Prevalence of spinal meningeal diverticula in autosomal dominant polycystic kidney disease.

BACKGROUND AND PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) patients develop cysts in the kidneys, liver, spleen, pancreas, prostate and arachnoid spaces. In addition, spinal meningeal diverticula have been reported. To determine whether spinal meningeal diverticula are associated with ADPKD, we compare their prevalence in ADPKD subjects to a control cohort without ADPKD. MATERIALS AND METHODS: ADPKD subjects and age-and gender-matched controls without ADPKD undergoing abdominal MRI from mid-thorax to the pelvis from 2003 to 2023 were retrospectively evaluated for spinal meningeal diverticula by 4 blinded observers. Prevalence of spinal meningeal diverticula in ADPKD was compared to control subjects, using t-test and correlated with clinical and laboratory data, and magnetic resonance imaging (MRI) features, including cyst volumes and cyst counts. RESULTS: Identification of spinal meningeal diverticula in ADPKD (n=285, median age, 47 [37,56]; 54% female) and control (n=285, median age, 47 [37,57]; 54% female) subjects had high inter-observer agreement (Pairwise Cohen kappa=0.74). Spinal meningeal diverticula were observed in 145 of 285 (51%) ADPKD subjects compared with 66 of 285 (23%) control subjects without ADPKD (p<0.001). Spinal meningeal diverticula in ADPKD were more prevalent in women (98 of 153 [64%]) than men (47 of 132 [36%], p<0.001). The mean number of spinal meningeal diverticula per affected ADPKD subject was 3.6 + 2.9 compared to 2.4 + 1.9 in controls with cysts (p<0.001). The median volume/interquartile range (IQR, 25%/75%) of spinal meningeal diverticula was 400 mm3 (210, 740) in ADPKD compared to 250 mm3 (180, 440) in controls (p<0.001). Mean/SD spinal meningeal diverticulum diameter was greater in the sacrum (7.3 + 4.1 mm) compared to thoracic (5.4 + 1.8 mm) and lumbar spine (5.8 + 2.0 mm), p<0.001, suggesting that that hydrostatic pressure contributed to enlargement. CONCLUSIONS: ADPKD has a high prevalence of spinal meningeal diverticula, particularly in women. ABBREVIATIONS: ADPKD = Autosomal dominant polycystic kidney disease.

A Primer for Utilizing Deep Learning and Abdominal MRI Imaging Features to Monitor Autosomal Dominant Polycystic Kidney Disease Progression.

Abdominal imaging of autosomal dominant polycystic kidney disease (ADPKD) has historically focused on detecting complications such as cyst rupture, cyst infection, obstructing renal calculi, and pyelonephritis; discriminating complex cysts from renal cell carcinoma; and identifying sources of abdominal pain. Many imaging features of ADPKD are incompletely evaluated or not deemed to be clinically significant, and because of this, treatment options are limited. However, total kidney volume (TKV) measurement has become important for assessing the risk of disease progression (i.e., Mayo Imaging Classification) and predicting tolvaptan treatment's efficacy. Deep learning for segmenting the kidneys has improved these measurements' speed, accuracy, and reproducibility. Deep learning models can also segment other organs and tissues, extracting additional biomarkers to characterize the extent to which extrarenal manifestations complicate ADPKD. In this concept paper, we demonstrate how deep learning may be applied to measure the TKV and how it can be extended to measure additional features of this disease.

Quantitative susceptibility mapping for detection of kidney stones, hemorrhage differentiation, and cyst classification in ADPKD.

BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). METHODS: Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images. Complex cysts were identified and classified into distinct subclasses based on their imaging features. Prevalence of each subclass was estimated. RESULTS: QSM visualized two renal calcifications measuring 9 and 10 mm and three pelvic phleboliths measuring 2 mm but missed 24 calcifications measuring 1 mm or less and 1 larger calcification at the edge of the field of view. A total of 121 complex T1 hyperintense/T2 hypointense renal cysts were detected. 52 (43%) Cysts appeared hyperintense on QSM consistent with hemorrhage; 60 (49%) cysts were isointense with respect to simple cysts and normal kidney parenchyma, while the remaining 9 (7%) were hypointense. The presentation of the latter two complex cyst subtypes is likely indicative of proteinaceous composition without hemorrhage. CONCLUSION: Our results indicate that QSM of ADPKD kidneys is possible and uniquely suited to detect large renal calculi without ionizing radiation and able to identify properties of complex cysts unattainable with traditional approaches.

"Problems you can live with" versus emergencies: how community members in rural Ethiopia contend with conditions requiring surgery.

BACKGROUND: 98% of people with surgical conditions living in low- and middle-income countries (LMICs) do not receive safe, timely and affordable surgical and anesthesia care. Research exploring barriers to receiving care has tended to be narrow in focus, often facility-based and ignoring the community beliefs, experiences and behaviours that will be an essential component of closing the gap in surgical care. Using qualitative methods, we captured diverse community perspectives in rural Ethiopia: exploring beliefs, perceptions, knowledge and experiences related to surgical conditions, with the overall aim of (re)constructing explanatory models. METHODS: Our study was nested within a community-based survey of surgical conditions conducted in the Butajira Health and Demographic Surveillance Site, southern Ethiopia, and a follow-up study of people accessing surgical care in two local hospitals. We carried out 24 semi-structured interviews. Participants were community members who needed but did/did not access surgical care, community-based healthcare workers and traditional bone-setters. Interviews were conducted in Amharic, audio-recorded, transcribed, and translated into English. We initially carried out thematic analysis and we recognized that emerging themes were aligned with Kleinman's explanatory models framework and decided to use this to guide the final stages of analysis. RESULTS: We found that community members primarily understood surgical conditions according to severity. We identified two categories: conditions you could live with and those which required urgent care, with the latter indicating a clear and direct path to surgical care whilst the former was associated with a longer, more complex and experimental pattern of help-seeking. Fear of surgery and poverty disrupted help-seeking, whilst community narratives based on individual experiences fed into the body of knowledge people used to inform decisions about care. CONCLUSIONS: We found explanatory models to be flexible, responsive to new evidence about what might work best in the context of limited community resources. Our findings have important implications for future research and policy, suggesting that community-level barriers have the potential to be responsive to carefully designed interventions which take account of local knowledge and beliefs.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

Axillary Lymphadenopathy After a COVID-19 Vaccine Booster Dose: Time to Resolution on Ultrasound Follow-Up and Associated Factors.

BACKGROUND. Because administration of booster doses of COVID-19 vaccines is ongoing, radiologists are continuing to encounter COVID-19 vaccine-related axillary lymphadenopathy on imaging. OBJECTIVE. The purposes of this study were to assess time to resolution of COVID-19 vaccine-related axillary lymphadenopathy identified on breast ultrasound after administration of a booster dose and to assess factors potentially associated with time to resolution. METHODS. This retrospective single-institution study included 54 patients (mean age, 57 years) with unilateral axillary lymphadenopathy ipsilateral to the site of injection of a booster dose of messenger RNA COVID-19 vaccine visualized on ultrasound (whether an initial breast imaging examination or follow-up to prior screening or diagnostic breast imaging) performed between September 1, 2021, and December 31, 2022, and who underwent follow-up ultrasound examinations until resolution of lymphadenopathy. Patient information was extracted from the EMR. Univariable and multivariable linear regression analyses were used to identify predictors of time to resolution. Time to resolution was compared with that in a previously described sample of 64 patients from the study institution that was used to evaluate time to resolution of axillary lymphadenopathy after the initial vaccination series. RESULTS. Six of the 54 patients had a history of breast cancer, and two had symptoms related to axillary lymphadenopathy (axillary pain in both patients). Among the 54 initial ultrasound examinations showing lymphadenopathy, 33 were screening examinations and 21 were diagnostic examinations. Lymphadenopathy had resolved a mean of 102 ± 56 (SD) days after administration of the booster dose and 84 ± 49 days after the initial ultrasound showing lymphadenopathy. Age, vaccine booster type (Moderna vs Pfizer-BioNTech), and history of breast cancer were not significantly associated with time to resolution in univariable or multivariable analyses (all p > .05). Time to resolution after administration of a booster dose was significantly shorter than time to resolution after administration of the first dose in the initial series (mean, 129 ± 37 days) (p = .01). CONCLUSION. Axillary lymphadenopathy after administration of a COVID-19 vaccine booster dose has a mean time to resolution of 102 days, shorter than the time to resolution after the initial vaccination series. CLINICAL IMPACT. The time to resolution after administration of a booster dose supports the current recommendation for a follow-up interval of at least 12 weeks when vaccine-related lymphadenopathy is suspected.

Pleural Effusions on MRI in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) has cystic fluid accumulations in the kidneys, liver, pancreas, arachnoid spaces as well as non-cystic fluid accumulations including pericardial effusions, dural ectasia and free fluid in the male pelvis. Here, we investigate the possible association of ADPKD with pleural effusion. ADPKD subjects (n = 268) and age-gender matched controls without ADPKD (n = 268) undergoing body magnetic resonance imaging from mid-thorax down into the pelvis were independently evaluated for pleural effusion by 3 blinded expert observers. Subjects with conditions associated with pleural effusion were excluded from both populations. Clinical and laboratory data as well as kidney, liver and spleen volume, pleural fluid volume, free pelvic fluid and polycystic kidney disease genotype were evaluated. Pleural effusions were observed in 56 of 268 (21%) ADPKD subjects compared with 21 of 268 (8%) in controls (p < 0.0001). In a subpopulation controlling for renal function by matching estimated glomerular filtration rate (eGFR), 28 of 110 (25%) ADPKD subjects had pleural effusions compared to 5 of 110 (5%) controls (p < 0.001). Pleural effusions in ADPKD subjects were more prevalent in females (37/141; 26%) than males (19/127,15%; p = 0.02) and in males were weakly correlated with the presence of free pelvic fluid (r = 0.24, p = 0.02). ADPKD subjects with pleural effusions were younger (48 ± 14 years old vs. 43 ± 14 years old) and weighed less (77 vs. 70 kg; p ≤ 0.02) than those without pleural effusions. For ADPKD subjects with pleural effusions, the mean volume of fluid layering dependently in the posterior−inferior thorax was 19 mL and was not considered to be clinically significant. Pleural effusion is associated with ADPKD, but its role in the pathogenesis of ADPKD requires further evaluation.

Associations of hiatus hernia with CT-based interstitial lung changes: the MESA Lung Study.

BACKGROUND: Hiatus hernia (HH) is prevalent in adults with pulmonary fibrosis. We hypothesised that HH would be associated with markers of lung inflammation and fibrosis among community-dwelling adults and stronger among MUC5B (rs35705950) risk allele carriers. METHODS: In the Multi-Ethnic Study of Atherosclerosis, HH was assessed from cardiac and full-lung computed tomography (CT) scans performed at Exam 1 (2000-2002, n=3342) and Exam 5 (2010-2012, n=3091), respectively. Percentage of high attenuation areas (HAAs; percentage of voxels with attenuation between -600 and -250 HU) was measured from cardiac and lung scans. Interstitial lung abnormalities (ILAs) were examined from Exam 5 scans (n=2380). Regression models were used to examine the associations of HH with HAAs, ILAs and serum matrix metalloproteinase-7 (MMP-7), and adjusted for age, sex, race/ethnicity, educational attainment, smoking, height, weight and scanner parameters for HAA analysis. RESULTS: HH detected from Exam 5 scans was associated with a mean percentage difference in HAAs of 2.23% (95% CI 0.57-3.93%) and an increase of 0.48% (95% CI 0.07-0.89%) per year, particularly in MUC5B risk allele carriers (p-value for interaction=0.02). HH was associated with ILAs among those <80 years of age (OR for ILAs 1.78, 95% CI 1.14-2.80) and higher serum MMP-7 level among smokers (p-value for smoking interaction=0.04). CONCLUSIONS: HH was associated with more HAAs over time, particularly among MUC5B risk allele carriers, and ILAs in younger adults, and may be a risk factor in the early stages of interstitial lung disease.

Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing.

There is no noninvasive method to estimate lung shunting fraction (LSF) in patients with liver tumors undergoing Yttrium-90 (Y90) therapy. We propose to predict LSF from noninvasive dynamic contrast enhanced (DCE) MRI using perfusion quantification. Two perfusion quantification methods were used to process DCE MRI in 25 liver tumor patients: Kety's tracer kinetic modeling with a delay-fitted global arterial input function (AIF) and quantitative transport mapping (QTM) based on the inversion of transport equation using spatial deconvolution without AIF. LSF was measured on SPECT following Tc-99m macroaggregated albumin (MAA) administration via hepatic arterial catheter. The patient cohort was partitioned into a low-risk group (LSF ≤ 10%) and a high-risk group (LSF > 10%). Results: In this patient cohort, LSF was positively correlated with QTM velocity |u| (r = 0.61, F = 14.0363, p = 0.0021), and no significant correlation was observed with Kety's parameters, tumor volume, patient age and gender. Between the low LSF and high LSF groups, there was a significant difference for QTM |u| (0.0760 ± 0.0440 vs. 0.1822 ± 0.1225 mm/s, p = 0.0011), and Kety's Ktrans (0.0401 ± 0.0360 vs 0.1198 ± 0.3048, p = 0.0471) and Ve (0.0900 ± 0.0307 vs. 0.1495 ± 0.0485, p = 0.0114). The area under the curve (AUC) for distinguishing between low LSF and high LSF was 0.87 for |u|, 0.80 for Ve and 0.74 for Ktrans. Noninvasive prediction of LSF is feasible from DCE MRI with QTM velocity postprocessing.

Mapping Alveolar Oxygen Partial Pressure in COPD Using Hyperpolarized Helium-3: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) 3He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP 3He MRI measuring pAO2, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm2/s) correlated with emphysema and heterogeneity in pAO2 measurements. Strong correlations were found between the heterogeneity of global pAO2 as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic pAO2 values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between pAO2 SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas pAO2 heterogeneity and the fraction of non-physiological pAO2 results increase in mild to moderate COPD. Measurements of pAO2 are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation.

Time for Resolution of COVID-19 Vaccine-Related Axillary Lymphadenopathy and Associated Factors.

BACKGROUND. The variable clinical course of subclinical lymphadenopathy detected on breast imaging after COVID-19 vaccination creates management challenges and has led to evolving practice recommendations. OBJECTIVE. The purpose of this study was to assess the duration of axillary lymphadenopathy ipsilateral to COVID-19 vaccination detected by breast imaging and to assess factors associated with the time until resolution. METHODS. This retrospective single-center study included 111 patients (mean age, 52 ± 12 years) with unilateral axillary lymphadenopathy ipsilateral to mRNA COVID-19 vaccine administration performed within the prior 8 weeks that was detected on breast ultrasound performed between January 1, 2021, and October 1, 2021, and who underwent follow-up ultrasound examinations at 4- to 12-week intervals until resolution of the lymphadenopathy. Patient information was extracted from medical records. Cortical thickness of the largest axillary lymph node on ultrasound was retrospectively measured and was considered enlarged when greater than 3 mm. Multivariable linear regression analysis was used to identify independent predictors of time until resolution. RESULTS. The mean cortical thickness at the initial ultrasound examination was 4.7 ± 1.2 mm. The lymphadenopathy resolved a mean of 97 ± 44 days after the initial ultrasound examination, 127 ± 43 days after the first vaccine dose, and 2.4 ± 0.6 follow-up ultrasound examinations. A significant independent predictor of shorter time to resolution was Pfizer-BioNTech (rather than Moderna) vaccination (ß = -18.0 [95% CI, -34.3 to -1.7]; p = .03]. Significant independent predictors of longer time to resolution were receipt of the second dose after the initial ultrasound examination (ß = 19.2 [95% CI, 3.1-35.2]; p = .02) and greater cortical thickness at the initial ultrasound examination (ß = 8.0 [95% CI, 1.5-14.5]; p = .02). Patient age, history of breast cancer, and axillary symptoms were not significantly associated with time to resolution (all p > .05). CONCLUSION. Axillary lymphadenopathy detected with breast ultrasound after COVID-19 mRNA vaccination lasts longer than reported in initial vaccine clinical trials. CLINICAL IMPACT. The prolonged time to resolution supports not delaying screening mammography because of recent COVID-19 vaccination. It also supports the professional society recommendation of a follow-up interval of at least 12 weeks when vaccine-related lymphadenopathy is suspected.

MR Angiography Series: Abdominal and Pelvic MR Angiography.

This review guides readers through the selection and setup of standardized MR angiography (MRA) protocols for the abdomen and pelvis for common clinical applications. Topics covered include renovascular MRA in potential kidney donors and in patients with hypertension; hepatic and mesenteric MRA in potential liver donors, patients with portal hypertension, and patients with chronic mesenteric ischemia; pelvic MRA for pretreatment planning before uterine fibroid embolization and in patients with pelvic congestion syndrome; and abdominal wall MRA for planning of breast reconstructive surgery. This module is the fifth in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2022.

Machine Learning Based Prediction Model for Closed-Loop Small Bowel Obstruction Using Computed Tomography and Clinical Findings.

PURPOSE: The aim of the study was to develop a prediction model for closed-loop small bowel obstruction integrating computed tomography (CT) and clinical findings. METHODS: The radiology database and surgical reports from 2 suburban teaching hospitals were retrospectively reviewed for patients undergoing surgery for suspected closed-loop small bowel obstruction (CLSBO). Two observers independently reviewed the CT scans for the presence of imaging features of CLSBO, blinded to the surgically confirmed diagnosis and clinical parameters. Random forest analysis was used to train and validate a prediction model for CLSBO, by combining CT and clinical findings, after randomly splitting the sample into 80% training and 20% test subsets. RESULTS: Surgery confirmed CLSBO in 185 of 223 patients with clinically suspected CLSBO. Age greater than 52 years showed 2.82 (95% confidence interval = 1.13-4.77) times higher risk for CLSBO (P = 0.021). Sensitivity/specificity of CT findings included proximal dilatation (97/5%), distal collapse (96/2%), mesenteric edema (94/5%), pneumatosis (1/100%), free air (1/98%), and portal venous gas (0/100%). The random forest model combining imaging/clinical findings yielded an area under receiver operating curve of 0.73 (95% confidence interval = 0.58-0.94), sensitivity of 0.72 (0.55-0.85), specificity of 0.8 (0.28-0.99), and accuracy of 0.73 (0.57-0.85). Prior surgery, age, lactate, whirl sign, U/C-shaped bowel configuration, and fecalization were the most important variables in predicting CLSBO. CONCLUSIONS: A random forest model found clinical factors including prior surgery, age, lactate, and imaging factors including whirl sign, fecalization, and U/C-shaped bowel configuration are helpful in improving the prediction of CLSBO. Individual CT findings in CLSBO had either high sensitivity or specificity, suggesting that accurate diagnosis requires systematic assessment of all CT signs.

IRIS-Intelligent Rapid Interactive Segmentation for Measuring Liver Cyst Volumes in Autosomal Dominant Polycystic Kidney Disease.

PURPOSE: To develop and integrate interactive features with automatic methods for accurate liver cyst segmentation in patients with autosomal dominant polycystic kidney and liver disease (ADPKD). METHODS: SmartClick and antiSmartClick were developed using iterative region growth guided by spatial and intensity connections and were integrated with automated level set (LS) segmentation and graphical user interface, forming an intelligent rapid interactive segmentation (IRIS) tool. IRIS and LS segmentations of liver cysts on T2 weighted images of patients with ADPKD (n = 17) were compared with manual segmentation as ground truth (GT). RESULTS: Compared to manual GT, IRIS reduced the segmentation time by more than 10-fold. Compared to automated LS, IRIS reduced the mean liver cyst volume error from 42.22% to 13.44% (p < 0.001). IRIS segmentation agreed well with manual GT (79% dice score and 99% intraclass correlation coefficient). CONCLUSION: IRIS is feasible for fast, accurate liver cyst segmentation in patients with ADPKD.

Quantitative transport mapping (QTM) for differentiating benign and malignant breast lesion: Comparison with traditional kinetics modeling and semi-quantitative enhancement curve characteristics.

PURPOSE: To test the feasibility of using quantitative transport mapping (QTM) method, which is based on the inversion of transport equation using spatial deconvolution without any arterial input function, for automatically postprocessing dynamic contrast enhanced MRI (DCE-MRI) to differentiate malignant and benign breast tumors. MATERIALS AND METHODS: Breast DCE-MRI data with biopsy confirmed malignant (n = 13) and benign tumors (n = 13) was used to assess QTM velocity (|u|) and diffusion coefficient (D), volume transfer constant (Ktrans), volume fraction of extravascular extracellular space (Ve) from kinetics method, and traditional enhancement curve characteristics (ECC: amplitude A, wash-in rate α, wash-out rate ß). A Mann-Whitney U test and receiver operating characteristic curve (ROC) analysis were performed to assess the diagnostic performance of these parameters for distinguishing between benign and malignant tumors. RESULTS: Between malignant and benign tumors, there was a significant difference in |u| and Ktrans, (p = 0.0066, 0.0274, respectively), but not in D, Ve, A, α and ß (p = 0.1119, 0.2382, 0.4418,0.2592 and 0.9591, respectively). ROC area-under-the-curve was 0.82, 0.75 (95% confidence level 0.60-0.95, 0.51-0.90) for |u| and Ktrans, respectively. CONCLUSION: QTM postprocesses DCE-MRI automatically through deconvolution in space and time to solve the inverse problem of the transport equation. Comparing with traditional kinetics method and ECC, QTM method showed better diagnostic accuracy in differentiating benign from malignant breast tumors in this study.

Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development of multiple cysts in the kidneys. It is often caused by pathogenic mutations in PKD1 and PKD2 genes that encode polycystin proteins. Although the molecular mechanisms for cystogenesis are not established, concurrent inactivating germline and somatic mutations in PKD1 and PKD2 have been previously observed in renal tubular epithelium (RTE). METHODS: To further investigate the cellular recessive mechanism of cystogenesis in RTE, we conducted whole-genome DNA sequencing analysis to identify germline variants and somatic alterations in RTE of 90 unique kidney cysts obtained during nephrectomy from 24 unrelated participants. RESULTS: Kidney cysts were overall genomically stable, with low burdens of somatic short mutations or large-scale structural alterations. Pathogenic somatic "second hit" alterations disrupting PKD1 or PKD2 were identified in 93% of the cysts. Of these, 77% of cysts acquired short mutations in PKD1 or PKD2 ; specifically, 60% resulted in protein truncations (nonsense, frameshift, or splice site) and 17% caused non-truncating mutations (missense, in-frame insertions, or deletions). Another 18% of cysts acquired somatic chromosomal loss of heterozygosity (LOH) events encompassing PKD1 or PKD2 ranging from 2.6 to 81.3 Mb. 14% of these cysts harbored copy number neutral LOH events, while the other 3% had hemizygous chromosomal deletions. LOH events frequently occurred at chromosomal fragile sites, or in regions comprising chromosome microdeletion diseases/syndromes. Almost all somatic "second hit" alterations occurred at the same germline mutated PKD1/2 gene. CONCLUSIONS: These findings further support a cellular recessive mechanism for cystogenesis in ADPKD primarily caused by inactivating germline and somatic variants of PKD1 or PKD2 genes in kidney cyst epithelium.

Mapping of population disparities in the cholangiocarcinoma urinary metabolome.

Phenotypic diversity in urinary metabolomes of different geographical populations has been recognized recently. In this study, urinary metabolic signatures from Western (United Kingdom) and South-East Asian (Thai) cholangiocarcinoma patients were characterized to understand spectral variability due to host carcinogenic processes and/or exogenous differences (nutritional, environmental and pharmaceutical). Urinary liquid chromatography mass spectroscopy (LC-MS) spectral profiles from Thai (healthy = 20 and cholangiocarcinoma = 14) and UK cohorts (healthy = 22 and cholangiocarcinoma = 10) were obtained and modelled using chemometric data analysis. Healthy metabolome disparities between the two distinct populations were primarily related to differences in dietary practices and body composition. Metabolites excreted due to drug treatment were dominant in urine specimens from cholangiocarcinoma patients, particularly in Western individuals. Urine from participants with sporadic (UK) cholangiocarcinoma contained greater levels of a nucleotide metabolite (uridine/pseudouridine). Higher relative concentrations of 7-methylguanine were observed in urine specimens from Thai cholangiocarcinoma patients. The urinary excretion of hippurate and methyladenine (gut microbial-host co-metabolites) showed a similar pattern of lower levels in patients with malignant biliary tumours from both countries. Intrinsic (body weight and body composition) and extrinsic (xenobiotic metabolism) factors were the main causes of disparities between the two populations. Regardless of the underlying aetiology, biological perturbations associated with cholangiocarcinoma urine metabolome signatures appeared to be influenced by gut microbial community metabolism. Dysregulation in nucleotide metabolism was associated with sporadic cholangiocarcinoma, possibly indicating differences in mitochondrial energy production pathways between cholangiocarcinoma tumour subtypes. Mapping population-specific metabolic disparities may aid in interpretation of disease processes and identification of candidate biomarkers.

Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study.

Background Pulmonary embolism (PE) commonly complicates SARS-CoV-2 infection, but incidence and mortality reported in single-center studies, along with risk factors, vary. Purpose To determine the incidence of PE in patients with COVID-19 and its associations with clinical and laboratory parameters. Materials and Methods In this HIPAA-compliant study, electronic medical records were searched retrospectively for demographic, clinical, and laboratory data and outcomes among patients with COVID-19 admitted at four hospitals from March through June 2020. PE found at CT pulmonary angiography and perfusion scintigraphy was correlated with clinical and laboratory parameters. The d-dimer level was used to predict PE, and the obtained threshold was externally validated among 85 hospitalized patients with COVID-19 at a fifth hospital. The association between right-sided heart strain and embolic burden was evaluated in patients with PE undergoing echocardiography. Results A total of 413 patients with COVID-19 (mean age, 60 years ± 16 [standard deviation]; age range, 20-98 years; 230 men) were evaluated. PE was diagnosed in 102 (25%; 95% CI: 21, 29) of 413 hospitalized patients with COVID-19 who underwent CT pulmonary angiography or perfusion scintigraphy. PE was observed in 21 (29%; 95% CI: 19, 41) of 73 patients in the intensive care unit (ICU) versus 81 (24%; 95% CI: 20, 29) of 340 patients who were not in the ICU (P = .37). PE was associated with male sex (odds ratio [OR], 1.74; 95% CI: 1.1, 2.8; P = .02); smoking (OR, 1.86; 95% CI: 1.0, 3.4; P = .04); and increased d-dimer (P < .001), lactate dehydrogenase (P < .001), ferritin (P = .001), and interleukin-6 (P = .02) levels. Mortality in hospitalized patients was similar between patients with PE and those without PE (14% [13 of 102]; 95% CI: 8, 22] vs 13% [40 of 311]; 95% CI: 9, 17; P = .98), suggesting that diagnosis and treatment of PE were not associated with excess mortality. The d-dimer levels greater than 1600 ng/mL [8.761 nmol/L] helped predict PE with 100% sensitivity and 62% specificity in an external validation cohort. Embolic burden was higher in patients with right-sided heart strain among the patients with PE undergoing echocardiography (P = .03). Conclusion Pulmonary embolism (PE) incidence was 25% in patients hospitalized with COVID-19 suspected of having PE. A d-dimer level greater than 1600 ng/mL [8.761 nmol/L] was sensitive for identification of patients who needed CT pulmonary angiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ketai in this issue.

Simultaneous hepatic iron and fat quantification with dual-energy CT in a rabbit model of coexisting iron and fat.

BACKGROUND: Liver iron and fat are often co-deposited, synergistically aggravating the progression of chronic liver disease. Accurate determination of liver iron and fat content is helpful for patient management. To assess the accuracy of hepatic iron/fat decomposition using dual-energy computed tomography (DECT) for simultaneously quantifying hepatic iron and fat when both are present. METHODS: Sixty-eight New Zealand rabbits on a high-fat/cholesterol diet plus iron injections were used to establish a model of coexisting hepatic iron/fat. Abdominal imaging was performed using dual-source DECT. The iron and fat fractions (Iron-CT and Fat-CT, respectively) were calculated using a 3-material decomposition algorithm. The spectroscopic liver iron concentration (LIC) grading (normal, mild, moderate, severe, and massive iron overload) and the histopathological fat fraction (Fat-ref) grading (normal, mild, moderate, severe steatosis) were used as references. Correlations between the DECT parameters and the references were analyzed. Hepatic iron/fat quantification equations were established and validated. Analysis of covariance was used to assess the influence of fat on iron measurements and vice versa. RESULTS: Iron-CT highly correlated with LIC (r=0.94, P<0.001), and Fat-CT highly correlated with Fat-ref (r=0.88, P<0.001). Both the Iron-CT- and Fat-CT-derived LIC and fat fraction showed good agreement with spectroscopy/histology. The linear relationship between Iron-CT and spectroscopic LIC was not affected by the grade of hepatic fat (F=1.93, P=0.16). The linear relationship between Fat-CT and Fat-ref was unaffected by hepatic iron grades from normal to severe (F=0.18, P=0.91). However, with massive iron overload [>15.0 mg Fe/g (270 µmol/g)] the regression began to deviate, causing fat underestimation (F=5.50, P=0.04). CONCLUSIONS: Our DECT-based iron/fat decomposition algorithm accurately measured hepatic iron and fat when both were present in a rabbit model. Hepatic fat may be underestimated when there is massive iron overload.