Purpose
This work aims to develop a new framework of image quality assessment using deep learning‐based model observer (DL‐MO) and to validate it in a low‐contrast lesion detection task that involves ...CT images with patient anatomical background.
Methods
The DL‐MO was developed using the transfer learning strategy to incorporate a pretrained deep convolutional neural network (CNN), a partial least square regression discriminant analysis (PLS‐DA) model and an internal noise component. The CNN was previously trained to achieve the state‐of‐the‐art classification accuracy over a natural image database. The earlier layers of the CNN were used as a deep feature extractor, with the assumption that similarity exists between the CNN and the human visual system. The PLSR model was used to further engineer the deep feature for the lesion detection task in CT images. The internal noise component was incorporated to model the inefficiency and variability of human observer (HO) performance, and to generate the ultimate DL‐MO test statistics. Seven abdominal CT exams were retrospectively collected from the same type of CT scanners. To compare DL‐MO with HO, 12 experimental conditions with varying lesion size, lesion contrast, radiation dose, and reconstruction types were generated, each condition with 154 trials. CT images of a real liver metastatic lesion were numerically modified to generate lesion models with four lesion sizes (5, 7, 9, and 11 mm) and three contrast levels (15, 20, and 25 HU). The lesions were inserted into patient liver images using a projection‐based method. A validated noise insertion tool was used to synthesize CT exams with 50% and 25% of routine radiation dose level. CT images were reconstructed using the weighted filtered back projection algorithm and an iterative reconstruction algorithm. Four medical physicists performed a two‐alternative forced choice (2AFC) detection task (with multislice scrolling viewing mode) on patient images across the 12 experimental conditions. DL‐MO was operated on the same datasets. Statistical analyses were performed to evaluate the correlation and agreement between DL‐MO and HO.
Results
A statistically significant positive correlation was observed between DL‐MO and HO for the 2AFC low‐contrast detection task that involves patient liver background. The corresponding Pearson product moment correlation coefficient was 0.986 95% confidence interval (0.950, 0.996). Bland–Altman agreement analysis did not indicate statistically significant differences.
Conclusions
The proposed DL‐MO is highly correlated with HO in a low‐contrast detection task that involves realistic patient liver background. This study demonstrated the potential of the proposed DL‐MO to assess image quality directly based on patient images in realistic, clinically relevant CT tasks.
Medical imaging is a rapidly advancing field enabling the repeated, noninvasive assessment of physiological structure and function. These beneficial characteristics can supplement studies in swine by ...mirroring the clinical functions of detection, diagnosis, and monitoring in humans. In addition, swine may serve as a human surrogate, facilitating the development and comparison of new imaging protocols for translation to humans. This study presents methods for pulmonary imaging developed for monitoring pulmonary disease initiation and progression in a pig exposure model with computed tomography and magnetic resonance imaging. In particular, a focus was placed on systematic processes, including positioning, image acquisition, and structured reporting to monitor longitudinal change. The image-based monitoring procedure was applied to 6 Yucatan miniature pigs. A subset of animals (n = 3) were injected with crystalline silica into the apical bronchial tree to induce silicosis. The methodology provided longitudinal monitoring and evidence of progressive lung disease while simultaneously allowing for a cross-modality comparative study highlighting the practical application of medical image data collection in swine. The integration of multimodality imaging with structured reporting allows for cross comparison of modalities, refinement of CT and MRI protocols, and consistently monitors potential areas of interest for guided biopsy and/or necropsy.
Current computer-aided diagnosis (CAD) models for determining pulmonary nodule malignancy characterize nodule shape, density, and border in computed tomography (CT) data. Analyzing the lung ...parenchyma surrounding the nodule has been minimally explored. We hypothesize that improved nodule classification is achievable by including features quantified from the surrounding lung tissue. To explore this hypothesis, we have developed expanded quantitative CT feature extraction techniques, including volumetric Laws texture energy measures for the parenchyma and nodule, border descriptors using ray-casting and rubber-band straightening, histogram features characterizing densities, and global lung measurements. Using stepwise forward selection and leave-one-case-out cross-validation, a neural network was used for classification. When applied to 50 nodules (22 malignant and 28 benign) from high-resolution CT scans, 52 features (8 nodule, 39 parenchymal, and 5 global) were statistically significant. Nodule-only features yielded an area under the ROC curve of 0.918 (including nodule size) and 0.872 (excluding nodule size). Performance was improved through inclusion of parenchymal (0.938) and global features (0.932). These results show a trend toward increased performance when the parenchyma is included, coupled with the large number of significant parenchymal features that support our hypothesis: the pulmonary parenchyma is influenced differentially by malignant versus benign nodules, assisting CAD-based nodule characterizations.
Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking.
...As experimental data suggest a role of bile acids in the regulation of hepatic drug metabolism at both the transcriptional and post-transcriptional level, the literature was screened for adverse drug reactions and drug interactions related to ursodeoxycholic acid.
A systematic review of the literature was performed using a refined search strategy to evaluate the adverse effects of ursodeoxycholic acid and its interactions with other drugs.
Ursodeoxycholic acid caused diarrhoea in a small proportion of patients. Rare skin reactions were due to drug adjuvants rather than the active substance. Decompensation of liver cirrhosis was reported after the administration of ursodeoxycholic acid in single cases of end-stage primary biliary cirrhosis. Recurrent right upper quadrant abdominal pain was incidentally observed. The absorption of ursodeoxycholic acid was impaired by colestyramine, colestimide, colestipol, aluminium hydroxide and smectite. Metabolic drug interactions were reported for the cytochrome P4503A substrates, ciclosporin, nitrendipine and dapsone.
Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected.
1 Department of Biology and Biochemistry, University of Houston, Houston, Texas;
2 Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland; and
3 ...Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia
Submitted 28 May 2009;
accepted in final form 15 September 2009
ABSTRACT
The purpose of the present study was to determine whether retinal activity can support long-term changes in synaptic strength in the developing dorsal lateral geniculate nucleus (LGN) of thalamus. To test for this we made use of a rodent in vitro explant preparation in which retinal afferents and the intrinsic circuitry of the LGN remain intact. We repetitively stimulated the optic tract with a tetanus protocol that approximated the temporal features of spontaneous retinal waves. We found the amplitude of extracellular field potentials evoked by retinal stimulation changed significantly after tetanus and that the polarity of these alterations was related to postnatal age. At a time when substantial pruning of retinal connections occurs (postnatal day 1 P1 to P14), high-frequency stimulation led to an immediate and long-term depression (LTD). However, at times when pruning wanes and adultlike patterns of connectivity are stabilizing (P16 to P30), the identical form of stimulation produced a modest form of potentiation (long-term potentiation LTP). The LTD was unaffected by the bath application of -aminobutyric acid type A and N -methyl- D -aspartate receptor antagonists. However, both LTD and LTP were blocked by L-type Ca 2+ -channel antagonists. Thus the Ca 2+ influx associated with L-type channel activation mediates the induction of synaptic plasticity and may signal the pruning and subsequent stabilization of developing retinogeniculate connections.
Address for reprint requests and other correspondence: W. Guido, Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, VA 23238 (E-mail: wguido{at}vcu.edu ).
Enamines and enol ethers are versatile synthons for chemical synthesis. While several methods have been developed to access such molecules, prefunctionalized starting materials are usually required, ...and direct desaturation methods remain rare. Herein, we report direct desaturation reactions of N-protected cyclic amines and cyclic ethers using a mild I(III) oxidant, PhI(OAc)2, and an electron-deficient manganese pentafluorophenylporphyrin catalyst, Mn(TPFPP)Cl. This system displays high efficiency for α,β-desaturation of various cyclic amines and ethers. Mechanistic probes suggest that the desaturation reaction occurs via an initial α–C-H hydroxylation pathway, which serves to protect the product from overoxidation.
A methodology for using model-free kinetic analysis for the determination of mechanical properties is presented. Furthermore, this approach is used in finite element simulations for the prediction of ...the failure behaviour of adhesively bonded joints using a cohesive zone material model. Therefore, kinetic analysis is combined with mechanical experiments such as the butt-bonded hollow cylinder as well as the tapered double cantilever beam for the description of adhesive failure in mode I in various states of the curing reaction. It is shown that model-free kinetic predictions together with degree of cure dependent material properties can be used in finite element simulations to predict the transient material behaviour during cure.
Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin generation but has a limited role in hemostasis. From preclinical models and human genetics, an inhibitor of FXIa ...has the potential to be an antithrombotic agent with superior efficacy and safety. Reversible and irreversible inhibitors of FXIa have demonstrated excellent antithrombotic efficacy without increased bleeding time in animal models ( Weitz, J. I. , Chan, N. C. Arterioscler. Thromb. Vasc. Biol. 2019, 39 (1), 7−12 ). Herein, we report the discovery of a novel series of macrocyclic FXIa inhibitors containing a pyrazole P2′ moiety. Optimization of the series for (pharmacokinetic) PK properties, free fraction, and solubility resulted in the identification of milvexian (BMS-986177/JNJ-70033093, 17, FXIa K i = 0.11 nM) as a clinical candidate for the prevention and treatment of thromboembolic disorders, suitable for oral administration.
The purpose of this study was to determine the correlation between human observer performance for localization of small low contrast lesions within uniform water background versus an anatomical liver ...background, under the conditions of varying dose, lesion size, and reconstruction algorithm. Liver lesions (5 mm, 7 mm, and 9 mm, contrast: -21 HU) were digitally inserted into CT projection data of ten normal patients in vessel-free liver regions. Noise was inserted into the projection data to create three image sets: full dose and simulated half and quarter doses. Images were reconstructed with a standard filtered back projection (FBP) and an iterative reconstruction (IR) algorithm. Lesion and noise insertion procedures were repeated with water phantom data. Two-dimensional regions of interest (66 lesion-present, 34 lesion-absent) were selected, randomized, and independently reviewed by three medical physicists to identify the most likely location of the lesion and provide a confidence score. Locations and confidence scores were assessed using the area under the localization receiver operating characteristic curve (Az
). We examined the correlation between human performance for the liver and uniform water backgrounds as dose, lesion size, and reconstruction algorithm varied. As lesion size or dose increased, reader localization performance improved. For full dose IR images, the Az
for 5, 7, and 9 mm lesions were 0.53, 0.91, and 0.97 (liver) and 0.51, 0.96, and 0.99 (uniform water), respectively. Similar trends were seen with other parameters. Performance values for liver and uniform backgrounds were highly correlated for both reconstruction algorithms, with a Spearman correlation of ρ = 0.97, and an average difference in Az
of 0.05 ± 0.04. For the task of localizing low contrast liver lesions, human observer performance was highly correlated between anatomical and uniform backgrounds, suggesting that lesion localization studies emulating a clinical test of liver lesion detection can be performed using a uniform background.
Determination of the effect of protocol modifications on diagnostic performance in CT with human observers is extremely time-consuming, limiting the applicability of such methods in routine clinical ...practice. In this work, we sought to determine whether a channelized Hotelling observer (CHO) could predict human observer performance for the task of liver lesion localization as background, reconstruction algorithm, dose, and lesion size were varied. Liver lesions (5 mm, 7 mm, and 9 mm) were digitally inserted into the CT projection data of patients with normal livers and water phantoms. The projection data were reconstructed with filtered back projection (FBP) and iterative reconstruction (IR) algorithms for three dose levels: full dose (liver CTDIvol = 10.5 ± 8.5 mGy, water phantom CTDIvol = 9.6 ± 0.1 mGy) and simulated half and quarter doses. For each of 36 datasets (3 dose levels × 2 reconstruction algorithms × 2 backgrounds × 3 sizes), 66 signal-present and 34 signal-absent 2D images were extracted from the reconstructed volumes. Three medical physicists independently reviewed each dataset and noted the lesion location and a confidence score for each image. A CHO with Gabor channels was calculated to estimate the performance for each of the 36 localization tasks. The CHO performances, quantified using localization receiver operating characteristic (LROC) analysis, were compared to the human observer performances. Performance values between human and model observers were highly correlated for equivalent parameters (same lesion size, dose, background, and reconstruction), with a Spearman's correlation coefficient of 0.93 (95% CI: 0.82-0.98). CHO performance values for the uniform background were strongly correlated (ρ = 0.94, CI: 0.80-1.0) with the human observer performance values for the liver background. Performance values between human observers and CHO were highly correlated as dose, reconstruction type and object size were varied for the task of localization of patient liver lesions in both uniform and liver backgrounds.
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