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Can deep learning effectively diagnose cardiac amyloidosis with 99mTc-PYP scintigraphy?

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Abstract

This study investigates the effectiveness of deep learning models in diagnosing cardiac amyloidosis using 99mTc-PYP scintigraphy. We evaluated more than 40 deep learning models, including both convolutional neural networks (CNNs) and Vision Transformer (ViT) models. The highest-performing model achieved 89.80% accuracy. The study highlights the potential of deep learning methods to improve diagnostic accuracy and reduce patient wait times. These results demonstrate the clinical value of deep learning models in early and accurate cardiac amyloidosis diagnosis, contributing to better patient outcomes and timely interventions.

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Background Recent studies suggest that cardiac amyloidosis (CA) is significantly underdiagnosed. For rare diseases like CA, the optimal selection of cases and controls for artificial intelligence model training is unknown and can significantly impact model performance. Objectives This study evaluates the performance of electrocardiogram (ECG) waveform-based artificial intelligence models for CA screening and assesses impact of different criteria for defining cases and controls. Methods Using a primary cohort of ∼1.3 million ECGs from 341,989 patients, models were trained using different case and control definitions. Case definitions included ECGs from patients with an amyloidosis diagnosis by International Classification of Diseases-9/10 code, patients with CA, and patients seen in CA clinic. Models were then tested on test cohorts with identical selection criteria as well as a Cedars-Sinai general patient population cohort. Results In matched held-out test data sets, different model AUCs ranged from 0.660 (95% CI: 0.642-0.736) to 0.898 (95% CI: 0.868-0.924). However, algorithms exhibited variable generalizability when tested on a Cedars-Sinai general patient population cohort, with AUCs dropping to 0.467 (95% CI: 0.443-0.491) to 0.898 (95% CI: 0.870-0.923). Models trained on more well-curated patient cases resulted in higher AUCs on similarly constructed test cohorts. However, all models performed similarly in the overall Cedars-Sinai general patient population cohort. A model trained with International Classification of Diseases 9/10 cases and population controls matched for age and sex resulted in the best screening performance. Conclusions Models performed similarly in population screening, regardless of stringency of cases used during training, showing that institutions without dedicated amyloid clinics can train meaningful models on less curated CA cases. Additionally, AUC or other metrics alone are insufficient in evaluating deep learning algorithm performance. Instead, evaluation in the most clinically meaningful population is key.
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Electric motors are increasingly used in various products, including turbines and electric vehicles. Precise temperature measurement is essential for the safe operation of a Permanent Magnet Synchronous Motor. Direct temperature detection of the permanent magnet and stator involves significant costs and hardware requirements. To overcome these challenges, Machine Learning models can eliminate the need for specialized sensors. This study used four diverse regression algorithms: Linear, K-Nearest Neighbor, XGBoost, and AdaBoost. The objective of this study is to model a Permanent Magnet Synchronous Motor used in electric vehicles and predict the temperatures of some of its parameters. The K-Nearest Neighbor Regressor outperformed the other algorithms, achieving a training accuracy of 99.65%, test accuracy of 98.72%, root-mean-square error of 2.16, R2 score of 98.72, and Cross-Validation R2 of 97.77%. These results enable low-cost, real-time temperature monitoring of electrical machinery, enhancing power density, safety, and efficiency.
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Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2, is an emerging and rapidly spreading type of coronavirus. One of the most important reasons for the rapid spread of the COVID-19 virus are the frequent mutations of the COVID-19 virus. One of the most important methods to overcome mutations of the COVID-19 virus is to predict these mutations before they occur. In this study, we propose a robust HyperMixer and long short-term memory based model with attention mechanisms, HyperAttCov, for COVID-19 virus mutation prediction. The proposed HyperAttCov model outperforms several state-of-the-art methods. Experimental results have showed that the proposed HyperAttCov model reached accuracy 70.0%, precision 92.0%, MCC 46.5% on the COVID-19 testing dataset. Similarly, the proposed HyperAttCov model reached accuracy 70.2%, precision 90.4%, MCC 46.2% on the COVID-19 testing dataset with an average of 10 random trail. Besides, When the proposed HyperAttCov model with 10 random trail has been compared with compared to the study in the literature, the average of performance values has been increased by accuracy 7.18%, precision 37.39%, MCC 49.51% on the testing dataset. As a result, the proposed HyperAttCov can successfully predict mutations occurring on the COVID-19 dataset in the 2022 year.
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Acute lymphoblastic leukemia (ALL) is considered the most fatal form of leukemia (also known as blood cancer). It propagates quickly among adults and children and could lead to their death. Early detection of ALL and ALL subtypes is the key factor in selecting effective treatment types and improving survival rates. However, routine diagnostic approaches have several drawbacks. Computer-assisted diagnosis (CAD) is the perfect solution to avoid these challenges and achieve a fast and accurate diagnosis. Current CAD models require enhancement/segmentation processing. Besides, they are either dependent on deep learning (DL) models or handcrafted features along with machine learning. Those CADs that employed DL approaches relied solely on spatial information during the training procedure. However, learning them with spectral temporal and temporal representations could improve performance. Furthermore, integrating deep features from DL models along with handcrafted features can increase the discrimination ability of attributes in medical image classification. This study aims to propose a novel CAD for ALL detection and subtype classification without pre-segmentation or enhancement steps. The proposed CAD extends the conventional DL models of convolutional neural networks by introducing an additional wavelet pooling, accompanied by a dense layer or a long-short-term memory (LSTM) layer, and then a SoftMax layer, acquiring spectral-temporal information along with temporal information. To further improve the framework's ability to discriminate, the introduced CAD then combines the wavelet-based deep features of every CNN with numerous handcrafted attributes. Afterward, a feature selection methodology is utilized to create a model with limited features and improved accuracy. The performance results show that the novel CAD is capable of achieving 100% ALL detection accuracy, as well as 100% ALL-subtype classification accuracy with just 88 and 146 features. Thus, this CAD can be employed to assist pathologists in the rapid and precise ALL identification and subcategories recognition.
Chapter
A Vision Transformer (ViT) is a simple neural architecture amenable to serve several computer vision tasks. It has limited built-in architectural priors, in contrast to more recent architectures that incorporate priors either about the input data or of specific tasks. Recent works show that ViTs benefit from self-supervised pre-training, in particular BerT-like pre-training like BeiT.In this paper, we revisit the supervised training of ViTs. Our procedure builds upon and simplifies a recipe introduced for training ResNet-50. It includes a new simple data-augmentation procedure with only 3 augmentations, closer to the practice in self-supervised learning. Our evaluations on Image classification (ImageNet-1k with and without pre-training on ImageNet-21k), transfer learning and semantic segmentation show that our procedure outperforms by a large margin previous fully supervised training recipes for ViT. It also reveals that the performance of our ViT trained with supervision is comparable to that of more recent architectures. Our results could serve as better baselines for recent self-supervised approaches demonstrated on ViT.
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Systemic amyloidosis encompasses a debilitating, under-diagnosed but increasingly recognized group of disorders characterized by the extracellular deposition of misfolded proteins in one or more organs. Cardiac amyloid deposition leads to an infiltrative or restrictive cardiomyopathy and is the major contributor to poor prognosis in patients with systemic amyloidosis. In total, >30 proteins can form amyloid fibrils, but the two main types of amyloid that can infiltrate the heart are monoclonal immunoglobulin light-chain amyloid and transthyretin amyloid. Cardiac amyloidosis can be acquired in older individuals or inherited from birth. Given the nonspecific symptoms of these disorders, a high index of suspicion is paramount in making the correct diagnosis, which can involve the use of non-invasive imaging methods such as echocardiography, bone scintigraphy and cardiovascular MRI. In the past decade, the use of cardiovascular MRI with tissue characterization and bone scintigraphy to diagnose cardiac amyloidosis has revolutionized our understanding of the disease, leading to changes in patient care. However, a need remains for improved awareness and expertise, and greater clinical suspicion, because the initial clues provided by electrocardiography and echocardiography might not be typical. With specific treatments now available, timely diagnosis of cardiac amyloidosis is more important than ever. In this Review, we discuss the current and novel approaches for the diagnostic imaging of cardiac amyloidosis.
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The amyloidoses are a group of systemic diseases characterized by organ deposition of misfolded protein fragments of diverse origins. The natural history of the disease, involvement of other organs, and treatment options vary significantly based on the protein of origin. In AL amyloidosis, amyloid protein is derived from immunoglobulin light chains, and most often involves the kidneys and the heart. ATTR amyloidosis is categorized as mutant or wild-type depending on the genetic sequence of the transthyretin (TTR) protein produced by the liver. Wild-type ATTR amyloidosis mainly involves the heart, although the reported occurrence of bilateral carpal tunnel syndrome, spinal stenosis and biceps tendon rupture in these patients speaks to more generalized protein deposition. Mutant TTR is marked by cardiac and/or peripheral nervous system involvement. Cardiac involvement is associated with symptoms of heart failure, and dictates the clinical course of the disease. Cardiac amyloidosis can be diagnosed noninvasively by echocardiography, cardiac MRI, or nuclear scintigraphy. Endomyocardial biopsy may be needed in the case of equivocal imaging findings or discordant data. Treatment is aimed at relieving congestive symptoms and targeting the underlying amyloidogenic process. This includes anti-plasma cell therapy in AL amyloidosis, and stabilization of the TTR tetramer or inhibition of TTR protein production in ATTR amyloidosis. Cardiac transplantation can be considered in highly selected patients in tandem with therapy aimed at suppressing the amyloidogenic process, and appears associated with durable long term survival.
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Gaining knowledge and actionable insights from complex, high-dimensional and heterogeneous biomedical data remains a key challenge in transforming health care. Various types of data have been emerging in modern biomedical research, including electronic health records, imaging, -omics, sensor data and text, which are complex, heterogeneous, poorly annotated and generally unstructured. Traditional data mining and statistical learning approaches typically need to first perform feature engineering to obtain effective and more robust features from those data, and then build prediction or clustering models on top of them. There are lots of challenges on both steps in a scenario of complicated data and lacking of sufficient domain knowledge. The latest advances in deep learning technologies provide new effective paradigms to obtain end-to-end learning models from complex data. In this article, we review the recent literature on applying deep learning technologies to advance the health care domain. Based on the analyzed work, we suggest that deep learning approaches could be the vehicle for translating big biomedical data into improved human health. However, we also note limitations and needs for improved methods development and applications, especially in terms of ease-of-understanding for domain experts and citizen scientists. We discuss such challenges and suggest developing holistic and meaningful interpretable architectures to bridge deep learning models and human interpretability.
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Cardiac amyloidosis occurs as a result of abnormal protein (amyloid) deposition in the cardiac tissue. Even with advanced diagnostic techniques and treatments, the prognosis of amyloidosis remains poor. The diagnosis of cardiac amyloidosis particularly needs to be in the differential in patients presenting with heart failure with preserved ejection fraction. This entity remains underdiagnosed due to lack of suspicion on the part of many clinicians. Involvement is cardiac tissue is the utmost determinant factor for available treatment options and prognosis. Many cases of cardiac amyloidosis usually remain undiagnosed or diagnosed only in advanced stages when treatment options are limited and associated with poor survival. Hence, early recognition of cardiac amyloidosis is indispensable in halting the disease process before irreversible changes occurs. The purpose of this review is to summarize the recent updates in the evaluation and management of cardiac amyloidosis and discuss potential future treatments options.
Article
Very deep convolutional networks have been central to the largest advances in image recognition performance in recent years. One example is the Inception architecture that has been shown to achieve very good performance at relatively low computational cost. Recently, the introduction of residual connections in conjunction with a more traditional architecture has yielded state-of-the-art performance in the 2015 ILSVRC challenge; its performance was similar to the latest generation Inception-v3 network. This raises the question of whether there are any benefit in combining the Inception architecture with residual connections. Here we give clear empirical evidence that training with residual connections accelerates the training of Inception networks significantly. There is also some evidence of residual Inception networks outperforming similarly expensive Inception networks without residual connections by a thin margin. We also present several new streamlined architectures for both residual and non-residual Inception networks. These variations improve the single-frame recognition performance on the ILSVRC 2012 classification task significantly. We further demonstrate how proper activation scaling stabilizes the training of very wide residual Inception networks. With an ensemble of three residual and one Inception-v4, we achieve 3.08 percent top-5 error on the test set of the ImageNet classification (CLS) challenge
Article
Amyloidosis is an increasingly recognized cause of heart disease, caused by the deposition of misfolded protein within the heart. These proteins may deposit systemically and include the heart or deposit only within the heart muscle itself. In either case, cardiac symptoms may be the primary manifestation. The diagnosis is usually made by the pathologist identifying amyloid within a tissue sample. The diagnosis, however, does not end with such visual recognition of the presence of amyloid. Newer generation pharmacotherapeutic agents that are protein specific necessitate a closer evaluation to determine the type of protein being deposited and accurately conveying this to the treating clinician. Herein, the gross and histopathologic features of cardiac amyloidosis are reviewed along with a review of amyloid typing strategies (both direct and indirect) that may be employed in the diagnostic workup as well as the nomenclature standards for reporting.
Article
Systemic amyloidosis is generally considered to be rare, but the heart is frequently involved and is a major determinant of prognosis. New diagnostic imaging methods have recently been developed with the capacity to enhance the accuracy of diagnosis, which will be ever more important with the variety of new treatments on the near horizon. Most cases of cardiac amyloidosis are of either monoclonal immunoglobulin light chain (AL) type, which can occur at any age from young adulthood onwards, or transthyretin (ATTR) type, which can be acquired in elderly individuals or inherited at a younger age. Cardiac involvement is the most serious manifestation of AL amyloidosis, and serum cardiac biomarkers have proved to be of great value in staging disease severity and response to an ever increasing array of chemotherapy agents. Cardiac involvement is the dominant manifestation of nonhereditary ATTR amyloidosis, also known as senile cardiac amyloidosis, the prevalence of which is not known but is probably much greater than currently recognized. A genetic variant in the gene for transthyretin (TTR), which is present in 3-4% of African Americans and probably a similar proportion of black individuals of African descent generally, appears to be associated with increased susceptibility to developing cardiac ATTR amyloidosis in older age. Several novel therapies are in the advanced stages of development for ATTR amyloidosis including TTR protein stabilizers and RNA inhibitors that greatly diminish TTR production. Here, we will review recent developments in the diagnosis and management of cardiac amyloidosis. © 2015 The Association for the Publication of the Journal of Internal Medicine.
Article
Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease. Electrocardiography and transthoracic echocardiography are important diagnostic and prognostic tools in patients with cardiac involvement. Cardiac magnetic resonance imaging better characterizes myocardial involvement, functional abnormalities and amyloid deposition due to its high spatial resolution. Nuclear imaging has a role in the diagnosis of transthyretin amyloid cardiomyopathy. Cardiac biomarkers are now used for risk stratification and staging of patients with light-chain systemic amyloidosis. Different types of cardiac complications may occur, including diastolic followed by systolic heart failure, atrial and/or ventricular arrhythmias, conduction disturbances, embolic events and sometimes sudden death. Senile amyloid and hereditary transthyretin amyloid cardiomyopathy have better prognoses than light-chain amyloidosis. Cardiac treatment of heart failure is usually ineffective and is often poorly tolerated because of its hypotensive and bradycardiac effects. The three main types of amyloid disease, despite their similar cardiac appearance, have specific new aetiological treatments that may change the prognosis of this disease. Cardiologists should be aware of this disease to allow early treatment.
Article
Cardiac amyloidosis describes clinically significant involvement of the heart by amyloid deposition, which may or may not be associated with involvement of other organs. The purpose of this review is to summarize the current state of evidence for the effective evaluation and management of cardiac amyloidosis. Acquired systemic amyloidosis occurs in more than 10 per million person-years in the U.S. population. Although no single noninvasive test or abnormality is pathognomonic of cardiac amyloid, case-control studies indicate that echocardiographic evidence of left ventricular wall thickening, biatrial enlargement, and increased echogenicity in conjunction with reduced electrocardiographic voltages is strongly suggestive of cardiac amyloidosis. Furthermore, newer echocardiographic techniques such as strain and strain rate imaging can demonstrate impairment in longitudinal function before ejection fraction becomes abnormal. Recent observational studies also suggest that cardiovascular magnetic resonance imaging yields characteristic findings in amyloidosis, offering promise for the early detection of cardiac involvement, and the presence of detectable cardiac troponin and elevated B-type natriuretic peptide in serum of affected patients portends an adverse prognosis. Management strategies for cardiac amyloid are largely based on nonrandomized single-center studies. One of the few published randomized studies shows the superiority of oral prednisolone and melphalan compared with colchicine in systemic AL amyloidosis. Intermediate-dose infusional chemotherapy regimes (such as vincristine, adriamycin, and dexamethasone) and high-dose chemotherapy with peripheral stem cell rescue have been used widely, but treatment-related mortality remains substantial with chemotherapy. Recent studies also indicate promising strategies to stabilize the native structures of amyloidogenic proteins; inhibit fibril formation; and disrupt established deposits using antibodies, synthetic peptides, and small-molecule drugs.
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