Per-patient Basis Research Articles

Synthetic electronic health records generated with variational graph autoencoders

Data-driven medical care delivery must always respect patient privacy—a requirement that is not easily met. This issue has impeded improvements to healthcare software and has delayed the long-predicted prevalence of artificial intelligence in healthcare. Until now, it has been very difficult to share data between healthcare organizations, resulting in poor statistical models due to unrepresentative patient cohorts. Synthetic data, i.e., artificial but realistic electronic health records, could overcome the drought that is troubling the healthcare sector. Deep neural network architectures, in particular, have shown an incredible ability to learn from complex data sets and generate large amounts of unseen data points with the same statistical properties as the training data. Here, we present a generative neural network model that can create synthetic health records with realistic timelines. These clinical trajectories are generated on a per-patient basis and are represented as linear-sequence graphs of clinical events over time. We use a variational graph autoencoder (VGAE) to generate synthetic samples from real-world electronic health records. Our approach generates health records not seen in the training data. We show that these artificial patient trajectories are realistic and preserve patient privacy and can therefore support the safe sharing of data across organizations.

Diagnostic accuracy of pelvis multiparametric MRI against CT virtual hysterosalpingography: a prospective study of tubal patency through female infertility assessment.

To evaluate the diagnostic accuracy of MRI-hysterosalpingogram (HSG) with semiquantitative dynamic contrast-enhanced perfusion, against the virtual multislice CT hysterosalpingogram (VHSG) as a reference standard. In this prospective study, 26 women (age >18 years) searching for infertility causes and with VHSG physician request. Thereafter, the assessment performance of both techniques was determined by two reader analyses. k statistics were used for the assessment of tubal patency. Receiver operating characteristic (ROC) analysis was used to compare the capability for tubal patency assessment between both exams on a per-patient and per-tube basis. The McNemar test was used to compare the diagnostic accuracy measures. Tubal patency, uterine morphological, ovarian, and extrauterine abnormalities were evaluated through both exams in all 26 women. There was no significant difference between diagnostic performance measurements between the methods. The ROC curve of VHSG was 0.852 for both per-patient and per-tube analyses, and one and 0.938 for MRI-HSG. Sensitivity and specificity for per-patient and per-tube for VHSG were 95.2 and 97.7, 80 and 87.5%, and for MRI-HSG 100% for both analyses and 100 and 87.5%, respectively. This study demonstrates the feasibility of diagnosing tubal patency through MRI, using a semi-quantitative dynamic contrast-enhanced perfusion sequence, and the satisfactory diagnosing of the uterine morphology, ovarian abnormalities, and ovarian and deep endometriosis. Multiparametric MRI with a perfusion real-time sequence as a HSG method can be used in the evaluation not only for uterine and ovarian abnormilities but also tubal patency.

Evaluation of Surgeon-Performed Ultrasonography With or Without Contrast Enhancement vs Scintigraphy in Patients With Primary Hyperparathyroidism

Scintigraphy and ultrasonography are common imaging modalities for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism. When comparing the 2 modalities, the benefits of ultrasonography in terms of convenience, patient comfort, duration, cost, and lack of radiation should be taken into account. To investigate whether surgeon-performed ultrasonography, with or without contrast-enhanced ultrasonography (CEUS), is noninferior to scintigraphy for localizing pathological parathyroid glands in patients with primary hyperparathyroidism. Prospective, paired, noninferiority cohort study performed at a high-volume tertiary referral center for parathyroidectomy with blinded examiners and a 6-month follow-up. Participants were adults (age ≥18 years) referred for parathyroidectomy due to primary hyperparathyroidism. Of 207 eligible patients, 35 were excluded, leaving 172 enrolled in the study. Inclusion lasted from September 2019 until February 2021. Follow-up ended in December 2021. 99mTechnetium-pertechnetate/99mtechnetium-sestamibi subtraction scintigraphy with 99mtechnetium-sestamibi single-photon emission computed tomography/computed tomography, followed by surgeon-performed ultrasonography and CEUS. The sensitivity of each imaging modality in localizing pathological parathyroid glands, calculated on a per-quadrant and a per-patient basis, respectively. The a priori noninferiority margin was a lower 95% confidence limit for the difference in sensitivity not falling below -10%. Out of 172 participants, 139 (80.8%) were women, the median (range) age was 65 (24-87) years, and the median (IQR) follow-up was 200.5 (181-280.25) days. Quadrant sensitivity (95% CI) was 70.9% (63.2%-78.5%) for ultrasonography, 68.4% (60.4%-76.5%) for ultrasonography plus CEUS, and 67.0% (60.0%-74.0%) for scintigraphy. The sensitivity difference (95% CI) compared with scintigraphy was 3.9% (-4.1% to 11.8%) for ultrasonography and 1.5% (-6.4% to 9.3%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Per-patient sensitivity was 81.4% (74.8%-86.9%) for ultrasonography and 79.1% (72.2%-84.9%) for both scintigraphy and ultrasonography plus CEUS. The sensitivity difference compared with scintigraphy was 2.3% (-6.8% to 11.4%) for ultrasonography and 0.0% (-9.1% to 9.1%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. In this cohort study, conventional ultrasonography by an experienced parathyroid surgeon-sonographer was noninferior to scintigraphy and may constitute a valid first-line imaging modality in patients with primary hyperparathyroidism, even without the addition of CEUS. Further imaging should be reserved for cases that are equivocal or nonlocalizing on ultrasonography.

Cerebral hemodynamics in symptomatic anterior circulation intracranial stenosis measured by angiography-based quantitative flow ratio: association with CT perfusion.

Cerebral hemodynamics is important for the management of intracranial atherosclerotic stenosis (ICAS). This study aimed to determine the utility of angiography-based quantitative flow ratio (QFR) to reflect cerebral hemodynamics in symptomatic anterior circulation ICAS by evaluating its association with CT perfusion (CTP). Sixty-two patients with unilateral symptomatic stenosis in the intracranial internal carotid artery or middle cerebral artery who received percutaneous transluminal angioplasty (PTA) or PTA with stenting were included. Murray law-based QFR (μQFR) was computed from a single angiographic view. CTP parameters including cerebral blood flow, cerebral blood volume, mean transit time (MTT), and time to peak (TTP) were calculated, and relative values were obtained as the ratio between symptomatic and contralateral hemispheres. Relationships between μQFR and perfusion parameters, and between μQFR and perfusion response after intervention, were analyzed. Thirty-eight patients had improved perfusion after treatment. μQFR was significantly correlated with relative values of TTP and MTT, with correlation coefficients of -0.45 and -0.26, respectively, on a per-patient basis, and -0.72 and -0.43, respectively, on a per-vessel basis (all p < 0.05). Sensitivity and specificity for μQFR to diagnose hypoperfusion at a cut-off value of 0.82 were 94.1% and 92.1%, respectively. Multivariate analysis revealed that μQFRpost (adjusted odds ratio [OR], 1.48; p = 0.002), collateral score (adjusted OR, 6.97; p = 0.01), and current smoking status (adjusted OR, 0.03; p = 0.01) were independently associated with perfusion improvement after treatment. μQFR was associated with CTP in patients with symptomatic anterior circulation ICAS and may be a potential marker for real-time hemodynamic evaluation during interventional procedures. • Murray law-based QFR (μQFR) is associated with CT perfusion parameters in intracranial atherosclerotic stenosis and can differentiate hypoperfusion from normal perfusion. • Post-intervention μQFR, collateral score, and current smoking status are independent factors associated with improved perfusion after treatment.

Economic Outcomes of Hexaminolevulinate Blue-Light Cystoscopy in Non-Muscle Invasive Bladder Cancer: A 5-Year, Medicare-Based Model.

Bladder cancer is the most expensive cancer to treat on a per-patient basis. Blue light cystoscopy with hexaminolevulinate (BLC) has demonstrated improved diagnostic accuracy compared with white light cystoscopy (WLC) in non-muscle invasive bladder cancer (NMIBC). With higher upfront costs, questions remain about long-term BLC cost outcomes. This study seeks to investigate the 5-year cost comparison of BLC and WLC from the Medicare payer perspective. A representative 5-year NMIBC management model was constructed and Medicare reimbursement values were overlaid. The primary outcome was mean year-over-year cumulative cost discounted to present value at a 3% annual percentage rate. The secondary outcome was the rate of clinical events. Patients in the BLC cohort experienced fewer recurrences. On a cumulative present value cost basis, BLC was more expensive per patient in years 1, 2, and 3 than WLC, however, in years 4 and 5, BLC was economically favorable. Year 5 BLC mean cumulative cost savings was $1,172 per patient. Overall, 31.6% of all patients in the BLC group generated cumulative cost savings compared to WLC at year 1 compared with 50.9% at the end of year 5. Despite a higher initial annual cost, a slight cumulative economic advantage of BLC is realized after surveillance year 3. Additionally, a greater proportion of patients who received BLC achieved cost savings at the end of year 5. As novel technology emerges, economic models can help health care systems predict associated costs and quality improvements.

Functional Assessment of Coronary Artery Stenosis from Coronary Angiography and Computed Tomography: Angio-FFR vs. CT-FFR.

This study was designed to compare the diagnostic performance of angio-FFR and CT-FFR for detecting hemodynamically significant coronary stenosis. Angio-FFR and CT-FFR were measured in 110 patients (139 vessels) with stable coronary disease using invasive FFR as the reference standard. On per-patient basis, angio-FFR was highly correlated with FFR (r =0.78, p <0.001), while the correlation was moderate between CT-FFR and FFR (r =0.68, p <0.001). Diagnostic accuracy, sensitivity, and specificity for angio-FFR were 94.6%, 91.4%, and 96.0%, respectively; and those of CT-FFR were 91.8%, 91.4%, and 92%, respectively. Bland-Altman analysis showed that angio-FFR had a larger average difference and a smaller root mean squared deviation than CT-FFR compared with FFR (-0.014±0.056 vs. 0.0003±0.072). Angio-FFR had a slightly higher AUC than that of CT-FFR (0.946 vs. 0.935, p =0.750). Angio-FFR and CT-FFR computed from coronary images could be accurate and efficient computational tools for detecting lesion-specific ischemia of coronary artery stenosis. Angio-FFR and CT-FFR calculated based on the two types of images can both accurately diagnose functional ischemia of coronary stenosis. CT-FFR can act as a gatekeeper to the catheter room, assisting doctors in determining whether patients need to be screened by coronary angiography. Angio-FFR can be used in the catheter room to determine the functional significant stenosis for helping decision-making in revascularization.

Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project

Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium and migrate into the vascular wall, promoting monocyte recruitment and influencing plaque phenotype and stability at all stages of its evolution. We aimed to evaluate, by flow cytometry, if blood neutrophil number and phenotype-including their phenotypic relationships with platelets, monocytes and lymphocytes-have an association with lipid-rich necrotic core volume (LRNCV), a generic index of coronary plaque vulnerability, in a group of stable patients with chronic coronary syndrome (CCS). In 55 patients, (68.53 ± 1.07 years of age, mean ± SEM; 71% male), the total LRNCV in each subject was assessed by a quantitative analysis of all coronary plaques detected by computed tomography coronary angiography (CTCA) and was normalized to the total plaque volume. The expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, CXCR4 and CD41a cell surface markers was quantified by flow cytometry. Adhesion molecules, cytokines and chemokines, as well as MMP9 plasma levels, were measured by ELISA. On a per-patient basis, LRNCV values were positively associated, by a multiple regression analysis, with the neutrophil count (n°/µL) (p = 0.02), neutrophil/lymphocyte ratio (p = 0.007), neutrophil/platelet ratio (p = 0.01), neutrophil RFI CD11b expression (p = 0.02) and neutrophil-platelet adhesion index (p = 0.01). Significantly positive multiple regression associations of LRNCV values with phenotypic ratios between neutrophil RFI CD11b expression and several lymphocyte and monocyte surface markers were also observed. In the bivariate correlation analysis, a significantly positive association was found between RFI values of neutrophil-CD41a+ complexes and neutrophil RFI CD11b expression (p < 0.0001). These preliminary findings suggest that a sustained increase in circulating neutrophils, together with the up-regulation of the integrin/activation membrane neutrophil marker CD11b may contribute, through the progressive intra-plaque accumulation of necrotic/apoptotic cells exceeding the efferocytosis/anti-inflammatory capacity of infiltrating macrophages and lymphocytes, to the relative enlargement of the lipid-rich necrotic core volume of coronary plaques in stable CAD patients, thus increasing their individual risk of acute complication.

A clinical strategy to improve the diagnostic performance of 3T non-contrast coronary MRA and noninvasively evaluate coronary distensibility: combination of diastole and systole imaging

BackgroundThe clinical application of coronary MR angiography (MRA) combining diastole and systole imaging has never been described comprehensively in coronary artery disease (CAD) patients. We aimed to design an optimal non-contrast coronary MRA scan protocol combining diastolic and systolic imaging and to (1) evaluate its diagnostic performance for detecting significant coronary stenosis; (2) evaluate the feasibility of this protocol to noninvasively measure the coronary distensibility index (CDI). MethodsFrom June 2021 to May 2022, 33 healthy volunteers and 91 suspected CAD patients scheduled for X-ray coronary angiography (CAG) were prospectively enrolled. 3T non-contrast water-fat coronary MRA was carried out twice at diastole and systole. Significant coronary stenosis was defined as a luminal diameter reduction of ≥ 50% using CAG as the reference and was evaluated as follows: (1) by coronary MRA in diastole alone; (2) by coronary MRA in systole alone; (3) by combined coronary MRA in diastole and systole. According to CAG, the patients were divided into significant CAD patients and non-significant CAD patients. The difference in CDI among participants was evaluated. ResultsCombined coronary MRA was completed in 31 volunteers and 76 patients. The per-patient sensitivity, specificity, and accuracy of combined coronary MRA were 97.5%, 83.3%, and 90.8%, respectively. Compared with single diastolic mode, combined coronary MRA showed equally high sensitivity but improved specificity on a per-patient basis (83.3% vs. 63.9%, adjusted P = 0.013). The CDI tested by coronary MRA decreased incrementally from healthy volunteers to non-significant and significant CAD patients. ConclusionCompared with single-phase mode, 3 T non-contrast combined coronary MRA significantly improved specificity and may have potential to be a simple noninvasive method to measure CDI.

A comparison of ICG-NIR with blue dye and technetium for the detection of sentinel lymph nodes in vulvar cancer.

The sentinel lymph node (SLN) procedure for vulva cancer is a safe alternative to a radical inguino-femoral lymphadenectomy (IFLN) for small unifocal tumours. SLN evaluation through biopsy and ultra-staging has helped gynaecological oncology surgeons improve operative morbidity with no cost to oncologic safety. Established techniques for groin SLN detection and excision in vulvar cancer use 99mTc-nanocolloid radiotracer and blue dye (BD) for identification of the SLN. Indocyanine green (ICG)-near infrared (ICG-NIR) techniques for SLN mapping have proven utility in other gynaecological cancer sites and is gaining interest as a technique for SLN mapping in vulvar cancer METHODS: Fifty consecutive patients with unifocal vulvar squamous cell cancers of <40mm lateral diameter and with depth of invasion > 1mm underwent SLN mapping and excision using a combination of 99mTc-nanocolloid, BD and ICG. SLN detection results were recorded on a per-patient and per-groin basis. The success rates SLN for detection by individual tracer substance or combinations of tracer were determined by presence of one or more tracer, detectable in the SLN specimen. 92% of patients had a successful SLN procedure. The per-groin detection rate was 84%. All successfully mapped SLN were identified with the combination of ICG-NIR and 99mTc-nanocolloid compared to 69% with BD 99mTc-nanocolloid. Success rates for the SLN procedure were not dependent on prior excision of the primary lesion or operator experience. Incorporation of ICG-NIR into standard SLN mapping protocols may allow for the abandonment of routine use of BD and its poor side effect profile.

Mycobacterial cavity on chest computed tomography: clinical implications and deep learning-based automatic detection with quantification.

This study aimed (I) to investigate the clinical implication of computed tomography (CT) cavity volume in tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD), and (II) to develop a three-dimensional (3D) nnU-Net model to automatically detect and quantify cavity volume on CT images. We retrospectively included conveniently sampled 206 TB and 186 NTM-PD patients in a tertiary referral hospital, who underwent thin-section chest CT scans from 2012 through 2019. TB was microbiologically confirmed, and NTM-PD was diagnosed by 2007 Infectious Diseases Society of America/American Thoracic Society guideline. The reference cavities were semi-automatically segmented on CT images and a 3D nnU-Net model was built with 298 cases (240 cases for training, 20 for tuning, and 38 for internal validation). Receiver operating characteristic curves were used to evaluate the accuracy of the CT cavity volume for two clinically relevant parameters: sputum smear positivity in TB and treatment in NTM-PD. The sensitivity and false-positive rate were calculated to assess the cavity detection of nnU-Net using radiologist-detected cavities as references, and the intraclass correlation coefficient (ICC) between the reference and the U-Net-derived cavity volumes was analyzed. The mean CT cavity volumes in TB and NTM-PD patients were 11.3 and 16.4 cm3, respectively, and were significantly greater in smear-positive TB (P<0.001) and NTM-PD necessitating treatment (P=0.020). The CT cavity volume provided areas under the curve of 0.701 [95% confidence interval (CI): 0.620-0.782] for TB sputum positivity and 0.834 (95% CI: 0.773-0.894) for necessity of NTM-PD treatment. The nnU-Net provided per-patient sensitivity of 100% (19/19) and per-lesion sensitivity of 83.7% (41/49) in the validation dataset, with an average of 0.47 false-positive small cavities per patient (median volume, 0.26 cm3). The mean Dice similarity coefficient between the manually segmented cavities and the U-Net-derived cavities was 78.9. The ICCs between the reference and U-Net-derived volumes were 0.991 (95% CI: 0.983-0.995) and 0.933 (95% CI: 0.897-0.957) on a per-patient and per-lesion basis, respectively. CT cavity volume was associated with sputum positivity in TB and necessity of treatment in NTM-PD. The 3D nnU-Net model could automatically detect and quantify mycobacterial cavities on chest CT, helping assess TB infectivity and initiate NTM-TB treatment.

Diagnostic performance of mammography and ultrasound in breast cancer: a systematic review and meta-analysis.

The purpose of this study was to assess the diagnostic performance of mammography (MMG) and ultrasound (US) imaging for detecting breast cancer. Comprehensive searches of PubMed, Scopus and EMBASE from 2008 to 2021 were performed. A summary receiver operating characteristic curve (SROC) was constructed to summarize the overall test performance of MMG and US. Histopathologic analysis and/or close clinical and imaging follow-up for at least 6months were used as golden reference. Analysis of the studies revealed that the overall validity estimates of MMG and US in detecting breast cancer were as follows: pooled sensitivity per-patient were 0.82 (95% CI 0.76-0.87) and 0.83 (95% CI 0.71-0.91) respectively, The pooled specificities for detection of breast cancer using MMG, and US were 0.84 (95% CI 0.73-0.92) and 0.84 (95% CI 0.74-0.91) respectively. AUC of MMG, and US were 0.8933 and 0.8310 respectively. Pooled sensitivity and specificity per-lesion was 76% (95% CI 0.62-0.86) and 82% (95% CI 0.66-0.91) for MMG and 94% (95% CI 0.87-0.97) and 84% (95% CI 0.74-0.91) for US. The meta-analysis found that, US and MMG has similar diagnostic performance in detecting breast cancer on per-patient basis after corrected threshold effect. However, on a per-lesion basis US was found to have a better diagnostic accuracy than MMG.

Evaluation of pericoronary adipose tissue attenuation on CT.

Pericoronary adipose tissue (PCAT) is the fat deposit surrounding coronary arteries. Although PCAT is part of the larger epicardial adipose tissue (EAT) depot, it has different pathophysiological features and roles in the atherosclerosis process. While EAT evaluation has been studied for years, PCAT evaluation is a relatively new concept. PCAT, especially the mean attenuation derived from CT images may be used to evaluate the inflammatory status of coronary arteries non-invasively. The most commonly used measure, PCATMA, is the mean attenuation of adipose tissue of 3 mm thickness around the proximal right coronary artery with a length of 40 mm. PCATMA can be analyzed on a per-lesion, per-vessel or per-patient basis. Apart from PCATMA, other measures for PCAT have been studied, such as thickness, and volume. Studies have shown associations between PCATMA and anatomical and functional severity of coronary artery disease. PCATMA is associated with plaque components and high-risk plaque features, and can discriminate patients with flow obstructing stenosis and myocardial infarction. Whether PCATMA has value on an individual patient basis remains to be determined. Furthermore, CT imaging settings, such as kV levels and clinical factors such as age and sex affect PCATMA measurements, which complicate implementation in clinical practice. For PCATMA to be widely implemented, a standardized methodology is needed. This review gives an overview of reported PCAT methodologies used in current literature and the potential use cases in clinical practice.

Development and validation of a nonenhanced CT based radiomics model to detect brown adipose tissue.

Purpose: It has been reported that brown adipose tissue (BAT) has a protective effect regarding cardiovascular disease. Positron emission tomography-computed tomography (PET-CT) is the reference method for detecting active BAT; however, it is not feasible to screen for BAT due to the required radionuclides and high-cost. The purpose of this study is to develop and validate a nonenhanced CT based radiomics model to detect BAT and to explore the relationship between CT radiomics derived BAT and cardiovascular calcification. Patients and methods: 146 patients undergoing 18F-FDG PET-CT were retrospectively included from two centers for model development (n = 86) and external validation (n = 60). The data for the model development were randomly divided into a training cohort and an internal validation cohort with a 7:3 ratio, while the external validation data were divided 1:1 into a propensity score matching (PSM) cohort and a randomly sex matched cohort. Radiomics features of BAT and non-BAT depots were extracted from regions of interest (ROI) on nonenhanced CT corresponding to PET studies. Inter-class correlation coefficient (ICC) and Pearson's correlation analysis were performed to select radiomics features with high consistency. Next, least absolute shrinkage and selection operator (LASSO) with linear regression model was used to select radiomics features for model construction. Support vector machine (SVM) was used to develop the model and a radiomics score (RS) was calculated for each depot. The diagnostic performance of the radiomics model was evaluated both on a per-depot and per-patient basis by calculating the area under the receiver operating characteristic curve (AUROC). We further divided patients into BAT-RS group and non-BAT-RS group based on radiomics score and compared their cardiovascular calcification by calculating calcium volume and score. Results: A total of 22 radiomics features were selected for model construction. On a per-depot basis, the AUROCs were 0.87 (95% CI: 0.83-0.9), 0.85 (95% CI: 0.79-0.90), 0.72 (95% CI: 0.67-0.77) and 0.74 (95% CI: 0.69-0.79) for detecting BAT in the training, internal validation, external validation 1 and external validation 2 cohorts, respectively. On a per-patient basis, the radiomics model had high AUROCs of 0.91 (95% CI: 0.84-0.98), 0.77 (95% CI: 0.61-0.92) and 0.85 (95% CI: 0.72-0.98) in the training, external validation 1 and external validation 2 cohorts, respectively. When grouping based on the radiomics model, the BAT-RS group had lower odds of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) compared with the non-BAT-RS group (CAC: 2.8% vs. 20.3%, p = 0.001; TAC: 19.4% vs. 39.2%, p = 0.009). The BAT-RS group had less CAC volume (4.1 ± 4.0 mm3 vs. 147.4 ± 274.3 mm3; p = 0.001), CAC score (2.8 ± 3.0 vs. 169.1 ± 311.5; p = 0.001), TAC volume (301.4 ± 450.2 mm3 vs. 635.3 ± 1100.7 mm3; p = 0.007) and TAC score (496.2 ± 132.6 vs. 749.2 ± 1297.3; p = 0.007) than the non-BAT-RS group. Conclusion: We developed and validated a nonenhanced CT based reliable radiomics model for detecting BAT with PET-CT findings as reference standard. Radiomics signatures from nonenhanced CT can reliably detect BAT and have promising potential to be used in routine clinical settings. Importantly, our study showed that patients with BAT had less cardiovascular calcification.

Impact of nitroglycerin on machine-learning fractional flow reserve in coronary computed tomography (CT)-angiography.

Nitroglycerin administration prior to examination improves stenosis assessment of coronary computed tomography (CT) angiography (CCTA). However, whether nitroglycerin influences CT-derived fractional flow reserve (FFR, CT-FFR) evaluation remains unclear. This study aimed to investigate the effect of nitroglycerin on diagnostic performance of CT-FFR. In this single-center retrospective study, 107 consecutive patients suspected of coronary artery disease (CAD) with nitroglycerin administration prior to CCTA in 2019 were matched to 107 patients without nitroglycerin in 2016 from Fuwai Hospital. All patients underwent CCTA and invasive FFR in a month. Vessel-based and patient-based accuracy and diagnostic performance of CT-FFR were compared between the two groups, as well as image quality, coronary artery diameter and evaluability. Quantitative variables were compared by Kruskal-Wallis H test. Categorical variables and rates were compared by χ2 test or Fisher exact test. A total of 214 patients (56.1±8.9 years, 155 male) with 237 target lesion vessels were analyzed, including 120 vessels in nitroglycerin and 117 vessels in non-nitroglycerin group. Per-vessel based accuracy of CT-FFR was higher in nitroglycerin group {80.0% [95% confidence interval (CI): 71.7-86.7%] vs. 68.4% (59.1-76.7%), P=0.041}. On a per-patient basis, nitroglycerin administration improved the accuracy [83.2% (74.7-89.7%) vs. 68.2% (58.5-76.9%), P=0.01], specificity [82.7% (69.7-91.8%) vs. 61.9% (48.8-73.9%), P=0.01], positive predictive value (PPV) [83.6% (73.6-90.4%) vs. 58.6% (50.0-66.9%), P=0.004], and area under the curve (AUC) [0.83 (0.75-0.89) vs. 0.71 (0.61-0.79), P=0.03] of CT-FFR. Vessel diameters (left main arteries: 4.3 vs. 3.8 mm, P<0.001; left anterior descending arteries: 3.1 vs. 2.9 mm, P=0.001; left circumflex arteries: 2.9 vs. 2.7 mm, P=0.01; right coronary arteries: 3.7 vs. 3.4 mm, P=0.001) and number of evaluable coronary arteries (11.0 vs. 8.0, P<0.001) were larger in nitroglycerin group. Nitroglycerin administration prior to CCTA has positive effects on diagnostic performance of CT-FFR.

Evaluation of Infection in Patients with Myelodysplastic Syndromes Treated with Hypomethylating Agents: A Systematic Review

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders associated with cytopenias and risk of febrile neutropenia and infection. Hypomethylating therapy, such as azacitidine and decitabine, form the backbone of outpatient chemotherapy for many patients with MDS. Current literature reports heterogeneous and variable frequency, location, and severity of infections among patients receiving this treatment. Further, the relationship between infection and neutropenia is not well established. OBJECTIVE: To facilitate evidence-informed supportive care therapy, we evaluated the incidence and severity of infection and neutropenia among patients with MDS treated with hypomethylating therapy. We also aimed to evaluate the relationship between neutropenia and infection (CRD42022339150). POPULATION: Adult patients (age ≥ 18 years) with MDS (≥80% of the study population) treated with hypomethylating agents. OUTCOMES: Our primary outcome was febrile neutropenia, as per the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes included infection of any grade, grade 3 or 4 infections, death due to infection, microbial and clinical infection subtype, frequency of grade 3 or 4 neutropenia, duration of neutropenia, and use of antimicrobial prophylaxis. METHODS: We identified randomized controlled trials (RCT) from Medline, Embase, CENTRAL, and CINAHL from inception to April 2021. RCTs were included if they evaluated hypomethylating therapy in patients with MDS and reported at least one outcome of interest. We used Freeman-Tukey transformation to calculate the weighted summary proportion using a random effects model. RESULTS: We included 21 unique trials enrolling 1380 patients. 14 trials evaluated azacitidine (n=946 patients) and 8 trials studied decitabine (n=434 patients). The median patient age was 70, and 56% were male. 10 trials (n=729 patients) reported risk by International Prognostic Scoring System, of which 5% were low risk, 30% were intermediate-1 risk, 41% were intermediate-2 risk, and 24% were high risk. 49% of patients had grade 3 or 4 neutropenia (95% confidence interval (CI) 34%-63%, n=10 trials, n=697 patients). Febrile neutropenia was reported in 22% of patients (95% confidence interval (CI) 16% to 29%; n=16 trials, n=1124 patients). Grade 3 or 4 infection was reported in 33% of patients (95% CI 0% to 67%; n=3 trials, n=294 patients). Death due to infection occurred in 7% of patients (95% CI 4%-10%; n=9 trials, n=528 patients). Reporting of infection location was inconsistent, and uninterpretable on a per-patient basis. Microbial subtype of infection, duration of neutropenia, and antimicrobial prophylaxis use were not reported. CONCLUSION: In patients with MDS treated with hypomethylating therapy, grade 3 or 4 neutropenia, febrile neutropenia, and grade 3 or 4 infection were common, yet reported rates were heterogeneous between trials. Limited information was available to define the relationship between neutropenia and infection, as well as the use of antimicrobial prophylaxis. Trials commonly reported infection events in the absence of patient-specific risk estimates. Comprehensive reporting of febrile neutropenia, infection and use of antimicrobial prophylaxis is needed to direct evidence-informed care.

NIMG-53. DELTA RELAXOMETRY WITH CONTRAST ENHANCED MAGNETIC RESONANCE FINGERPRINTING: INITIAL APPLICATION TO DIFFERENTIATE BRAIN METASTASES AND GLIOBLASTOMA

Abstract PURPOSE The utility of post-contrast magnetic resonance fingerprinting (MRF) for brain tumor assessment has not been assessed. The aim of this work is to report differences in MRF-derived delta-relaxometry metrics between brain metastases and glioblastoma, offering a new strategy for tumor differentiation. METHODS Post- and pre-contrast MRF (T1, T2 and proton density maps) were acquired from 29 patients (14 brain metastases (Met), 15 glioblastoma (GB)) along with conventional MRI (T1w, T1w-Gd, T2w, T2w-FLAIR, and ADC). Post-contrast MRF was skull-stripped and non-linearly co-registered with pre-contrast MRF. Delta relaxometry metrics (ΔR1/ΔR2 ratio, ΔR1, ΔR2, and normalized ΔR1/ΔR2) were calculated in the native image space (1.2x1.2x3.0 mm3). Tumor regions were segmented using DeepMedic into necrotic core (NC), enhancing tumor (ET), and peritumoral edema (ED). ROI-averaged means of delta relaxometry metrics were compared using paired t-test for ET and ED regions in Met vs GB. Voxel-wise ΔR1/ΔR2 ratios (log transformed) were compared using unpaired two-tailed t-test with Bonferroni correction to quantify distribution differences in delta relaxometry between Met and GB. RESULTS Across all voxels of all patients in each group, ΔR1/ΔR2 ratios between Met and GB were different (0.272±0.61 vs 0.247±0.66 in ED, p &amp;lt; .001; 0.278±0.69 vs 0.264±0.67 in ET, p &amp;lt; .001). On a per-patient basis, the median, 75th percentile, and 90th percentile of ΔR1/ΔR2 ratios were different between ET and ED regions (p &amp;lt; .001). Within-ROI (NC, ET, and ED) averaged mean ΔR1/R2 ratios were not significantly different between Met and GB. CONCLUSION Voxel-wise distribution of ΔR1/ΔR2 ratios was different between tumor types (Met and GB) in both ET and ED regions. ROI-averaged ΔR1/ΔR2 ratios were different between ET and ED regions, but not specific for tumor type. Delta relaxometry provides a unique tumor-specific contrast and shows potential for solid tumor as well as peritumoral edema differentiation between Met and GB.

Imaging Properties and Tumor Targeting of 68Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.

Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3-4 h post injection (first six patients) and static PET scans 2 and 3-4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant 68Ga-NeoBOMB1 uptake (median SUVmax 11.8 [range 2.8-51.1] 2 h p.i. and 13.2 [range 2.5-53.8] 3-4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p &lt; 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. 68Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.

Abstract 12983: Diagnostic Performance of an Automated Blood Pressure Monitor With an Irregular Heartbeat Algorithm Designed to Detect Atrial Fibrillation

Introduction: Patients with atrial fibrillation (AF) are constantly exposed to the risk of developing stroke, and early detection to initiate appropriate treatment for AF is important to prolong their healthy life. In previous reports, automated blood pressure (BP) monitors manufactured by A&amp;D Co., Ltd. was equipped with an irregular heartbeat (IHB) algorithm specifically designed to detect AF, suggesting its usefulness for AF monitoring in hypertensive patients with a high prevalence of AF. Purpose: The aim of this study was to evaluate the diagnostic performance for AF of the A&amp;D BP monitor UM-212 with an IHB algorithm in a clinical setting. Methods: A total of 242 consecutive patients was enrolled (mean age: 67.5 years, 62.3% male). BP measurements were performed three times per one patient using UM-212 and the presence or absence of IHB detection was recorded for each measurement. The definition of IHB algorithm designed to detect AF is as follows: the number of pulse waves varying more than 15% from the mean of the pulse peak interval is greater than 20% of the total pulse wave count. A 3ch real-time ECG was recorded during all BP measurements. The interpretation by automated ECG analysis software manufactured by Fukuda Denshi Co., Ltd. and the final ECG diagnosis by two cardiologists were performed separately. Results: Of the 242 patients, 31 had AF and 66 had non-AF arrhythmia. On a per-measurement basis (726 total), IHB detection had 98.9% of sensitivity and 90.7% of specificity for diagnosing AF. Under the same condition, ECG analysis software had 90.3% of sensitivity and 96.5% of specificity for diagnosing AF. On a per-patient basis, IHB detection in all three BP measurements had 96.8% of sensitivity and 95.7% of specificity for diagnosing AF. Under the same condition, ECG analysis software had 80.6% of sensitivity and 99.1% of specificity for diagnosing AF. Conclusions: The IHB algorithm designed to detect AF built into A&amp;D BP monitors showed high sensitivity and high specificity for diagnosing AF in a clinical setting, especially its sensitivity tended to exceed that of automated ECG analysis software. Utilizing the IHB algorithm during routine BP measurements is expected to monitor AF in hypertensive patients and contribute to their health management.

Evaluation of HASTE T2 weighted image with reduced echo time for detecting focal liver lesions in patients at risk of developing hepatocellular carcinoma

PurposeTo compare the image quality and performance of half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences, using compressed sensing (HASTE-CS) and deep-learning based reconstruction (HASTE-DL) in detecting focal liver lesions (FLLs), to those of T2-weighted image using BLADE sequence (T2WI) in patients at risk of developing hepatocellular carcinoma (HCC). Materials and methodsThis retrospective study included patients at risk of developing HCC who underwent liver MRI including HASTE-DL, HASTE-CS, T2WI and DWI between January and June 2020. Three radiologists independently reviewed the image quality along with FLL detection in the three T2-based sequences and DWI. Reference lesion characterization was done using the complete set of MRI sequences according to the Liver Imaging Reporting and Data System (LI-RADS) v2018. ResultsA total of 227 patients with 88 of whom had FLLs (n = 194, mean size 11.7 ± 10.9 mm) were included. HASTE-DL yielded the highest overall image quality, followed by HASTE-CS and T2WI (3.4 ± 0.5, 3.1 ± 0.6, 2.4 ± 0.5, respectively, P < 0.001 for all). In the detection of FLLs, HASTE-DL showed significantly higher sensitivity than T2WI (51.5 % vs 43.6 %, P = 0.007) whereas HASTE-CS and T2WI bore respectively little difference (P > 0.017) on per-patient basis. For LR-4, -5, -M lesions, HASTE-DL had significantly higher figure of merit than that of T2WI (0.58 vs 0.52, P < 0.001) in per-lesion basis. ConclusionHASTE-DL demonstrated better image quality and higher performance for FLL detection than conventional T2WI in patients at risk of developing HCC.

FDG-PET/MRI for the preoperative diagnosis and staging of peritoneal carcinomatosis: a prospective multireader pilot study.

To assess the diagnostic performance of FDG-PET/MRI for the preoperative diagnosis and staging of peritoneal carcinomatosis (PC) using surgical Sugarbaker's PC index (PCI) as the reference in a multireader pilot study. Fourteen adult patients (M/F: 3/11, mean age: 57 ± 12year) with PC were prospectively included in this single-center study. Patients underwent FDG-PET/MRI prior to surgery (mean delay: 14d, range: 1-63d). Images were reviewed independently by 2 abdominal radiologists and 2 nuclear medicine physicians. The radiologists assessed contrast-enhanced abdominal MR images, while the nuclear medicine physicians assessed PET images fused with T2-weighted images. The abdomen was divided in 13 regions, scored from 0 to 3. A hybrid FDG-PET/MRI radiological PCI was created by combining the study data. Radiological PCI was compared to the surgical PCI on a per-patient and per-region basis. Inter-reader agreement was evaluated. Mean surgical PCI was 10 ± 8 (range: 0-24). Inter-reader agreement was almost perfect for all sets for radiologic PCI (Kappa: 0.81-0.98). PCI scores for all reading sets significantly correlated with the surgical PCI score (r range: 0.57-0.74, p range: < 0.001-0.003). Pooled per-patient sensitivity, specificity, and accuracy were 75%/50%/71.4% for MRI, 66.7%/50%/64.3% for FDG-PET, and 91.7%/50%/85.7% for FDG-PET/MRI, without significant difference (p value range 0.13-1). FDG-PET/MRI achieved 100% sensitivity and 100% specificity for a cutoff PCI of 20. Per-region sensitivity and accuracy were lower: 37%/61.8% for MRI, 17.8%/64.3% for FDG-PET, and 52.7%/60.4% for FDG-PET/MRI, with significantly higher sensitivity for FDG-PET/MRI. Per-region specificity was higher for FDG-PET (95%) compared to MRI (78.4%) and FDG-PET/MRI (66.5%). FDG-PET/MRI achieved an excellent diagnostic accuracy per-patient and weaker performance per-region for detection of PC. The added value of PET/MRI compared to MRI and FDG-PET remains to be determined.