Functional lung imaging with synchrotron radiation: Methods and preclinical applications

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.     

Computed tomography and automated image analysis of prehistoric femora

Non-invasive characterization of limb bone cross-sectional geometry would be useful for biomechanical analyses of skeletal collections. Computed tomography (CT) is potentially the method of choice. Additionally, CT images are suitable for automated analysis. CT is here shown to be both accurate and precise in the analysis of cross-sectional geometry of prehistoric femora. Beam hardening artifacts can be reduced by using a water bath. As the availability of CT for research increases, both bone density and geometry could be determined simultaneously with this method.     

Binding characteristics of dermorphin, and [dermorphin1-7]-beta c-endorphin in rat brain membranes

Dermorphin and a camel beta-endorphin (beta c-EP) analog in which residues 1-7 correspond to the dermorphin sequence ([Dermorphin1-7]-beta c-EP) have been investigated with respect to their receptor binding characteristics using human and camel beta-EP as reference peptides. Tritiated dihydromorphine, [D-Ala2, D-Leu5]-enkephalin, ethylketocyclazocine and human beta-endorphin were used as primary ligands in the rat brain membrane preparation for radioreceptor assay. Camel beta-endorphin was the most potent peptide in all experiments. [Dermorphin1-7]-beta c-EP is significantly less potent towards 3H-ethylketocyclazocine and 3H-[D-Ala2, D-Leu5]-enkephalin but is as potent towards 3H-dihydromorphine and 3H-human beta-endorphin. Dermorphin itself weakly displaces tritiated dihydromorphine, [D-Ala2, D-Leu5]-enkephalin and ethylketocyclazocine (potency relative to camel beta-EP, 1-4%) but it is more potent (9%) in competition with tritiated human beta-endorphin. Dermorphin and the [Dermorphin-1-7]-beta c-EP appear to interact preferentially with mu opiate receptors.     

THE LASER TOMOGRAPHICAL METHOD USINGMINIMUM OF PROJECTION FOR BIOLOGICAL OBJECT STRUCTURE STUDY

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Changes in human jaw muscles with age and dental state

The effects of ageing and dental state on the cross-sectional area and density of two jaw muscles, the masseter and medial pterygoid, were investigated using computed tomography. The study involved 84 male and 70 female subjects between the ages of 20 and 90 years. The cross-sectional area of both muscles showed a significant reduction with age; values for female subjects being found in the lower range of the distribution. When consideration was given to the presence or absence of a natural dentition, the cross-sectional area of both muscles in edentulous subjects showed a greater decease throughout the age range studied. There was a significant decrease in the density of the muscles with increasing age. Previously, this has been interpreted to indicate a progressive increase in fat and fibrous tissue. Subject gender and the absence of teeth appeared to have little effect on this parameter. Changes in the cross-sectional area and density of these muscles would appear to be consistent with a general age related change of muscle tissue in the body as a whole and may specifically indicate a reduction in the masticatory forces which can be or are being utilised by ageing patients, many of whom have no remaining natural dentition.     

Paleopediatrics: Or when did human infants really become human?

Modern human children take about twice as long as their closest biological relative, the chimpanzee, to mature. One standard explanation for the evolution of “delayed maturation” at an early stage of human evolution is that it provided the time necessary for immature individuals to learn complex skills, most notably those relating to tool-making abilities. However, after comparing dental maturational profiles of early hominids from South Africa (who apparently did make and use stone tools) (Susman [1994] Science 265:1570–1573) to those of extant humans and chimpanzees, we find no evidence to document an association between “delayed maturation” and tool-making abilities in the early stages of human evolution. This also suggests that the assumed association between prolonged childhood dependency and other behaviors often associated with the advent of tool-making such as cooperative hunting, food sharing, home bases, sexual division of labor, etc., is also suspect. Instead, we must look for other, or additional, selective pressures for the evolution of “delayed maturation,” which may postdate the australopithecine radiation. © 1995 Wiley-Liss, Inc.     

Higher patient doses through X-ray imaging procedures

Medical imaging using X-rays has been one of the most popular imaging modalities ever since the discovery of X-rays 125 years ago. With unquestionable benefits, concerns about radiation risks have frequently been raised. Computed tomography (CT) and fluoroscopic guided interventional procedures have the potential to impart higher radiation exposure to patients than radiographic examinations. Despite technological advances, there have been instances of increased doses per procedure mainly because of better diagnostic information in images. However, cumulative dose from multiple procedures is creating new concerns as effective doses >100 mSv are not uncommon. There is a need for action at all levels. Manufacturers must produce equipment that can provide a quality diagnostic image at substantially lesser dose and better implementation of optimization strategies by users. There is an urgent need for the industry to develop CT scanners with sub-mSv radiation dose, a goal that has been lingering. It appears that a new monochromatic X-ray source will lead to replacement of X-ray tubes all over the world in coming years and will lead to a drastic reduction in radiation doses. This innovation will impact all X-ray imaging and will help dose reduction. For interventional procedures, the likely employment of robotic systems in practice may drastically reduce radiation exposures to operators- but patient exposure will still remain an issue. Training needs always need to be emphasized and practiced.     

A novel fast kilovoltage switching dual-energy CT with deep learning: Accuracy of CT number on virtual monochromatic imaging and iodine quantification

PurposeA novel fast kilovoltage switching dual-energy CT with deep learning [Deep learning based-spectral CT (DL-Spectral CT)], which generates a complete sinogram for each kilovolt using deep learning views that complement the measured views at each energy, was commercialized in 2020. The purpose of this study was to evaluate the accuracy of CT numbers in virtual monochromatic images (VMIs) and iodine quantifications at various radiation doses using DL-Spectral CT.Materials and methodsTwo multi-energy phantoms (large and small) using several rods representing different materials (iodine, calcium, blood, and adipose) were scanned by DL-Spectral CT at varying radiation doses. Images were reconstructed using three reconstruction parameters (body, lung, bone). The absolute percentage errors (APEs) for CT numbers on VMIs at 50, 70, and 100 keV and iodine quantification were compared among different radiation dose protocols.ResultsThe APEs of the CT numbers on VMIs were <15% in both the large and small phantoms, except at the minimum dose in the large phantom. There were no significant differences among radiation dose protocols in computed tomography dose index volumes of 12.3 mGy or larger. The accuracy of iodine quantification provided by the body parameter was significantly better than those obtained with the lung and bone parameters. Increasing the radiation dose did not always improve the accuracy of iodine quantification, regardless of the reconstruction parameter and phantom size.ConclusionThe accuracy of iodine quantification and CT numbers on VMIs in DL-Spectral CT was not affected by the radiation dose, except for an extremely low radiation dose for body size.     

A lonely dot on the map: Exploring the climate signal in tree-ring density and stable isotopes of clanwilliam cedar,South Africa

Clanwilliam cedar (Widdringtonia cedarbergensis; WICE), a long-lived conifer with distinct tree rings in Cape Province, South Africa, has potential to provide a unique high-resolution climate proxy for southern Africa. However, the climate signal in WICE tree-ring width (TRW) is weak and the dendroclimatic potential of other WICE tree-ring parameters therefore needs to be explored. Here, we investigate the climatic signal in various tree-ring parameters, including TRW, Minimum Density (MND), Maximum Latewood Density (MXD), Maximum Latewood Blue Intensity (MXBI), and stable carbon and oxygen isotopes (δ¹⁸O and δ¹³C) measured in WICE samples collected in 1978. MND was negatively influenced by early spring (October-November) precipitation whereas TRW was positively influenced by spring November-December precipitation. MXD was negatively influenced by autumn (April-May) temperature whereas MXBI was not influenced by temperature. Both MXD and MXBI were negatively influenced by January-March and January-May precipitation respectively. We did not find a significant climate signal in either of the stable isotope time series, which were measured on a limited number of samples. WICE can live to be at least 356 years old and the current TRW chronology extends back to 1564 CE. The development of full-length chronologies of alternative tree-ring parameters, particularly MND, would allow for an annually resolved, multi-century spring precipitation reconstruction for this region in southern Africa, where vulnerability to future climate change is high.     

Automatic lung segmentation in COVID-19 patients: Impact on quantitative computed tomography analysis

PurposeTo assess the impact of lung segmentation accuracy in an automatic pipeline for quantitative analysis of CT images.MethodsFour different platforms for automatic lung segmentation based on convolutional neural network (CNN), region-growing technique and atlas-based algorithm were considered. The platforms were tested using CT images of 55 COVID-19 patients with severe lung impairment. Four radiologists assessed the segmentations using a 5-point qualitative score (QS). For each CT series, a manually revised reference segmentation (RS) was obtained. Histogram-based quantitative metrics (QM) were calculated from CT histogram using lung segmentationsfrom all platforms and RS. Dice index (DI) and differences of QMs (ΔQMs) were calculated between RS and other segmentations.ResultsHighest QS and lower ΔQMs values were associated to the CNN algorithm. However, only 45% CNN segmentations were judged to need no or only minimal corrections, and in only 17 cases (31%), automatic segmentations provided RS without manual corrections. Median values of the DI for the four algorithms ranged from 0.993 to 0.904. Significant differences for all QMs calculated between automatic segmentations and RS were found both when data were pooled together and stratified according to QS, indicating a relationship between qualitative and quantitative measurements. The most unstable QM was the histogram 90th percentile, with median ΔQMs values ranging from 10HU and 158HU between different algorithms.ConclusionsNone of tested algorithms provided fully reliable segmentation. Segmentation accuracy impacts differently on different quantitative metrics, and each of them should be individually evaluated according to the purpose of subsequent analyses.