Automated lung outline reconstruction in ventilation-perfusion scans using principal component analysis techniques

The present work addresses the development of an automated software-based system utilized in order to create an outline reconstruction of lung images from ventilation-perfusion scans for the purpose of diagnosing pulmonary embolism. The proposed diagnostic software procedure would require a standard set of digitized ventilation-perfusion scans in addition to correlated chest X-rays as key components in the identification of an ideal template match used to approximate and reconstruct the outline of the lungs. These reconstructed lung images would then be used to extract the necessary PIOPED-compliant features which would warrant a pulmonary embolism diagnosis. In order to evaluate this issue, two separate principal component analysis (PCA) algorithms were employed independently, including Eigenlungs, which was adapted from the Eigenfaces method, and an artificial neural network. The results obtained through MATLAB(TM) simulation indicated that lung outline reconstruction through the PCA approach carries significant viability.     

Automated lung segmentation of diseased and artifact-corrupted magnetic resonance sections

Segmentation of the lungs within magnetic resonance (MR) scans is a necessary step in the computer-based analysis of thoracic MR images. This process is often confounded by image acquisition artifacts and disease-induced morphological deformation. We have developed an automated method for lung segmentation that is insensitive to these complications. The automated method was applied to 23 thoracic MR scans (413 sections) obtained from 10 patients. Two radiologists manually outlined the lung regions in a random sample of 101 sections (n=202 lungs), and the extent to which disease or artifact confounded lung border visualization was evaluated. Accuracy of lung regions extracted by the automated segmentation method was quantified by comparison with the radiologist-defined lung regions using an area overlap measure (AOM) that ranged from 0 (disjoint lung regions) to 1 (complete overlap). The AOM between each observer and the automated method was 0.82 when averaged over all lungs. The average AOM in the lung bases, where lung segmentation is most difficult, was 0.73.     

Defining the lung outline from a gamma camera transmission attenuation map

Segmentation of the lung outline from gamma camera transmission images of the thorax is useful in attenuation correction and quantitative image analysis. This paper describes and compares two threshold-based methods of segmentation. Simulated gamma camera transmission images of test objects were used to produce a knowledge base of the variation of threshold defining the lung outline with image resolution and chest wall thickness. Two segmentation techniques based on global (GT) and context-sensitive (CST) thresholds were developed and evaluated in simulated transmission images of realistic thoraces. The segmented lung volumes were compared to the true values used in the simulation. The mean distances between segmented and true lung surface were calculated. The techniques were also applied to three real human subject transmission images. The lung volumes were estimated and the segmentations were compared visually. The CST segmentation produced significantly superior segmentations than the GT technique in the simulated data. In human subjects, the GT technique underestimated volumes by 13% compared to the CST technique. It missed areas that clearly belonged to the lungs. In conclusion, both techniques segmented the lungs with reasonable accuracy and precision. The CST approach was superior, particularly in real human subject images.     

Effects of Central Airway Shunting on the Mechanical Impedance of the Mouse Lung

The mechanical properties of the lung are embodied in its mechanical input impedance, which it is interpreted in physiological terms by being fit with a mathematical model. The normal lung is extremely well described by a model consisting of a single uniformly ventilated compartment comprised of tissue having a constant-phase impedance, but to describe the abnormal lung it frequently becomes necessary to invoke additional compartments. To date, all evidence of regional mechanical heterogeneity in the mouse lung has been assumed to be of the parallel variety. We therefore investigated the use of a serial heterogeneity model, relative to parallel heterogeneity and homogeneous models, for describing impedance spectra in mice subjected to a variety of interventions designed to make their lungs heterogeneous. We found that functional evidence of the finite stiffness of the airway wall in mice with airways obstruction can sometimes be apparent in lung impedance below 20 Hz. The model estimates of airway stiffness were smaller than direct estimates obtained from micro-CT images of the lung in vivo, suggesting that the conducting airways alone are likely not the precise anatomical correlate of proximal functional stiffness in the lung. Nevertheless, we conclude that central airway shunting in mice can sometimes be an important physiological phenomenon.     

Localization of inter-rib spaces for lung texture analysis and computer-aided diagnosis in digital chest images

An automated method for sampling lung textures in digital posterior/anterior chest images is being developed for use in computer-aided diagnosis of interstitial pulmonary diseases. In our present approach, two vertical profiles in the periphery of both lungs are fitted with a shift-variant sinusoidal function from which we estimate locations of posterior ribs and inter-rib spaces. Regions of interest (ROI's) for sampling lung textures are then automatically centered on the calculated locations of inter-rib spaces. In tests with 66 chest images, the overall success rate in placing 6.4 mm X 6.4 mm ROI's within inter-rib spaces with this method was 71%, with an average of 18 ROI's selected in 4-5 s/image by a VAX11/750 computer. When four additional alternative ROI's were selected on the sides of each original ROI, the success rate in having at least one ROI correctly located in an inter-rib space increased to 94%. Since we are still developing a fully automated sampling method, the present approach has been incorporated into a semiautomated method that is currently being used to sample lung textures from a large number of clinical cases.     

Biomechanical interpretation of a free-breathing lung motion model

The purpose of this paper is to develop a biomechanical model for free-breathing motion and compare it to a published heuristic five-dimensional (5D) free-breathing lung motion model. An ab initio biomechanical model was developed to describe the motion of lung tissue during free breathing by analyzing the stress-strain relationship inside lung tissue. The first-order approximation of the biomechanical model was equivalent to a heuristic 5D free-breathing lung motion model proposed by Low et al in 2005 (Int. J. Radiat. Oncol. Biol. Phys. 63 921-9), in which the motion was broken down to a linear expansion component and a hysteresis component. To test the biomechanical model, parameters that characterize expansion, hysteresis and angles between the two motion components were reported independently and compared between two models. The biomechanical model agreed well with the heuristic model within 5.5% in the left lungs and 1.5% in the right lungs for patients without lung cancer. The biomechanical model predicted that a histogram of angles between the two motion components should have two peaks at 39.8° and 140.2° in the left lungs and 37.1° and 142.9° in the right lungs. The data from the 5D model verified the existence of those peaks at 41.2° and 148.2° in the left lungs and 40.1° and 140° in the right lungs for patients without lung cancer. Similar results were also observed for the patients with lung cancer, but with greater discrepancies. The maximum-likelihood estimation of hysteresis magnitude was reported to be 2.6 mm for the lung cancer patients. The first-order approximation of the biomechanical model fit the heuristic 5D model very well. The biomechanical model provided new insights into breathing motion with specific focus on motion trajectory hysteresis.     

A Novel Supervised Approach for Segmentation of Lung Parenchyma from Chest CT for Computer-Aided Diagnosis

Segmentation of lung parenchyma from the chest computed tomography is an important task in analysis of chest computed tomography for diagnosis of lung disorders. It is a challenging task especially in the presence of peripherally placed pathology bearing regions. In this work, we propose a segmentation approach to segment lung parenchyma from chest. The first step is to segment the lungs using iterative thresholding followed by morphological operations. If the two lungs are not separated, the lung junction and its neighborhood are identified and local thresholding is applied. The second step is to extract shape features of the two lungs. The third step is to use a multilayer feed forward neural network to determine if the segmented lung parenchyma is complete, based on the extracted features. The final step is to reconstruct the two lungs in case of incomplete segmentation, by exploiting the fact that in majority of the cases, at least one of the two lungs would have been segmented correctly by the first step. Hence, the complete lung is determined based on the shape and region properties and the incomplete lung is reconstructed by applying graphical methods, namely, reflection and translation. The proposed approach has been tested in a computer-aided diagnosis system for diagnosis of lung disorders, namely, bronchiectasis, tuberculosis, and pneumonia. An accuracy of 97.37 % has been achieved by the proposed approach whereas the conventional thresholding approach was unable to detect peripheral pathology-bearing regions. The results obtained prove to be better than that achieved using conventional thresholding and morphological operations.     

An automated roentgenologist's workplace

Conclusions 1. Two-level architecture of the AWPR software optimizes the speed of computation and allows real-time processing of medical images. This significantly improves interpretation efficiency and information content of processed images.2. A technology for digital processing of linear tomograms of lungs has been developed on the basis of the AWPR. The technology is designed for early preclinical diagnosis of peripheral lung cancer.3. Clinical testing supported diagnostic efficiency of the developed technology in differential diagnosis of spherical neoplasms in lungs.4. In combination with visual analysis, the proposed quantitative technology avoids subjective factor and uncertainty in diagnosis of peripheral lung cancer.Institute for Problems of Information Transmission, Russian Academy of Sciences. Sechenov Moscow Medical Academy. Translated from Meditsinskaya Tekhnika, No. 1, pp. 7–14, January–February, 1995.     

Recurrence of bronchioloalveolar carcinoma in donor lung after lung transplantation: microsatellite analysis demonstrates a recipient origin

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.     

Improved contralateral subtraction images by use of elastic matching technique

A contralateral subtraction technique has been developed to assist radiologists in the detection of asymmetric abnormalities such as lung nodules on a single chest radiograph. With this technique, a contralateral subtraction image is obtained by subtracting a right/left reversed "mirror" image from the original one. The lesions in the subtraction image may be enhanced because most of the symmetric skeletal structures, such as peripheral ribs, are eliminated. Although the quality of the previous contralateral subtraction images is relatively good, severe misregistration artifacts, mainly due to serious asymmetry of the ribs in the two lungs of the original image, were observed in some cases, and minor misregistration artifacts were also observed in many cases. In this study, we employed three image warping techniques. An initial global warping technique was applied to reduce severe misregistration artifacts in the subtraction image caused by asymmetric rib structures. Additional two iterative warping techniques based on an elastic matching technique were used for accurate registration of the local structures of ribs, so that minor artifacts present in many subtraction images obtained with the previous technique were greatly reduced. With the new technique, the percentage of chest images, which were rated as being of adequate, good, or excellent quality of subtraction images by use of a subjective evaluation method, was improved from 91% to 97%. In particular, the number of cases with excellent quality was greatly increased from 15% to 42%. The contralateral subtraction technique can be used for detection of asymmetric abnormalities, such as lung nodules, pneumothorax, pneumonia, and emphysema, on peripheral lungs in single chest radiographs, and it therefore has potential utility in a large proportion of abnormal chest images.     

Donor lungs with pulmonary embolism evaluated with ex vivo lung perfusion

Acute pulmonary embolism (PE) compromises oxygenation and is typically considered a contraindication to lung donation for transplantation. We report the use of ex vivo lung perfusion (EVLP) to evaluate and possibly improve a pair of donor lungs with PE and poor oxygen exchange to a condition that might have been suitable for subsequent transplantation. A pair of donor lungs was procured for research after being declined for clinical use and placed on the EVLP circuit for 7 hours. Functional monitoring of the lungs revealed an increase in the partial pressure of oxygen to fraction of inspired oxygen ratio (P/F ratio) from 268 in situ to 458 after EVLP. While on the circuit, pulmonary vascular resistance decreased as dynamic compliance of the lungs increased, suggesting they might have been acceptable for transplantation.     

Image feature analysis and computer-aided diagnosis in digital radiography: detection and characterization of interstitial lung disease in digital chest radiographs

We are developing an automated method for determining physical measures of lung textures in digital chest radiographs in order to detect and characterize interstitial lung disease. With this method, the underlying background density variations caused by the gross lung and chest wall anatomy are corrected for in order to isolate the fluctuating patterns of the underlying lung texture for subsequent computer analysis. The power spectrum of lung texture, which is obtained from the two-dimensional Fourier transform, is filtered by the visual system response of the human observer. The magnitude and coarseness (or fineness) of the lung textures are then quantified by the root-mean-square (rms) variation and the first moment of the power spectrum, respectively. Preliminary results indicate that the rms variations and/or the first moments of the texture of abnormal lungs with various interstitial diseases are clearly different from those of normal lungs. Our results suggest strongly that quantitative texture measures calculated from digital chest images may be useful to radiologists in their assessment of interstitial disease.     

High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmunotherapy: correlation with histology

A model lung tumor system has been developed in mice for the evaluation of vascular targeted radioimmunotherapy. In this model, EMT-6 mammary carcinoma tumors growing in the lung are treated with 213Bi, an alpha particle emitter, which is targeted to lung blood vessels using a monoclonal antibody. Smaller tumors (< 100 microm in diameter) are cured, but larger tumors undergo a period of regression and then regrow and ultimately prove lethal. The goal of this work was to determine if external imaging with MRI or CT could be used routinely to monitor the growth/ regression of lung tumors in live mice. To attempt to evaluate individual tumors in vivo, animals were initially imaged with magnetic resonance imaging (MRI). High resolution MRI images could be obtained only after sacrifice when lungs were not moving. In contrast, high resolution computed tomography (CT) produced evaluable images from anesthetized animals. Serial CT images (up to 5/animal) were collected over a 17 day period of tumor growth and treatment. When tumored animals became moribund, animals were sacrificed and lungs were inflated with fixative, embedded in paraffin, and then sectioned serially to compare the detection of tumors by high resolution CT with detection by histology. CT proved most useful in detecting lung tumors located in the hilar area and least useful in detecting serosal surface and anterior lobe tumor foci. Overall, CT images of live animals revealed tumors in approximately 2/3 of cases detected in histologic serial sections when relatively few tumors were present per lung. Detection of lesions and their resolution post therapy were complicated due to residual hemorrhagic, regressing tumor nodules and the development of lung edema both of which appeared as high density areas in the CT scans. We conclude that the microCT method used could identify some lung tumors as small as 100 microm in diameter; however, no concrete evaluation of therapy induced regression of the tumors could be made with CT analyses alone.     

Orientation correction for chest images

This report presents an automatic procedure that determines the orientation of computed radiography (CR) chest images and rotates them to a standard position to be viewed by radiologists. As an input, CR images of a normalized size of 1,000 x 1,000 or 2,000 x 2,000 pixels are used. The analysis is performed in three steps. First, the orientation of the spine within the image is determined. Then, a function searches for upper extremities and the subdiaphragm. Finally, the lungs are extracted and their areas are compared. This indicates whether the image needs to be y-axis flipped. These three steps set the value of three parameters on the basis of which the final rotation angle is determined. The procedure has been implemented in the clinics at UCLA. The rate of correctly rotated images is 95.4%.     

Development of a Voxel-Matching Technique for Substantial Reduction of Subtraction Artifacts in Temporal Subtraction Images Obtained from Thoracic MDCT

A temporal subtraction image, which is obtained by subtraction of a previous image from a current one, can be used for enhancing interval changes (such as formation of new lesions and changes in existing abnormalities) on medical images by removing most of the normal structures. However, subtraction artifacts are commonly included in temporal subtraction images obtained from thoracic computed tomography and thus tend to reduce its effectiveness in the detection of pulmonary nodules. In this study, we developed a new method for substantially removing the artifacts on temporal subtraction images of lungs obtained from multiple-detector computed tomography (MDCT) by using a voxel-matching technique. Our new method was examined on 20 clinical cases with MDCT images. With this technique, the voxel value in a warped (or nonwarped) previous image is replaced by a voxel value within a kernel, such as a small cube centered at a given location, which would be closest (identical or nearly equal) to the voxel value in the corresponding location in the current image. With the voxel-matching technique, the correspondence not only between the structures but also between the voxel values in the current and the previous images is determined. To evaluate the usefulness of the voxel-matching technique for removal of subtraction artifacts, the magnitude of artifacts remaining in the temporal subtraction images was examined by use of the full width at half maximum and the sum of a histogram of voxel values, which may indicate the average contrast and the total amount, respectively, of subtraction artifacts. With our new method, subtraction artifacts due to normal structures such as blood vessels were substantially removed on temporal subtraction images. This computerized method can enhance lung nodules on chest MDCT images without disturbing misregistration artifacts.     

Scanning electron microscope study of the morphology of the reptilian lung: the Savanna monitor lizard Varanus exanthematicus and the pancake tortoise Malacochersus tornieri

The morphology of the lungs of two reptilian species, Varanus exanthematicus and Malacochersus tornieri, have been studied on gross preparations, latex casts, and critical-point-dried tissues. The shape of these lungs was observed to conform with that of the body, the lung of the monitor lizard (Varanus) being long and ovoid while that of the pancake tortoise (Malacochersus) was rounded and laterally indented. With respect to the size distribution of the gas exchange compartments, the lungs were observed to be notably heterogenous. In both species these units were generally smaller in diameter in the cranial region of the lung while those in the caudal region were larger. The gas exchange compartments in the tortoise were more profusely compartmented with the primary, secondary, and tertiary septa being well developed while in the lizard only the primary and secondary septa were observed. The tertiary septa in the tortoise lung and the secondary septa in that of the monitor lizard defined the terminal gas exchange units, the faveoli. The cast impressions closely resembled the actual lung tissue and convincingly revealed the hierarchical design of the gas exchange compartments as they radiate from the air chambers and ducts, terminally giving rise to the faveoli. This stratification clearly increases the surface area available for gas exchange in these lungs. Disparate refinements of the basic reptilian lung design, as noted here, may lead to differing anatomic pulmonary diffusing capacities for oxygen to which characteristics like energetics and mode of respiration in this taxon may be attributed.     

Acute stress reduces intraparenchymal lung natural killer cells via beta-adrenergic stimulation

There are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home-cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors.     

Cancerous nuclei detection on digitized pathological lung color images

In this paper, we propose a methodology (in the form of a software package) for automatic extraction of the cancerous nuclei in lung pathological color images. We first segment the images using an unsupervised Hopfield artificial neural network classifier and we label the segmented image based on chromaticity features and histogram analysis of the RGB color space components of the raw image. Then, we fill the holes inside the extracted nuclei regions based on the maximum drawable circle algorithm. All corrected nuclei regions are then classified into normal and cancerous using diagnostic rules formulated with respect to the rules used by experimented pathologist. The proposed method provides quantitative results in diagnosing a lung pathological image set of 16 cases that are comparable to an expert's diagnosis.     

Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer

Lung cancer is the most malignant cancer today; in order to develop an effective drug delivery system for lung cancer therapy, gelatin nanoparticles (GPs) were modified with NeutrAvidin^FITC-biotinylated epidermal growth factor (EGF) to form EGF receptor (EGFR)-seeking nanoparticles (GP-Av-bEGF). Aerosol droplets of the GP-Av-bEGF were generated by using a nebulizer and were delivered to mice model of lung cancer via aerosol delivery.

Analysis of the aerosol size revealed that 99% of the nanoparticles after nebulization had a mass median aerodynamic diameter (MMAD) within the suitable range (0.5–5 μm) for lower airway deposition. The safety of inhaled nanoparticles was examined by lung edema and myeloperoxidase (MPO) activity assay. There's no finding suggestive of acute lung inflammation following inhalation. The fluorescence images obtained from live mice showed that the GP-Av-bEGF could target the cancerous lungs in a more specific manner. Fluorescence analysis of the organs revealed that the GP-Av-bEGF was mainly distributed in cancerous lungs. In contrast, nanoparticle accumulation was lower in normal lungs. The histological results indicated that the fluorescent GP-Av-bEGF was colocalized with the anti-EGFR-immunostain due to EGFR binding.

The results of this study revealed that GP-Av-bEGF could target to the EGFR-overexpression cancer cells in vivo and may prove to be beneficial drug carriers when administered by simple aerosol delivery for the treatment of lung cancer.     

Comparison of hyperpolarized 3He MRI rat lung volume measurement with micro‐computed tomography

In this study, the upper‐limit volume (gas plus partial tissue volume) as well as absolute volume (gas only) of lungs measured with hyperpolarized ³He‐MR imaging is compared with that determined by micro‐computed tomography (CT) under similar ventilation conditions in normal rats. Five Brown Norway rats (210–259 g) were ventilated with O₂, alternately with ³He, using a computer‐controlled ventilator, and 3D density‐weighted images of the lungs were acquired during a breath hold after six wash‐in breaths of ³He. The rats were then transferred to a micro‐CT scanner, and a similar experimental setup was used to obtain images of the lungs during a breath hold of air with an airway pressure equal to that of the MR imaging breath hold. The upper‐limit and absolute volumes obtained from ³He‐MR and micro‐CT methods were not significantly different (p > 0.05). The good agreement between the lung volumes measured with the two imaging methods suggests that ³He‐MR imaging can be used for quantitative analysis of lung volume changes in longitudinal studies without the exposure to the ionizing radiation which accompanies micro‐CT imaging. Copyright © 2010 John Wiley & Sons, Ltd.