Radiolabeled white blood cells scan in the diagnostic work-out of IE and CIED infection

Clinical performance of the Duke Endocarditis Service criteria to establish the diagnosis of infectious endocarditis (IE) and cardiac implantable electronic device (CIED) infection can be improved through functional imaging procedures such as radiolabeled leukocytes (99mTc-HMPAO-WBC). Methods: We assessed the value of 99mTc-HMPAO-WBC scintigraphy including SPECT/CT acquisitions in two series of 131 and 56 consecutive patients with suspected IE and CIED, respectively. 99mTc-HMPAO-WBC scintigraphy results were correlated with transthoracic (TTE) or transesophageal (TEE) echocardiography, blood culture and the Duke criteria. Results: The scan was particularly valuable in patients with negative and/or difficult-to-interpret echocardiographic findings. Conclusions: Our results demonstrate 99mTc-HMPAO-WBC scintigraphy ability to reduce the rate of misdiagnosed IE when combined to the standard diagnostic tests (a) in patients with high clinical suspicion but inconclusive echocardiographic findings; (b) for the differential diagnosis between septic and sterile vegetations detected at echocardiography; (c) when echocardiographic, laboratory and clinical data are contradictory, as also to exclude valve involvement (especially of a prosthetic valve) during febrile episodes, sepsis or post-surgical infections

Dual adversarial deconfounding autoencoder for joint batch-effects removal from multi-center and multi-scanner radiomics data

Abstract Medical imaging represents the primary tool for investigating and monitoring several diseases, including cancer. The advances in quantitative image analysis have developed towards the extraction of biomarkers able to support clinical decisions. To produce robust results, multi-center studies are often set up. However, the imaging information must be denoised from confounding factors—known as batch-effect—like scanner-specific and center-specific influences. Moreover, in non-solid cancers, like lymphomas, effective biomarkers require an imaging-based representation of the disease that accounts for its multi-site spreading over the patient’s body. In this work, we address the dual-factor deconfusion problem and we propose a deconfusion algorithm to harmonize the imaging information of patients affected by Hodgkin Lymphoma in a multi-center setting. We show that the proposed model successfully denoises data from domain-specific variability (p-value < 0.001) while it coherently preserves the spatial relationship between imaging descriptions of peer lesions (p-value = 0), which is a strong prognostic biomarker for tumor heterogeneity assessment. This harmonization step allows to significantly improve the performance in prognostic models with respect to state-of-the-art methods, enabling building exhaustive patient representations and delivering more accurate analyses (p-values < 0.001 in training, p-values < 0.05 in testing). This work lays the groundwork for performing large-scale and reproducible analyses on multi-center data that are urgently needed to convey the translation of imaging-based biomarkers into the clinical practice as effective prognostic tools. The code is available on GitHub at this https://github.com/LaraCavinato/Dual-ADAE

Imaging-based representation and stratification of intra-tumor heterogeneity via tree-edit distance

Personalized medicine is the future of medical practice. In oncology, tumor heterogeneity assessment represents a pivotal step for effective treatment planning and prognosis prediction. Despite new procedures for DNA sequencing and analysis, non-invasive methods for tumor characterization are needed to impact on daily routine. On purpose, imaging texture analysis is rapidly scaling, holding the promise to surrogate histopathological assessment of tumor lesions. In this work, we propose a tree-based representation strategy for describing intra-tumor heterogeneity of patients affected by metastatic cancer. We leverage radiomics information extracted from PET/CT imaging and we provide an exhaustive and easily readable summary of the disease spreading. We exploit this novel patient representation to perform cancer subtyping according to hierarchical clustering technique. To this purpose, a new heterogeneity-based distance between trees is defined and applied to a case study of prostate cancer. Clusters interpretation is explored in terms of concordance with severity status, tumor burden and biological characteristics. Results are promising, as the proposed method outperforms current literature approaches. Ultimately, the proposed method draws a general analysis framework that would allow to extract knowledge from daily acquired imaging data of patients and provide insights for effective treatment planning

Alternative Nuclear Imaging Tools for Infection Imaging

Purpose of Review Cardiovascular infections are serious disease associated with high morbidity and mortality. Their diagnosis is challenging, requiring a proper management for a prompt recognition of the clinical manifestations, and a multidisciplinary approach involving cardiologists, cardiothoracic surgeons, infectious diseases specialist, imagers, and microbiologists. Imaging plays a central role in the diagnostic workout, including molecular imaging techniques. In this setting, two different strategies might be used to image infections: the first is based on the use of agents targeting the microorganism responsible for the infection. Alternatively, we can target the components of the pathophysiological changes of the inflammatory process and/or the host response to the infectious pathogen can be considered. Understanding the strength and limitations of each strategy is crucial to select the most appropriate imaging tool. Recent Findings Currently, multislice computed tomography (MSCT) and nuclear imaging (F-18-fluorodeoxyglucose positron emission tomography/computed tomography, and leucocyte scintigraphy) are part of the diagnostic strategies. The main role of nuclear medicine imaging (PET/CT and SPECT/CT) is the confirmation of valve/CIED involvement and/or associated perivalvular infection and the detection of distant septic embolism. Proper patients' preparation, imaging acquisition, and reconstruction as well as imaging reading are crucial to maximize the diagnostic information. In this manuscript, we described the use of molecular imaging techniques, in particular WBC imaging, in patients with infective endocarditis, cardiovascular implantable electronic device infections, and infections of composite aortic graft, underlying the strength and limitations of such approached as compared to the other imaging modalities

Image Embeddings Extracted from CNNs Outperform Other Transfer Learning Approaches in Classification of Chest Radiographs

To identify the best transfer learning approach for the identification of the most frequent abnormalities on chest radiographs (CXRs), we used embeddings extracted from pretrained convolutional neural networks (CNNs). An explainable AI (XAI) model was applied to interpret black-box model predictions and assess its performance. Seven CNNs were trained on CheXpert. Three transfer learning approaches were thereafter applied to a local dataset. The classification results were ensembled using simple and entropy-weighted averaging. We applied Grad-CAM (an XAI model) to produce a saliency map. Grad-CAM maps were compared to manually extracted regions of interest, and the training time was recorded. The best transfer learning model was that which used image embeddings and random forest with simple averaging, with an average AUC of 0.856. Grad-CAM maps showed that the models focused on specific features of each CXR. CNNs pretrained on a large public dataset of medical images can be exploited as feature extractors for tasks of interest. The extracted image embeddings contain relevant information that can be used to train an additional classifier with satisfactory performance on an independent dataset, demonstrating it to be the optimal transfer learning strategy and overcoming the need for large private datasets, extensive computational resources, and long training times

Prosthetic Valve Endocarditis

Prosthetic valve infective endocarditis (PVE) is associated with high morbidity and mortality. With the increasing number of prostheses implanted every year, the incidence of PVE is expected to rise. The diagnosis of PVE is challenging as blood cultures are often negative and the sensitivity of echocardiography is suboptimal in the presence of prosthetic valves. In 2015, the European Society of Cardiology introduced 18F-fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) as a major criterion for the diagnosis of PVE, based on its ability to identify valve infection and to detect septic emboli. In addition, FDG-PET/CT can detect PVE portal of entry, which may lead to change in management. This chapter will discuss the epidemiology and clinical presentations of PVE. In addition, the role of FDG-PET/CT in PVE as well as optimal imaging protocols will be reviewed.</p

ED-B fibronectin expression is a marker of epithelial-mesenchymal transition in translational oncology

Fibronectin is a component of the extracellular matrix that links collagen fibers to integrins on the cell's surface. The splicing isoforms, containing the ED-B domain, are not expressed in adult tissues but only in tumor stroma or during embryonic development. Fibroblasts and endothelial cells express ED-B fibronectin during angiogenesis. Also cancer cells can synthetize ED-B fibronectin, but its function in tumor growth needs to be further elucidated. We evaluated the expression of ED-B fibronectin in prostate cancer cell lines: PC3 and DU145. Using TGF-β, we induced epithelial to mesenchymal transition in culture and observed an increase of ED-B fibronectin expression. Thereafter, we evaluated the expression of ED-B fibronectin in multipotent mesangiogenic progenitor cells, and in mesenchymal stromal cells. The expression of ED-B fibronectin was much higher in mesenchymal than prostate cancer cells even after the epithelial to mesenchymal transition. Epithelial to mesenchymal transition is a key step for tumor progression contributing to the metastatic spread. Therefore, circulating cancer cells could seed into the metastatic niche taking advantage from the ED-B fibronectin that secrete their own

The role of imaging in the diagnosis of recurrence of primary seminal vesicle adenocarcinoma

Primary seminal vesicle (SV) adenocarcinoma is a rare tumor. A small amount of data about the role of imaging to detect tumor recurrence is available. We report the case of a 58-year-old patient with primary SV clear-cell well-differentiated adenocarcinoma. Clinical and instrumental examinations were negative for the 32 months after treatments when computed tomography scan, [(18)F]fluoro-D-glucose positron emission tomography/computed tomography and pelvic magnetic resonance imaging showed the appearance of a lesion in the left perineal muscle suspected for recurrence. Patient was symptomless. Cytology of the suspected lesion confirmed SV adenocarcinoma recurrence. The combined approach, using radiological and nuclear medicine techniques, seems to be effective in the follow-up of SV adenocarcinoma. Technological advances, together with awareness of this rare tumor, have the potential of improving patients outcomes not only by providing earlier detection and accurate staging, but also by detecting recurrence and thereby avoiding delays and therapeutic dilemmas

What to Trust, PSA or [Ga-68]Ga-PSMA-11:Learn from Experience

Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient's management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [Ga-68]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [Ga-68]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition - from the vertex to thigh - should be always considered, regardless of the PSA level

ED-B-Containing Isoform of Fibronectin in Tumor Microenvironment of Thymomas:A Target for a Theragnostic Approach

Simple Summary The extra-domain B fibronectin (ED-B FN) is highly expressed in thymic epithelial tumors (TETs), as demonstrated by in vivo targeting using 131I-labeled L19 small immunoprotein (131I-L19-SIP) and immunohistochemistry with a predominant expression by stromal cells of a thymoma microenvironment rather than epithelial cells. Such high expression derived from the induction of stromal cells shifts FN production to the ED-B subtype. Our results suggest that Radretumab radioimmunotherapy (R-RIT) inefficacy is not related to low TET ED-B expression but to multifactorial aspects including patients' inherent characteristics, the pattern expression of the target, the biological characteristics of the tumor, and the format of the target agent, which contribute to the resistance of tumor cells to treatment. Aim: to exploit tissue-specific interactions among thymic epithelial tumor (TETs) cells and extra-domain B fibronectin (ED-B FN). Material and methods: The stromal pattern of ED-B FN expression was investigated through tumor specimen collection and molecular profiling in 11 patients with recurrent TETs enrolled in prospective theragnostic phase I/II trials with Radretumab, an ED-B FN specific recombinant human antibody. Radretumab radioimmunotherapy (R-RIT) was offered to patients who exhibited the target expression. Experiments included immunochemical analysis (ICH), cell cultures, immunophenotypic analysis, Western blot, slot-blot assay, and quantitative RT-PCR of two primary thymoma cultures we obtained from patients' samples and in the Ty82 cell line. Results: The in vivo scintigraphic demonstration of ED-B FN expression resulted in R-RIT eligibility in 8/11 patients, of which seven were treated. The best observed response was disease stabilization (n = 5/7) with a duration of 4.3 months (range 3-5 months). IHC data confirmed high ED-B FN expression in the peripherical microenvironment rather than in the center of the tumor, which was more abundant in B3 thymomas. Further, there was a predominant expression of ED-B FN by the stromal cells of the thymoma microenvironment rather than the epithelial cells. Conclusions: Our data support the hypothesis that thymomas induce stromal cells to shift FN production to the ED-B subtype, likely representing a favorable hallmark for tumor progression and metastasis. Collectively, results derived from clinical experience and molecular insights of the in vitro experiments suggested that R-RIT inefficacy is unlikely related to low target expression in TET, being the mechanism of R-RIT resistance eventually related to patients' susceptibility (i.e., inherent characteristics), the pattern expression of the target (i.e., at periphery), the biological characteristics of the tumor (i.e., aggressive and resistant phenotypes), and/or to format of the target agent (i.e., 131I-L19-SIP)