Establishing Medical Intelligence - Leveraging FHIR to Improve Clinical Management: a retrospective cohort and clinical implementation study.

BACKGROUND: FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. OBJECTIVE: Here, we designed and implemented a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. METHODS: A Python package for the utilization of multimodal FHIR data (FHIRPACK) was developed and pioneered in five real-world clinical use cases, i.e., myocardial infarction (MI), stroke, diabetes, sepsis, and prostate cancer (PC). Patients were identified based on ICD-10 codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. RESULTS: For 2022, 1,302,988 patient encounters were analyzed. MI: In 72.7% of cases (N=261) medication regimens fulfilled guideline recommendations. Stroke: Out of 1,277 patients, 165 patients received thrombolysis and 108 thrombectomy. Diabetes: In 443,866 serum glucose and 16,180 HbA1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (N=13,887). Among those with dysglycemia, diagnosis was coded in 44.2% (N=6,138) of the patients. Sepsis: In 1,803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (N=773, 28.9%) and piperacillin/tazobactam was the primarily prescribed antibiotic (N=593, 37.2%). PC: Three out of 54 patients who received radical prostatectomy were identified as cases with PSA persistence or biochemical recurrence. CONCLUSIONS: Leveraging FHIR data through large-scale analytics can enhance healthcare quality and improve patient outcomes across five clinical specialties. We identified i) sepsis patients requiring less broad antibiotic therapy, ii) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, iii) stroke patients with longer than recommended times to intervention, iv) patients with hyperglycemia who could benefit from specialist referral and v) PC patients with early increases in cancer markers.

Impact of imaging biomarkers from body composition analysis on outcome of endovascularly treated acute ischemic stroke patients.

BACKGROUND: We investigate the association of imaging biomarkers extracted from fully automated body composition analysis (BCA) of computed tomography (CT) angiography images of endovascularly treated acute ischemic stroke (AIS) patients regarding angiographic and clinical outcome. METHODS: Retrospective analysis of AIS patients treated with mechanical thrombectomy (MT) at three tertiary care-centers between March 2019-January 2022. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge were noted. Multiple tissues, such as muscle, bone, and adipose tissue were acquired with a deep-learning-based, fully automated BCA from CT images of the supra-aortic angiography. RESULTS: A total of 290 stroke patients who underwent MT due to cerebral vessel occlusion in the anterior circulation were included in the study. In the univariate analyses, among all BCA markers, only the lower sarcopenia marker was associated with a poor outcome (P=0.007). It remained an independent predictor for an unfavorable outcome in a logistic regression analysis (OR 0.6, 95% CI 0.3 to 0.9, P=0.044). Fat index (total adipose tissue/bone) and myosteatosis index (inter- and intramuscular adipose tissue/total adipose tissue*100) did not affect clinical outcomes. CONCLUSION: Acute ischemic stroke patients with a lower sarcopenia marker are at risk for an unfavorable outcome. Imaging biomarkers extracted from BCA can be easily obtained from existing CT images, making it readily available at the beginning of treatment. However, further research is necessary to determine whether sarcopenia provides additional value beyond established outcome predictors. Understanding its role could lead to optimized, individualized treatment plans for post-stroke patients, potentially improving recovery outcomes.

AI-derived body composition parameters as prognostic factors in patients with HCC undergoing TACE in a multicenter study.

Background & Aims: Body composition assessment (BCA) parameters have recently been identified as relevant prognostic factors for patients with hepatocellular carcinoma (HCC). Herein, we aimed to investigate the role of BCA parameters for prognosis prediction in patients with HCC undergoing transarterial chemoembolization (TACE). Methods: This retrospective multicenter study included a total of 754 treatment-naïve patients with HCC who underwent TACE at six tertiary care centers between 2010-2020. Fully automated artificial intelligence-based quantitative 3D volumetry of abdominal cavity tissue composition was performed to assess skeletal muscle volume (SM), total adipose tissue (TAT), intra- and intermuscular adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) on pre-intervention computed tomography scans. BCA parameters were normalized to the slice number of the abdominal cavity. We assessed the influence of BCA parameters on median overall survival and performed multivariate analysis including established estimates of survival. Results: Univariate survival analysis revealed that impaired median overall survival was predicted by low SM (p <0.001), high TAT volume (p = 0.013), and high SAT volume (p = 0.006). In multivariate survival analysis, SM remained an independent prognostic factor (p = 0.039), while TAT and SAT volumes no longer showed predictive ability. This predictive role of SM was confirmed in a subgroup analysis of patients with BCLC stage B. Conclusions: SM is an independent prognostic factor for survival prediction. Thus, the integration of SM into novel scoring systems could potentially improve survival prediction and clinical decision-making. Fully automated approaches are needed to foster the implementation of this imaging biomarker into daily routine. Impact and implications: Body composition assessment parameters, especially skeletal muscle volume, have been identified as relevant prognostic factors for many diseases and treatments. In this study, skeletal muscle volume has been identified as an independent prognostic factor for patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Therefore, skeletal muscle volume as a metaparameter could play a role as an opportunistic biomarker in holistic patient assessment and be integrated into decision support systems. Workflow integration with artificial intelligence is essential for automated, quantitative body composition assessment, enabling broad availability in multidisciplinary case discussions.

SAROS: A dataset for whole-body region and organ segmentation in CT imaging.

The Sparsely Annotated Region and Organ Segmentation (SAROS) dataset was created using data from The Cancer Imaging Archive (TCIA) to provide a large open-access CT dataset with high-quality annotations of body landmarks. In-house segmentation models were employed to generate annotation proposals on randomly selected cases from TCIA. The dataset includes 13 semantic body region labels (abdominal/thoracic cavity, bones, brain, breast implant, mediastinum, muscle, parotid/submandibular/thyroid glands, pericardium, spinal cord, subcutaneous tissue) and six body part labels (left/right arm/leg, head, torso). Case selection was based on the DICOM series description, gender, and imaging protocol, resulting in 882 patients (438 female) for a total of 900 CTs. Manual review and correction of proposals were conducted in a continuous quality control cycle. Only every fifth axial slice was annotated, yielding 20150 annotated slices from 28 data collections. For the reproducibility on downstream tasks, five cross-validation folds and a test set were pre-defined. The SAROS dataset serves as an open-access resource for training and evaluating novel segmentation models, covering various scanner vendors and diseases.

Body composition impacts outcome of bronchoscopic lung volume reduction in patients with severe emphysema: a fully automated CT-based analysis.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV1%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.

Elexacaftor/tezacaftor/ivacaftor influences body composition in adults with cystic fibrosis: a fully automated CT-based analysis.

A poor nutritional status is associated with worse pulmonary function and survival in people with cystic fibrosis (pwCF). CF transmembrane conductance regulator modulators can improve pulmonary function and body weight, but more data is needed to evaluate its effects on body composition. In this retrospective study, a pre-trained deep-learning network was used to perform a fully automated body composition analysis on chest CTs from 66 adult pwCF before and after receiving elexacaftor/tezacaftor/ivacaftor (ETI) therapy. Muscle and adipose tissues were quantified and divided by bone volume to obtain body size-adjusted ratios. After receiving ETI therapy, marked increases were observed in all adipose tissue ratios among pwCF, including the total adipose tissue ratio (+ 46.21%, p < 0.001). In contrast, only small, but statistically significant increases of the muscle ratio were measured in the overall study population (+ 1.63%, p = 0.008). Study participants who were initially categorized as underweight experienced more pronounced effects on total adipose tissue ratio (p = 0.002), while gains in muscle ratio were equally distributed across BMI categories (p = 0.832). Our findings suggest that ETI therapy primarily affects adipose tissues, not muscle tissue, in adults with CF. These effects are primarily observed among pwCF who were initially underweight. Our findings may have implications for the future nutritional management of pwCF.

Early Metabolic Response by PET Predicts Sensitivity to Next-Line Targeted Therapy in EGFR-Mutated Lung Cancer with Unknown Mechanism of Acquired Resistance.

Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has established the precision oncology paradigm in lung cancer. Most patients with EGFR-mutated lung cancer respond but eventually acquire resistance. Methods: Patients exhibiting the EGFR p.T790M resistance biomarker benefit from sequenced targeted therapy with osimertinib. We hypothesized that metabolic response as detected by 18F-FDG PET after short-course osimertinib identifies additional patients susceptible to sequenced therapy. Results: Fourteen patients with EGFR-mutated lung cancer and resistance to first- or second-generation EGFR TKI testing negatively for EGFR p.T790M were enrolled in a phase II study. Five patients (36%) achieved a metabolic 18F-FDG PET response and continued osimertinib. In those, the median duration of treatment was not reached (95% CI, 24 mo to not estimable), median progression-free survival was 18.7 mo (95% CI, 14.6 mo to not estimable), and median overall survival was 41.5 mo. Conclusion: Connecting theranostic osimertinib treatment with early metabolic response assessment by PET enables early identification of patients with unknown mechanisms of TKI resistance who derive dramatic clinical benefit from sequenced osimertinib. This defines a novel paradigm for personalization of targeted therapies in patients with lung cancer dependent on a tractable driver oncogene.

Fully automated MR-based virtual biopsy of primary CNS lymphomas.

Background: Primary central nervous system lymphomas (PCNSL) pose a challenge as they may mimic gliomas on magnetic resonance imaging (MRI) imaging, compelling precise differentiation for appropriate treatment. This study focuses on developing an automated MRI-based workflow to distinguish between PCNSL and gliomas. Methods: MRI examinations of 240 therapy-naive patients (141 males and 99 females, mean age: 55.16 years) with cerebral gliomas and PCNSLs (216 gliomas and 24 PCNSLs), each comprising a non-contrast T1-weighted, fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted sequence were included in the study. HD-GLIO, a pre-trained segmentation network, was used to generate segmentations automatically. To validate the segmentation efficiency, 237 manual segmentations were prepared (213 gliomas and 24 PCNSLs). Subsequently, radiomics features were extracted following feature selection and training of an XGBoost algorithm for classification. Results: The segmentation models for gliomas and PCNSLs achieved a mean Sørensen-Dice coefficient of 0.82 and 0.80 for whole tumors, respectively. Three classification models were developed in this study to differentiate gliomas from PCNSLs. The first model differentiated PCNSLs from gliomas, with an area under the curve (AUC) of 0.99 (F1-score: 0.75). The second model discriminated between high-grade gliomas and PCNSLs with an AUC of 0.91 (F1-score: 0.6), and the third model differentiated between low-grade gliomas and PCNSLs with an AUC of 0.95 (F1-score: 0.89). Conclusions: This study serves as a pilot investigation presenting an automated virtual biopsy workflow that distinguishes PCNSLs from cerebral gliomas. Prior to clinical use, it is necessary to validate the results in a prospective multicenter setting with a larger number of PCNSL patients.

Addressing the Contrast Media Recognition Challenge: A Fully Automated Machine Learning Approach for Predicting Contrast Phases in CT Imaging.

OBJECTIVES: Accurately acquiring and assigning different contrast-enhanced phases in computed tomography (CT) is relevant for clinicians and for artificial intelligence orchestration to select the most appropriate series for analysis. However, this information is commonly extracted from the CT metadata, which is often wrong. This study aimed at developing an automatic pipeline for classifying intravenous (IV) contrast phases and additionally for identifying contrast media in the gastrointestinal tract (GIT). MATERIALS AND METHODS: This retrospective study used 1200 CT scans collected at the investigating institution between January 4, 2016 and September 12, 2022, and 240 CT scans from multiple centers from The Cancer Imaging Archive for external validation. The open-source segmentation algorithm TotalSegmentator was used to identify regions of interest (pulmonary artery, aorta, stomach, portal/splenic vein, liver, portal vein/hepatic veins, inferior vena cava, duodenum, small bowel, colon, left/right kidney, urinary bladder), and machine learning classifiers were trained with 5-fold cross-validation to classify IV contrast phases (noncontrast, pulmonary arterial, arterial, venous, and urographic) and GIT contrast enhancement. The performance of the ensembles was evaluated using the receiver operating characteristic area under the curve (AUC) and 95% confidence intervals (CIs). RESULTS: For the IV phase classification task, the following AUC scores were obtained for the internal test set: 99.59% [95% CI, 99.58-99.63] for the noncontrast phase, 99.50% [95% CI, 99.49-99.52] for the pulmonary-arterial phase, 99.13% [95% CI, 99.10-99.15] for the arterial phase, 99.8% [95% CI, 99.79-99.81] for the venous phase, and 99.7% [95% CI, 99.68-99.7] for the urographic phase. For the external dataset, a mean AUC of 97.33% [95% CI, 97.27-97.35] and 97.38% [95% CI, 97.34-97.41] was achieved for all contrast phases for the first and second annotators, respectively. Contrast media in the GIT could be identified with an AUC of 99.90% [95% CI, 99.89-99.9] in the internal dataset, whereas in the external dataset, an AUC of 99.73% [95% CI, 99.71-99.73] and 99.31% [95% CI, 99.27-99.33] was achieved with the first and second annotator, respectively. CONCLUSIONS: The integration of open-source segmentation networks and classifiers effectively classified contrast phases and identified GIT contrast enhancement using anatomical landmarks.

Radiomics Analysis of Multiparametric PET/MRI for N- and M-Staging in Patients with Primary Cervical Cancer.

PURPOSE: The aim of this study was to investigate the potential of multiparametric 18F-FDG PET/MR imaging as a platform for radiomics analysis and machine learning algorithms based on primary cervical cancers to predict N- and M-stage in patients. MATERIALS AND METHODS: A total of 30 patients with histopathological confirmation of primary and untreated cervical cancer were prospectively enrolled for a multiparametric 18F-FDG PET/MR examination, comprising a dedicated protocol for imaging of the female pelvis. The primary tumor in the uterine cervix was manually segmented on post-contrast T1-weighted images. Quantitative features were extracted from the segmented tumors using the Radiomic Image Processing Toolbox for the R software environment for statistical computing and graphics. 45 different image features were calculated from non-enhanced as well as post-contrast T1-weighted TSE images, T2-weighted TSE images, the ADC map, the parametric Ktrans, Kep, Ve and iAUC maps and PET images, respectively. Statistical analysis and modeling was performed using Python 3.5 and the scikit-learn software machine learning library for the Python programming language. RESULTS: Prediction of M-stage was superior when compared to N-stage. Prediction of M-stage using SVM with SVM-RFE as feature selection obtained the highest performance providing sensitivity of 91 % and specificity of 92 %. Using receiver operating characteristic (ROC) analysis of the pooled predictions, the area under the curve (AUC) was 0.97. Prediction of N-stage using RBF-SVM with MIFS as feature selection reached sensitivity of 83 %, specificity of 67 % and an AUC of 0.82. CONCLUSION: M- and N-stage can be predicted based on isolated radiomics analyses of the primary tumor in cervical cancers, thus serving as a template for noninvasive tumor phenotyping and patient stratification using high-dimensional feature vectors extracted from multiparametric PET/MRI data. KEY POINTS: · Radiomics analysis based on multiparametric PET/MRI enables prediction of the metastatic status of cervical cancers. · Prediction of M-stage is superior to N-stage. · Multiparametric PET/MRI displays a valuable platform for radiomics analyses .

AI-based digital histopathology for perihilar cholangiocarcinoma: A step, not a jump.

Introduction: Perihilar cholangiocarcinoma (PHCC) is a rare malignancy with limited survival prediction accuracy. Artificial intelligence (AI) and digital pathology advancements have shown promise in predicting outcomes in cancer. We aimed to improve prognosis prediction for PHCC by combining AI-based histopathological slide analysis with clinical factors. Methods: We retrospectively analyzed 317 surgically treated PHCC patients (January 2009-December 2018) at the University Hospital of Essen. Clinical data, surgical details, pathology, and outcomes were collected. Convolutional neural networks (CNN) analyzed whole-slide images. Survival models incorporated clinical and histological features. Results: Among 142 eligible patients, independent survival predictors were tumor grade (G), tumor size (T), and intraoperative transfusion requirement. The CNN-based model combining clinical and histopathological features demonstrates proof of concept in prognosis prediction, limited by histopathological complexity and feature extraction challenges. However, the CNN-based model generated heatmaps assisting pathologists in identifying areas of interest. Conclusion: AI-based digital pathology showed potential in PHCC prognosis prediction, though refinement is necessary for clinical relevance. Future research should focus on enhancing AI models and exploring novel approaches to improve PHCC patient prognosis prediction.

Falling off the screening grid-Predictors for postponed utilization of psycho-oncological support in cancer patients and its implications for distress assessment and management.

OBJECTIVE: Distress assessment of cancer patients is considered state-of-the-art. In addition to distress scores, individual care needs are an important factor for the initiation of psycho-oncological interventions. In a mono-centric, observational study, we aimed for characterization of patients indicating a subjective need but declining to utilize support services immediately to facilitate implementation of adapted screenings. METHODS: This study analyzed retrospective data from routine distress screening and associated data from hospital records. Descriptive, variance and regression analyses were used to assess characteristics of postponed support utilization in patients with mixed cancer diagnoses in different treatment settings. RESULTS: Of the total sample (N = 1863), 13% indicated a subjective need but postponed support utilization. This subgroup presented as being as burdened by symptoms of depression (p < 0.001), anxiety (p < 0.001) and distress (p < 0.001) as subjectively distressed patients with intent to directly utilize support. Time periods since diagnosis were shorter (p = 0.007) and patients were more often inpatients (p = 0.045). CONCLUSIONS: Despite high heterogeneity among the subgroups, this study identified distress-related factors and time since diagnosis as possible predictors for postponed utilization of psycho-oncological interventions. Results suggest the necessity for time-individualized support which may improve utilization by distressed patients.

Optimizing platelet transfusion through a personalized deep learning risk assessment system for demand management.

ABSTRACT: Platelet demand management (PDM) is a resource-consuming task for physicians and transfusion managers of large hospitals. Inpatient numbers and institutional standards play significant roles in PDM. However, reliance on these factors alone commonly results in platelet shortages. Using data from multiple sources, we developed, validated, tested, and implemented a patient-specific approach to support PDM that uses a deep learning-based risk score to forecast platelet transfusions for each hospitalized patient in the next 24 hours. The models were developed using retrospective electronic health record data of 34 809 patients treated between 2017 and 2022. Static and time-dependent features included demographics, diagnoses, procedures, blood counts, past transfusions, hematotoxic medications, and hospitalization duration. Using an expanding window approach, we created a training and live-prediction pipeline with a 30-day input and 24-hour forecast. Hyperparameter tuning determined the best validation area under the precision-recall curve (AUC-PR) score for long short-term memory deep learning models, which were then tested on independent data sets from the same hospital. The model tailored for hematology and oncology patients exhibited the best performance (AUC-PR, 0.84; area under the receiver operating characteristic curve [ROC-AUC], 0.98), followed by a multispecialty model covering all other patients (AUC-PR, 0.73). The model specific to cardiothoracic surgery had the lowest performance (AUC-PR, 0.42), likely because of unexpected intrasurgery bleedings. To our knowledge, this is the first deep learning-based platelet transfusion predictor enabling individualized 24-hour risk assessments at high AUC-PR. Implemented as a decision-support system, deep-learning forecasts might improve patient care by detecting platelet demand earlier and preventing critical transfusion shortages.

FHIR-PYrate: a data science friendly Python package to query FHIR servers.

BACKGROUND: We present FHIR-PYrate, a Python package to handle the full clinical data collection and extraction process. The software is to be plugged into a modern hospital domain, where electronic patient records are used to handle the entire patient's history. Most research institutes follow the same procedures to build study cohorts, but mainly in a non-standardized and repetitive way. As a result, researchers spend time writing boilerplate code, which could be used for more challenging tasks. METHODS: The package can improve and simplify existing processes in the clinical research environment. It collects all needed functionalities into a straightforward interface that can be used to query a FHIR server, download imaging studies and filter clinical documents. The full capacity of the search mechanism of the FHIR REST API is available to the user, leading to a uniform querying process for all resources, thus simplifying the customization of each use case. Additionally, valuable features like parallelization and filtering are included to make it more performant. RESULTS: As an exemplary practical application, the package can be used to analyze the prognostic significance of routine CT imaging and clinical data in breast cancer with tumor metastases in the lungs. In this example, the initial patient cohort is first collected using ICD-10 codes. For these patients, the survival information is also gathered. Some additional clinical data is retrieved, and CT scans of the thorax are downloaded. Finally, the survival analysis can be computed using a deep learning model with the CT scans, the TNM staging and positivity of relevant markers as input. This process may vary depending on the FHIR server and available clinical data, and can be customized to cover even more use cases. CONCLUSIONS: FHIR-PYrate opens up the possibility to quickly and easily retrieve FHIR data, download image data, and search medical documents for keywords within a Python package. With the demonstrated functionality, FHIR-PYrate opens an easy way to assemble research collectives automatically.

Deep learning in computational dermatopathology of melanoma: A technical systematic literature review.

Deep learning (DL) has become one of the major approaches in computational dermatopathology, evidenced by a significant increase in this topic in the current literature. We aim to provide a structured and comprehensive overview of peer-reviewed publications on DL applied to dermatopathology focused on melanoma. In comparison to well-published DL methods on non-medical images (e.g., classification on ImageNet), this field of application comprises a specific set of challenges, such as staining artifacts, large gigapixel images, and various magnification levels. Thus, we are particularly interested in the pathology-specific technical state-of-the-art. We also aim to summarize the best performances achieved thus far with respect to accuracy, along with an overview of self-reported limitations. Accordingly, we conducted a systematic literature review of peer-reviewed journal and conference articles published between 2012 and 2022 in the databases ACM Digital Library, Embase, IEEE Xplore, PubMed, and Scopus, expanded by forward and backward searches to identify 495 potentially eligible studies. After screening for relevance and quality, a total of 54 studies were included. We qualitatively summarized and analyzed these studies from technical, problem-oriented, and task-oriented perspectives. Our findings suggest that the technical aspects of DL for histopathology in melanoma can be further improved. The DL methodology was adopted later in this field, and still lacks the wider adoption of DL methods already shown to be effective for other applications. We also discuss upcoming trends toward ImageNet-based feature extraction and larger models. While DL has achieved human-competitive accuracy in routine pathological tasks, its performance on advanced tasks is still inferior to wet-lab testing (for example). Finally, we discuss the challenges impeding the translation of DL methods to clinical practice and provide insight into future research directions.

Individualized scan protocols for CT angiography: an animal study for contrast media or radiation dose optimization.

BACKGROUND: We investigated about optimization of contrast media (CM) dose or radiation dose in thoracoabdominal computed tomography angiography (CTA) by automated tube voltage selection (ATVS) system configuration and CM protocol adaption. METHODS: In six minipigs, CTA-optimized protocols were evaluated regarding objective (contrast-to-noise ratio, CNR) and subjective (6 criteria assessed by Likert scale) image quality. Scan parameters were automatically adapted by the ATVS system operating at 90-kV semi-mode and configured for standard, CM saving, or radiation dose saving (image task, quality settings). Injection protocols (dose, flow rate) were adapted manually. This approach was tested for normal and simulated obese conditions. RESULTS: Radiation exposure (volume-weighted CT dose index) for normal (obese) conditions was 2.4 ± 0.7 (5.0 ± 0.7) mGy (standard), 4.3 ± 1.1 (9.0 ± 1.3) mGy (CM reduced), and 1.7 ± 0.5 (3.5 ± 0.5) mGy (radiation reduced). The respective CM doses for normal (obese) settings were 210 (240) mgI/kg, 155 (177) mgI/kg, and 252 (288) mgI/kg. No significant differences in CNR (normal; obese) were observed between standard (17.8 ± 3.0; 19.2 ± 4.0), CM-reduced (18.2 ± 3.3; 20.5 ± 4.9), and radiation-saving CTAs (16.0 ± 3.4; 18.4 ± 4.1). Subjective analysis showed similar values for optimized and standard CTAs. Only the parameter diagnostic acceptability was significantly lower for radiation-saving CTA compared to the standard CTA. CONCLUSIONS: The CM dose (-26%) or radiation dose (-30%) for thoracoabdominal CTA can be reduced while maintaining objective and subjective image quality, demonstrating the feasibility of the personalization of CTA scan protocols. KEY POINTS: • Computed tomography angiography protocols could be adapted to individual patient requirements using an automated tube voltage selection system combined with adjusted contrast media injection. • Using an adapted automated tube voltage selection system, a contrast media dose reduction (-26%) or radiation dose reduction (-30%) could be possible.

Preoperative PET-SUVmax and volume based PET parameters of the primary tumor fail to predict nodal upstaging in early-stage lung cancer.

OBJECTIVES: Accurate nodal staging is of utmost importance in patients with lung cancer. FDG-PET/CT imaging is now part of the routine staging. Despite thorough preoperative staging nodal upstaging still occurs in early-stage lung cancer. However, the predictive value of preoperative PET metrics of the primary tumor on nodal upstaging remains to be unexplored. Our aim was to assess the association of these preoperative PET-parameters with nodal upstaging in histologically confirmed lung adenocarcinoma and squamous cell carcinoma. METHODS: From January 2016 to November 2018, 500 patients with pT1-T2/cN0 lung cancer received an anatomical resection with curative intent. 171 patients with adenocarcinoma and squamous cell carcinoma and available PET-CTs were retrospectively included. We analyzed the the association of nodal upstaging with preoperative PET-SUVmax and metabolic PET metrics including total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with different defined thresholds. RESULTS: High values of preoperative PET-SUVmax of the primary tumor were associated with squamous cell carcinoma (p < 0.0001) and with larger tumors (p < 0.0001). Increased preoperative C-reactive protein levels (<1mg/dL) correlated significantly with high preoperative PET-SUVmax values (p < 0.0001). No significant relationship between PET-SUVmax and lactate dehydrogenase activity (p = 0.6818), white blood cell count (p = 0.7681), gender (p = 0.1115) or age (p = 0.9284) was observed. Nodal upstaging rate was 14.0 % with 8.8 % N1 and 5.3 % N2 upstaging. Tumor size (p = 0.0468) and number of removed lymph nodes (p = 0.0461) were significant predictors of nodal upstaging but no significant association was found with histology or PET parameters. Of note, increased MTV - regardless of the threshold - tended to associate with nodal upstaging. CONCLUSION: Early-stage lung cancer patients with squamous histology and T2 tumors presented increased preoperative PET-SUVmax values. Nevertheless, beyond tumor size and number of removed lymph nodes neither SUVmax nor metabolic PET parameters MTV and TLG were significant predictors of nodal upstaging.

Deep learning-based assessment of body composition and liver tumour burden for survival modelling in advanced colorectal cancer.

BACKGROUND: Personalized therapy planning remains a significant challenge in advanced colorectal cancer care, despite extensive research on prognostic and predictive markers. A strong correlation of sarcopenia or overall body composition and survival has been described. Here, we explore whether automated assessment of body composition and liver metastases from standard of care CT images can add to clinical parameters in personalized survival risk prognostication. METHODS: We retrospectively analysed clinical imaging data from 85 patients (50.6% female, mean age 58.9 SD 12.2 years) with colorectal cancer and synchronous liver metastases. Pretrained deep learning models were used to assess body composition and liver metastasis geometry from abdominal CT images before the initiation of systemic treatment. Abdominal muscle-to-bone ratio (MBR) was calculated by dividing abdominal muscle volume by abdominal bone volume. MBR was compared with body mass index (BMI), abdominal muscle volume, and abdominal muscle volume divided by height squared. Differences in overall survival based on body composition and liver metastasis parameters were compared using Kaplan-Meier survival curves. Results were correlated with clinical and biomarker data to develop a machine learning model for survival risk prognostication. RESULTS: The MBR, unlike abdominal muscle volume or BMI, was significantly associated with overall survival (HR 0.39, 95% CI: 0.19-0.80, P = 0.009). The MBR (P = 0.022), liver metastasis surface area (P = 0.01) and primary tumour sidedness (P = 0.007) were independently associated with overall survival in multivariate analysis. Body composition parameters did not correlate with KRAS mutational status or primary tumour sidedness. A prediction model based on MBR, liver metastasis surface area and primary tumour sidedness achieved a concordance index of 0.69. CONCLUSIONS: Automated segmentation enables to extract prognostic parameters from routine imaging data for personalized survival modelling in advanced colorectal cancer patients.

A Systematic Comparison of Task Adaptation Techniques for Digital Histopathology.

Due to an insufficient amount of image annotation, artificial intelligence in computational histopathology usually relies on fine-tuning pre-trained neural networks. While vanilla fine-tuning has shown to be effective, research on computer vision has recently proposed improved algorithms, promising better accuracy. While initial studies have demonstrated the benefits of these algorithms for medical AI, in particular for radiology, there is no empirical evidence for improved accuracy in histopathology. Therefore, based on the ConvNeXt architecture, our study performs a systematic comparison of nine task adaptation techniques, namely, DELTA, L2-SP, MARS-PGM, Bi-Tuning, BSS, MultiTune, SpotTune, Co-Tuning, and vanilla fine-tuning, on five histopathological classification tasks using eight datasets. The results are based on external testing and statistical validation and reveal a multifaceted picture: some techniques are better suited for histopathology than others, but depending on the classification task, a significant relative improvement in accuracy was observed for five advanced task adaptation techniques over the control method, i.e., vanilla fine-tuning (e.g., Co-Tuning: P(≫) = 0.942, d = 2.623). Furthermore, we studied the classification accuracy for three of the nine methods with respect to the training set size (e.g., Co-Tuning: P(≫) = 0.951, γ = 0.748). Overall, our results show that the performance of advanced task adaptation techniques in histopathology is affected by influencing factors such as the specific classification task or the size of the training dataset.

Prediction of left lobe hypertrophy after right lobe radioembolization of the liver using a clinical data model with external validation.

In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a "curative intention" treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.