelligence to CT imaging have enabled the automatic evaluation of musculoskeletal pathologies. In this review, the authors discuss the current state of the above CT technologies, their respective advantages and disadvantages, and their projected future directions for various musculoskeletal applications.

Extramedullary Hematopoiesis: A Forgotten Diagnosis and a Great Mimicker of Malignancy.

ABSTRACT: Radiology errors have been reported in up to 30% of cases when patients have abnormal imaging findings. Although more than half of errors are failures to detect critical findings, over 40% of errors are when findings are recognized but the correct diagnosis or interpretation is not made. One common source of error is when imaging findings from one process simulate imaging findings from another process but the correct diagnosis is not made. This can result in additional imaging studies, unnecessary biopsies, or surgery. Extramedullary hematopoiesis is one of those uncommon disease processes that can produce many imaging findings that may lead to misdiagnosis. The objective of this article is to review the common and uncommon imaging features of extramedullary hematopoiesis while presenting a series of interesting relevant illustrative cases with emphasis on CT.

Augmented Reality With Cinematic Rendered 3-Dimensional Images From Volumetric Computed Tomography Data.

ABSTRACT: Recent advances in 3-dimensional visualization of volumetric computed tomography data have led to the novel technique of cinematic rendering (CR), which provides photorealistic images with enhanced surface detail and realistic shadowing effects that are generally not possible with older methods such as volume rendering. The emergence of CR coincides with the increasingly widespread availability of virtual reality (VR)/augmented reality (AR) interfaces including wearable headsets. The intersection of these technologies suggests many potential advances, including the ability of interpreting radiologists to look at photorealistic images of patient pathology in real time with surgeons and other referring providers, so long as VR/AR headsets are deployed and readily available. In this article, we will present our initial experience with viewing and manipulating CR images in the context of a VR/AR headset. We include a description of key aspects of the software and user interface, and provide relevant pictorial examples that may help potential adopters understand the initial steps of using this exciting convergence of technologies. Ultimately, trials evaluating the added value of the combination of CR with VR/AR will be necessary to understand the potential impact of these methods on medical practice.

Radiologists' Expectations of Artificial Intelligence in Pancreatic Cancer Imaging: How Good Is Good Enough?

BACKGROUND: Existing (artificial intelligence [AI]) tools in radiology are modeled without necessarily considering the expectations and experience of the end user-the radiologist. The literature is scarce on the tangible parameters that AI capabilities need to meet for radiologists to consider them useful tools. OBJECTIVE: The purpose of this study is to explore radiologists' attitudes toward AI tools in pancreatic cancer imaging and to quantitatively assess their expectations of these tools. METHODS: A link to the survey was posted on the www.ctisus.com website, advertised in the www.ctisus.com email newsletter, and publicized on LinkedIn, Facebook, and Twitter accounts. This survey asked participants about their demographics, practice, and current attitudes toward AI. They were also asked about their expectations of what constitutes a clinically useful AI tool. The survey consisted of 17 questions, which included 9 multiple choice questions, 2 Likert scale questions, 4 binary (yes/no) questions, 1 rank order question, and 1 free text question. RESULTS: A total of 161 respondents completed the survey, yielding a response rate of 46.3% of the total 348 clicks on the survey link. The minimum acceptable sensitivity of an AI program for the detection of pancreatic cancer chosen by most respondents was either 90% or 95% at a specificity of 95%. The minimum size of pancreatic cancer that most respondents would find an AI useful at detecting was 5 mm. Respondents preferred AI tools that demonstrated greater sensitivity over those with greater specificity. Over half of respondents anticipated incorporating AI tools into their clinical practice within the next 5 years. CONCLUSION: Radiologists are open to the idea of integrating AI-based tools and have high expectations regarding the performance of these tools. Consideration of radiologists' input is important to contextualize expectations and optimize clinical adoption of existing and future AI tools.

Pancreatoblastoma in an elderly woman: A case report simulating a pancreatic neuroendocrine tumour with emphasis on cytomorphological features.

Pancreatoblastoma (PB), a rare malignant epithelial neoplasm, is the most common pancreatic neoplasm of childhood. It is exceptionally rare in the adult population and its occurrence is limited to case reports. Although the neoplastic cells of PB can have a number of different directions of differentiation, PB is defined by the combination of neoplastic cells with acinar differentiation and squamoid morules. We report a case of a female patient in her 70s who presented with elevated creatinine level, concerning a kidney disorder, and was found to have an abdominal mass on CT scan. Fine needle aspiration (FNA) showed cellular smears with numerous 3-dimentional clusters of acinar cells and scattered squamoid morules. A cell block showed sheets of cells, some of which formed acini. Numerous squamoid morules were noted and were highlighted by nuclear labelling with antibodies to B-catenin in the cell block. The FNA diagnosis was rendered as "carcinoma with acinar differentiation, favour pancreatoblastoma." Subsequent histological findings confirmed the PB diagnosis. Next generation sequencing detected a CTNNB1 mutation. Given the wide usage of FNA in the preoperative diagnosis of pancreatic masses, the cytopathologist needs to be aware of the morphological features of PB and its cytological differential diagnosis, even in an elderly patient. The differential diagnosis includes acinar cell carcinoma, pancreatic neuroendocrine tumour, and solid pseudopapillary neoplasm. In conclusion, the cytological finding of neoplastic cells with acinar differentiation combined with squamous morules and/or mesenchymal elements in the smears and more commonly in the cell blocks appears to be the most specific finding for the diagnosis of PB.

Emergent and unusual presentations of endometriosis: pearls and pitfalls.

The purpose of this pictorial essay is to highlight atypical and unusual presentations of endometriosis that can be missed or misinterpreted in the emergency setting. Although endometriosis is a chronic disease, it can present acutely with symptoms and imaging mimicking more common acute gynecologic, gastrointestinal, or urinary conditions as well as neoplasms. Furthermore, patients may present emergently prior to an established diagnosis of endometriosis. Here, we present a range of cases including endometrioma rupture and infection, urinary tract involvement and obstruction, bowel obstruction, appendicitis, gastrointestinal infiltration, abdominal masses, and thoracic involvement. Pelvic ultrasound and MRI are the most valuable imaging modalities in the assessment of endometriosis. CT findings are non-specific, but given the widespread use of CT in emergency settings, it is important to recognize CT findings suggestive of the diagnosis in the right clinical setting.

Evaluation of extensive inflammatory conditions of the bowel using three-dimensional CT cinematic rendering: focus on inflammatory bowel disease.

Inflammatory conditions that affect long segments of bowel and/or the mesentery and mesenteric vasculature are a common cause of emergency department visits and evaluation by cross-sectional imaging. Inflammatory bowel disease, specifically Crohn disease and ulcerative colitis, can be unsuspected at presentation and may only be eventually diagnosed based on initial imaging findings. Traditional 2D axial reconstructions and multi-planar reformations can be limited in their ability to globally assess the extent of disease. 3D methods such as volume rendering (VR) are often used as adjunctive means of visualizing the pathology in such patients. Recently, a novel technique known as cinematic rendering (CR) has emerged, utilizing advanced lighting models and ray tracing to simulate photon interactions with tissues, resulting in realistic shadows and enhanced surface detail compared to VR. Generating CR images from select presets takes an experienced radiologist approximately 5 min, meaning that the technique can be incorporated into meaningful emergency department workflows. Given the apparent advantages of CR, we highlight its application in a series of cases in which patients had inflammatory conditions that affected long segments of bowel and/or involved the mesentery, particularly those patients with inflammatory bowel disease, but also including patients with mesenteric venous thrombosis and lymphedema. Those conditions included inflammatory bowel disease, mesenteric venous thrombosis, and bowel lymphedema. We present examples of those conditions in this pictorial essay and describe the potential of CR to visualize key findings. As CR exhibits possible advantages, further studies are warranted to support its broader clinical adoption and assess its efficacy in diagnosing and guiding managing of inflammatory conditions in emergency settings.

Cinematic rendering in the evaluation of complex vascular injury of the lower extremities: how we do it.

Lower extremity trauma is one of the most common injury patterns seen in emergency medical and surgical practice. Vascular injuries occur in less than one percent of all civilian fractures. However, if not treated promptly, such injuries can lead to ischemia and death. Computed tomography angiography (CTA) is the non-invasive imaging gold standard and plays a crucial part in the decision-making process for treating lower extremity trauma. A novel, FDA-approved 3D reconstruction technique known as cinematic rendering (CR) yields photorealistic reconstructions of lower extremity vascular injuries depicting clinically important aspects of those injuries, aiding in patient workup and surgical planning, and thus improving patient outcomes. In this article, we provide clinical examples of the use of CR in evaluating lower extremity vascular injuries, including the relationship of these injuries to adjacent osseous structures and overlying soft tissues, and its role in management of lower extremity trauma.