Artificial Intelligence and Infectious Disease Imaging.

The mass production of the graphics processing unit and the coronavirus disease 2019 (COVID-19) pandemic have provided the means and the motivation, respectively, for rapid developments in artificial intelligence (AI) and medical imaging techniques. This has led to new opportunities to improve patient care but also new challenges that must be overcome before these techniques are put into practice. In particular, early AI models reported high performances but failed to perform as well on new data. However, these mistakes motivated further innovation focused on developing models that were not only accurate but also stable and generalizable to new data. The recent developments in AI in response to the COVID-19 pandemic will reap future dividends by facilitating, expediting, and informing other medical AI applications and educating the broad academic audience on the topic. Furthermore, AI research on imaging animal models of infectious diseases offers a unique problem space that can fill in evidence gaps that exist in clinical infectious disease research. Here, we aim to provide a focused assessment of the AI techniques leveraged in the infectious disease imaging research space, highlight the unique challenges, and discuss burgeoning solutions.

Molecular Imaging of ACE2 Expression in Infectious Disease and Cancer.

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that plays a critical role in the pathogenesis of SARS-CoV-2 infection. Through the use of ligands engineered for the receptor, ACE2 imaging has emerged as a valuable tool for preclinical and clinical research. These can be used to visualize the expression and distribution of ACE2 in tissues and cells. A variety of techniques including optical, magnetic resonance, and nuclear medicine contrast agents have been developed and employed in the preclinical setting. Positron-emitting radiotracers for highly sensitive and quantitative tomography have also been translated in the context of SARS-CoV-2-infected and control patients. Together this information can be used to better understand the mechanisms of SARS-CoV-2 infection, the potential roles of ACE2 in homeostasis and disease, and to identify potential therapeutic modulators in infectious disease and cancer. This review summarizes the tools and techniques to detect and delineate ACE2 in this rapidly expanding field.

Label-free single-particle imaging approach for ultra-rapid detection of pathogenic bacteria in clinical samples.

Rapid detection of pathogenic bacteria within a few minutes is the key to control infectious disease. However, rapid detection of pathogenic bacteria in clinical samples is quite a challenging task due to the complex matrix, as well as the low abundance of bacteria in real samples. Herein, we employ a label-free single-particle imaging approach to address this challenge. By tracking the scattering intensity variation of single particles in free solution, the morphological heterogeneity can be well identified with particle size smaller than the diffraction limit, facilitating the morphological identification of single bacteria from a complex matrix in a label-free manner. Furthermore, the manipulation of convection in free solution enables the rapid screening of low-abundance bacteria in a small field of view, which significantly improves the sensitivity of single-particle detection. As a proof of concept demonstration, we are able to differentiate the group B streptococci (GBS)-positive samples within 10 min from vaginal swabs without using any biological reagents. This is the most rapid and low-cost method to the best of our knowledge. We believe that such a single-particle imaging approach will find wider applications in clinical diagnosis and disease control due to its high sensitivity, rapidity, simplicity, and low cost.

Impact of unknown incidental findings in PET/CT examinations of patients with proven or suspected vascular graft or endograft infections.

Vascular graft or endograft Infections (VGEI) are rare but severe complications of vascular reconstructive surgery, and associated with significant mortality and morbidity risk. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT) has been shown to have a high diagnostic accuracy in the detection of VGEI. In this single-center prospective cohort study, we assessed the rate and the impact on patient management of relevant unknown incidental findings in PET/CT of patients with proven or suspected VGEI, and clinical follow-up of all patients was performed. Our study results show a comparably high rate of relevant unknown incidental findings (181 in 502 examinations), with documented direct impact on patient management in 80 of 181 (44%) of all findings. PET/CT scan- and patient-based evaluation revealed impact on patient management in 76 of 502 (17%) of all PET/CT scans, and in 59 of 162 (36%) of all patients, respectively. Furthermore, PET/CT correctly identified the final diagnosis in 20 of 36 (56%) patients without VGEI. In conclusion, in proven and suspected VGEI, PET/CT detects a high rate of relevant unknown incidental findings with high impact on patient management.

Deep Learning for Imaging and Detection of Microorganisms.

Despite tremendous recent interest, the application of deep learning in microbiology has still not reached its full potential. To tackle the challenges faced by human-operated microscopy, deep-learning-based methods have been proposed for microscopic image analysis of a wide range of microorganisms, including viruses, bacteria, fungi, and parasites. We believe that deep-learning technology-based systems will be on the front line of monitoring and investigation of microorganisms.

Aplicaciones emergentes de la ecografía clínica / Emerging applications of clinical ultrasonography

En el documento actual introduciremos las áreas más emergentes y frontera del uso de la ecografía clínica a la cabecera del paciente, que son numerosas. De entre todas ellas se revisarán 3: 1) la ecografía clínica en las enfermedades infecciosas y patología tropical (se abordará su utilidad en el diagnóstico y seguimiento de los principales síndromes, así como los usos para patología tropical y en áreas con escasos recursos); 2) la utilidad de la ecografía clínica para la evaluación de la respuesta a la infusión de volumen en pacientes graves (se revisarán conceptos básicos, así como las principales variables estáticas y dinámicas utilizadas para realizar esta evaluación); y por último, 3) se abordará la utilización de la ecografía clínica para la valoración de la masa muscular en la sarcopenia primaria de las personas ancianas (se repasarán los principales músculos y medidas que se utilizan para ello) (AU)

In this work, we introduce the numerous emerging areas and frontiers in the use of point-of-care ultrasonography. Of these, we review the following three: 1) the use of clinical ultrasonography in infectious and tropical diseases (we address its usefulness in the diagnosis and follow-up of the main syndromes, in tropical diseases, and in areas with scarce resources); 2) the usefulness of clinical ultrasonography in the assessment of response to volume infusion in severely ill patients (we review basic concepts and the main static and dynamic variables used for this evaluation); and 3) the use of clinical ultrasonography in the assessment of muscle mass in elderly patients with primary sarcopenia (we review the main muscles and measurements used for it) (AU)

Chest complications in immunocompromised patients without acquired immunodeficiency syndrome (AIDS): differentiation between infectious and non-infectious diseases using high-resolution CT findings.

AIM: To differentiate between infectious and non-infectious diseases occurring in immunocompromised patients without acquired immunodeficiency syndrome (AIDS) using high-resolution computed tomography (HRCT). MATERIALS AND METHODS: HRCT images of 555 patients with chest complications were reviewed retrospectively. Infectious diseases (n=341) included bacterial pneumonia (n=123), fungal infection (n=80), septic emboli (n=11), tuberculosis (n=15), pneumocystis pneumonia (n=101), and cytomegalovirus pneumonia (n=11), while non-infectious diseases (n=214) included drug toxicity (n=84), infiltration of underlying diseases (n=83), idiopathic pneumonia syndrome (n=34), diffuse alveolar haemorrhage (n=8), and pulmonary oedema (n=5). Lung parenchymal abnormalities were compared between the two groups using the χ2 test and multiple logistic regression analysis. RESULTS: The χ2 test results showed significant differences in many HRCT findings between the two groups. Multiple logistic regression analysis results indicated the presence of nodules with a halo and the absence of interlobular septal (ILS) thickening were the significant indicators that could differentiate infectious from non-infectious diseases. ILS thickening was generally less frequent among most infectious diseases and more frequent among most non-infectious diseases, with a good odds ratio (7.887, p<0.001). The sensitivity and accuracy for infectious diseases in the absence of ILS thickening were better (70% and 73%, respectively) than those of nodules with a halo (19% and 48%, respectively), while the specificity in the nodules with a halo was better (93%) than that of ILS thickening (78%). CONCLUSIONS: The presence of nodules with a halo or the absence of ILS thickening tends to suggest infectious disease. Specifically, ILS thickening seems to be a more reliable indicator.

Total-Body PET Imaging in Infectious Diseases.

Total-body PET enables high-sensitivity imaging with dramatically improved signal-to-noise ratio. These enhanced performance characteristics allow for decreased PET scanning times acquiring data "total-body wide" and can be leveraged to decrease the amount of radiotracer required, thereby permitting more frequent imaging or longer imaging periods during radiotracer decay. Novel approaches to PET imaging of infectious diseases are emerging, including those that directly visualize pathogens in vivo and characterize concomitant immune responses and inflammation. Efforts to develop these imaging approaches are hampered by challenges of traditional imaging platforms, which may be overcome by novel total-body PET strategies.

PET/Computed Tomography in the Evaluation of Fever of Unknown Origin and Infectious/Inflammatory Disease in Pediatric Patients.

Fever in children is common. If it persists and its cause cannot be identified in a reasonable time, along with laboratory and conventional imaging investigations, it is defined as fever of unknown origin (FUO). 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is well established in the evaluation of malignancy, which is a possible cause of FUO. FDG often locates inflammatory and infectious lesions considered nonspecific or false-positive for oncology; however, these findings are beneficial in FUO evaluation because infectious and inflammatory diseases are important FUO causes. FDG-PET/CT is being increasingly used for investigation of FUO as well as infectious/inflammatory disease.

Update on the "Choosing Wisely" initiative in infectious diseases in Germany.

PURPOSE: The Choosing Wisely® initiative is an international campaign addressing over- and underuse of diagnostic and therapeutic measures in infectious diseases among others. Since 2016, the German Society for Infectious Diseases (DGI) has constantly designed new items in this regard. Here we report the most recent recommendations. METHODS: The recommendations of the DGI are part of the "Klug entscheiden" initiative of the German Society of Internal Medicine (DGIM). Topics for the new items were suggested by members of the DGI, checked for scientific evidence and consented within the DGI and the DGIM before publication. RESULTS: The new recommendations are: (1) individuals with immune-suppression, advanced liver cirrhosis or renal insufficiency should receive a dual pneumococcal vaccination. (2) In case of positive blood cultures with Candida spp. thorough diagnostics and treatment should be initiated. (3) In case of suspected meningitis, adult patients should receive dexamethasone and antibiotics immediately after venipuncture for blood cultures and before potential imaging. (4) In case of suspected meningitis a CT scan before lumbar puncture should not be ordered-except for symptoms indicating high CSF pressure or focal brain pathology or in cases of severe immune-suppression. (5) In patients with suspected severe infections, a minimum of two pairs of blood cultures should be drawn using separate venipunctures prior to antibiotic therapy-regardless of body temperature. There is no need of a minimum time interval in between the blood draws. CONCLUSION: Applying these new Choosing Wisely® recommendations will increase patient safety and the value of health care.

Sonographic assessment of infectious diseases of the gastrointestinal tract: from scanning to diagnosis.

BACKGROUND: Sonography of the gastrointestinal (GI) tract is a practical, safe, inexpensive, and reproducible diagnostic tool for the evaluation, diagnosis, and follow-up of infectious bowel disease. The modality is rapidly gaining prominence among clinicians on a global scale. In the United States, however, ultrasound of the bowel remains underutilized primarily due to insufficient experience among radiologists and sonographers in performing sonographic bowel assessment. This lack of experience and knowledge results in misinterpretations, missed diagnoses, and underutilization of this modality in patients with acute abdomen, with the majority of GI pathology on sonography discovered incidentally. OBJECTIVES: This article aims to demonstrate the characteristic sonographic findings associated with GI infectious processes as well as provide dedicated ultrasound protocols for evaluation of the GI tract. CONCLUSION: This article serves a twofold purpose, raising awareness of the utility of this imaging modality within the radiology community and also providing practical teaching points for sonographic evaluation of infectious disorders of the GI tract.

[Development of Molecular Probes for Live Imaging of Cancer and Infectious Diseases].

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are powerful molecular imaging methods for examining disease-related factors in the whole body using specific imaging probes. Recently, we tried to develop molecular imaging probes that specifically visualize pathological factors associated with cancers and infectious diseases. Although survivin is highly expressed in several cancers, its expression is undetectable in non-dividing tissues. Thus, we developed several small molecular imaging probes that target survivin. These ligands not only showed high affinity for survivin protein, but also showed consistent cellular accumulation with respect to survivin expression levels, thereby indicating the feasibility of their backbones as scaffolds for tumor-specific imaging agents that target survivin. Prion diseases are fatal neurodegenerative diseases characterized by the deposition of amyloid plaques containing abnormal prion protein aggregates (PrPSc). Thus, we developed flavonoids, acridines, and benzofurans as PrPSc-imaging probes. A styrylchromone derivative ([123I]SC-OMe) appears to be a particularly promising SPECT radioligand for monitoring prion deposit levels in living brains. Gallium-68 is a positron emitter in clinical PET applications that can be produced by a 68Ge/68Ga generator without a cyclotron. Notably, we developed new adsorbents for 68Ge by introducing N-methylglucamine groups into the Sephadex series to serve as a hydrophilic polymer matrix. We also demonstrated that generator-eluted 68Ga-citrate could be used for PET imaging of infectious mouse models. Our polysaccharide-based 68Ge/68Ga generators were shown to be prospectively cost-effective production systems for 68Ga radiopharmaceuticals. This Review describes the major findings of these three studies and the future prospect of these fields.

Diagnostic Performance of 18F-FDG PET/CT in Infectious and Inflammatory Diseases according to Published Meta-Analyses.

Purpose: To date, several meta-analyses have reported data about the diagnostic performance of 18F-FDG PET/CT in infectious and inflammatory diseases. This article aims to summarize the published evidence-based data about the diagnostic performance of 18F-FDG PET/CT in this setting. Methods: A comprehensive computer literature search of meta-analyses published in PubMed/MEDLINE and Cochrane library database from January 2009 through December 2018 and regarding the diagnostic performance of 18F-FDG PET/CT in infectious and inflammatory diseases was carried out. This combination of key words was used: (i) "PET" OR "positron emission tomography" OR "FDG" OR "fluorodeoxyglucose" AND (ii) meta-analysis. Only records on inflammatory or infectious diseases were selected. Results: The diagnostic performance of 18F-FDG PET/CT in detecting inflammatory and infectious diseases has been summarized taking into account 36 meta-analyses published in the literature. Evidence-based data demonstrated good diagnostic performance of 18F-FDG PET/CT for several inflammatory and infectious diseases, in particular cardiovascular infectious and inflammatory diseases and some musculoskeletal infections. Conclusions: Evidence-based data about the diagnostic performance of 18F-FDG PET/CT in infectious and inflammatory diseases are increasing, with good diagnostic performance of this imaging method for some indications. More prospective multicenter studies and cost-effective analyses are warranted.

Evaluation of Region of Interest Digital Cytology Compared to Light Microscopy for Veterinary Medicine.

Digital microscopy (DM) has been employed for primary diagnosis in human medicine and for research and teaching applications in veterinary medicine, but there are few veterinary DM validation studies. Region of interest (ROI) digital cytology is a subset of DM that uses image-stitching software to create a low-magnification image of a slide, then selected ROI at higher magnification, and stitches the images into a relatively small file of the embedded magnifications. This study evaluated the concordance of ROI-DM compared to traditional light microscopy (LM) between 2 blinded clinical pathologists. Sixty canine and feline cytology samples from a variety of anatomic sites, including 31 cases of malignant neoplasia, 15 cases of hyperplastic or benign neoplastic lesions, and 14 infectious/inflammatory lesions, were evaluated. Two separate nonblinded adjudicating clinical pathologists evaluated the reports and diagnoses and scored each paired case as fully concordant, partially concordant, or discordant. The average overall concordance (full and partial concordance) for both pathologists was 92%. Full concordance was significantly higher for malignant lesions than benign. For the 40 neoplastic lesions, ROI-DM and LM agreed on general category of tumor type in 78 of 80 cases (98%). ROI-DM cytology showed robust concordance with the current gold standard of LM cytology and is potentially a viable alternative to current LM cytology techniques.

Sound Around the World: Ultrasound for Tropical Diseases.

Ultrasound for diagnosis and staging of schistosomiasis and echinococcosis have paved the way over the past several decades for the application of ultrasound in tropical diseases. Until recently, the size and cost of ultrasound systems limited the application in low-resource settings. The increase in portable ultrasound systems has given more clinicians access to ultrasound, and clinically based protocols for the care of patients have emerged, such as focused assessment with sonography for HIV/TB and tropical cardiac ultrasound. This article explores the history and current use of ultrasound in these diseases and highlights their application in the care of patients.

Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults.

OBJECTIVES: To examine the association between hospitalization, critical illness, and infection occurring during middle- and late-life and structural brain abnormalities in older adults. DESIGN: Prospective cohort study. SETTING: Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: A community sample of adults who were 44 to 66 years of age at study baseline. MEASUREMENTS: Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24-year surveillance period. Subsequently, a subset of participants underwent 3-Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). RESULTS: Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate-adjusted regression, hospitalization was associated with 0.12-standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00-0.24) and poorer white matter microstructural integrity (0.17-SD lower FA, 95% CI=-0.27 to -0.06; 0.16-SD greater MD, 95% CI=0.07-0.25) than no hospitalization. There was a dose-dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p-trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (-1.64 cm3 , 95% CI=-3.16 to -0.12); major infection was associated with smaller AD signature region (-1.28 cm3 , 95% CI=-2.21 to -0.35) and larger ventricular volume (3.79 cm3 , 95% CI= 0.81-6.77). CONCLUSIONS: Whereas all-cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.

Microscopy in Infectious Disease Research-Imaging Across Scales.

A comprehensive understanding of host-pathogen interactions requires quantitative assessment of molecular events across a wide range of spatiotemporal scales and organizational complexities. Due to recent technical developments, this is currently only achievable with microscopy. This article is providing a general perspective on the importance of microscopy in infectious disease research, with a focus on new imaging modalities that promise to have a major impact in biomedical research in the years to come. Every major technological breakthrough in light microscopy depends on, and is supported by, advancements in computing and information technologies. Bioimage acquisition and analysis based on machine learning will pave the way toward more robust, automated and objective implementation of new imaging modalities and in biomedical research in general. The combination of novel imaging technologies with machine learning and near-physiological model systems promises to accelerate discoveries and breakthroughs in our understanding of infectious diseases, from basic research all the way to clinical applications.