Seasonally adjusted laboratory reference intervals to improve the performance of machine learning models for classification of cardiovascular diseases.

BACKGROUND: Variation in laboratory healthcare data due to seasonal changes is a widely accepted phenomenon. Seasonal variation is generally not systematically accounted for in healthcare settings. This study applies a newly developed adjustment method for seasonal variation to analyze the effect seasonality has on machine learning model classification of diagnoses. METHODS: Machine learning methods were trained and tested on ~ 22 million unique records from ~ 575,000 unique patients admitted to Danish hospitals. Four machine learning models (adaBoost, decision tree, neural net, and random forest) classifying 35 diseases of the circulatory system (ICD-10 diagnosis codes, chapter IX) were run before and after seasonal adjustment of 23 laboratory reference intervals (RIs). The effect of the adjustment was benchmarked via its contribution to machine learning models trained using hyperparameter optimization and assessed quantitatively using performance metrics (AUROC and AUPRC). RESULTS: Seasonally adjusted RIs significantly improved cardiovascular disease classification in 24 of the 35 tested cases when using neural net models. Features with the highest average feature importance (via SHAP explainability) across all disease models were sex, C- reactive protein, and estimated glomerular filtration. Classification of diseases of the vessels, such as thrombotic diseases and other atherosclerotic diseases consistently improved after seasonal adjustment. CONCLUSIONS: As data volumes increase and data-driven methods are becoming more advanced, it is essential to improve data quality at the pre-processing level. This study presents a method that makes it feasible to introduce seasonally adjusted RIs into the clinical research space in any disease domain. Seasonally adjusted RIs generally improve diagnoses classification and thus, ought to be considered and adjusted for in clinical decision support methods.

Quantitative Evaluation of Dendritic Nanoparticles in Mice: Biodistribution Dynamics and Downstream Tumor Efficacy Outcomes.

A physiologically based pharmacokinetic model was developed to describe the tissue distribution kinetics of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) in plasma, liver, spleen, and tumors. Tumor growth data from MV-4-11 tumor-bearing mice were incorporated to investigate the exposure/efficacy relationship. The nanoparticle demonstrated improved antitumor activity compared to the conventional API formulation, owing to the extended released API concentrations at the site of action. Model simulations further enabled the identification of critical parameters that influence API exposure in tumors and downstream efficacy outcomes upon nanoparticle administration. The model was utilized to explore a range of dosing schedules and their effect on tumor growth kinetics, demonstrating the improved antitumor activity of nanoparticles with less frequent dosing compared to the same dose of naked APIs in conventional formulations.

Image Quality and Lesion Detection on Deep Learning Reconstruction and Iterative Reconstruction of Submillisievert Chest and Abdominal CT.

OBJECTIVE. The objective of this study was to compare image quality and clinically significant lesion detection on deep learning reconstruction (DLR) and iterative reconstruction (IR) images of submillisievert chest and abdominopelvic CT. MATERIALS AND METHODS. Our prospective multiinstitutional study included 59 adult patients (33 women, 26 men; mean age ± SD, 65 ± 12 years old; mean body mass index [weight in kilograms divided by the square of height in meters] = 27 ± 5) who underwent routine chest (n = 22; 16 women, six men) and abdominopelvic (n = 37; 17 women, 20 men) CT on a 640-MDCT scanner (Aquilion ONE, Canon Medical Systems). All patients gave written informed consent for the acquisition of low-dose (LD) CT (LDCT) after a clinically indicated standard-dose (SD) CT (SDCT). The SDCT series (120 kVp, 164-644 mA) were reconstructed with interactive reconstruction (IR) (adaptive iterative dose reduction [AIDR] 3D, Canon Medical Systems), and the LDCT (100 kVp, 120 kVp; 30-50 mA) were reconstructed with filtered back-projection (FBP), IR (AIDR 3D and forward-projected model-based iterative reconstruction solution [FIRST], Canon Medical Systems), and deep learning reconstruction (DLR) (Advanced Intelligent Clear-IQ Engine [AiCE], Canon Medical Systems). Four subspecialty-trained radiologists first read all LD image sets and then compared them side-by-side with SD AIDR 3D images in an independent, randomized, and blinded fashion. Subspecialty radiologists assessed image quality of LDCT images on a 3-point scale (1 = unacceptable, 2 = suboptimal, 3 = optimal). Descriptive statistics were obtained, and the Wilcoxon sign rank test was performed. RESULTS. Mean volume CT dose index and dose-length product for LDCT (2.1 ± 0.8 mGy, 49 ± 13mGy·cm) were lower than those for SDCT (13 ± 4.4 mGy, 567 ± 249 mGy·cm) (p < 0.0001). All 31 clinically significant abdominal lesions were seen on SD AIDR 3D and LD DLR images. Twenty-five, 18, and seven lesions were detected on LD AIDR 3D, LD FIRST, and LD FBP images, respectively. All 39 pulmonary nodules detected on SD AIDR 3D images were also noted on LD DLR images. LD DLR images were deemed acceptable for interpretation in 97% (35/37) of abdominal and 95-100% (21-22/22) of chest LDCT studies (p = 0.2-0.99). The LD FIRST, LD AIDR 3D, and LD FBP images had inferior image quality compared with SD AIDR 3D images (p < 0.0001). CONCLUSION. At submillisievert chest and abdominopelvic CT doses, DLR enables image quality and lesion detection superior to commercial IR and FBP images.

What Patients Want to Know about Imaging Examinations: A Multiinstitutional U.S. Survey in Adult and Pediatric Teaching Hospitals on Patient Preferences for Receiving Information before Radiologic Examinations.

Purpose To identify what information patients and parents or caregivers found useful before an imaging examination, from whom they preferred to receive information, and how those preferences related to patient-specific variables including demographics and prior radiologic examinations. Materials and Methods A 24-item survey was distributed at three pediatric and three adult hospitals between January and May 2015. The χ2 or Fisher exact test (categorical variables) and one-way analysis of variance or two-sample t test (continuous variables) were used for comparisons. Multivariate logistic regression was used to determine associations between responses and demographics. Results Of 1742 surveys, 1542 (89%) were returned (381 partial, 1161 completed). Mean respondent age was 46.2 years ± 16.8 (standard deviation), with respondents more frequently female (1025 of 1506, 68%) and Caucasian (1132 of 1504, 75%). Overall, 78% (1117 of 1438) reported receiving information about their examination most commonly from the ordering provider (824 of 1292, 64%), who was also the most preferred source (1005 of 1388, 72%). Scheduled magnetic resonance (MR) imaging or nuclear medicine examinations (P < .001 vs other examination types) and increasing education (P = .008) were associated with higher rates of receiving information. Half of respondents (757 of 1452, 52%) sought information themselves. The highest importance scores for pre-examination information (Likert scale ≥4) was most frequently assigned to information on examination preparation and least frequently assigned to whether an alternative radiation-free examination could be used (74% vs 54%; P < .001). Conclusion Delivery of pre-examination information for radiologic examinations is suboptimal, with half of all patients and caregivers seeking information on their own. Ordering providers are the predominant and preferred source of examination-related information, with respondents placing highest importance on information related to examination preparation. © RSNA, 2018 Online supplemental material is available for this article.

Diagnostic Yield of CT-Guided Percutaneous Transthoracic Needle Biopsy for Diagnosis of Anterior Mediastinal Masses.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic yield and accuracy of CT-guided percutaneous biopsy of anterior mediastinal masses and assess prebiopsy characteristics that may help to select patients with the highest diagnostic yield. MATERIALS AND METHODS: Retrospective review of all CT-guided percutaneous biopsies of the anterior mediastinum conducted at our institution from January 2003 through December 2012 was performed to collect data regarding patient demographics, imaging characteristics of biopsied masses, presence of complications, and subsequent surgical intervention or medical treatment (or both). Cytology, core biopsy pathology, and surgical pathology results were recorded. A per-patient analysis was performed using two-tailed t test, Fisher's exact test, and Pearson chi-square test. RESULTS: The study cohort included 52 patients (32 men, 20 women; mean age, 49 years) with mean diameter of mediastinal mass of 6.9 cm. Diagnostic yield of CT-guided percutaneous biopsy was 77% (40/52), highest for thymic neoplasms (100% [11/11]). Non-diagnostic results were seen in 12 of 52 patients (23%), primarily in patients with lymphoma (75% [9/12]). Fine-needle aspiration yielded the correct diagnosis in 31 of 52 patients (60%), and core biopsy had a diagnostic rate of 77% (36/47). None of the core biopsies were discordant with surgical pathology. There was no statistically significant difference between the diagnostic and the nondiagnostic groups in patient age, lesion size, and presence of necrosis. The complication rate was 3.8% (2/52), all small self-resolving pneumothoraces. CONCLUSION: CT-guided percutaneous biopsy is a safe diagnostic procedure with high diagnostic yield (77%) for anterior mediastinal lesions, highest for thymic neoplasms (100%), and can potentially obviate more invasive procedures.

The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program.

On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. Online supplemental material is available for this article.

Dose reduction for chest CT: comparison of two iterative reconstruction techniques.

BACKGROUND: Lowering radiation dose in computed tomography (CT) scan results in low quality noisy images. Iterative reconstruction techniques are used currently to lower image noise and improve the quality of images. PURPOSE: To evaluate lesion detection and diagnostic acceptability of chest CT images acquired at CTDIvol of 1.8 mGy and processed with two different iterative reconstruction techniques. MATERIAL AND METHODS: Twenty-two patients (mean age, 60 ± 14 years; men, 13; women, 9; body mass index, 27.4 ± 6.5 kg/m(2)) gave informed consent for acquisition of low dose (LD) series in addition to the standard dose (SD) chest CT on a 128 - multidetector CT (MDCT). LD images were reconstructed with SafeCT C4, L1, and L2 settings, and Safire S1, S2, and S3 settings. Three thoracic radiologists assessed LD image series (S1, S2, S3, C4, L1, and L2) for lesion detection and comparison of lesion margin, visibility of normal structures, and diagnostic confidence with SD chest CT. Inter-observer agreement (kappa) was calculated. RESULTS: Average CTDIvol was 6.4 ± 2.7 mGy and 1.8 ± 0.2 mGy for SD and LD series, respectively. No additional lesion was found in SD as compared to LD images. Visibility of ground-glass opacities and lesion margins, as well as normal structures visibility were not affected on LD. CT image visibility of major fissure and pericardium was not optimal in some cases (n = 5). Objective image noise in some low dose images processed with SafeCT and Safire was similar to SD images (P value > 0.5). CONCLUSION: Routine LD chest CT reconstructed with iterative reconstruction technique can provide similar diagnostic information in terms of lesion detection, margin, and diagnostic confidence as compared to SD, regardless of the iterative reconstruction settings.

Protocol for EHR laboratory data preprocessing and seasonal adjustment using R and RStudio.

Seasonality in laboratory healthcare data is associated with possible under- and overdiagnoses of patients in the clinic. Here, we present a protocol to analyze electronic health record data for seasonality patterns and adjust existing reference intervals for these changes using R software. We describe steps for preprocessing population-wide patient laboratory data into a single dataset. We then detail steps for defining strata, normalizing to median, and fitting data to selected functions. For complete details on the use and execution of this protocol, please refer to Muse et al. (2023).1.

Stratification of Kidney Transplant Recipients Into Five Subgroups Based on Temporal Disease Trajectories.

Background: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival. Methods: First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed. Results: The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found. Conclusions: This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more fine-grained, homogenous subgroups to better discover associations relevant for the individual patient and thereby enable more personalized disease-management and improve long-term outcomes and survival.

Assessing the Seasonality of Lab Tests Among Patients with Alzheimer's Disease and Related Dementias in OneFlorida Data Trust.

About 1 in 9 older adults over 65 has Alzheimer's disease (AD), many of whom also have multiple other chronic conditions such as hypertension and diabetes, necessitating careful monitoring through laboratory tests. Understanding the patterns of laboratory tests in this population aids our understanding and management of these chronic conditions along with AD. In this study, we used an unimodal cosinor model to assess the seasonality of lab tests using electronic health record (EHR) data from 34,303 AD patients from the OneFlorida+ Clinical Research Consortium. We observed significant seasonal fluctuations-higher in winter in lab tests such as glucose, neutrophils per 100 white blood cells (WBC), and WBC. Notably, certain leukocyte types like eosinophils, lymphocytes, and monocytes are elevated during summer, likely reflecting seasonal respiratory diseases and allergens. Seasonality is more pronounced in older patients and varies by gender. Our findings suggest that recognizing these patterns and adjusting reference intervals for seasonality would allow healthcare providers to enhance diagnostic precision, tailor care, and potentially improve patient outcomes.

Population-wide analysis of hospital laboratory tests to assess seasonal variation and temporal reference interval modification.

We identified mortality-, age-, and sex-associated differences in relation to reference intervals (RIs) for laboratory tests in population-wide data from nearly 2 million hospital patients in Denmark and comprising more than 300 million measurements. A low-parameter mathematical wave-based modification method was developed to adjust for dietary and environment influences during the year. The resulting mathematical fit allowed for improved association rates between re-classified abnormal laboratory tests, patient diagnoses, and mortality. The study highlights the need for seasonally modified RIs and presents an approach that has the potential to reduce over- and underdiagnosis, affecting both physician-patient interactions and electronic health record research as a whole.

Correlation of Radiomics with Treatment Response in Liver Metastases.

RATIONALE AND OBJECTIVES: To assess differences in radiomics derived from semi-automatic segmentation of liver metastases for stable disease (SD), partial response (PR), and progressive disease (PD) based on RECIST1.1 and to assess if radiomics alone at baseline can predict response. MATERIALS AND METHODS: Our IRB-approved study included 203 women (mean age 54 ± 11 years) with metastatic liver disease from breast cancer. All patients underwent contrast abdomen-pelvis CT in the portal venous phase at two points: baseline (pre-treatment) and follow-up (between 3 and 12 months following treatment). Patients were subcategorized into three subgroups based on RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors version 1.1): 66 with SD, 69 with PR, and 68 with PD on follow-up CT. The deidentified baseline and follow-up CT images were exported to the radiomics prototype. The prototype enabled semi-automatic segmentation of the target liver lesions for the extraction of first and high order radiomics. Statistical analyses with logistic regression and random forest classifiers were performed to differentiate SD from PD and PR. RESULTS: There was no significant difference between the radiomics on the baseline and follow-up CT images of patients with SD (area under the curve (AUC): 0.3). Random forest classifier differentiated patients with PR with an AUC of 0.845. The most relevant feature was the large dependence emphasis's high and low pass wavelet filter (derived gray level dependence matrix features). Random forest classifier differentiated PD with an AUC of 0.731, with the most relevant feature being the surface-to-volume ratio. There was no difference in radiomics among the three groups at baseline; therefore, a response could not be predicted. CONCLUSION: Radiomics of liver metastases with semi-automatic segmentation demonstrate differences between SD from PR and PD. SUMMARY STATEMENT: Semiautomatic segmentation and radiomics of metastatic liver disease demonstrate differences in SD from the PR and progressive metastatic on the baseline and follow-up CT. Despite substantial variations in the scanners, acquisition, and reconstruction parameters, radiomics had an AUC of 0.84-0.89 for differentiating stable hepatic metastases from decreasing and increasing metastatic disease.

Multifocal micronodular pneumocyte hyperplasia: computed tomographic appearance and follow-up in tuberous sclerosis complex.

OBJECTIVE: To characterize pulmonary nodules in patients with tuberous sclerosis complex (TSC) using computed tomography. METHODS: We retrospectively reviewed chest computed tomographic images of 73 patients with TSC (22 males and 51 females; mean ± SD age, 31.5 ± 13.2 years; range, 13.8-63.5 years). RESULTS: Multiple pulmonary nodules were identified in 42 (58%) of 73 patients (mean ± SD size, 6.6 ± 3.0 mm; range, 2-14 mm). Solid nodules were present in 11 (26%) of 42 patients, ground-glass nodules were present in 3 (7%) of 42 patients, and both solid and ground-glass nodules were present in 28 (67%) of 42 patients. The presence of multiple nodules was independent of sex and lymphangioleiomyomatosis. Follow-up images were available for 22 patients with multiple nodules (mean ± SD follow-up, 2.0 ± 1.1 years; range, 0.9-4.9 years), none of whom had change in nodule size or number. CONCLUSIONS: Most men and women with TSC have multiple pulmonary nodules, which likely represent multifocal micronodular pneumocyte hyperplasia in the absence of known predisposing factors.

Thoracic Imaging Manifestations of Treated Lymphomas: Response Evaluation, Posttherapeutic Sequelae, and Complications.

Lymphoma is the most common hematologic malignancy comprising a diverse group of neoplasms arising from multiple blood cell lineages. Any structure of the thorax may be involved at any stage of disease. Imaging has a central role in the initial staging, response assessment, and surveillance of lymphoma, and updated standardized assessment criteria are available to assist with imaging interpretation and reporting. Radiologists should be aware of the modern approaches to lymphoma treatment, the role of imaging in posttherapeutic surveillance, and manifestations of therapy-related complications.

Evaluation of an Artificial Intelligence Model for Detection of Pneumothorax and Tension Pneumothorax in Chest Radiographs.

Importance: Early detection of pneumothorax, most often via chest radiography, can help determine need for emergent clinical intervention. The ability to accurately detect and rapidly triage pneumothorax with an artificial intelligence (AI) model could assist with earlier identification and improve care. Objective: To compare the accuracy of an AI model vs consensus thoracic radiologist interpretations in detecting any pneumothorax (incorporating both nontension and tension pneumothorax) and tension pneumothorax. Design, Setting, and Participants: This diagnostic study was a retrospective standalone performance assessment using a data set of 1000 chest radiographs captured between June 1, 2015, and May 31, 2021. The radiographs were obtained from patients aged at least 18 years at 4 hospitals in the Mass General Brigham hospital network in the United States. Included radiographs were selected using 2 strategies from all chest radiography performed at the hospitals, including inpatient and outpatient. The first strategy identified consecutive radiographs with pneumothorax through a manual review of radiology reports, and the second strategy identified consecutive radiographs with tension pneumothorax using natural language processing. For both strategies, negative radiographs were selected by taking the next negative radiograph acquired from the same radiography machine as each positive radiograph. The final data set was an amalgamation of these processes. Each radiograph was interpreted independently by up to 3 radiologists to establish consensus ground-truth interpretations. Each radiograph was then interpreted by the AI model for the presence of pneumothorax and tension pneumothorax. This study was conducted between July and October 2021, with the primary analysis performed between October and November 2021. Main Outcomes and Measures: The primary end points were the areas under the receiver operating characteristic curves (AUCs) for the detection of pneumothorax and tension pneumothorax. The secondary end points were the sensitivities and specificities for the detection of pneumothorax and tension pneumothorax. Results: The final analysis included radiographs from 985 patients (mean [SD] age, 60.8 [19.0] years; 436 [44.3%] female patients), including 307 patients with nontension pneumothorax, 128 patients with tension pneumothorax, and 550 patients without pneumothorax. The AI model detected any pneumothorax with an AUC of 0.979 (95% CI, 0.970-0.987), sensitivity of 94.3% (95% CI, 92.0%-96.3%), and specificity of 92.0% (95% CI, 89.6%-94.2%) and tension pneumothorax with an AUC of 0.987 (95% CI, 0.980-0.992), sensitivity of 94.5% (95% CI, 90.6%-97.7%), and specificity of 95.3% (95% CI, 93.9%-96.6%). Conclusions and Relevance: These findings suggest that the assessed AI model accurately detected pneumothorax and tension pneumothorax in this chest radiograph data set. The model's use in the clinical workflow could lead to earlier identification and improved care for patients with pneumothorax.