PurposeThe limited volume of medical training data remains one of the leading challenges for machine learning for diagnostic applications. Object detectors that identify and localize pathologies require training with a large volume of labeled images, which are often expensive and time-consuming to curate. To reduce this challenge, we present a method to support distant supervision of object detectors through generation of synthetic pathology-present labeled images.ApproachOur method employs the previously proposed cyclic generative adversarial network (cycleGAN) with two key innovations: (1) use of “near-pair” pathology-present regions and pathology-absent regions from similar locations in the same subject for training and (2) the addition of a realism metric (Fréchet inception distance) to the generator loss term. We trained and tested this method with 2800 fracture-present and 2800 fracture-absent image patches from 704 unique pediatric chest radiographs. The trained model was then used to generate synthetic pathology-present images with exact knowledge of location (labels) of the pathology. These synthetic images provided an augmented training set for an object detector.ResultsIn an observer study, four pediatric radiologists used a five-point Likert scale indicating the likelihood of a real fracture (1 = definitely not a fracture and 5 = definitely a fracture) to grade a set of real fracture-absent, real fracture-present, and synthetic fracture-present images. The real fracture-absent images scored 1.7±1.0, real fracture-present images 4.1±1.2, and synthetic fracture-present images 2.5±1.2. An object detector model (YOLOv5) trained on a mix of 500 real and 500 synthetic radiographs performed with a recall of 0.57±0.05 and an F2 score of 0.59±0.05. In comparison, when trained on only 500 real radiographs, the recall and F2 score were 0.49±0.06 and 0.53±0.06, respectively.ConclusionsOur proposed method generates visually realistic pathology and that provided improved object detector performance for the task of rib fracture detection.
This study proposes different deep learning approaches to automatically classify pneumoconiosis based on the International Labour Office (“ILO”) classification system. Through collaboration with the National Institute for Occupational Safety and Health (NIOSH), this study curated a custom dataset of chest radiographs with (N=520) and without (N=149) pneumoconiosis. The four-point major category scale of profusion (concentration) of small opacities (0, 1, 2, or 3) were considered in this study. Several deep learning models were evaluated for classifying different levels of profusion grades including: 1) Transfer learning with models pre-trained with public chest radiograph repositories, 2) Hand-crafted radiomic feature extraction, and 3) Hybrid architecture that integrates hand-crafted radiomic features with transfer-learned features using a loss function that incorporates the inherent ordinality within the profusion grade scale. For profusion grade 0 vs. grade 3, both the transfer learning and radiomic feature extraction methods obtained test-set accuracies of greater than 91%. The highest prediction accuracy for normal (profusion grade 0) vs. abnormal (profusion grade 1, 2 and 3) was 83% using the transfer learning method. Under the setting of multi-class identification of four profusion grades, ResNet model adapted to a ordinal multi-task loss function notably outperforms traditional models reliant on cross-entropy loss (with accuracy 58%) and achieves an accuracy of approximately 61%. The amalgamation of radiomic and ResNetderived features, coupled with the application of multi-task loss, culminates in the highest recorded accuracy of approximately 62%. This demonstrates an example case where the integration of hand-crafted and deep-learned features, along with modeling the ordinality of the classes, improves classification performance of chest radiographs.
Rib fractures are a sentinel injury for physical abuse in young children. When rib fractures are detected in young children, 80-100% of the time it is the result of child abuse. Rib fractures can be challenging to detect on pediatric radiographs given that they can be non-displaced, incomplete, superimposed over other structures, or oriented obliquely with respect to the detector. This work presents our efforts to develop an object detection method for rib fracture detection on pediatric chest radiographs. We propose a method entitled “avalanche decision” motivated by the reality that pediatric patients with rib fractures commonly present with multiple fractures; in our dataset, 76% of patients with fractures had more than one fracture. This approach is applied at inference and uses a decision threshold that decreases as a function of the number of proposals that clear the current threshold. These contributions were added to two leading single stage detectors: RetinaNet and YOLOv5. These methods were trained and tested with our curated dataset of 704 pediatric chest radiographs, for which pediatric radiologists labeled fracture locations and achieved an expert reader-to-reader F2 score of 0.76. Comparing base RetinaNet to RetinaNet+Avalanche yielded F2 scores of 0.55 and 0.65, respectively. F2 scores of base YOLOv5 and YOLOv5+Avalanche were 0.58 and 0.65, respectively. The proposed avalanche inferencing approaches provide increased recall and F2 scores over the standalone models.
Estimating myocardial blood flow (MBF) is essential for diagnosing and risk stratifying myocardial ischemia. Currently, positron emission tomography (PET) is a gold standard for non-invasive, quantitative MBF measurements. In this work, we compare our machine learning derived MBF estimates to PET derived estimates, and 2-compartmental model derived MBF estimates. Our best performing model (ensemble regression tree) had a root mean squared error (RMSE) of 0.47 ml/min/g. Comparatively, the compartmental model achieved an RMSE of 0.80 ml/min/g. Including CAD risk factors improved flow estimation accuracy for models that trained on feature selected TAC data and worsened accuracy for models that trained on PCA data. Overall, our machine learning approach produces comparable MBF estimations to verified DCE-CT and PET estimates and can provide rapid assessments for myocardial ischemia.
Fractional Flow Reserve (FFR) is a widely used metric to quantify the functional significance of stenoses in coronary arteries. FFR is the ratio of pressure before and after a stenosis and is measured using a transducer during coronary catheterization. To avoid unnecessary catheterization, many analytical and data-driven models based on non-invasive imaging have been proposed for FFR estimation. In this study, we construct physics-informed analytical models and datadriven machine learning models for FFR estimation based on CT-derived information. All four models require simple information about suspect stenoses, offering rapid, practical approaches for functional assessment. The four models we study are: (1) a patient-specific blood flow informed pressure drop model based on Navier-Stokes equations, (2) a purely geometric model based on stenosis area reduction, (3) a Gaussian process regression model trained on patient specific stenosis geometry and blood flow data, and (4) a Gaussian process regression model trained only on patient specific stenosis geometry. The models were developed and tested using a simulation study with ground truth FFR values from computational fluid dynamics analysis of blood flow through a population of stenosed arteries. In total, 60 different stenosis conditions based on known prevalence were simulated with a range of measurement errors leading to 10000 data sets. The RMSE of the model estimates for approach 1 through 4 are, 0.19, 0.45, 0.06, 0.14. The flow informed machine learning model leads to ~1% lower bias and ~12% lower variance than the flow informed analytical model. Considering the improved variance performance, the machine learning models likely outperform analytic expressions because they learn optimal regression associations robust to noise. This work suggests that machine learned approaches may be superior to conventional analytic expressions for FFR estimation, particularly when inputs contain realistic measurement error.
Convolutional neural networks (CNN) are increasingly used for image classification tasks. In general, the architectures of these networks are set ad hoc with little justification for selecting various components, such as the number of layers, layer depth, and convolution settings. In this work, we develop a structured approach to explore and select architectures that provide optimal classification performance. This was developed with an IRB-approved data set with 9,216 2-D maximum intensity projection (MIP) MRI breast images, containing breast cancer malignant or benign classes. This data set was divided into 7,372 training, 922 validation, and 922 test images. The architecture search method employs a genetic algorithm to find optimal ResNet-based classification architectures through crossover and mutation. Each generation, new model architectures are created from the genetic algorithm and trained with supervised machine learning. This search method identifies the model with the highest area under the ROC curve (AUC). The genetic algorithm produced an optimal model architecture which classifies malignancy in images with 76% accuracy and achieves an AUC score of .83. This approach offers a rational framework for automatic architecture exploration, potentially leading to a set of more efficient and generalizable CNN-based classifiers.
Thyroid nodules are extremely common, with a prevalence of up to 68% in adults. Ultrasound imaging is usually performed to detect and evaluate thyroid nodules for malignancy. Many patients undergo follow-up biopsy in the form of fine-needle aspiration (FNA) to determine if a nodule is malignant or benign, although most nodules are benign. In order to reduce the number of unnecessary FNAs, radiologists will often use classification systems such as Thyroid Imaging, Reporting, and Data System (TI-RADS) to provide risk stratification and a recommendation regarding whether FNA is necessary. This scoring is both subjective and time-consuming, leading to discrepancies between radiologists and recommendations that can be inaccurate. We hypothesize that a machine learned classifier can be identified with accurate and generalizable performance, potentially offering more consistent results than manual evaluation. We created a network from two ResNet-50 branches accepting two inputs, shear-wave elastography and B-mode ultrasound images. We performed a grid search to determine the optimal hyperparameters for our model, resulting in a network that predicted malignancy of nodules with 88.7% accuracy and an AUC of 0.91. Along with identifying the training hyperparameters with optimal classification accuracy, the grid search also allowed us to select training parameters that led to more generalizable model performance on test data sets. These initial performance results suggest that our model offers a promising strategy for thyroid nodule classification and a strategy to help identify more generalizable models.
Surgical procedures often require the use of catheters, tubes, and lines, collectively called lines. Misplaced lines can cause serious complications, such as pneumothorax, cardiac perforation, or thrombosis. To prevent these problems, radiologists examine chest radiographs after insertion and throughout intensive care to evaluate their placement. This process is time consuming, and incorrect interpretations occur with notable frequency. Fast and reliable automatic interpretations could potentially reduce the cost of these surgical operations, decrease the workload of radiologists, and improve the quality of care for patients. We develop a segmentation model which can highlight the medically relevant lines in pediatric chest radiographs using deep learning. We propose a two-stage segmentation network which first classifies whether images have medically relevant lines and then segments images with lines. For the segmentation stage, we use the popular U-Net architecture substituting the encoder path with multiple state-of-the-art CNN encoders. Our study compares the performance of different permutations of model architectures for the task of highlighting lines in pediatric chest radiographs and demonstrates the effectiveness of the two-stage architecture.
Chest radiographs are a common diagnostic tool in pediatric care, and several computer-augmented decision tasks for radiographs would benefit from knowledge of the anatomic locations within the thorax. For example, a pre-segmented chest radiograph could provide context for algorithms designed for automatic grading of catheters and tubes. This work develops a deep learning approach to automatically segment chest radiographs into multiple regions to provide anatomic context for future automatic methods. This type of segmentation offers challenging aspects in its goal of multi-class segmentation with extreme class imbalance between regions. In an IRB-approved study, pediatric chest radiographs were collected and annotated with custom software in which users drew boundaries around seven regions of the chest: left and right lung, left and right subdiaphragm, spine, mediastinum, and carina. We trained a U-Net-style architecture on 328 annotated radiographs, comparing model performance with various combinations of loss functions, weighting schemes, and data augmentation. On a test set of 70 radiographs, our best-performing model achieved 93.8% mean pixel accuracy and a mean Dice coefficient of 0.83. We find that (1) cross-entropy consistently outperforms generalized Dice loss, (2) light augmentation, including random rotations, improves overall performance, and (3) pre-computed pixel weights that account for class frequency provide small performance boosts. Overall, our approach produces realistic eight-class chest segmentations that can provide anatomic context for line placement and potentially other medical applications.
Dynamic contrast enhanced cardiac CT acquisitions can quantify myocardial blood flow (MBF) in absolute units (ml/min/g), but repeated scans increase X-ray radiation dose to the patient. We propose a novel approach using high temporal sampling of the input function with reduced temporal sampling of the myocardial tissue response. This type of data could be acquired with current bolus tracking acquisitions or with new acquisition sequences offering reduced radiation dose and potentially easier data processing and flow estimation. To evaluate this type of data, we prospectively acquired a full dynamic series [12 -18 frames (mean 14.5±1.4) over 23 to 44 seconds (mean 31.3±5.0 sec)] on 28 patients at rest and stress (N=56 studies) and examined the relative performance of myocardial perfusion estimation when the myocardial data is subsampled down to 8, 4, 2 or 1 frame(s). Unlike previous studies, for all frame rates, we consider a well-sampled input function. As expected, subsampling linearly reduces radiation dose while progressively decreasing estimation accuracy, with the typical absolute error in MBF (as compared to the full-length series) increasing from 0.22 to 0.30 to 0.35 to 1.12 ml/min/g as the number of frames used for estimation decreases from 8 to 4 to 2 to 1, respectively. These results suggest that high temporal sampling of the input function with low temporal sampling of the myocardial response can provide much of the benefit of dynamic CT for MBF quantification with dramatic reductions in the required number of myocardial acquisitions and the associated radiation dose (e.g. 77% dose reduction for 2-frame case).
Various Computer Aided Diagnosis (CAD) systems have been developed that characterize thyroid nodules using the features extracted from the B-mode ultrasound images and Shear Wave Elastography images (SWE). These features, however, are not perfect predictors of malignancy. In other domains, deep learning techniques such as Convolutional Neural Networks (CNNs) have outperformed conventional feature extraction based machine learning approaches. In general, fully trained CNNs require substantial volumes of data, motivating several efforts to use transfer learning with pre-trained CNNs. In this context, we sought to compare the performance of conventional feature extraction, fully trained CNNs, and transfer learning based, pre-trained CNNs for the detection of thyroid malignancy from ultrasound images. We compared these approaches applied to a data set of 964 B-mode and SWE images from 165 patients. The data were divided into 80% training/validation and 20% testing data. The highest accuracies achieved on the testing data for the conventional feature extraction, fully trained CNN, and pre-trained CNN were 0.80, 0.75, and 0.83 respectively. In this application, classification using a pre-trained network yielded the best performance, potentially due to the relatively limited sample size and sub-optimal architecture for the fully trained CNN.
Quantification of myocardial blood flow (MBF) can aid in the diagnosis and treatment of coronary artery disease. However, there are no widely accepted clinical methods for estimating MBF. Dynamic cardiac perfusion computed tomography (CT) holds the promise of providing a quick and easy method to measure MBF quantitatively. However, the need for repeated scans can potentially result in a high patient radiation dose, limiting the clinical acceptance of this approach. In our previous work, we explored techniques to reduce the patient dose by either uniformly reducing the tube current or by uniformly reducing the number of temporal frames in the dynamic CT sequence. These dose reduction techniques result in noisy time-attenuation curves (TACs), which can give rise to significant errors in MBF estimation. We seek to investigate whether nonuniformly varying the tube current and/or sampling intervals can yield more accurate MBF estimates for a given dose. Specifically, we try to minimize the dose and obtain the most accurate MBF estimate by addressing the following questions: when in the TAC should the CT data be collected and at what tube current(s)? We hypothesize that increasing the sampling rate and/or tube current during the time frames when the myocardial CT number is most sensitive to the flow rate, while reducing them elsewhere, can achieve better estimation accuracy for the same dose. We perform simulations of contrast agent kinetics and CT acquisitions to evaluate the relative MBF estimation performance of several clinically viable variable acquisition methods. We find that variable temporal and tube current sequences can be performed that impart an effective dose of 5.5 mSv and allow for reductions in MBF estimation root-mean-square error on the order of 20% compared to uniform acquisition sequences with comparable or higher radiation doses.
KEYWORDS: Positron emission tomography, Imaging systems, Systems modeling, Scanners, Signal to noise ratio, Signal detection, Image quality, Ranging, Data modeling, Data acquisition
The early detection of abnormal regions with increased tracer uptake in positron emission tomography (PET) is a key driver of imaging system design and optimization as well as choice of imaging protocols. Detectability, however, remains difficult to assess due to the need for realistic objects mimicking the clinical scene, multiple lesion-present and lesion-absent images and multiple observers. Fillable phantoms, with tradeoffs between complexity and utility, provide a means to quantitatively test and compare imaging systems under truth-known conditions. These phantoms, however, often focus on quantification rather than detectability. This work presents extensions to a novel phantom design and analysis techniques to evaluate detectability in the context of realistic, non-piecewise constant backgrounds. The design consists of a phantom filled with small solid plastic balls and a radionuclide solution to mimic heterogeneous background uptake. A set of 3D-printed regular dodecahedral ‘features’ were included at user-defined locations within the phantom to create ‘holes’ within the matrix of chaotically-packed balls. These features fill at approximately 3:1 contrast to the lumpy background. A series of signal-known-present (SP) and signal-known-absent (SA) sub-images were generated and used as input for observer studies. This design was imaged in a head-like 20 cm diameter, 20 cm long cylinder and in a body-like 36 cm wide by 21 cm tall by 40 cm long tank. A series of model observer detectability indices were compared across scan conditions (count levels, number of scan replicates), PET image reconstruction methods (with/without TOF and PSF) and between PET/CT scanner system designs using the same phantom imaged on multiple systems. The detectability index was further compared to the noise-equivalent count (NEC) level to characterize the relationship between NEC and observer SNR.
Low dose CT imaging is typically constrained to be diagnostic. However, there are applications for even lowerdose CT imaging, including image registration across multi-frame CT images and attenuation correction for PET/CT imaging. We define this as the ultra-low-dose (ULD) CT regime where the exposure level is a factor of 10 lower than current low-dose CT technique levels. In the ULD regime it is possible to use statistically-principled image reconstruction methods that make full use of the raw data information. Since most statistical based iterative reconstruction methods are based on the assumption of that post-log noise distribution is close to Poisson or Gaussian, our goal is to understand the statistical distribution of ULD CT data with different non-positivity correction methods, and to understand when iterative reconstruction methods may be effective in producing images that are useful for image registration or attenuation correction in PET/CT imaging. We first used phantom measurement and calibrated simulation to reveal how the noise distribution deviate from normal assumption under the ULD CT flux environment. In summary, our results indicate that there are three general regimes: (1) Diagnostic CT, where post-log data are well modeled by normal distribution. (2) Lowdose CT, where normal distribution remains a reasonable approximation and statistically-principled (post-log) methods that assume a normal distribution have an advantage. (3) An ULD regime that is photon-starved and the quadratic approximation is no longer effective. For instance, a total integral density of 4.8 (ideal pi for ~24 cm of water) for 120kVp, 0.5mAs of radiation source is the maximum pi value where a definitive maximum likelihood value could be found. This leads to fundamental limits in the estimation of ULD CT data when using a standard data processing stream
Due to the wide variability of intra-patient respiratory motion patterns, traditional short-duration cine CT used in respiratory gated PET/CT may be insufficient to match the PET scan data, resulting in suboptimal attenuation correction that eventually compromises the PET quantitative accuracy. Thus, extending the duration of cine CT can be beneficial to address this data mismatch issue. In this work, we propose to use a long-duration cine CT for respiratory gated PET/CT, whose cine acquisition time is ten times longer than a traditional short-duration cine CT. We compare the proposed long-duration cine CT with the traditional short-duration cine CT through numerous phantom simulations with 11 respiratory traces measured during patient PET/CT scans. Experimental results show that, the long-duration cine CT reduces the motion mismatch between PET and CT by 41% and improves the overall reconstruction accuracy by 42% on average, as compared to the traditional short-duration cine CT. The long-duration cine CT also reduces artifacts in PET images caused by misalignment and mismatch between adjacent slices in phase-gated CT images. The improvement in motion matching between PET and CT by extending the cine duration depends on the patient, with potentially greater benefits for patients with irregular breathing patterns or larger diaphragm movements.
Cardiac computed tomography (CT) acquisitions for perfusion assessment can be performed in a dynamic or static mode. Either method may be used for a variety of clinical tasks, including (1) stratifying patients into categories of ischemia and (2) using a quantitative myocardial blood flow (MBF) estimate to evaluate disease severity. In this simulation study, we compare method performance on these classification and quantification tasks for matched radiation dose levels and for different flow states, patient sizes, and injected contrast levels. Under conditions simulated, the dynamic method has low bias in MBF estimates (0 to 0.1 ml/min/g) compared to linearly interpreted static assessment (0.45 to 0.48 ml/min/g), making it more suitable for quantitative estimation. At matched radiation dose levels, receiver operating characteristic analysis demonstrated that the static method, with its high bias but generally lower variance, had superior performance (p<0.05) in stratifying patients, especially for larger patients and lower contrast doses [area under the curve (AUC)=0.95 to 96 versus 0.86]. We also demonstrate that static assessment with a correctly tuned exponential relationship between the apparent CT number and MBF has superior quantification performance to static assessment with a linear relationship and to dynamic assessment. However, tuning the exponential relationship to the patient and scan characteristics will likely prove challenging. This study demonstrates that the selection and optimization of static or dynamic acquisition modes should depend on the specific clinical task.
Quantification of myocardial blood flow (MBF) can aid in the diagnosis and treatment of coronary artery disease (CAD). However, there are no widely accepted clinical methods for estimating MBF. Dynamic CT holds the promise of providing a quick and easy method to measure MBF quantitatively, however the need for repeated scans has raised concerns about the potential for high radiation dose. In our previous work, we explored techniques to reduce the patient dose by either uniformly reducing the tube current or by uniformly reducing the number of temporal frames in the dynamic CT sequence. These dose reduction techniques result in very noisy data, which can give rise to large errors in MBF estimation. In this work, we seek to investigate whether nonuniformly varying the tube current or sampling intervals can yield more accurate MBF estimates. Specifically, we try to minimize the dose and obtain the most accurate MBF estimate through addressing the following questions: when in the time attenuation curve (TAC) should the CT data be collected and at what tube current(s). We hypothesize that increasing the sampling rate and/or tube current during the time frames when the myocardial CT number is most sensitive to the flow rate, while reducing them elsewhere, can achieve better estimation accuracy for the same dose. We perform simulations of contrast agent kinetics and CT acquisitions to evaluate the relative MBF estimation performance of several clinically viable adaptive acquisition methods. We found that adaptive temporal and tube current sequences can be performed that impart an effective dose of about 5 mSv and allow for reductions in MBF estimation RMSE on the order of 11% compared to uniform acquisition sequences with comparable or higher radiation doses.
Cardiac CT acquisitions for perfusion assessment can be performed in a dynamic or static mode. In this simulation study, we evaluate the relative classification and quantification performance of these modes for assessing myocardial blood flow (MBF). In the dynamic method, a series of low dose cardiac CT acquisitions yields data on contrast bolus dynamics over time; these data are fit with a model to give a quantitative MBF estimate. In the static method, a single CT acquisition is obtained, and the relative CT numbers in the myocardium are used to infer perfusion states. The static method does not directly yield a quantitative estimate of MBF, but these estimates can be roughly approximated by introducing assumed linear relationships between CT number and MBF, consistent with the ways such images are typically visually interpreted. Data obtained by either method may be used for a variety of clinical tasks, including 1) stratifying patients into differing categories of ischemia and 2) using the quantitative MBF estimate directly to evaluate ischemic disease severity. Through simulations, we evaluate the performance on each of these tasks. The dynamic method has very low bias in MBF estimates, making it particularly suitable for quantitative estimation. At matched radiation dose levels, ROC analysis demonstrated that the static method, with its high bias but generally lower variance, has superior performance in stratifying patients, especially for larger patients.
Dynamic contrast-enhanced computed tomography (CT) could provide an accurate and widely available technique for myocardial blood flow (MBF) estimation to aid in the diagnosis and treatment of coronary artery disease. However, one of its primary limitations is the radiation dose imparted to the patient. We are exploring techniques to reduce the patient dose by either reducing the tube current or by reducing the number of temporal frames in the dynamic CT sequence. Both of these dose reduction techniques result in noisy data. In order to extract the MBF information from the noisy acquisitions, we have explored several data-domain smoothing techniques. In this work, we investigate two specific smoothing techniques: the sinogram restoration technique in both the spatial and temporal domains and the use of the Karhunen–Loeve (KL) transform to provide temporal smoothing in the sinogram domain. The KL transform smoothing technique has been previously applied to dynamic image sequences in positron emission tomography. We apply a quantitative two-compartment blood flow model to estimate MBF from the time-attenuation curves and determine which smoothing method provides the most accurate MBF estimates in a series of simulations of different dose levels, dynamic contrast-enhanced cardiac CT acquisitions. As measured by root mean square percentage error (% RMSE) in MBF estimates, sinogram smoothing generally provides the best MBF estimates except for the cases of the lowest simulated dose levels (tube current=25 mAs, 2 or 3 s temporal spacing), where the KL transform method provides the best MBF estimates. The KL transform technique provides improved MBF estimates compared to conventional processing only at very low doses (<7 mSv). Results suggest that the proposed smoothing techniques could provide high fidelity MBF information and allow for substantial radiation dose savings.
The objective of this investigation was to propose techniques for determining which patients are likely to benefit from quantitative respiratory-gated imaging by correlating respiratory patterns to changes in positron emission tomography (PET) metrics. Twenty-six lung and liver cancer patients underwent PET/computed tomography exams with recorded chest/abdominal displacements. Static and adaptive amplitude-gated [F18]fluoro-D-glucose (FDG) PET images were generated from list-mode acquisitions. Patients were grouped by respiratory pattern, lesion location, or degree of lesion attachment to anatomical structures. Respiratory pattern metrics were calculated during time intervals corresponding to PET field of views over lesions of interest. FDG PET images were quantified by lesion maximum standardized uptake value (SUVmax). Relative changes in SUVmax between static and gated PET images were tested for association to respiratory pattern metrics. Lower lung lesions and liver lesions had significantly higher changes in SUVmax than upper lung lesions (14 versus 3%, p<0.0001). Correlation was highest (0.42±0.10, r2=0.59, p<0.003) between changes in SUVmax and nonstandard respiratory pattern metrics. Lesion location had a significant impact on changes in PET quantification due to respiratory gating. Respiratory pattern metrics were correlated to changes in SUVmax, though sample size limited statistical power. Validation in larger cohorts may enable selection of patients prior to acquisition who would benefit from respiratory-gated PET imaging.
KEYWORDS: Blood circulation, Smoothing, Iodine, Computed tomography, Signal attenuation, Data modeling, Arteries, Computer aided diagnosis and therapy, Image filtering, Bone
There is a strong need for an accurate and easily available technique for myocardial blood flow (MBF) estimation to aid in the diagnosis and treatment of coronary artery disease (CAD). Dynamic CT would provide a quick and widely available technique to do so. However, its biggest limitation is the dose imparted to the patient. We are exploring techniques to reduce the patient dose by either reducing the tube current or by reducing the number of temporal frames in the dynamic CT sequence. Both of these dose reduction techniques result in very noisy data. In order to extract the myocardial blood flow information from the noisy sinograms, we have been looking at several data-domain smoothing techniques. In our previous work,1 we explored the sinogram restoration technique in both the spatial and temporal domain. In this work, we explore the use of Karhunen-Loeve (KL) transform to provide temporal smoothing in the sinogram domain. This technique has been applied previously to dynamic image sequences in PET.2, 3 We find that the cluster-based KL transform method yields noticeable improvement in the smoothness of time attenuation curves (TAC). We make use of a quantitative blood flow model to estimate MBF from these TACs and determine which smoothing method provides the most accurate MBF estimates.
Contrast enhancement on cardiac CT provides valuable information about myocardial perfusion and methods have been
proposed to assess perfusion with static and dynamic acquisitions. There is a lack of knowledge and consensus on the
appropriate approach to ensure 1) sufficient diagnostic accuracy for clinical decisions and 2) low radiation doses for
patient safety. This work developed a thorough dynamic CT simulation and several accepted blood flow estimation
techniques to evaluate the performance of perfusion assessment across a range of acquisition and estimation scenarios.
Cardiac CT acquisitions were simulated for a range of flow states (Flow = 0.5, 1, 2, 3 ml/g/min, cardiac output = 3,5,8
L/min). CT acquisitions were simulated with a validated CT simulator incorporating polyenergetic data acquisition and
realistic x-ray flux levels for dynamic acquisitions with a range of scenarios including 1, 2, 3 sec sampling for 30 sec
with 25, 70, 140 mAs. Images were generated using conventional image reconstruction with additional image-based
beam hardening correction to account for iodine content. Time attenuation curves were extracted for multiple regions
around the myocardium and used to estimate flow. In total, 2,700 independent realizations of dynamic sequences were
generated and multiple MBF estimation methods were applied to each of these. Evaluation of quantitative kinetic
modeling yielded blood flow estimates with an root mean square error (RMSE) of ~0.6 ml/g/min averaged across
multiple scenarios. Semi-quantitative modeling and qualitative static imaging resulted in significantly more error
(RMSE = ~1.2 and ~1.2 ml/min/g respectively). For quantitative methods, dose reduction through reduced temporal
sampling or reduced tube current had comparable impact on the MBF estimate fidelity. On average, half dose
acquisitions increased the RMSE of estimates by only 18% suggesting that substantial dose reductions can be employed
in the context of quantitative myocardial blood flow estimation. In conclusion, quantitative model-based dynamic
cardiac CT perfusion assessment is capable of accurately estimating MBF across a range of cardiac outputs and tissue
perfusion states, outperforms comparable static perfusion estimates, and is relatively robust to noise and temporal
subsampling.
Dynamic contrast enhanced CT has been successfully applied in cardiac imaging for the estimation of myocardial
blood flow (MBF). In general, these acquisitions impart a relatively high radiation dose because they require
continuous or gated imaging of the heart for 15-40 seconds. At present, there is no consensus on the appropriate
estimation method to derive MBF and on the appropriate acquisition technique to minimize dose while
maintaining MBF estimation accuracy and precision. This work explores the tradeoff of accuracy and precision
of MBF estimates with several estimation methods and acquisition techniques in support of the fundamental
goal of optimizing dynamic cardiac CT in terms of radiation dose and MBF estimation fidelity. We simulated
time attenuation curves (TACs) for a range of flow states (Flow = [0.8, 1.6, 2.4, 3.2] ml/g/min) and several
acquisition techniques. We estimated MBF with 5 different methods for each simulated TAC. From multiple
independent realizations, we assessed the accuracy and precision of each method. Results show that acquisition
techniques with 1/3 tube current or 1/3 temporal sampling permits accurate MBF estimates with most methods
with reduction in MBF estimate precision by on average 30%. Furthermore, reduction in model complexity can
be beneficial for improving the precision of MBF estimates.
Iterative image reconstruction offers improved signal to noise properties for CT imaging. A primary challenge
with iterative methods is the substantial computation time. This computation time is even more prohibitive in
4D imaging applications, such as cardiac gated or dynamic acquisition sequences. In this work, we propose only
updating the time-varying elements of a 4D image sequence while constraining the static elements to be fixed or
slowly varying in time. We test the method with simulations of 4D acquisitions based on measured cardiac patient
data from a) a retrospective cardiac-gated CT acquisition and b) a dynamic perfusion CT acquisition. We target
the kinetic elements with one of two methods: 1) position a circular ROI on the heart, assuming area outside ROI
is essentially static throughout imaging time; and 2) select varying elements from the coefficient of variation image
formed from fast analytic reconstruction of all time frames. Targeted kinetic elements are updated with each
iteration, while static elements remain fixed at initial image values formed from the reconstruction of data from
all time frames. Results confirm that the computation time is proportional to the number of targeted elements;
our simulations suggest that <30% of elements need to be updated in each frame leading to >3 times reductions
in reconstruction time. The images reconstructed with the proposed method have matched mean square error
with full 4D reconstruction. The proposed method is amenable to most optimization algorithms and offers the
potential for significant computation improvements, which could be traded off for more sophisticated system
models or penalty terms.
We evaluate the energy dependent noise and bias properties of monoenergetic images synthesized from dual-energy CT
(DECT) acquisitions used to estimate attenuation coefficients at PET or SPECT energies. This is becoming more
relevant with the increased used of quantitative imaging by PET/CT and SPECT/CT. There are, however, variations in
the noise and bias properties of synthesized monoenergetic images as a function of energy. We used analytic
approximations and simulations to estimate the bias and noise of synthesized monoenergetic images of a water-filled
cylinder from 10 to 525 keV. The dual-energy spectra were based on the GE Lightspeed VCT scanner at 80 and 140
kVp. Both analytic calculations and simulations for increasing energy the relative noise plateaued near 140 keV (i.e.
SPECT with 99mTc), and then remained constant with increasing energy up to 511 keV and beyond (i.e. PET). If DECT
is being used for attenuation correction at higher energies, there is a noise amplification that is dependent on the energy
of the synthesized monoenergetic image of linear attenuation coefficients. For SPECT and PET imaging the bias and
noise levels of DECT based attenuation correction is unlikely to affect image quality.
Accurate quantitation of PET tracer uptake levels in small tumors remains a challenge. This work uses an improved reconstruction algorithm to reduce the quantitative errors due to limited system resolution and due to necessary image noise reduction. We propose a method for finding and using the detection system response in the projection matrix of a statistical reconstruction algorithm. In addition we use aligned anatomical information, available in PET/CT scanners, to govern the penalty term applied during each image update. These improvements are combined with FORE rebinning in a clinically feasible algorithm for reconstructing fully 3D PET data. Simulated results show improved tumor bias and variance characteristics with the new algorithm.
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