RESUMO
Autosomal dominant polycystic kidney disease (ADPKD), characterized by progressive cyst formation/expansion, results in enlarged kidneys and often end stage kidney disease. ADPKD is genetically heterogeneous; PKD1 and PKD2 are the common loci (â¼78% and â¼15% of families) and GANAB, DNAJB11, and ALG9 are minor genes. PKD is a ciliary-associated disease, a ciliopathy, and many syndromic ciliopathies have a PKD phenotype. In a multi-cohort/-site collaboration, we screened ADPKD-diagnosed families that were naive to genetic testing (n = 834) or for whom no PKD1 and PKD2 pathogenic variants had been identified (n = 381) with a PKD targeted next-generation sequencing panel (tNGS; n = 1,186) or whole-exome sequencing (WES; n = 29). We identified monoallelic IFT140 loss-of-function (LoF) variants in 12 multiplex families and 26 singletons (1.9% of naive families). IFT140 is a core component of the intraflagellar transport-complex A, responsible for retrograde ciliary trafficking and ciliary entry of membrane proteins; bi-allelic IFT140 variants cause the syndromic ciliopathy, short-rib thoracic dysplasia (SRTD9). The distinctive monoallelic phenotype is mild PKD with large cysts, limited kidney insufficiency, and few liver cysts. Analyses of the cystic kidney disease probands of Genomics England 100K showed that 2.1% had IFT140 LoF variants. Analysis of the UK Biobank cystic kidney disease group showed probands with IFT140 LoF variants as the third most common group, after PKD1 and PKD2. The proximity of IFT140 to PKD1 (â¼0.5 Mb) in 16p13.3 can cause diagnostic confusion, and PKD1 variants could modify the IFT140 phenotype. Importantly, our studies link a ciliary structural protein to the ADPKD spectrum.
Assuntos
Alelos , Proteínas de Transporte , Predisposição Genética para Doença , Mutação , Rim Policístico Autossômico Dominante/genética , Adulto , Idoso , Substituição de Aminoácidos , Bancos de Espécimes Biológicos , Cílios/patologia , Variações do Número de Cópias de DNA , Feminino , Estudos de Associação Genética , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Rim Policístico Autossômico Dominante/diagnóstico , Análise de Sequência de DNA , Reino Unido , Sequenciamento do ExomaRESUMO
RATIONALE & OBJECTIVE: Body mass index (BMI) is an independent predictor of kidney disease progression in individuals with autosomal dominant polycystic kidney disease (ADPKD). Adipocytes do not simply act as a fat reservoir but are active endocrine organs. We hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 1,053 patients enrolled in the TEMPO 3:4 tolvaptan trial with ADPKD and at high risk of rapid disease progression. PREDICTOR: Estimates of visceral adiposity extracted from coronal plane magnetic resonance imaging (MRI) scans using deep learning. OUTCOME: Annual change in total kidney volume (TKV) and effect of tolvaptan on kidney growth. ANALYTICAL APPROACH: Multinomial logistic regression and linear mixed models. RESULTS: In fully adjusted models, the highest tertile of visceral adiposity was associated with greater odds of annual change in TKV of≥7% versus<5% (odds ratio [OR], 4.78 [95% CI, 3.03-7.47]). The association was stronger in women than men (interaction P<0.01). In linear mixed models with an outcome of percent change in TKV per year, tolvaptan efficacy (% change in TKV) was reduced with higher visceral adiposity (3-way interaction of treatment ∗ time ∗ visceral adiposity, P=0.002). Visceral adiposity significantly improved classification performance of predicting rapid annual percent change in TKV for individuals with a normal BMI (DeLong's test z score: -2.03; P=0.04). Greater visceral adiposity was not associated with estimated glomerular filtration rate (eGFR) slope in the overall cohort; however, visceral adiposity was associated with more rapid decline in eGFR slope (below the median) in women (fully adjusted OR, 1.06 [95% CI, 1.01-1.11] per 10 unit increase in visceral adiposity) but not men (OR, 0.98 [95% CI, 0.95-1.02]). LIMITATIONS: Retrospective; rapid progressors; computational demand of deep learning. CONCLUSIONS: Visceral adiposity that can be quantified by MRI in the coronal plane using a deep learning segmentation model independently associates with more rapid kidney growth and improves classification of rapid progression in individuals with a normal BMI. Tolvaptan efficacy decreases with increasing visceral adiposity. PLAIN-LANGUAGE SUMMARY: We analyzed images from a previous study with the drug tolvaptan conducted in patients with autosomal dominant polycystic kidney disease (ADPKD) to measure the amount of fat tissue surrounding the kidneys (visceral fat). We had previously shown body mass index can predict kidney growth in this population; now we determined whether visceral fat was an important factor associated with kidney growth. Using a machine learning tool to automate measurement of fat in images, we observed that visceral fat was independently associated with kidney growth, that it was a better predictor of faster kidney growth in lean patients than body mass index, and that having more visceral fat made treatment of ADPKD with tolvaptan less effective.
Assuntos
Progressão da Doença , Gordura Intra-Abdominal , Rim Policístico Autossômico Dominante , Tolvaptan , Humanos , Rim Policístico Autossômico Dominante/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Tolvaptan/uso terapêutico , Tolvaptan/farmacologia , Adulto , Gordura Intra-Abdominal/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos de Coortes , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Obesidade Abdominal , Índice de Massa Corporal , Imageamento por Ressonância Magnética , AdiposidadeRESUMO
RATIONALE & OBJECTIVE: Simple kidney cysts, which are common and usually considered of limited clinical relevance, are associated with older age and lower glomerular filtration rate (GFR), but little has been known of their association with progressive chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Patients with presurgical computed tomography or magnetic resonance imaging who underwent a radical nephrectomy for a tumor; we reviewed the retained kidney images to characterize parenchymal cysts at least 5mm in diameter according to size and location. EXPOSURE: Parenchymal cysts at least 5mm in diameter in the retained kidney. Cyst characteristics were correlated with microstructural findings on kidney histology. OUTCOME: Progressive CKD defined by dialysis, kidney transplantation, a sustained≥40% decline in eGFR for at least 3 months, or an eGFR<10mL/min/1.73m2 that was at least 5mL/min/1.73m2 below the postnephrectomy baseline for at least 3 months. ANALYTICAL APPROACH: Cox models assessed the risk of progressive CKD. Models adjusted for baseline age, sex, body mass index, hypertension, diabetes, eGFR, proteinuria, and tumor volume. Nonparametric Spearman's correlations were used to examine the association of the number and size of the cysts with clinical characteristics, kidney function, and kidney volumes. RESULTS: There were 1,195 patients with 50 progressive CKD events over a median 4.4 years of follow-up evaluation. On baseline imaging, 38% had at least 1 cyst, 34% had at least 1 cortical cyst, and 8.7% had at least 1 medullary cyst. A higher number of cysts was associated with progressive CKD and was modestly correlated with larger nephrons and more nephrosclerosis on kidney histology. The number of medullary cysts was more strongly associated with progressive CKD than the number of cortical cysts. LIMITATIONS: Patients who undergo a radical nephrectomy may differ from the general population. A radical nephrectomy may accelerate the risk of progressive CKD. Genetic testing was not performed. CONCLUSIONS: Cysts in the kidney, particularly the medulla, should be further examined as a potentially useful imaging biomarker of progressive CKD beyond the current clinical evaluation of kidney function and common CKD risk factors. PLAIN-LANGUAGE SUMMARY: Kidney cysts are common and often are considered of limited clinical relevance despite being associated with lower glomerular filtration rate. We studied a large cohort of patients who had a kidney removed due to a tumor to determine whether cysts in the retained kidney were associated with kidney health in the future. We found that more cysts in the kidney and, in particular, cysts in the deepest tissue of the kidney (the medulla) were associated with progressive kidney disease, including kidney failure where dialysis or a kidney transplantation is needed. Patients with cysts in the kidney medulla may benefit from closer monitoring.
Assuntos
Progressão da Doença , Taxa de Filtração Glomerular , Doenças Renais Císticas , Nefrectomia , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/patologia , Doenças Renais Císticas/cirurgia , Doenças Renais Císticas/etiologia , Idoso , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Estudos de Coortes , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
RATIONALE & OBJECTIVE: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.8 [22.7-30.4] kg/m2; estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103±18mL/min/1.73m2; height-adjusted total kidney volume [HTKV], 731±370mL/m; Mayo classifications 1B [5%], 1C [42%], 1D [21%], and 1E [32%]) and 11 controls in normal weight category (NWC) (age, 25±3 years; 45% women; BMI, 22.5 [21.7-24.2] kg/m2; eGFR, 113±15mL/min/1.73m2; HTKV, 159±31mL/m) at the University of Colorado Anschutz Medical Campus. PREDICTORS: ADPKD status (yes/no) and severity (Mayo classifications). OUTCOME: HTKV and cyst burden by magnetic resonance imaging, kidney oxidative metabolism, and perfusion by 11C-acetate positron emission tomography/computed tomography, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]). ANALYTICAL APPROACH: For categorical variables, χ2/Fisher's exact tests, and for continuous variables t tests/Mann-Whitney U tests. Pearson correlation was used to estimate the relationships between variables. RESULTS: Compared with NWC individuals, the participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs 0.424±0.171 [mg/kg lean/min]/(µIU/mL), P=0.04), lower median cortical perfusion (1.93 [IQR, 1.80-2.09] vs 0.68 [IQR, 0.47-1.04] mL/min/g, P<0.001) and lower median total kidney oxidative metabolism (0.17 [IQR, 0.16-0.19] vs. 0.14 [IQR, 0.12-0.15] min-1, P=0.001) in voxel-wise models excluding cysts. HTKV correlated inversely with cortical perfusion (r: -0.83, P < 0.001), total kidney oxidative metabolism (r: -0.61, P<0.001) and M/I (r: -0.41, P = 0.03). LIMITATIONS: Small sample size and cross-sectional design. CONCLUSIONS: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements. FUNDING: Grants from government (National Institutes of Health, Centers for Disease Control and Prevention) and not-for-profit (JDRF) entities. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study numbers NCT04407481 and NCT04074668. PLAIN-LANGUAGE SUMMARY: In our study, we explored how a common genetic kidney condition, autosomal dominant polycystic kidney disease (ADPKD), relates to kidney metabolism. ADPKD leads to the growth of numerous cysts in the kidneys, which can impact their ability to work properly. We wanted to understand the kidneys' ability to process oxygen and blood flow in ADPKD. Our approach involved using advanced imaging techniques to observe kidney metabolism and blood flow in people with ADPKD compared with healthy individuals. We discovered that those with ADPKD had significant changes in kidney oxygen metabolism even when their kidney function was still normal. These findings are crucial as they provide deeper insights into ADPKD, potentially guiding future treatments to target these changes.
Assuntos
Taxa de Filtração Glomerular , Rim , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Feminino , Projetos Piloto , Masculino , Adulto , Estudos Transversais , Rim/patologia , Rim/diagnóstico por imagem , Rim/metabolismo , Adulto Jovem , Metabolismo Energético/fisiologia , Cistos/metabolismo , Cistos/patologia , Cistos/diagnóstico por imagemRESUMO
OBJECTIVES: Transvaginal ultrasound is typically the initial diagnostic approach in patients with postmenopausal bleeding for detecting endometrial atypical hyperplasia/cancer. Although transvaginal ultrasound demonstrates notable sensitivity, its specificity remains limited. The objective of this study was to enhance the diagnostic accuracy of transvaginal ultrasound through the integration of artificial intelligence. By using transvaginal ultrasound images, we aimed to develop an artificial intelligence based automated segmentation model and an artificial intelligence based classifier model. METHODS: Patients with postmenopausal bleeding undergoing transvaginal ultrasound and endometrial sampling at Mayo Clinic between 2016 and 2021 were retrospectively included. Manual segmentation of images was performed by four physicians (readers). Patients were classified into cohort A (atypical hyperplasia/cancer) and cohort B (benign) based on the pathologic report of endometrial sampling. A fully automated segmentation model was developed, and the performance of the model in correctly identifying the endometrium was compared with physician made segmentation using similarity metrics. To develop the classifier model, radiomic features were calculated from the manually segmented regions-of-interest. These features were used to train a wide range of machine learning based classifiers. The top performing machine learning classifier was evaluated using a threefold approach, and diagnostic accuracy was assessed through the F1 score and area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 302 patients were included. Automated segmentation-reader agreement was 0.79±0.21 using the Dice coefficient. For the classification task, 92 radiomic features related to pixel texture/shape/intensity were found to be significantly different between cohort A and B. The threefold evaluation of the top performing classifier model showed an AUC-ROC of 0.90 (range 0.88-0.92) on the validation set and 0.88 (range 0.86-0.91) on the hold-out test set. Sensitivity and specificity were 0.87 (range 0.77-0.94) and 0.86 (range 0.81-0.94), respectively. CONCLUSIONS: We trained an artificial intelligence based algorithm to differentiate endometrial atypical hyperplasia/cancer from benign conditions on transvaginal ultrasound images in a population of patients with postmenopausal bleeding.
RESUMO
SIGNIFICANCE STATEMENT: Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. BACKGROUND: Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. METHODS: We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. RESULTS: Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. CONCLUSIONS: Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations.
Assuntos
Hipertensão , Insuficiência Renal Crônica , Humanos , Feminino , Néfrons/patologia , Rim/patologia , Glomérulos Renais , Hipertensão/patologia , Taxa de Filtração GlomerularRESUMO
SIGNIFICANCE STATEMENT: Segmentation of multiple structures in cross-sectional imaging is time-consuming and impractical to perform manually, especially if the end goal is clinical implementation. In this study, we developed, validated, and demonstrated the capability of a deep learning algorithm to segment individual medullary pyramids in a rapid, accurate, and reproducible manner. The results demonstrate that cortex volume, medullary volume, number of pyramids, and mean pyramid volume is associated with patient clinical characteristics and microstructural findings and provide insights into the mechanisms that may lead to CKD. BACKGROUND: The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes. METHODS: After applying a previously validated algorithm to segment the cortex and medulla, a deep-learning algorithm was developed and validated to segment and count individual medullary pyramids on contrast-enhanced computed tomography images of living kidney donors before donation. The association of cortex volume, medullary volume, number of pyramids, and mean pyramid volume with concurrent clinical characteristics (kidney function and CKD risk factors), kidney biopsy morphology (nephron number, glomerular volume, and nephrosclerosis), and short- and long-term GFR <60 or <45 ml/min per 1.73 m 2 was assessed. RESULTS: Among 2876 living kidney donors, 1132 had short-term follow-up at a median of 3.8 months and 638 had long-term follow-up at a median of 10.0 years. Larger cortex volume was associated with younger age, male sex, larger body size, higher GFR, albuminuria, more nephrons, larger glomeruli, less nephrosclerosis, and lower risk of low GFR at follow-up. Larger pyramids were associated with older age, female sex, larger body size, higher GFR, more nephrons, larger glomerular volume, more nephrosclerosis, and higher risk of low GFR at follow-up. More pyramids were associated with younger age, male sex, greater height, no hypertension, higher GFR, lower uric acid, more nephrons, less nephrosclerosis, and a lower risk of low GFR at follow-up. CONCLUSIONS: Cortex volume and medullary pyramid volume and count reflect underlying variation in nephron number and nephron size as well as merging of pyramids because of age-related nephrosclerosis, with loss of detectable cortical columns separating pyramids.
Assuntos
Transplante de Rim , Rim , Nefroesclerose , Insuficiência Renal Crônica , Feminino , Humanos , Masculino , Biópsia , Taxa de Filtração Glomerular , Rim/patologia , Nefroesclerose/patologia , Insuficiência Renal Crônica/cirurgiaRESUMO
New image-derived biomarkers for patients affected by autosomal dominant polycystic kidney disease are needed to improve current clinical management. The measurement of total kidney volume (TKV) provides critical information for clinicians to drive care decisions. However, patients with similar TKV may present with very different phenotypes, often requiring subjective decisions based on other factors (e.g., appearance of healthy kidney parenchyma, a few cysts contributing significantly to overall TKV, etc.). In this study, we describe a new technique to individually segment cysts and quantify biometric parameters including cyst volume, cyst number, parenchyma volume, and cyst parenchyma surface area. Using data from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study the utility of these new parameters was explored, both quantitatively as well as visually. Total cyst number and cyst parenchyma surface area showed superior prediction of the slope of estimated glomerular filtration rate decline, kidney failure and chronic kidney disease stages 3A, 3B, and 4, compared to TKV. In addition, presentations such as a few large cysts contributing significantly to overall kidney volume were shown to be much better stratified in terms of outcome predictions. Thus, these new image biomarkers, which can be obtained automatically, will have great utility in future studies and clinical care for patients affected by autosomal dominant polycystic kidney disease.
Assuntos
Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Progressão da Doença , Imageamento por Ressonância Magnética/métodos , Prognóstico , Rim/diagnóstico por imagem , Biomarcadores , Taxa de Filtração GlomerularRESUMO
BACKGROUND & AIMS: Our purpose was to detect pancreatic ductal adenocarcinoma (PDAC) at the prediagnostic stage (3-36 months before clinical diagnosis) using radiomics-based machine-learning (ML) models, and to compare performance against radiologists in a case-control study. METHODS: Volumetric pancreas segmentation was performed on prediagnostic computed tomography scans (CTs) (median interval between CT and PDAC diagnosis: 398 days) of 155 patients and an age-matched cohort of 265 subjects with normal pancreas. A total of 88 first-order and gray-level radiomic features were extracted and 34 features were selected through the least absolute shrinkage and selection operator-based feature selection method. The dataset was randomly divided into training (292 CTs: 110 prediagnostic and 182 controls) and test subsets (128 CTs: 45 prediagnostic and 83 controls). Four ML classifiers, k-nearest neighbor (KNN), support vector machine (SVM), random forest (RM), and extreme gradient boosting (XGBoost), were evaluated. Specificity of model with highest accuracy was further validated on an independent internal dataset (n = 176) and the public National Institutes of Health dataset (n = 80). Two radiologists (R4 and R5) independently evaluated the pancreas on a 5-point diagnostic scale. RESULTS: Median (range) time between prediagnostic CTs of the test subset and PDAC diagnosis was 386 (97-1092) days. SVM had the highest sensitivity (mean; 95% confidence interval) (95.5; 85.5-100.0), specificity (90.3; 84.3-91.5), F1-score (89.5; 82.3-91.7), area under the curve (AUC) (0.98; 0.94-0.98), and accuracy (92.2%; 86.7-93.7) for classification of CTs into prediagnostic versus normal. All 3 other ML models, KNN, RF, and XGBoost, had comparable AUCs (0.95, 0.95, and 0.96, respectively). The high specificity of SVM was generalizable to both the independent internal (92.6%) and the National Institutes of Health dataset (96.2%). In contrast, interreader radiologist agreement was only fair (Cohen's kappa 0.3) and their mean AUC (0.66; 0.46-0.86) was lower than each of the 4 ML models (AUCs: 0.95-0.98) (P < .001). Radiologists also recorded false positive indirect findings of PDAC in control subjects (n = 83) (7% R4, 18% R5). CONCLUSIONS: Radiomics-based ML models can detect PDAC from normal pancreas when it is beyond human interrogation capability at a substantial lead time before clinical diagnosis. Prospective validation and integration of such models with complementary fluid-based biomarkers has the potential for PDAC detection at a stage when surgical cure is a possibility.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos de Casos e Controles , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Carcinoma Ductal Pancreático/diagnóstico por imagem , Aprendizado de Máquina , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: In kidney transplantation, a contrast CT scan is obtained in the donor candidate to detect subclinical pathology in the kidney. Recent work from the Aging Kidney Anatomy study has characterized kidney, cortex, and medulla volumes using a manual image-processing tool. However, this technique is time consuming and impractical for clinical care, and thus, these measurements are not obtained during donor evaluations. This study proposes a fully automated segmentation approach for measuring kidney, cortex, and medulla volumes. METHODS: A total of 1930 contrast-enhanced CT exams with reference standard manual segmentations from one institution were used to develop the algorithm. A convolutional neural network model was trained (n=1238) and validated (n=306), and then evaluated in a hold-out test set of reference standard segmentations (n=386). After the initial evaluation, the algorithm was further tested on datasets originating from two external sites (n=1226). RESULTS: The automated model was found to perform on par with manual segmentation, with errors similar to interobserver variability with manual segmentation. Compared with the reference standard, the automated approach achieved a Dice similarity metric of 0.94 (right cortex), 0.90 (right medulla), 0.94 (left cortex), and 0.90 (left medulla) in the test set. Similar performance was observed when the algorithm was applied on the two external datasets. CONCLUSIONS: A fully automated approach for measuring cortex and medullary volumes in CT images of the kidneys has been established. This method may prove useful for a wide range of clinical applications.
Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Córtex Renal/diagnóstico por imagem , Medula Renal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Meios de Contraste , Aprendizado Profundo , Seleção do Doador/métodos , Seleção do Doador/estatística & dados numéricos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Transplante de Rim , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Variações Dependentes do Observador , Tomografia Computadorizada por Raios X/estatística & dados numéricosRESUMO
The aim of this study is to investigate the use of an exponential-plateau model to determine the required training dataset size that yields the maximum medical image segmentation performance. CT and MR images of patients with renal tumors acquired between 1997 and 2017 were retrospectively collected from our nephrectomy registry. Modality-based datasets of 50, 100, 150, 200, 250, and 300 images were assembled to train models with an 80-20 training-validation split evaluated against 50 randomly held out test set images. A third experiment using the KiTS21 dataset was also used to explore the effects of different model architectures. Exponential-plateau models were used to establish the relationship of dataset size to model generalizability performance. For segmenting non-neoplastic kidney regions on CT and MR imaging, our model yielded test Dice score plateaus of [Formula: see text] and [Formula: see text] with the number of training-validation images needed to reach the plateaus of 54 and 122, respectively. For segmenting CT and MR tumor regions, we modeled a test Dice score plateau of [Formula: see text] and [Formula: see text], with 125 and 389 training-validation images needed to reach the plateaus. For the KiTS21 dataset, the best Dice score plateaus for nn-UNet 2D and 3D architectures were [Formula: see text] and [Formula: see text] with number to reach performance plateau of 177 and 440. Our research validates that differing imaging modalities, target structures, and model architectures all affect the amount of training images required to reach a performance plateau. The modeling approach we developed will help future researchers determine for their experiments when additional training-validation images will likely not further improve model performance.
Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias Renais , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estudos Retrospectivos , Redes Neurais de Computação , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X , Neoplasias Renais/diagnóstico por imagemRESUMO
The objective of this study was to validate a fully automated total kidney volume measurement method for pre-clinical rodent trials that is fast, accurate, reproducible, and to provide these resources to the research community. Rodent studies that involve imaging are crucial for monitoring treatment efficacy in diseases such as polycystic kidney disease. Previous studies utilize manual or semi-automated segmentations, which are time consuming and potentially biased. To develop our automated system, a total of 150 axial magnetic resonance images (MRI) from a variety of mouse models were manually segmented and used to train/validate an automated algorithm. To test the longitudinal application of the model, four mutant and four wild-type mice were imaged sequentially over three to twelve weeks via MRI. Segmentations of the kidneys (excluding the renal pelvis) were generated by the automated method and two different readers, with one reader repeating the measurements. Similarity metrics and longitudinal analysis were calculated to assess the performance of the automated compared to the manual methods. The automated approach required no user input, besides a final visual quality control step. Similarity metrics of the automated method versus the manual segmentations were on par with inter- and intra-reader comparisons. Thus, our fully automated approach described here can be safely used in longitudinal, pre-clinical trials that involve the segmentation of rodent kidneys in T2-weighted MRIs.
Assuntos
Rim , Doenças Renais Policísticas , Animais , Modelos Animais de Doenças , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , CamundongosRESUMO
Autosomal dominant polycystic kidney disease (ADPKD), primarily due to PKD1 or PKD2 mutations, causes progressive kidney cyst development and kidney failure. There is significant intrafamilial variability likely due to the genetic background and environmental/lifestyle factors; variability that can be modeled in PKD mice. Here, we characterized mice homozygous for the PKD1 hypomorphic allele, p.Arg3277Cys (Pkd1RC/RC), inbred into the BALB/cJ (BC) or the 129S6/SvEvTac (129) strains, plus F1 progeny bred with the previously characterized C57BL/6J (B6) model; F1(BC/B6) or F1(129/B6). By one-month cystic disease in both the BC and 129 Pkd1RC/RC mice was more severe than in B6 and continued with more rapid progression to six to nine months. Thereafter, the expansive disease stage plateaued/declined, coinciding with increased fibrosis and a clear decline in kidney function. Greater severity correlated with more inter-animal and inter-kidney disease variability, especially in the 129-line. Both F1 combinations had intermediate disease severity, more similar to B6 but progressive from one-month of age. Mild biliary dysgenesis, and an early switch from proximal tubule to collecting duct cysts, was seen in all backgrounds. Preclinical testing with a positive control, tolvaptan, employed the F1(129/B6)-Pkd1RC/RC line, which has moderately progressive disease and limited isogenic variability. Magnetic resonance imaging was utilized to randomize animals and provide total kidney volume endpoints; complementing more traditional data. Thus, we show how genetic background can tailor the Pkd1RC/RC model to address different aspects of pathogenesis and disease modification, and describe a possible standardized protocol for preclinical testing.
Assuntos
Rim Policístico Autossômico Dominante , Animais , Patrimônio Genético , Rim , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genéticaRESUMO
BACKGROUND. Imaging biomarkers of response to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDA) are needed to optimize treatment decisions and long-term outcomes. OBJECTIVE. The purpose of this study was to investigate metrics from PET/MRI and CT to assess pathologic response of PDA to NAT and to predict overall survival (OS). METHODS. This retrospective study included 44 patients with 18F-FDG-avid borderline resectable or locally advanced PDA on pretreatment PET/MRI who also underwent post-NAT PET/MRI before surgery between August 2016 and February 2019. Carbohydrate antigen 19-9 (CA 19-9) level, metabolic metrics from PET/MRI, and morphologic metrics from CT (n = 34) were compared between pathologic responders (College of American Pathologists scores 0 and 1) and nonresponders (scores 2 and 3). AUCs were measured for metrics significantly associated with pathologic response. Relation to OS was evaluated with Cox proportional hazards models. RESULTS. Among 44 patients (22 men, 22 women; mean age, 62 ± 11.6 years), 19 (43%) were responders, and 25 (57%) were nonresponders. Median OS was 24 months (range, 6-42 months). Before treatment, responders and nonresponders did not differ in CA 19-9 level, metabolic metrics, or CT metrics (p > .05). After treatment, responders and nonresponders differed in complete metabolic response (CMR) (responders, 89% [17/19]; nonresponders, 40% [10/25]; p = .04], mean change in SUVmax (ΔSUVmax; responders, -70% ± 13%; nonresponders, -37% ± 42%; p < .001), mean change in SUVmax corrected to serum glucose level (ΔSUVgluc) (responders, -74% ± 12%; nonresponders, -30% ± 58%; p < .001), RECIST response on CT (responders, 93% [13/14]; nonresponders, 50% [10/20]; p = .02)], and mean change in tumor volume on CT (ΔTvol) (responders, -85% ± 21%; nonresponders, 57% ± 400%; p < .001). The AUC of CMR for pathologic response was 0.75; ΔSUVmax, 0.83; ΔSUVgluc, 0.87; RECIST, 0.71; and ΔTvol 0.86. The AUCs of bivariable PET/MRI and CT models were 0.83 (CMR and ΔSUVmax), 0.87 (CMR and ΔSUVgluc), and 0.87 (RECIST and ΔTvol). OS was associated with CMR (p = .03), ΔSUVmax (p = .003), ΔSUVgluc (p = .003), and RECIST (p = .046). CONCLUSION. Unlike CA 19-9 level, changes in metabolic metrics from PET/MRI and morphologic metrics from CT after NAT were associated with pathologic response and OS in patients with PDA, warranting prospective validation. CLINICAL IMPACT. Imaging metrics associated with pathologic response and OS in PDA could help guide clinical management and outcomes for patients with PDA who undergo emergency therapeutic interventions.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Total kidney volume (TKV) is the main imaging biomarker used to monitor disease progression and to classify patients affected by autosomal dominant polycystic kidney disease (ADPKD) for clinical trials. However, patients with similar TKVs may have drastically different cystic presentations and phenotypes. In an effort to quantify these cystic differences, we developed the first 3D semantic instance cyst segmentation algorithm for kidneys in MR images. We have reformulated both the object detection/localization task and the instance-based segmentation task into a semantic segmentation task. This allowed us to solve this unique imaging problem efficiently, even for patients with thousands of cysts. To do this, a convolutional neural network (CNN) was trained to learn cyst edges and cyst cores. Images were converted from instance cyst segmentations to semantic edge-core segmentations by applying a 3D erosion morphology operator to up-sampled versions of the images. The reduced cysts were labeled as core; the eroded areas were dilated in 2D and labeled as edge. The network was trained on 30 MR images and validated on 10 MR images using a fourfold cross-validation procedure. The final ensemble model was tested on 20 MR images not seen during the initial training/validation. The results from the test set were compared to segmentations from two readers. The presented model achieved an averaged R2 value of 0.94 for cyst count, 1.00 for total cyst volume, 0.94 for cystic index, and an averaged Dice coefficient of 0.85. These results demonstrate the feasibility of performing cyst segmentations automatically in ADPKD patients.
Assuntos
Cistos , Semântica , Cistos/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Rim , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The formation and growth of cysts in kidneys, and often liver, in autosomal dominant polycystic kidney disease (ADPKD) cause progressive increases in total kidney volume (TKV) and liver volume (TLV). Laborious and time-consuming manual tracing of kidneys and liver is the current gold standard. We developed a fully automated segmentation method for TKV and TLV measurement that uses a deep learning network optimized to perform semantic segmentation of kidneys and liver. METHODS: We used 80% of a set of 440 abdominal magnetic resonance images (T2-weighted HASTE coronal sequences) from patients with ADPKD to train the network and the remaining 20% for validation. Both kidneys and liver were also segmented manually. To evaluate the method's performance, we used an additional test set of images from 100 patients, 45 of whom were also involved in longitudinal analyses. RESULTS: TKV and TLV measured by the automated approach correlated highly with manually traced TKV and TLV (intraclass correlation coefficients, 0.998 and 0.996, respectively), with low bias and high precision (<0.1%±2.7% for TKV and -1.6%±3.1% for TLV); this was comparable with inter-reader variability of manual tracing (<0.1%±3.5% for TKV and -1.5%±4.8% for TLV). For longitudinal analysis, bias and precision were <0.1%±3.2% for TKV and 1.4%±2.9% for TLV growth. CONCLUSIONS: These findings demonstrate a fully automated segmentation method that measures TKV, TLV, and changes in these parameters as accurately as manual tracing. This technique may facilitate future studies in which automated and reproducible TKV and TLV measurements are needed to assess disease severity, disease progression, and treatment response.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Adulto , Biomarcadores/metabolismo , Estudos Transversais , Aprendizado Profundo , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Variações Dependentes do Observador , Reconhecimento Automatizado de Padrão , Rim Policístico Autossômico Dominante/patologia , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
Purpose To develop and evaluate a fully automated algorithm for segmenting the abdomen from CT to quantify body composition. Materials and Methods For this retrospective study, a convolutional neural network based on the U-Net architecture was trained to perform abdominal segmentation on a data set of 2430 two-dimensional CT examinations and was tested on 270 CT examinations. It was further tested on a separate data set of 2369 patients with hepatocellular carcinoma (HCC). CT examinations were performed between 1997 and 2015. The mean age of patients was 67 years; for male patients, it was 67 years (range, 29-94 years), and for female patients, it was 66 years (range, 31-97 years). Differences in segmentation performance were assessed by using two-way analysis of variance with Bonferroni correction. Results Compared with reference segmentation, the model for this study achieved Dice scores (mean ± standard deviation) of 0.98 ± 0.03, 0.96 ± 0.02, and 0.97 ± 0.01 in the test set, and 0.94 ± 0.05, 0.92 ± 0.04, and 0.98 ± 0.02 in the HCC data set, for the subcutaneous, muscle, and visceral adipose tissue compartments, respectively. Performance met or exceeded that of expert manual segmentation. Conclusion Model performance met or exceeded the accuracy of expert manual segmentation of CT examinations for both the test data set and the hepatocellular carcinoma data set. The model generalized well to multiple levels of the abdomen and may be capable of fully automated quantification of body composition metrics in three-dimensional CT examinations. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Chang in this issue.
Assuntos
Composição Corporal , Aprendizado Profundo , Reconhecimento Automatizado de Padrão , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Abdominal , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
While zebrafish embryos in the first five days after fertilization are clear and amenable to optical analysis, older juveniles and adults are not, due to pigmentation development and tissue growth. Thus other imaging methods are needed to image adult specimens. NMR is a versatile tool for studies of biological systems and has been successfully used for in vivo zebrafish microscopy. In this work we use NMR microscopy (MRM) for assessment of zebrafish specimens, which includes imaging of formalin fixed (FF), formalin fixed and paraffin embedded (FFPE), fresh (unfixed), and FF gadolinium doped specimens. To delineate the size and shape of various organs we concentrated on 3D MRM. We have shown that at 7 T a 3D NMR image can be obtained with isotropic resolution of 50 µm/pxl within 10 min and 25 µm/pxl within 4 h. Also, we have analyzed sources of contrast and have found that in FF specimens the best contrast is obtained by T1 weighting (3D FLASH, 3D FISP), whereas in FFPE specimens T2 weighting (3D RARE) is the best. We highlight an approach to perform segmentation of the organs in order to study morphological changes associated with mutations. The broader implication of this work is development of NMR methodology for high contrast and high resolution serial imaging and automated analysis of morphology of various zebrafish mutants.
Assuntos
Imageamento Tridimensional , Espectroscopia de Ressonância Magnética , Microscopia/métodos , Peixe-Zebra/fisiologia , Animais , Gadolínio/química , Inclusão em Parafina , Fixação de TecidosRESUMO
BACKGROUND: Approximately 30% of Persian cats have a c.10063C > A variant in polycystin 1 (PKD1) homolog causing autosomal dominant polycystic kidney disease (ADPKD). The variant is lethal in utero when in the homozygous state and is the only ADPKD variant known in cats. Affected cats have a wide range of progression and disease severity. However, cats are an overlooked biomedical model and have not been used to test therapeutics and diets that may support human clinical trials. To reinvigorate the cat as a large animal model for ADPKD, the efficacy of imaging modalities was evaluated and estimates of kidney and fractional cystic volumes (FCV) determined. METHODS: Three imaging modalities, ultrasonography, computed tomography (CT), and magnetic resonance imaging examined variation in disease presentation and disease progression in 11 felines with ADPKD. Imaging data was compared to well-known biomarkers for chronic kidney disease and glomerular filtration rate. Total kidney volume, total cystic volume, and FCV were determined for the first time in ADPKD cats. Two cats had follow-up examinations to evaluate progression. RESULTS: FCV measurements were feasible in cats. CT was a rapid and an efficient modality for evaluating therapeutic effects that cause alterations in kidney volume and/or FCV. Biomarkers, including glomerular filtration rate and creatinine, were not predictive for disease progression in feline ADPKD. The wide variation in cystic presentation suggested genetic modifiers likely influence disease progression in cats. All imaging modalities had comparable resolutions to those acquired for humans, and software used for kidney and cystic volume estimates in humans proved useful for cats. CONCLUSIONS: Routine imaging protocols used in veterinary medicine are as robust and efficient for evaluating ADPKD in cats as those used in human medicine. Cats can be identified as fast and slow progressors, thus, could assist with genetic modifier discovery. Software to measure kidney and cystic volume in human ADPKD kidney studies is applicable and efficient in cats. The longer life and larger kidney size span than rodents, similar genetics, disease presentation and progression as humans suggest cats are an efficient biomedical model for evaluation of ADPKD therapeutics.
Assuntos
Modelos Animais de Doenças , Rim/diagnóstico por imagem , Rim/patologia , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/patologia , Animais , Gatos , Progressão da Doença , Feminino , Testes de Função Renal , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Rim Policístico Autossômico Dominante/fisiopatologia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Deep-learning algorithms typically fall within the domain of supervised artificial intelligence and are designed to "learn" from annotated data. Deep-learning models require large, diverse training datasets for optimal model convergence. The effort to curate these datasets is widely regarded as a barrier to the development of deep-learning systems. We developed RIL-Contour to accelerate medical image annotation for and with deep-learning. A major goal driving the development of the software was to create an environment which enables clinically oriented users to utilize deep-learning models to rapidly annotate medical imaging. RIL-Contour supports using fully automated deep-learning methods, semi-automated methods, and manual methods to annotate medical imaging with voxel and/or text annotations. To reduce annotation error, RIL-Contour promotes the standardization of image annotations across a dataset. RIL-Contour accelerates medical imaging annotation through the process of annotation by iterative deep learning (AID). The underlying concept of AID is to iteratively annotate, train, and utilize deep-learning models during the process of dataset annotation and model development. To enable this, RIL-Contour supports workflows in which multiple-image analysts annotate medical images, radiologists approve the annotations, and data scientists utilize these annotations to train deep-learning models. To automate the feedback loop between data scientists and image analysts, RIL-Contour provides mechanisms to enable data scientists to push deep newly trained deep-learning models to other users of the software. RIL-Contour and the AID methodology accelerate dataset annotation and model development by facilitating rapid collaboration between analysts, radiologists, and engineers.