Identifying Robust Radiomics Features for Lung Cancer by Using In-Vivo and Phantom Lung Lesions.

We propose a novel framework for determining radiomics feature robustness by considering the effects of both biological and noise signals. This framework is preliminarily tested in a study predicting the epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) patients. Pairs of CT images (baseline, 3-week post therapy) of 46 NSCLC patients with known EGFR mutation status were collected and a FDA-customized anthropomorphic thoracic phantom was scanned on two vendors' scanners at four different tube currents. Delta radiomics features were extracted from the NSCLC patient CTs and reproducible, non-redundant, and informative features were identified. The feature value differences between EGFR mutant and EGFR wildtype patients were quantitatively measured as the biological signal. Similarly, radiomics features were extracted from the phantom CTs. A pairwise comparison between settings resulted in a feature value difference that was quantitatively measured as the noise signal. Biological signals were compared to noise signals at each setting to determine if the distributions were significantly different by two-sample t-test, and thus robust. Four optimal features were selected to predict EGFR mutation status, Tumor-Mass, Sigmoid-Offset-Mean, Gabor-Energy and DWT-Energy, which quantified tumor mass, tumor-parenchyma density transition at boundary, line-like pattern inside tumor and intratumoral heterogeneity, respectively. The first three variables showed robustness across the majority of studied CT acquisition parameters. The textual feature DWT-Energy was less robust. The proposed framework was able to determine robustness of radiomics features at specific settings by comparing biological signal to noise signal. Identification of robust radiomics features may improve the generalizability of radiomics models in future studies.

Radiation dose descriptors: BERT, COD, DAP, and other strange creatures.

Over the years, a number of terms have been used to describe radiation dose. Eight common radiation dose descriptors include background equivalent radiation time (BERT), critical organ dose (COD), surface absorbed dose (SAD), dose area product (DAP), diagnostic acceptable reference level (DARLing), effective dose (ED), fetal absorbed dose (FAD), and total imparted energy (TIE). BERT is compared to the annual natural background radiation (about 3 mSv per year) and is easily understandable for the general public. COD refers to the radiation dose delivered to an individual critical organ. SAD is the radiation dose delivered at the skin surface. DAP is a product of the irradiated surface area multiplied by the radiation dose at the surface. DARLing is usually the radiation level that encompasses 75% (the third quartile) of the data derived from a nationwide or regional survey. DARLings are meant for voluntary guidance. Consistently higher patient doses should be investigated for possible equipment deficiencies or suboptimal protocols. ED is obtained by multiplying the radiation dose delivered to each organ by its weighting factor and then by adding those values to get the sum. It can be used to assess the risk of radiation-induced cancers and serious hereditary effects to future generations, regardless of the procedure being performed, and is the most useful radiation dose descriptor. FAD is the radiation dose delivered to the fetus, and TIE is the sum of the energy imparted to all irradiated tissue. Each of these descriptors is intended to relate radiation dose ultimately to potential biologic effects. To avoid confusion, the key is to avoid using the terms interchangeably. It is important to understand each of the radiation dose descriptors and their derivation in order to correctly evaluate radiation dose and to consult with patients concerned about the risks of radiation.

An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents.

Drug-herb interactions can result from the modulation of the activities of cytochrome P450 (P450) and/or drug transporters. The effect of extracts and individual constituents of goldenseal, Ginkgo biloba (and its hydrolyzate), grape seed, milk thistle, and ginseng on the activities of cytochrome P450 enzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes were determined using enzyme-selective probe substrates, and their effect on human P-glycoprotein (Pgp) was determined using a baculovirus expression system by measuring the verapamil-stimulated, vanadate-sensitive ATPase activity. Extracts were analyzed by HPLC to standardize their concentration(s) of constituents associated with the pharmacological activity, and to allow comparison of their effects on P450 and Pgp with literature values. Many of the extracts/constituents exerted > or = 50 % inhibition of P450 activity. These include those from goldenseal (normalized to alkaloid content) inhibiting CYP2C8, CYP2D6, and CYP3A4 at 20 microM, ginkgo inhibiting CYP2C8 at 10 microM, grape seed inhibiting CYP2C9 and CYP3A4 at 10 microM, milk thistle inhibiting CYP2C8 at 10 microM, and ginsenosides F1 and Rh1 (but not ginseng extract) inhibiting CYP3A4 at 10 microM. Goldenseal extracts/constituents (20 microM, particularly hydrastine) and ginsenoside Rh1 stimulated ATPase at about half of the activity of the model substrate, verapamil (20 microM). The data suggest that the clearance of a variety of drugs may be diminished by concomitant use of these herbs via inhibition of P450 enzymes, but less so by Pgp-mediated effects.

Influence of flat-panel fluoroscopic equipment variables on cardiac radiation doses.

PURPOSE: To assess the influence of physician-selectable equipment variables on the potential radiation dose reductions during cardiac catheterization examinations using modern imaging equipment. MATERIALS: A modern bi-plane angiography unit with flat-panel image receptors was used. Patients were simulated with 15-30 cm of acrylic plastic. The variables studied were: patient thickness, fluoroscopy pulse rates, record mode frame rates, image receptor field-of-view (FoV), automatic dose control (ADC) mode, SID/SSD geometry setting, automatic collimation, automatic positioning, and others. RESULTS: Patient radiation doses double for every additional 3.5-4.5 cm of soft tissue. The dose is directly related to the imaging frame rate; a decrease from 30 pps to 15 pps reduces the dose by about 50%. The dose is related to [(FoV)(-N )] where 2.0 < N < 3.0. Suboptimal positioning of the patient can nearly double the dose. The ADC system provides three selections that can vary the radiation level by 50%. For pediatric studies (2-5 years old), the selection of equipment variables can result in entrance radiation doses that range between 6 and 60 cGy for diagnostic cases and between 15 and 140 cGy for interventional cases. For adult studies, the equipment variables can produce entrance radiation doses that range between 13 and 130 cGy for diagnostic cases and between 30 and 400 cGy for interventional cases. CONCLUSIONS: Overall dose reductions of 70-90% can be achieved with pediatric patients and about 90% with adult patients solely through optimal selection of equipment variables.

Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro.

Reported adverse drug interactions with the popular herb kava have spurred investigation of the mechanisms by which kava could mediate these effects. In vivo and in vitro experiments were conducted to examine the effects of kava extract and individual kavalactones on cytochrome P450 (P450) and P-glycoprotein activity. The oral pharmacokinetics of the kavalactone, kawain (100 mg/kg), were determined in rats with and without coadministration of kava extract (256 mg/kg) to study the effect of the extract on drug disposition. Kawain was well absorbed, with >90% of the dose eliminated within 72 h, chiefly in urine. Compared with kawain alone, coadministration with kava extract caused a tripling of kawain AUC(0-8 h) and a doubling of C(max). However, a 7-day pretreatment with kava extract (256 mg /kg/day) had no effect on the pharmacokinetics of kawain administered on day 8. The 7-day pretreatment with kava extract only modestly induced hepatic P450 activities. The human hepatic microsomal P450s most strongly inhibited by kava extract (CYP2C9, CYP2C19, CYP2D6, CYP3A4) were inhibited to the same degree by a "composite" kava formulation composed of the six major kavalactones contained in the extract. K(i) values for the inhibition of CYP2C9 and CYP2C19 activities by methysticin, dihydromethysticin, and desmethoxyyangonin ranged from 5 to 10 microM. Kava extract and kavalactones (< or =9 microM) modestly stimulated P-glycoprotein ATPase activities. Taken together, the data indicate that kava can cause adverse drug reactions via inhibition of drug metabolism.

New automated fluoroscopic systems for pediatric applications.

Pediatric patients are at higher risk to the adverse effects from exposure to ionizing radiation than adults. The smaller sizes of the anatomy and the reduced X-ray attenuation of the tissues provide special challenges. The goal of this effort is to investigate strategies for pediatric fluoroscopy in order to minimize the radiation exposure to these individuals, while maintaining effective diagnostic image quality. Modern fluoroscopy systems are often entirely automated and computer controlled. In this paper, various selectable and automated modes are examined to determine the influence of the fluoroscopy parameters upon the patient radiation exposures and image quality. These parameters include variable X-ray beam filters, automatic brightness control programs, starting kilovolt peak levels, fluoroscopic pulse rates, and other factors. Typical values of radiation exposure rates have been measured for a range of phantom thicknesses from 5 cm to 20 cm of acrylic. Other factors that have been assessed include spatial resolution, low contrast discrimination, and temporal resolution. The selection menu for various procedures is based upon the examination type, anatomical region, and patient size. For pediatric patients, the automated system can employ additional filtration, special automatic brightness control curves, pulsed fluoroscopy, and other features to reduce the patient radiation exposures without significantly compromising the image quality. The benefits gained from an optimal selection of automated programs and settings for fluoroscopy include ease of operation, better image quality, and lower patient radiation exposures.

Pediatric high KV/filtered airway radiographs: comparison of CR and film-screen systems.

The imaging of pediatric airways presents a challenge because of the superimposition of the airway over the bone of the spine on the AP view. In recent years, some radiology departments have replaced conventional X-ray films by computed radiography (CR). The effect of the various changes upon image quality and radiation doses has not been clearly demonstrated. The goal of this paper was to investigate and identify potential improvements and/or degradations to pediatric airways imaging from the application of new technology, in particular to high KV/filtered radiographs; a new filter was designed. Two modern film-screen combinations and a CR system were evaluated for a range of tube potentials from 60 to 140 kVp. The spatial resolutions were measured for different geometrical magnifications. Relative radiation doses were also determined. Clinical airway images of children taken with the different imaging methods were subjectively compared. Our study confirmed that the visualization of the pediatric airways is enhanced by using high X-ray tube potentials with proper X-ray beam filtration. For CR systems, the selection of the cassette size, cassette type, focal spot, and geometrical magnification impact upon the image quality. Despite the increased dynamic range and image processing advantage with CR systems, CR techniques need to be improved to be more comparable with high kVp filtered magnification radiographs using film screens and small X-ray tube focal spots. With appropriate X-ray beam filtration and high kVp's, CR image receptors can provide adequate image quality for pediatric airway imaging. However, the transition to digital radiography involves certain caveats. In general, radiation doses with CR systems are greater than typical doses with film-screen systems.